Will PBMs move into Medicaid territory? 22 VA and IHS make mail-order work for millions 32 Measuring success: Monthly Rx safety audits 48 VOL. 155 NO. 2 В® Voice of the Pharmacist DrugTopics.com February 2011 Medicare Part D Audits Tips on how to prepare and respond PAGE 30 CREDIT: 2.0 Medication Errors: Causes, prevention, liability PAGE 36 Earn CE credit for this activity at DrugTopics.com Teva’s Budesonide Inhalation Suspension AN Rated and Bioequivalent to Pulmicort RespulesВ®* ly Available Exclusive from Teva To place your order, call your wholesaler or distributor today. Please see brief summary of prescribing information on adjacent page. Budesonide Inhalation Suspension STRENGTH SIZE NDC# 0.25 mg/2 mL 2 mL x 30 00093-6815-73 0.5 mg/2 mL 2 mL x 30 00093-6816-73 Intended for inhalation use only with compressed air driven nebulizer systems, also known as jet nebulizers. *Pulmicort RespulesВ® is a registered trademark of AstraZeneca. В©2011, Teva Pharmaceuticals USA 1090 Horsham Road • North Wales, PA 19454 800.545.8800 • www.tevausa.com 10147 BRIEF SUMMARY BUDESONIDE INHALATION SUSPENSION CLINICAL PHARMACOLOGY Pharmacokinetics Special Populations Nursing Mothers The disposition of budesonide when delivered by inhalation from a dry powder inhaler at doses of 200 or 400 mcg twice daily for at least 3 months was studied in eight lactating women with asthma from 1 to 6 months postpartum. Systemic exposure to budesonide in these women appears to be comparable to that in non-lactating women with asthma from other studies. Breast milk obtained over eight hours post-dose revealed that the maximum concentration of budesonide for the 400 and 800 mcg doses was 0.39 and 0.78 nmol/L, respectively, and occurred within 45 minutes after dosing. The estimated oral daily dose of budesonide from breast milk to the infant is approximately 0.007 and 0.014 mcg/kg/day for the two-dose regimens used in this study, which represents approximately 0.3% to 1% of the dose inhaled by the mother. Budesonide levels in plasma samples obtained from five infants at about 90 minutes after breast-feeding (and about 140 minutes after drug administration to the mother) were below quantifiable levels (< 0.02 nmol/L in four infants and < 0.04 nmol/L in one infant) (see PRECAUTIONS, Nursing Mothers). Pharmacodynamics The effects of budesonide inhalation suspension on the hypothalamic-pituitaryadrenal (HPA) axis were studied in three, 12-week, double-blind, placebocontrolled studies in 293 pediatric patients, 6 months to 8 years of age, with persistent asthma. For most patients, the ability to increase cortisol production in response to stress, as assessed by the short cosyntropin (ACTH) stimulation test, remained intact with budesonide inhalation suspension treatment. In a subgroup of children age 6 months to 2 years (n = 21) treated with a total daily dose of budesonide inhalation suspension up to 1 mg or placebo, the mean change from baseline in ACTH-stimulated cortisol levels showed a decline in peak stimulated cortisol at 12 weeks compared to an increase in the placebo group. These mean differences were not statistically significant compared to placebo. Another 12-week study was conducted in 141 pediatric patients 6 to 12 months of age with mild to moderate asthma or recurrent/persistent wheezing. All patients were treated with a total daily dose of either 0.5 mg or 1 mg of budesonide inhalation suspension or placebo. A total of 28, 17, and 31 patients in the budesonide inhalation suspension 0.5 mg, 1 mg, and placebo arms respectively had an evaluation of serum cortisol levels post-ACTH stimulation both at baseline and at the end of the study. The mean change from baseline to Week 12 ACTH-stimulated minus basal plasma cortisol levels did not indicate adrenal suppression in patients treated with budesonide inhalation suspension versus placebo. However, 7 patients in this study (4 of whom received budesonide inhalation suspension 0.5 mg, 2 of whom received budesonide inhalation suspension 1 mg and 1 of whom received placebo) showed a shift from normal baseline stimulated cortisol level (≥ 500 nmol/L) to a subnormal level (< 500 nmol/L) at Week 12. In 4 of these patients receiving budesonide inhalation suspension, the cortisol values were near the cutoff value of 500 nmol/L. CLINICAL TRIALS Three double-blind, placebo-controlled, parallel group, randomized U.S. clinical trials of 12-weeks duration each were conducted in 1018 pediatric patients, 6 months to 8 years of age, with persistent asthma of varying disease duration (2 to 107 months) and severity. Doses of 0.25 mg and 0.5 mg administered twice daily were compared to placebo to provide information about appropriate dosing to cover a range of asthma severity. A Pari-LC-Jet Plus Nebulizer (with a face mask or mouthpiece) connected to a Pari Master compressor was used to deliver budesonide inhalation suspension to patients in the 3 U.S. controlled clinical trials. The co-primary endpoints were nighttime and daytime asthma symptom scores (0 to 3 scale). Each of the doses discussed below were studied in one or two, but not all three of the U.S. studies. Results of the 3 controlled clinical trials for recommended dosages of budesonide inhalation suspension (0.25 mg to 0.5 mg twice daily, up to a total daily dose of 1 mg) in patients, 12 months to 8 years of age, are presented below. Compared to placebo, budesonide inhalation suspension significantly decreased both nighttime and daytime symptom scores of asthma at doses of 0.25 mg twice daily, and 0.5 mg twice daily. Symptom reduction in response to budesonide inhalation suspension occurred across gender and age. Budesonide inhalation suspension significantly reduced the need for bronchodilator therapy at all the doses studied. Improvements in lung function were associated with budesonide inhalation suspension treatment in the subgroup of patients capable of performing lung function testing. Significant improvements were seen in FEV1 [budesonide inhalation suspension 0.5 mg twice daily] and morning PEF [budesonide inhalation suspension 0.25 mg twice daily and 0.5 mg twice daily] compared to placebo. A numerical reduction in nighttime and daytime symptom scores (0 to 3 scale) of asthma was observed within 2 to 8 days, although maximum benefit was not achieved for 4 to 6 weeks after starting treatment. The reduction in nighttime and daytime asthma symptom scores was maintained throughout the 12 weeks of the double-blind trials. CONTRAINDICATIONS Budesonide Inhalation Suspension is contraindicated as the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Hypersensitivity to budesonide inhalation suspension or any of the ingredients of this preparation contraindicates the use of budesonide inhalation suspension. WARNINGS Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA)-axis function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA-axis suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although budesonide inhalation suspension may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instructions. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to budesonide inhalation suspension. Lung function (FEV1 or AM PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to budesonide inhalation suspension may unmask allergic or other immunologic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eosinophilic conditions, eczema, and arthritis (see DOSAGE AND ADMINISTRATION). Patients who are on drugs which suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible pediatric patients or adults on immunosuppressant doses of corticosteroids. In pediatric or adult patients who have not had these diseases, or who have not been properly vaccinated, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. The clinical course of chicken pox or measles infection in patients on inhaled corticosteroids has not been studied. However, a clinical study has examined the immune responsiveness of asthma patients 12 months to 8 years of age who were treated with budesonide inhalation suspension (see PRECAUTIONS, Pediatric Use). If a patient on immunosuppressant doses of corticosteroids is exposed to chicken pox, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated (see the respective package inserts for complete VZIG and IG prescribing information). If chicken pox develops, treatment with antiviral agents may be considered. Budesonide inhalation suspension is not a bronchodilator and is not indicated for the rapid relief of acute bronchospasm or other acute episodes of asthma. As with other inhaled asthma medications, bronchospasm, with an immediate increase in wheezing, may occur after dosing. If acute bronchospasm occurs following dosing with budesonide inhalation suspension, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with budesonide inhalation suspension should be discontinued and alternate therapy instituted. Patients should be instructed to contact their physician immediately when episodes of asthma not responsive to their usual doses of bronchodilators occur during treatment with budesonide inhalation suspension. Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm have been reported with use of budesonide inhalation suspension . Discontinue budesonide inhalation suspension if such reactions occur (see CONTRAINDICATIONS and ADVERSE REACTIONS). PRECAUTIONS General During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/ or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function (see DOSAGE AND ADMINISTRATION). Because budesonide is absorbed into the circulation and may be systemically active, particularly at higher doses, suppression of HPA function may be associated when budesonide inhalation suspension is administered at doses exceeding those recommended (see DOSAGE AND ADMINISTRATION), or when the dose is not titrated to the lowest effective dose. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing budesonide inhalation suspension. Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with budesonide inhalation suspension should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients post-operatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism, reduced bone mineral density, and adrenal suppression may appear in a small number of patients, particularly at higher doses. If such changes occur, budesonide inhalation suspension should be reduced slowly, consistent with accepted procedures for management of asthma symptoms and for tapering of systemic corticosteroids. Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. A reduction in growth velocity may occur as a result of inadequate control of asthma or from use of corticosteroids for treatment. The potential effects of prolonged treatment on growth velocity should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including budesonide inhalation suspension, each patient should be titrated to his/her lowest effective dose (see PRECAUTIONS, Pediatric Use). Although patients in clinical trials have received budesonide inhalation suspension on a continuous basis for periods of up to 1 year, the long-term local and systemic effects of budesonide inhalation suspension in human subjects are not completely known. In particular, the effects resulting from chronic use of budesonide inhalation suspension on developmental or immunological processes in the mouth, pharynx, trachea, and lung are unknown. In clinical trials with budesonide inhalation suspension, localized infections with Candida albicans occurred in the mouth and pharynx in some patients. The incidences of localized infections of Candida albicans were similar between the placebo and budesonide inhalation suspension treatment groups. If these infections develop, they may require treatment with appropriate antifungal therapy and/or discontinuance of treatment with budesonide inhalation suspension. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids. Information for Patients Patients being treated with budesonide inhalation suspension should receive the following information and instructions. This information is intended to aid the patient in the safe and effective use of the medication. It is not a disclosure of all possible adverse or intended effects. For instructions on the proper use of budesonide inhalation suspension and to attain the maximum improvement in asthma symptoms, the patient or the parent/guardian of the patient should receive, read, and follow the available patient information and instructions carefully. z Patients should take budesonide inhalation suspension at regular intervals twice a day as directed, since its effectiveness depends on regular use. The patient should not alter the prescribed dosage unless advised to do so by the physician. z The effects of mixing budesonide inhalation suspension with other nebulizable medications have not been adequately assessed. Budesonide inhalation suspension should be administered separately in the nebulizer. z Budesonide inhalation suspension is not a bronchodilator, and its use is not intended to treat acute life-threatening episodes of asthma. z Budesonide inhalation suspension should be administered with a jet nebulizer connected to a compressor with an adequate air flow, equipped with a mouthpiece or suitable face mask. The face mask should be properly adjusted to optimize delivery and to avoid exposing the eyes to the nebulized medication (see DOSAGE AND ADMINISTRATION). z Ultrasonic nebulizers are not suitable for the adequate administration of budesonide inhalation suspension and, therefore, are not recommended (see DOSAGE AND ADMINISTRATION). z Rinsing the mouth with water after each treatment may decrease the risk of development of local candidiasis. Corticosteroid effects on the skin can be avoided if the face is washed after the use of a face mask. z Improvement in asthma control following treatment with budesonide inhalation suspension can occur within 2 to 8 days of beginning treatment, although maximum benefit may not be achieved for 4 to 6 weeks after starting treatment. If the asthma symptoms do not improve in that time frame, or if the condition worsens, the patient or the patient’s parent/ guardian should be instructed not to increase the dosage, but to contact the physician. z Patients should not stop the use of budesonide inhalation suspension abruptly without consulting with their prescribing physician. z Patients whose chronic systemic corticosteroids have been reduced or withdrawn should be instructed to carry a warning card indicating that they may need supplemental systemic corticosteroids during periods of stress or an asthma attack that does not respond to bronchodilators. z As always, care should be taken to avoid exposure to persons with chicken pox and measles. If exposure to such a person occurs, and the child has not had chicken pox or been properly vaccinated, a physician should be consulted without delay (see WARNINGS and PRECAUTIONS, Pediatric Use). z Long-term use of inhaled corticosteroids, including budesonide, may increase the risk of some eye problems (cataracts or glaucoma). Regular eye examinations should be considered. z Patients or their parents/guardians considering use of budesonide inhalation suspension should consult with their physician if they are allergic to budesonide or any other orally inhaled corticosteroid. z Physicians should be informed of other medications patients are taking as budesonide inhalation suspension may not be suitable in some circumstances and the physician may wish to use a different medicine. z Budesonide inhalation suspension should be stored upright at controlled room temperature 20Вє to 25ВєC (68Вє to 77ВєF) and protected from light. Budesonide inhalation suspension should not be refrigerated or frozen. z When an aluminum foil envelope has been opened, the shelf life of the unused vials is two weeks when protected from light. The date the envelope was opened should be recorded on the front of the envelope in the space provided. z After opening the aluminum foil envelope, the unused vials should be returned to the envelope to protect them from light. Any individually opened vials must be used promptly. z For proper usage of budesonide inhalation suspension and to attain maximum improvement, the available Patient’s Instructions for Use should be read and followed. Drug Interactions In clinical studies, concurrent administration of budesonide and other drugs commonly used in the treatment of asthma has not resulted in an increased frequency of adverse events. The main route of metabolism of budesonide, as well as other corticosteroids, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a potent inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of other known inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, erythromycin, etc.) may inhibit the metabolism of, and increase the systemic exposure to, budesonide. Care should be exercised when budesonide is coadministered with long-term ketoconazole and other known CYP3A4 inhibitors. Omeprazole did not have effects on the pharmacokinetics of oral budesonide, while cimetidine, primarily an inhibitor of CYP1A2, caused a slight decrease in budesonide clearance and a corresponding increase in its oral bioavailability. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies were conducted in rats and mice using oral administration to evaluate the carcinogenic potential of budesonide. In a two-year study in Sprague-Dawley rats, budesonide caused a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg (less than the maximum recommended daily inhalation dose in adults and children on a mcg/m2 basis). No tumorigenicity was seen in male and female rats at respective oral doses up to 25 and 50 mcg/kg (less than the maximum recommended daily inhalation dose in adults and children on a mcg/m2 basis). In two additional two-year studies in male Fischer and Sprague-Dawley rats, budesonide caused no gliomas at an oral dose of 50 mcg/kg (less than the maximum recommended daily inhalation dose in adults and children on a mcg/m2 basis). However, in the male Sprague-Dawley rats, budesonide caused a statistically significant increase in the incidence of hepatocellular tumors at an oral dose of 50 mcg/kg (less than the maximum recommended daily inhalation dose in adults and children on a mcg/m2 basis). The concurrent reference corticosteroids (prednisolone and triamcinolone acetonide) in these two studies showed similar findings. In a 91-week study in mice, budesonide caused no treatment-related carcinogenicity at oral doses up to 200 mcg/kg (less than the maximum recommended daily inhalation dose in adults and children on a mcg/m2 basis). Budesonide was not mutagenic or clastogenic in six different test systems: Ames Salmonella/microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hepatocyte culture. In rats, budesonide had no effect on fertility at subcutaneous doses up to 80 mcg/kg (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). However, it caused a decrease in prenatal viability and viability in the pups at birth and during lactation, along with a decrease in maternal body-weight gain, at subcutaneous doses of 20 mcg/kg and above (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). No such effects were noted at 5 mcg/kg (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). Pregnancy Teratogenic Effects Pregnancy category B As with other corticosteroids, budesonide was teratogenic and embryocidal in rabbits and rats. Budesonide produced fetal loss, decreased pup weights, and skeletal abnormalities at subcutaneous doses of 25 mcg/kg in rabbits (less than the maximum recommended daily inhalation dose in adults on a mcg/m2 basis) and 500 mcg/kg in rats (approximately 4 times the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). In another study in rats, no teratogenic or embryocidal effects were seen at inhalation doses up to 250 mcg/kg (approximately 2 times the maximum recommended daily inhalation dose in adults on a mcg/m2 basis). Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. Studies of pregnant women, however, have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy. The results from a large population-based prospective cohort epidemiological study reviewing data from three Swedish registries covering approximately 99% of the pregnancies from 1995 to 1997 (i.e., Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology Registry) indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy. Congenital malformations were studied in 2014 infants born to mothers reporting the use of inhaled budesonide for asthma in early pregnancy (usually 10 to 12 weeks after the last menstrual period), the period when most major organ malformations occur. The rate of recorded congenital malformations was similar compared to the general population rate (3.8% vs. 3.5%, respectively). In addition, after exposure to inhaled budesonide, the number of infants born with orofacial clefts was similar to the expected number in the normal population (4 children vs. 3.3, respectively). These same data were utilized in a second study bringing the total to 2534 infants whose mothers were exposed to inhaled budesonide. In this study, the rate of congenital malformations among infants whose mothers were exposed to inhaled budesonide during early pregnancy was not different from the rate for all newborn babies during the same period (3.6%). Despite the animal findings, it would appear that the possibility of fetal harm is remote if the drug is used during pregnancy. Nevertheless, because the studies in humans cannot rule out the possibility of harm, budesonide inhalation suspension should be used during pregnancy only if clearly needed. Non-Teratogenic Effects Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully observed. Nursing Mothers Budesonide, like other corticosteroids, is secreted in human milk. Data with budesonide delivered via dry powder inhaler indicates that the total daily oral dose of budesonide in breast milk to the infant is approximately 0.3% to 1% of the dose inhaled by the mother (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Nursing Mothers). No studies have been conducted in breastfeeding women with budesonide inhalation suspension; however, the dose of budesonide available to the infant in breast milk, as a percentage of the maternal dose, would be expected to be similar. Budesonide should be used in nursing women only if clinically appropriate. Prescribers should weigh the known benefits of breastfeeding for the mother and the infant against the potential risks of minimal budesonide exposure in the infant. Pediatric Use Safety in pediatric patients six months to 12 months of age has been evaluated. Safety and effectiveness in pediatric patients 12 months to 8 years of age have been established (see CLINICAL PHARMACOLOGY, Pharmacodynamics, CLINICAL TRIALS and ADVERSE REACTIONS). It has been reported a study in pediatric patients 6 to 12 months of age with mild to moderate asthma or recurrent/persistent wheezing. All patients were randomized to receive either budesonide inhalation suspension or placebo. Adrenal axis function was assessed with an ACTH stimulation test at the beginning and end of the study, and mean changes from baseline in this variable did not indicate adrenal suppression in patients who received budesonide inhalation suspension versus placebo. However, on an individual basis, 7 patients in this study (6 in the budesonide inhalation suspension treatment arms and 1 in the placebo arm) experienced a shift from having a normal baseline stimulated cortisol level to having a subnormal level at Week 12 (see CLINICAL PHARMACOLOGY, Pharmacodynamics). Pneumonia was observed more frequently in patients treated with budesonide inhalation suspension than in patients treated with placebo, (N = 2, 1, and 0) in the budesonide inhalation suspension 0.5 mg, 1 mg, and placebo groups, respectively. A dose dependent effect on growth was also noted in this 12-week trial. Infants in the placebo arm experienced an average growth of 3.7 cm over 12 weeks compared with 3.5 cm and 3.1 cm in the budesonide inhalation suspension 0.5 mg and 1 mg arms respectively. This corresponds to estimated mean (95% CI) reductions in 12-week growth velocity between placebo and budesonide inhalation suspension 0.5 mg of 0.2 cm (-0.6 to 1) and between placebo and budesonide inhalation suspension 1 mg of 0.6 cm (-0.2 to 1.4). These findings support that the use of budesonide inhalation suspension in infants 6 to 12 months of age may result in systemic effects and are consistent with findings of growth suppression in other studies with inhaled corticosteroids. Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. In these studies, the mean reduction in growth velocity was approximately one centimeter per year (range 0.3 to 1.8 cm per year) and appears to be related to dose and duration of exposure. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA)-axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA-axis function. The long-term effects of this reduction in growth velocity associated with inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch up” growth following discontinuation of treatment with inhaled corticosteroids has not been adequately studied. In a study of asthmatic children 5 to 12 years of age, those treated with budesonide administered via a dry powder inhaler 200 mcg twice daily (n = 311) had a 1.1-centimeter reduction in growth compared with those receiving placebo (n = 418) at the end of one year; the difference between these two treatment groups did not increase further over three years of additional treatment. By the end of four years, children treated with the budesonide dry powder inhaler and children treated with placebo had similar growth velocities. Conclusions drawn from this study may be confounded by the unequal use of corticosteroids in the treatment groups and inclusion of data from patients attaining puberty during the course of the study. The growth of pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks and benefits associated with alternative therapies. To minimize the systemic effects of inhaled corticosteroids, including budesonide inhalation suspension, each patient should be titrated to his/her lowest effective dose. An open-label non-randomized clinical study examined the immune responsiveness of varicella vaccine in 243 asthma patients 12 months to 8 years of age who were treated with a total daily dose of budesonide inhalation suspension up to 1 mg (n = 151) or non-corticosteroid asthma therapy (n = 92) (i.e., beta2-agonists, leukotriene receptor antagonists, cromones). The percentage of patients developing a seroprotective antibody titer of ≥ 5 (gpELISA value) in response to the vaccination was similar in patients treated with budesonide inhalation suspension (85%) compared to patients treated with non-corticosteroid asthma therapy (90%). No patient treated with budesonide inhalation suspension developed chicken pox as a result of vaccination. Geriatric Use Of the 215 patients in 3 clinical trials of budesonide inhalation suspension in adult patients, 65 (30%) were 65 years of age or older, while 22 (10%) were 75 years of age or older. No overall differences in safety were observed between these patients and younger patients, and other reported clinical or medical surveillance experience has not identified differences in responses between the elderly and younger patients. ADVERSE REACTIONS The following adverse reactions were reported in pediatric patients treated with budesonide inhalation suspension. The incidence of common adverse reactions is based on three double-blind, placebo-controlled, US clinical trials in which 945 patients, 12 months to 8 years of age, (98 patients ≥ 12 months and < 2 years of age; 225 patients ≥ 2 and < 4 years of age; and 622 patients ≥ 4 and ≤ 8 years of age) were treated with budesonide inhalation suspension or vehicle placebo. The incidence and nature of adverse events reported for budesonide inhalation suspension was comparable to that reported for placebo. The following table shows the incidence of adverse events in US controlled clinical trials, regardless of relationship to treatment, in patients previously receiving bronchodilators and/or inhaled corticosteroids. This population included a total of 605 male and 340 female patients. Adverse Events With ≥ 3% Incidence Reported By Patients On Budesonide Budesonide Vehicle Total Daily Dose Placebo 1 mg 0.5 mg (n = 227) (n = 223) (n = 317) Adverse Events % % % Respiratory System Disorder 35 38 36 Respiratory Infection 11 12 9 Rhinitis 9 8 5 Coughing Resistance Mechanism Disorders 11 9 11 Otitis Media 5 3 3 Viral Infection 3 4 2 Moniliasis Gastrointestinal System Disorders 5 5 4 Gastroenteritis 4 4 3 Vomiting 4 2 2 Diarrhea 2 3 2 Abdominal Pain Hearing and Vestibular Disorders 4 5 4 Ear Infection Platelet, Bleeding, and Clotting Disorders 4 3 1 Epistaxis Vision Disorders 4 2 2 Conjunctivitis Skin and Appendages Disorders 4 2 3 Rash The above table shows all adverse events with an incidence of 3% or more in at least one active treatment group where the incidence was higher with budesonide inhalation suspension than with placebo. The following adverse events occurred with an incidence of 3% or more in at least one budesonide inhalation suspension group where the incidence was equal to or less than that of the placebo group: fever, sinusitis, pain, pharyngitis, bronchospasm, bronchitis, and headache. Incidence 1% to ≤ 3% (by Body System) The information below includes all adverse events with an incidence of 1 to ≤ 3%, in at least one budesonide inhalation suspension treatment group where the incidence was higher with budesonide inhalation suspension than with placebo, regardless of relationship to treatment. Body as a Whole Allergic reaction, chest pain, fatigue, flu-like disorder Respiratory System Stridor Resistance Mechanisms Herpes simplex, external ear infection, infection Central & Peripheral Nervous System Dysphonia, hyperkinesia Skin & Appendages Eczema, pustular rash, pruritus Hearing & Vestibular Earache Vision Eye infection Psychiatric Anorexia, emotional lability Musculoskeletal System Fracture, myalgia Application Site Contact dermatitis Platelet, Bleeding & Clotting Purpura White Cell and Resistance Cervical lymphadenopathy The incidence of reported adverse events was similar between the 447 budesonide inhalation suspension-treated (mean total daily dose 0.5 to 1 mg) and 223 conventional therapy-treated pediatric asthma patients followed for one year in three open-label studies. Cases of growth suppression have been reported for inhaled corticosteroids including post-marketing reports for budesonide inhalation suspension (see PRECAUTIONS, Pediatric Use). Less frequent adverse events (<1%) reported in the published literature, long-term, open-label clinical trials, or from worldwide marketing experience with any formulation of inhaled budesonide include: immediate and delayed hypersensitivity reactions including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm (see WARNINGS, Hypersensitivity Reactions Including Anaphylaxis ); symptoms of hypocorticism and hypercorticism; glaucoma, cataracts; psychiatric symptoms including depression, aggressive reactions, irritability, anxiety, and psychosis; and bone disorders including avascular necrosis of the femoral head and osteoporosis. DOSAGE AND ADMINISTRATION Patients Maintained on Chronic Oral Corticosteroids Initially, budesonide inhalation suspension should be used concurrently with the patient’s usual maintenance dose of systemic corticosteroid. After approximately one week, gradual withdrawal of the systemic corticosteroid may be initiated by reducing the daily or alternate daily dose. Further incremental reductions may be made after an interval of one or two weeks, depending on the response of the patient. Generally, these decrements should not exceed 25% of the prednisone dose or its equivalent. A slow rate of withdrawal is strongly recommended. During reduction of oral corticosteroids, patients should be carefully monitored for asthma instability, including objective measures of airway function, and for adrenal insufficiency (see WARNINGS). During withdrawal, some patients may experience symptoms of systemic corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement in pulmonary function. Such patients should be encouraged to continue with budesonide inhalation suspension but should be monitored for objective signs of adrenal insufficiency. If evidence of adrenal insufficiency occurs, the systemic corticosteroid doses should be increased temporarily and thereafter withdrawal should continue more slowly. During periods of stress or a severe asthma attack, transfer patients may require supplementary treatment with systemic corticosteroids. A Pari-LC-Jet Plus Nebulizer (with face mask or mouthpiece) connected to a Pari Master compressor was used to deliver budesonide inhalation suspension to each patient in 3 U.S. controlled clinical studies. The safety and efficacy of budesonide inhalation suspension delivered by other nebulizers and compressors have not been established. Budesonide inhalation suspension should be administered via jet nebulizer connected to an air compressor with an adequate air flow, equipped with a mouthpiece or suitable face mask. Ultrasonic nebulizers are not suitable for the adequate administration of budesonide inhalation suspension and, therefore, are NOT recommended. Manufactured In England By: IVAX PHARMACEUTICALS UK Runcorn, Cheshire WA7 3FA England Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev. D 10/2009 В® EDITORIAL ADVISORY BOARD Philip P. Burgess, RPh, MBA Mary E. Inguanti RPh, MPH, FASCP Chairman Community Pharmacy Foundation Illinois Board of Pharmacy Chicago, Ill. Gene Memoli Jr., RPh, FASCP Director Customer Development, Omnicare Cheshire, Conn. Senior Vice President, Operations Charter Oak Health Center Hartford, Conn. Perry Cohen, PharmD, FAMCP James A. Jorgenson RPh, MS, FASHP The Pharmacy Group LLC Glastonbury, Conn. Marvin R. Moore, PharmD Chief Pharmacy Ofп¬Ѓcer, VP Clarian Health Indianapolis, Ind. Pharmacy manager and co-owner The Medicine Shoppe/ Pharmacy Solutions Inc. Two Rivers, Wisc. David J. Fong, PharmD Frederick S. Mayer, RPh, MPH Jack Rosenberg, PharmD, PhD Former community chain store senior pharmacy executive Danville, Calif. President Pharmacists Planning Service Inc. San Rafael, Calif. Professor Emeritus Pharmacy Practice and Pharmacology Long Island University Brooklyn, N.Y. Anna Garrett PharmD, BCPS Christina Medina, PharmD Stephen W. Schondelmeyer PharmD, PhD Manager Professional and College Relations CVS Caremark Hollywood, Fla. Manager Outpatient Clinical Pharmacy Programs Mission Hospital Asheville, N.C. Editorial Mission: Drug Topics, a monthly news magazine guided by an editorial advisory board of pharmacy experts, reports on all phases of community, retail, and health-system issues and trends. We offer a forum for the bench pharmacist to share practical ideas for better pharmacy management and patient care. LIST MANAGER Director, PRIME Institute College of Pharmacy University of Minnesota Minneapolis, Minn. Tamara Phillips (440) 891-2773 / [email protected] PERMISSIONS AND LICENSING Maureen Cannon (440) 891-2742 or (800) 225-4569 ext. 2742 Fax: (440) 891-2650 / [email protected] ACCOUNT MANAGER, DISPLAY AND MARKETPLACE ADVERTISING Heather Joseph Loggia Schlosser CHIEF EXECUTIVE OFFICER (440) 891-2779 / [email protected] Tom Ehardt CLASSIFIED RECRUITMENT Joanna Shippoli EXECUTIVE VICE PRESIDENT, CHIEF ADMINISTRATIVE OFFICER 800-225-4569 x 2615 / [email protected] Steve Sturm EDITORIAL REPRINT SERVICES DIRECTOR OF EDITORIAL Dan EDITOR-IN-CHIEF Julia Schwartz EXECUTIVE VICE PRESIDENT, CHIEF MARKETING OFFICER (800) 290-5460, ext. 100 / [email protected] (717) 505-9701, ext. 100 (international inquiries) Talsma Ted Alpert EXECUTIVE VICE PRESIDENT, FINANCE, CFO (440) 891-2792 / [email protected] MANAGING EDITOR PRODUCTION Julianne Stein SENIOR PRODUCTION MANAGER Terri (440) 826-2834 / [email protected] Georgiann De Cenzo Johnstone (218) 740-6310 [email protected] ASSOCIATE EDITOR Christina Phillis Eric Lisman EXECUTIVE VICE PRESIDENT (440) 891-2766 / [email protected] EDITORIAL ASSOCIATE Alicia EXECUTIVE VICE PRESIDENT CIRCULATION Hoisington CONTRIBUTING EDITORS Christine Blank, Fred Gebhart, Jim Plagakis, RPh, Gretchen L. Schwenker, PhD SUBSCRIPTION CUSTOMER SERVICE / ADDRESS CHANGES J. Vaughn VICE PRESIDENT, INFORMATION TECHNOLOGY (877) 922-2022 / magazines@superп¬Ѓll.com PO Box 6079, Duluth, MN 55806-6079, USA Francis Heid VICE PRESIDENT, MEDIA OPERATIONS CONTACT US Nancy Nugent SALES AND MARKETING 24950 COUNTRY CLUB BLVD., SUITE 200 VICE PRESIDENT, HUMAN RESOURCES PUBLISHER James NORTH OLMSTED, OHIO 44070 Ward D. Hewins MAIN NUMBER: (440) 243-8100 VICE PRESIDENT, GENERAL COUNSEL Granato (732) 346-3071 / [email protected] MAIN FAX NUMBER: (440) 891-2735 SALES MANAGER Ana Santiso CUSTOMER SERVICE: (877) 922-2022 (732) 346-3032 / [email protected] ACCOUNT MANAGER Lisa CLASSIFIED AND RECRUITMENT SALES: (800) 225-4569 Noble (732) 346-3060 / [email protected] SALES SUPPORT ADMINISTRATOR Samyu Danny Phillips EXECUTIVE VICE PRESIDENT E-MAIL ADDRESS: [email protected] Chris DeMoulin WEBSITE: DRUGTOPICS.COM EXECUTIVE VICE PRESIDENT Ganesh (732) 346-3077 / [email protected] DrugTopics .c om Februar y 2011 DRUG TOPICS 3 CONTENTS F E B R U A R Y 2 011 VO L . 1 5 5 N O . 2 DrugTopics.com COVER STORY Medicare Part D Audits With federal agencies taking a long, hard look at Medicare transactions, now’s a good time to make sure your pharmacy is ready for its close-up. PAGE 30 Pharmacy abroad PAGE 16 Melissa Corrigan, RPh PRESCRIBED READING 22 Mike LaRosa, PharmD cand. Phoning it in PAGE 28 Should PBMs put the moves on Medicaid? A new report claims it’s a no-brainer for the bottom line. NCPA disagrees. 27 Part D rules change may jar LTC Long-term care may have to retool for 7-day п¬Ѓlls — with 30-day bills. Pharm techs step up In towns without pharmacists, necessity is the mother of invention. Pamela Schweitzer, PharmD A five-star success PAGE 32 SPECIAL REPORT 32 A place for mail-order A collaboration between the VA and Indian Health Services is making life a little easier for many American Indians. Ken Baker, BS Pharm, JD Monthly safety audits PAGE 48 Sign up for your own Drug Topics E-newsletter Take your pick of Drug Topics’ 2 weekly e-newsletters: Community Pharmacists’ Report and Hospital Pharmacists’ Report To sign up, visit DrugTopics.com/enewssignup Dennis Miller, RPh Efficiency at any cost PAGE 56 4 DRUG TOPICS Februar y 2011 DrugTopics .c om GETTY IMAGES/PHOTOGRAPHER’S CHOICE RF/SNAP DECISION (PILL BOTTLE), GETTY IMAGES/PHOTODISC/ MEDIOIMAGES (NUMBERS, LEFT), GETTY IMAGES/THE IMAGE BANK/DAVID GOULD (REDLINE NUMBERS) 28 Meet the face of health care in the community. Now meet the pharmaceutical company dedicated to helping her do her best. Today’s pharmacist does so much more than dispense medications. She’s an immunizer, health condition screener, patient counselor, and basic medical advisor. That’s why, at Takeda, we do everything we can to give pharmacists the tools and time they need to use their expert knowledge to beneп¬Ѓt patients. From industry-leading patient education materials to medication adherence programs, we believe in the importance of strong partnerships with the pharmacist community—and all the communities they serve. For product information, visit www.tpna.com/products CONTENTS F E B R U A R Y 2011 VO L . 1 5 5 N O . 2 CONTINUING EDUCATION What’s happening now at Medication errors What you need to know: • Why they happen • How to prevent them • Who may be liable • How to apologize PAGE 36 DT BLOG No fries with that “How long can it take to put some pills in a bottle?” One pharmacist who has heard all the questions spends her drive home polishing answers she’ll never give. CLINICAL 10 GUEST EDITORIAL E-tracking is not the answer 35 ANTICOAGULATION The latest info on VTE in HIV; intracerebral hemorrhage; and antiplatelet/warfarin combinations 13 LETTERS How many pharmacists does it take to п¬Ѓll a prescription? 14 JP AT LARGE Some things you don’t forget 16 IN MY VIEW A student reports on pharmacy practice in Turkey 56 VIEWPOINT When efп¬Ѓciency is the only thing that counts ISSUES & TRENDS 18 UPFRONT A new pharmacy school takes a hands-on approach to learning REGULATORY & LEGAL 48 RISK MANAGEMENT & CQI Two success measures that every pharmacy should post 49 LEGAL COMPLIANCE Have state laws caught up with telepharmacy? Is she thinking what you’re thinking? To п¬Ѓnd out, visit the DT blog at our homepage at DrugTopics.com. WEB EXCLUSIVES ASHP lobbies for laws to ease drug shortage DrugTopics.com/shortage USP wants new Rx labels DrugTopics.com/labels ACIP updates antiviral guidelines for flu treatment DrugTopics.com/acip DIGITAL EDITION PRODUCT UPDATES 50 OTC Foot-care products 53 NEW PRODUCTS Alsuma preп¬Ѓlled auto-injectors for migraine and cluster headaches Subscribe to the monthly digital edition of Drug Topics and receive the journal electronically with live links. Go to DrugTopics.com/digital Drug Topics (ISSN# 0012-6616) is published monthly and Drug Topics Digital Edition (ISSN# 1937-8157) is issued every week by Advanstar Communications, Inc., 131 West First St., Duluth, MN 55806-2065. One-year subscription rates: $61 in the United States & Possessions; $109 in Canada and Mexico; all other countries, $109. Single copies (prepaid only) $10 in the United States; $10 in Canada and Mexico; all other countries, $15. Include $6 per copy for U.S. postage and handling. Periodicals postage paid at Duluth, MN 55806 and additional mailing ofп¬Ѓces. POSTMASTER: Please send address changes to Drug Topics, P.O. Box 6079, Duluth, MN 55806-6079. Canadian G.S.T. number: R-124213133RT001. Publications Mail Agreement Number 40017597. Printed in the U.S.A. Subscription inquiries/ address changes: toll-free (888) 527-7008, or dial direct (218) 723-9477. В©2011 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical including by photocopy, recording, or information storage and retrieval without permission in writing from the publisher. 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Advanstar Communications provides certain customer contact data (such as customers’ names, addresses, phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, services, and other opportunities that may be of interest to you. If you do not want Advanstar Communications to make your contact information available to third parties for marketing purposes, simply call toll-free (888) 527-7008 between the hours of 7:30 am and 5 pm CT and a customer service representative will assist you in removing your name from Advanstar’s lists. Outside the U.S., please phone (218) 740-6477. DRUG TOPICS does not verify any claims or other information appearing in any of the advertisements contained in the publication, and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. DRUG TOPICS welcomes unsolicited articles, manuscripts, photographs and other materials but cannot be held responsible for their safekeeping or return. 6 DRUG TOPICS Februar y 2011 DrugTopics .c om GETTY IMAGES/BLEND IMAGES/TERRY VINE (SENIOR HISPANIC WOMAN LOOKING AT MEDICATION BOTTLE); OJO IMAGES/ TOM MERTON (MAN READING INSTRUCTIONS ON PILL BOTTLE); PHOTODISC/SETH JOEL (MEDICINE CABINET WITH PRESCRIPTION BOTTLES) COUNTER POINTS Indication: Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus. Adverse reactions: The most common adverse reactions, reported in > 5% of metformin-treated patients, are: diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. Contraindications and precautions: Metformin hydrochloride tablets are contraindicated in patients with: Mylan Metformin is Berry Nice. 1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels * 1.5 mg/dL [males], * 1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia. 2. Known hypersensitivity to metformin hydrochloride. 3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. Metformin should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. Before initiation of metformin therapy and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and metformin discontinued if evidence of renal impairment is present. WARNINGS: LACTIC ACIDOSIS Lactic acidosis is a rare but serious, metabolic complication that can occur because of metformin accumulation. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function and by use of the minimum effective dose. Other conditions that increase the risk of lactic acidosis include: sepsis, dehydration, excess alcohol intake, hepatic insufficiency and acute congestive heart failure. When lactic acidosis occurs, it is fatal in approximately 50% of cases. The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient years). The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If acidosis is suspected, metformin should be discontinued and the patient hospitalized immediately. Metformin treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. Please see adjacent Brief Summary of Prescribing Information, including BOXED WARNING with complete details about lactic acidosis. В©2010 Mylan Pharmaceuticals Inc. MYNMET003 A metformin tablet that doesn’t smell like fish. • A blackberry-scented formulation designed to mask the “fishy smell” associated with some metformin tablets1 • Therapeutically equivalent to GlucophageВ®* • Available in 500 mg, 850 mg and 1000 mg tablets *Registered trademark of Bristol-Myers Squibb. Reference: 1. Pelletier AL, Butler AM, Gillies RA, et al. Metformin Stinks, Literally. Ann Intern Med. 2010;152:267-268. METFORMIN HYDROCHLORIDE TABLETS, USP 500 mg, 850 mg and 1000 mg Rx Only BRIEF SUMMARY: Please see package insert for full prescribing information. INDICATIONS AND USAGE: Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus. CONTRAINDICATIONS: Metformin hydrochloride tablets are contraindicated in patients with: 1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥ 1.5 mg/dL [males], ≥ 1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS). 2. Known hypersensitivity to metformin hydrochloride. 3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. Metformin should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. (See also PRECAUTIONS.) WARNINGS: Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is signiп¬Ѓcant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (> 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/ pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patientyears exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with signiп¬Ѓcant renal insufп¬Ѓciency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be signiп¬Ѓcantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration or sepsis. Because impaired hepatic function may signiп¬Ѓcantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin, since alcohol potentiates the effects of metformin on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS). The onset of lactic acidosis often is subtle, and accompanied only by nonspeciп¬Ѓc symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspeciп¬Ѓc abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Metformin should be withdrawn until the situation is clariп¬Ѓed. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug-related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity or technical problems in sample handling. (See also PRECAUTIONS.) Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.) PRECAUTIONS: General: Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with metformin hydrochloride tablets or any other anti-diabetic drug. Monitoring of Renal Function: Metformin is known to be substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive metformin. In patients with advanced age, metformin should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those ≥ 80 years of age, renal function should be monitored regularly and, generally, metformin should not be titrated to the maximum dose (see WARNINGS and DOSAGE AND ADMINISTRATION in full prescribing information). Before initiation of metformin therapy and at least annually thereafter, renal function should be assessed and veriп¬Ѓed as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and metformin discontinued if evidence of renal impairment is present. Use of Concomitant Medications That May Affect Renal Function or Metformin Disposition: Concomitant medication(s) that may affect renal function or result in signiп¬Ѓcant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion (see PRECAUTIONS: Drug Interactions), should be used with caution. Radiologic Studies Involving the Use of Intravascular Iodinated Contrast Materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials): Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin (see CONTRAINDICATIONS). Therefore, in patients in whom any such study is planned, metformin should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. Hypoxic States: Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on metformin therapy, the drug should be promptly discontinued. Surgical Procedures: Metformin therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. Alcohol Intake: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving metformin. Impaired Hepatic Function: Since impaired hepatic function has been associated with some cases of lactic acidosis, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Vitamin B12 Levels: In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on metformin and any apparent abnormalities should be appropriately investigated and managed (see PRECAUTIONS: Laboratory Tests). Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. In these patients, routine serum vitamin B12 measurements at 2- to 3-year intervals may be useful. Change in Clinical Status of Patients with Previously Controlled Type 2 Diabetes: A patient with type 2 diabetes previously well controlled on metformin who develops laboratory abnormalities or clinical illness (especially vague and poorly deп¬Ѓned illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate and metformin levels. If acidosis of either form occurs, metformin must be stopped immediately and other appropriate corrective measures initiated (see also WARNINGS). Hypoglycemia: Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deп¬Ѓcient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufп¬Ѓciency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difп¬Ѓcult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. Loss of Control of Blood Glucose: When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold metformin and temporarily administer insulin. Metformin may be reinstituted after the acute episode is resolved. The effectiveness of oral antidiabetic drugs in lowering blood glucose to a targeted level decreases in many patients over a period of time. This phenomenon, which may be due to progression of the underlying disease or to diminished responsiveness to the drug, is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective during initial therapy. Should secondary failure occur with either metformin or sulfonylurea monotherapy, combined therapy with metformin and sulfonylurea may result in a response. Should secondary failure occur with combined metformin/sulfonylurea therapy, it may be necessary to consider therapeutic alternatives including initiation of insulin therapy. Information for Patients: Patients should be informed of the potential risks and beneп¬Ѓts of metformin and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose, glycosylated hemoglobin, renal function and hematologic parameters. Page 1 of 2 The risks of lactic acidosis, its symptoms, and conditions that predispose to its development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to patients. Patients should be advised to discontinue metformin immediately and to promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence or other nonspeciп¬Ѓc symptoms occur. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Patients should be counselled against excessive alcohol intake, either acute or chronic, while receiving metformin. Metformin hydrochloride tablets alone do not usually cause hypoglycemia, although it may occur when metformin is used in conjunction with oral sulfonylureas and insulin. When initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. (See Patient Information in full prescribing information.) Laboratory Tests: Response to all diabetic therapies should be monitored by periodic measurements of fasting blood glucose and glycosylated hemoglobin levels, with a goal of decreasing these levels toward the normal range. During initial dose titration, fasting glucose can be used to determine the therapeutic response. Thereafter, both glucose and glycosylated hemoglobin should be monitored. Measurements of glycosylated hemoglobin may be especially useful for evaluating long-term control (see also DOSAGE AND ADMINISTRATION in full prescribing information). Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with metformin therapy, if this is suspected, vitamin B12 deп¬Ѓciency should be excluded. Drug Interactions (Clinical Evaluation of Drug Interactions Conducted with Metformin): Glyburide: In a single-dose interaction study in type 2 diabetes patients, coadministration of metformin and glyburide did not result in any changes in either metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical signiп¬Ѓcance of this interaction uncertain (see DOSAGE AND ADMINISTRATION: Concomitant Metformin Hydrochloride Tablet and Oral Sulfonylurea Therapy in Adult Patients in full prescribing information). Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any signiп¬Ѓcant change in metformin renal clearance. When administered with metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any signiп¬Ѓcant change in furosemide renal clearance. No information is available about the interaction of metformin and furosemide when coadministered chronically. Nifedipine: A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine. Cationic Drugs: Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of metformin and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system. Other: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving metformin, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, the patient should be observed closely for hypoglycemia. In healthy volunteers, the pharmacokinetics of metformin and propranolol and metformin and ibuprofen were not affected when coadministered in single-dose interaction studies. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately four times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumorigenic potential observed with metformin in male rats. There was however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day. There was no evidence of a mutagenic potential of metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative. Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons. Pregnancy: Teratogenic Effects. Pregnancy Category B: Recent information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, metformin should not be used during pregnancy unless clearly needed. There are no adequate and well controlled studies in pregnant women with metformin. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about two and six times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin. Nursing Mothers: Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If metformin is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered. Pediatric Use: The safety and effectiveness of metformin for the treatment of type 2 diabetes have been established in pediatric patients ages 10 to 16 years (studies have not been conducted in pediatric patients below the age of 10 years). Use of metformin in this age group is supported by evidence from adequate and well controlled studies of metformin in adults with additional data from a controlled clinical study in pediatric patients ages 10 to 16 years with type 2 diabetes, which demonstrated a similar response in glycemic control to that seen in adults. (See CLINICAL PHARMACOLOGY: Pediatric Clinical Studies in full prescribing information.) In this study, adverse effects were similar to those described in adults. (See ADVERSE REACTIONS: Pediatric Patients.) A maximum daily dose of 2000 mg is recommended. (See DOSAGE AND ADMINISTRATION: Recommended Dosing Schedule: Pediatrics in full prescribing information.) Geriatric Use: Controlled clinical studies of metformin did not include sufп¬Ѓcient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identiп¬Ѓed differences in responses between the elderly and younger patients. Metformin is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, metformin should only be used in patients with normal renal function (see CONTRAINDICATIONS, WARNINGS, and CLINICAL PHARMACOLOGY: Pharmacokinetics in full prescribing information). Because aging is associated with reduced renal function, metformin should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin (see also WARNINGS and DOSAGE AND ADMINISTRATION in full prescribing information). ADVERSE REACTIONS: In a U.S. double-blind clinical study of metformin in patients with type 2 diabetes, a total of 141 patients received metformin therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the metformin patients, and that were more common in metformin- than placebo-treated patients, are listed in Table 1. Table 1. Most Common Adverse Reactions (> 5%) in a Placebo-Controlled Clinical Study of Metformin Monotherapy* Metformin Monotherapy Placebo (n = 141) (n = 145) Adverse Reaction % of Patients Diarrhea 53.2 11.7 Nausea/Vomiting 25.5 8.3 Flatulence 12.1 5.5 Asthenia 9.2 5.5 Indigestion 7.1 4.1 Abdominal Discomfort 6.4 4.8 Headache 5.7 4.8 * Reactions that were more common in metformin- than placebo-treated patients. Diarrhea led to discontinuation of study medication in 6% of patients treated with metformin. Additionally, the following adverse reactions were reported in ≥ 1 to ≤ 5% of metformin patients and were more commonly reported with metformin than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. Pediatric Patients: In clinical trials with metformin in pediatric patients with type 2 diabetes, the proп¬Ѓle of adverse reactions was similar to that observed in adults. OVERDOSAGE: Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases (see WARNINGS). Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. Manufactured in India by: Matrix Laboratories Limited Secunderabad — 500 003, India Code No.: MH/DRUGS/25/NKD/89 Manufactured for: MYLANВ® Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. REVISED JANUARY 2010 BS:MX:METB:R1ppt Page 2 of 2 Counter Points As part of our ongoing initiative to encourage dialogue on issues of interest to pharmacists, each month Drug Topics will present an editorial by a guest columnist writing on a subject of his or her choice. Send us your feedback; we look forward to sharing it in an upcoming issue. DISPENSED AS WRITTEN Kent Shaw Let’s eliminate meth labs, not п¬Ѓnd more of them I write this in response to the recent Drug Topics editorial r titled “E-tracking is the right prescription for U.S. meth problems”[January 2011]. The notion that an m e-tracking system is a better solution for our nation’s meth-lab crises rather than returning pseudoephedrine (PSE) to its prescription status ignores one simple fact: E-tracking systems are incapable of reducing meth labs. In fact, e-tracking systems are fueling our PSE smurп¬Ѓng epidemic. Meth incidents increase in e-tracking states The latest twist with e-tracking is a Meth Offender Registry that attempts to prevent criminals from buying PSE. The reality is that meth cookers don’t need to buy PSE — there are hordes of people willing to make a quick buck by purchasing the PSE for them. Coupled with the rampant availability of false identiп¬Ѓcations, anyone can buy PSE as often as they choose. This is why states with e-tracking systems continue to have increasing numbers of meth labs. According to a recent AP investigation, since 2008 meth incidents have increased the most in the 3 states that have e-tracking systems. Meth incidents rose a combined 67% in those states — 34% in Arkansas, 65% in Kentucky, and 164% in Oklahoma. Tennessee developed its own tracking system and has arrested large numbers of meth cookers, but in 2010 Tennessee had another record-setting year for meth-lab seizures (an average of 5 meth labs a day were seized — a 41% increase compared to seizures in 2009). Clearly this is not a problem we can arrest our way out of, nor can we afford to keep trying to do so. eliminating PSE smurп¬Ѓng and reducing the number of meth labs from several hundred to 13 in 2010. Mississippi passed a similar law in July of 2010 and has already experienced a 70% reduction in meth-related cases statewide. Drug-endangered children need protection There is another important topic not discussed in the editorial. This debate isn’t just about people making meth and ruining their own lives. It’s also about drug-endangered children. In the 4ВЅ years since Oregon passed its law, Oregon has removed only 2 children from meth labs, instead of the approximately 40 children it used to rescue each year. Since passing its law, Mississippi has seen a 75% reduction in the number of children removed from meth labs. What is a child’s safety worth to our society? Who in good conscious can advocate for e-tracking when the facts show that it is reactive at best, has proved ineffective, and is only exasperating a problem that costs us lives and a great deal of money? I say shame on those who are proп¬Ѓting from this misery and thwarting attempts to implement a real solution. Prescription PSE is important for all Americans, not just for a select few who think they must have PSE, a product that by all medical standards is considered to be a nonessential medication that doesn’t cure anything and for which there are plenty of alternatives. The opinions expressed by guest editorial writers are their own and do not necessarily represent the views of Drug Topics’ staff or the staff of Advanstar Communications. Kent Shaw is the assistant chief of the California Department of Prescription PSE the only viable solution The facts clearly dictate that prescription PSE is our only viable solution if we want to eliminate PSE smurп¬Ѓng and greatly reduce meth labs. In 2006, Oregon returned PSE to its prescription status, 10 DRUG TOPICS Februar y 2011 Justice, Bureau of Narcotic Enforcement. He is a 25-year lawenforcement veteran. He is also a member of the advisory board of the National Methamphetamine and Pharmaceutical Initiative. He can be reached at 916-319-8292. DrugTopics .c om First and only FDA-approved, single-ingredient colchicine TOUGH, BUT GENTLE COLCRYSВ® (colchicine, USP) is a modern standard of care for gout flares. Help your patients save money on COLCRYS at www.COLCRYS.com. Important Safety Information COLCRYS (colchicine, USP) tablets are indicated taking colchicine. Rhabdomyolysis has been for prophylaxis and the treatment of gout flares. occasionally observed, especially when colchicine COLCRYS is contraindicated in patients with renal is prescribed in combination with other drugs or hepatic impairment who are concurrently known to cause this effect. Monitoring is prescribed P-gp inhibitors or strong inhibitors of recommended for patients with a history of blood CYP3A4 as life-threatening or fatal toxicity has dyscrasias or rhabdomyolysis. been reported. Dose adjustments of COLCRYS may be required when co-administered with P-gp or CYP3A4 inhibitors. The most common adverse events in clinical trials for the prophylaxis and treatment of gout were diarrhea and pharyngolaryngeal pain. Rarely, myelosuppression, thrombocytopenia, and leukopenia have been reported in patients You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1.800. FDA.1088. You may also report negative side effects to the manufacturer of COLCRYS by calling 1.888.351.3786. Please see brief summary of full Prescribing Information on adjacent page. Distributed by AR Scientiп¬Ѓc, Inc. A URL Pharma company. Philadelphia, PA www.urlpharma.com В©2011 URL Pharma, Inc. All rights reserved. COL-359 Jan 2011 Printed in USA. www.COLCRYS.com 1.888.351.3786 24 hours, and occurring in up to 20% of patients given therapeutic doses. Typical symptoms include cramping, nausea, diarrhea, abdominal pain, and vomiting. These events should be viewed as dose-limiting if severe as they can herald the onset of more signiп¬Ѓcant toxicity. В® COLCRYS (colchicine, USP) tablets for oral use Brief Summary of full Prescribing Information The following is a brief summary only. Please see full Prescribing Information for complete product information. INDICATIONS AND USAGE COLCRYSВ® (colchicine, USP) tablets are indicated for prophylaxis and the treatment of gout flares. Prophylaxis of Gout Flares: COLCRYS is indicated for prophylaxis of gout flares. Treatment of Gout Flares: COLCRYS is indicated for treatment of acute gout flares when taken at the п¬Ѓrst sign of a flare. Familial Mediterranean fever (FMF): COLCRYS is indicated in adults and children 4 years or older for treatment of familial Mediterranean fever (FMF). CONTRAINDICATIONS Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors, except Fosamprenavir). In these patients, lifethreatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses. WARNINGS AND PRECAUTIONS Fatal Overdose: Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. COLCRYS should be kept out of the reach of children. Blood Dyscrasias: Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported with colchicine used in therapeutic doses. Drug Interactions: Colchicine is a P-gp and CYP3A4 substrate. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors. If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient’s dose of colchicine may need to be reduced or interrupted [see DRUG INTERACTIONS]. Use of COLCRYS in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors, except Fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see CONTRAINDICATIONS]. Monitor for toxicity and if present consider temporary interruption or discontinuation of COLCRYS. Neuromuscular Toxicity: Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, gemп¬Ѓbrozil, fenoп¬Ѓbrate, fenoп¬Ѓbric acid, or benzaп¬Ѓbrate (themselves associated with myotoxicity) or cyclosporine with COLCRYS may potentiate the development of myopathy [see DRUG INTERACTIONS]. Once colchicine is stopped, the symptoms generally resolve within 1 week to several months. ADVERSE REACTIONS Prophylaxis of Gout Flares: The most commonly reported adverse reaction in clinical trials of colchicine for the prophylaxis of gout was diarrhea. Treatment of Gout Flares: The most common adverse reactions reported in the clinical trial with COLCRYS for treatment of gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%). FMF: Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating COLCRYS, usually presenting within DRUG INTERACTIONS COLCRYS is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine. If COLCRYS is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely. Fatal drug interactions have been reported. Physicians should ensure that patients are suitable candidates for treatment with COLCRYS and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction. Signs and symptoms of COLCRYS toxicity should be evaluated promptly and, if toxicity is suspected, COLCRYS should be discontinued immediately. See full Prescribing Information for a complete list of reported potential interactions. USE IN SPECIFIC POPULATIONS s In the presence of mild to moderate renal or hepatic impairment, adjustment of dosing is not required for treatment of gout flare, prophylaxis of gout flare, and FMF but patients should be monitored closely. s In patients with severe renal impairment for prophylaxis of gout flares the starting dose should be 0.3 mg/day, for gout flares no dose adjustment is required but a treatment course should be repeated no more than once every 2 weeks. In FMF patients, start with 0.3 mg/day and any increase in dose should be done with close monitoring. s In patients with severe hepatic impairment, a dose reduction may be needed in prophylaxis of gout flares and FMF patients; while a dose reduction may not be needed in gout flares, a treatment course should be repeated no more than once every 2 weeks. s For patients undergoing dialysis, the total recommended dose for prophylaxis of gout flares should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares, the total recommended dose should be reduced to 0.6 mg (1 tablet) x 1 dose and the treatment course should not be repeated more than once every two weeks. For FMF patients the starting dose should be 0.3 mg per day and dosing can be increased with close monitoring. s Pregnancy: Use only if the potential beneп¬Ѓt justiп¬Ѓes the potential risk to the fetus. s Nursing Mothers: Caution should be exercised when administered to a nursing woman. s Geriatric Use: The recommended dose of colchicine should be based on renal function. Manufactured for: AR SCIENTIFIC, INC. Philadelphia, PA 19124 USA by: MUTUAL PHARMACEUTICAL COMPANY, INC. Philadelphia, PA 19124 USA Rev 04, May 2010 Distributed by AR Scientiп¬Ѓc, Inc. A URL Pharma company. Philadelphia, PA www.urlpharma.com COL-272 Counter Points Letters Re: “Single, poor, and desperate” [JP at Large, January 2011]: I remember when I worked retail and folks would come in to п¬Ѓll prescriptions for their sick children. I’ve seen the looks on their faces when they found out how much their prescriptions cost. Some parents would turn around and try to leave without antibiotics a sick child needed because they couldn’t afford them. I would take the time to call the doctor and switch the drug to something else that was just as effective (more effective, in some instances) and cost a lot less. It’s hard for some patients when they have to choose between food on the table, rent, getting to work, and paying for doctors and meds. GETTY IMAGES/PHOTODISC/MATTHIAS TUNGER Making the call Debbie Bair, PharmD TACOMA, WASH. Coping with shortages Follow the money Q: How many pharmacists does it take to п¬Ѓll a prescription? A: Four. One to call the manufacturer, another to call the wholesaler, a third to call the doctor and ask for therapeutic substitution, and a fourth to put whatever is left on the shelf into a bottle! The drug shortage problem is growing worse. The “Drug Shortages Summit Report,” based on the Nov. 10, 2010, meeting in Bethesda, Md., is featured in the January 19th, 2011, e-mail from ASHP Advocacy. The report suggests reasons for the shortages and strategies for coping with them; we all need to get involved with this. Every patient deserves a good pharmacist, and the patients who don’t get one are going to feel it until we all п¬Ѓgure out a way through this crisis. Susan J. Bliss, RPh, MBA The article by Kathryn Foxhall about counterfeit drugs [“Counterfeit drug war continues,” December 2010] is right on target. What is baffling is the way pharmaceutical companies continue to flock to the countries that make the counterfeit drugs. China is known to be the counterfeit capital of the world, yet companies like Pfizer (Viagra) and Hoffmann-La Roche (Tamiflu) insist on staying despite the counterfeiting and contamination of their products. Also, it would be nice to have a law that requires a pharmaceutical product to indicate where that product was actually manufactured. The pharmaceutical companies do not want this as proп¬Ѓt is more important to them than patient safety. Robert S. Katz, RPh PORTLAND, ORE. STAMFORD, CONN. DrugTopics .c om A little list with a big agenda I can think of 3 things that would help with the counterfeit drug problem. 1. Return drug manufacture to the United States. (FDA would have oversight and it would help the unemployment problem.) 2. Big pharma should go back to charging reasonable prices for drugs instead of what the market will bear. 3. Place a tariff on imported drugs (raw materials or processed). J. Davis, RPh WAXAHACHIE, TEXAS R2D2 as RPh Your article on Plan B [DT blog: DrugTopics. com] was biased and did not represent my beliefs on the use of the product. It was a real disappointment. The premise that a pharmacist could be required to dispense product is deprofessionalizing to pharmacy, the profession you purport to promote. Just as a prescriber has the “right” to prescribe the drug he considers the proper drug for a patient, based on his knowledge and preferences, so should a pharmacist have the ability to decide whether to dispense. Otherwise pharmacy professionals are merely vending machines. Bob Wilbanks, RPh CLEVELAND, MISS. Editor’s note: The DT blog is a forum for expression of reader opinion. All contributions that respect the limits of civil discourse are welcome. We want to hear from you Printed and e-mailed letters should be brief and include the writer’s name, address, daytime phone number, and date of the issue you are referencing: Editor, Drug Topics, 24950 Country Club Blvd., Suite 200, North Olmsted, OH 44070-5351. E-mail address: [email protected]. Letters may be edited for length, style, content, and clarity at our discretion. Februar y 2011 DRUG TOPICS 13 Counter Points JP AT LARGE Jim Plagakis, RPh Pharmacy moments remembered Snapshot. I was walking out front when I saw a young man in his mid-teens staring at the label of an OTC pain medicine. He was very well dressed. His shoes were well made, probably by hand, probably in Italy. “Alfonso,” I said, “You’re back.” I offered a few blocks from the drugstore where I work. Shriners hospital is the preeminent my hand. “SeГ±or Pharmaceutico,” he smiled. burn center for children in the western “¡Hola. It has been a long time.” His smile hemisphere. It is a charity hospital, but Alfonso’s parents pay full price for his care. was luminescent. His eyes bright. Alfonso was back in town for another “Are you back for a short visit?” In a way, I was uncomfortable. I was hoping round of surgeries. He was staying at a that he did not have to stay for months. It halfway house for teenagers. There’s a girl from Peru he likes a lot, he said, but was the Christmas season. What frightens me the most is what she would be leaving after the bandages I do not know and how that ignorance come off and the docs make sure there is can cause me to act in a way that I am no infection. “Es difГcil,” he shrugged. “I have that not proud of. The п¬Ѓrst time I met Alfonso, I asked if Latin blood and I am in love, Senor. Es I could help him and then looked away muy difГcil. She is my п¬Ѓrst love.” His eyes quickly. When I returned my gaze to sparkled. “I am just a boy.” I asked Alfonso if he would see her him, he was smiling. I must have looked stunned. Patient care is the cornerstone again and he sadly told me that her many of my practice of pharmacy, and at п¬Ѓrst surgeries were complete. “My parents are I couldn’t even look at this kid. I did not pleased. They want to protect me like I was still a niГ±o. They expect his appearance, believe that she would and I still cringe when I did not expect only be heartache beI remember how JP’s his appearance, cause she is beautiful, famous patient-centric and I still look like viewpoint crashed. and I still cringe this.” He spoke in heavily when I remember “Perhaps someday.” accented English. “It’s how JP’s famous Why didn’t I just keep okay,” he said. “I am patient-centric quiet? used to it.” Alfonso is viewpoint “MaГ±ana,” he spat a shopper who wants crashed. and then rattled off to be informed about something in Spanish. the OTC drugs he may He paused, “Always want to use. He comes from a country that does not have a nan- maГ±ana, but SeГ±or, tomorrow never ny government. He knows that he is on comes.” Snapshot. There are times when I go his own. He asks lots of questions. The Shriners Hospital for Children is through my days on automatic. I do my associated with UTMB (University of Texas job like a robot and do not really keep my Medical Branch at Galveston) and is only head in the game. There is a man whom 14 DRUG TOPICS Februar y 2011 I have decided I don’t like very well. He is way too mouthy for my tastes and has the nerve to call me buddy, as if we’re best friends. I am polite, but I can be polite and chilly at the same time. He came in with 3 prescriptions the other day. He looked a bit out of sorts. His hair was greasy and his clothes were wrinkled. His prescriptions were for Vicodin, Soma, and a new one for him: alprazolam. Of course, in my head, I labeled him a drug-seeker and even made a comment to the technician about what a loser he is. When I took his prescriptions to the register, I noticed that a little boy, perhaps 4 years old, was holding his hand. “Your boy?” I asked. “He’s all mine now,” he said. “My wife left us last month, and I’ll be raising him all by myself. I thought of the alprazolam and felt a chill of shame for judging him so harshly. This was 2 weeks before Christmas. Snapshot. This week, I saw 2 teenage girls looking at cosmetics. They were all giggly, the way teenage girls can get. It sort of irritated me that they were handling the lipsticks. Then I saw their faces. They were from Shriners hospital, and I could see that each had many surgeries to go. They were happy, though, and when they smiled and their eyes sparkled, I saw beauty. They were gorgeous. Jim Plagakis is a community pharmacist in Galveston, Texas. You can e-mail him at [email protected] and cc us at [email protected]. You can also check out his website at jimplagakis.com. DrugTopics .c om magenta cyan yellow black 20611030304R1_1-1.pgs 03.04.2011 18:03 ADVANSTAR_PDF/X-1a Counter Points IN MY VIEW Mike LaRosa, PharmD candidate Through the eyes of a student: Pharmacy practice in Istanbul, Turkey This summer I observed pharmacy practice as few in the United States have seen it. I was entering my third year of professional study and interested in a practice experience abroad. In this country, while avenues of practice keep expanding, most would agree that of pharmaceutical care is familiar and standardized. I wanted to see how that would th t delivery d li change in a country characterized by different politics, beliefs, and attitudes. In July I headed to Istanbul, Turkey. My experience began amid a surging, immensely crowded population of 12 million people, 98% of whom are Muslim. The community practice I was going to was located right off Istiklal Avenue in Taksim Square, in the Beyoglu district — perhaps the most diverse and progressive sector of a city steeped in rich tradition. interactions are very direct. Chairs in which waiting patients may sit are arranged around the walls, facing into the center of the room. Overall, in a Turkish pharmacy one sees an emphasis on the intimate nature of a patient encounter. Patient expectations When you understand the structure of a Turkish pharmacy, even if it’s from the point of view of community pharmacy only, Routes to professional practice I quickly learned that for pharmacists in Turkey, primary pro- you can understand the quality of care provided in such a pharfessional options are in either industry or community phar- macy as well as what patients expect from their pharmacists. My pharmacist made the point that patients are looking macy, speciп¬Ѓcally independent pharmacy. This is in notable for remedies to illness, not monitoring of outcontrast to the status quo in America, where comes. In this regard community pharmacists most career paths lead to either retail chains or in Turkey feel somewhat frustrated, since they hospitals and health systems. Patients are have the pharmaceutical knowledge and see Conversations with Turkish pharmacy students looking for enough patients to know which medication is gave me the impression that industry offered remedies to associated with the most favorable outcomes. attractive beneп¬Ѓts, including the opportunity to illness, not However, in the view of most patients, the docbalance reimbursement (i.e., work) with quality monitoring of tor is the only individual responsible for betof life, a major concern of new pharmacists. This tering their health. The pharmacist is simply a issue drives career decisions and ultimately the outcomes. means to an end. way the profession evolves. I also observed that I think the most valuable lesson I learned the training students receive is designed almost exclusively along the lines of industrial practice. In Turkey we during my visit to Turkey was just how much pharmacy is won’t п¬Ѓnd the clinically focused care model we’re used to; the evolving. Both my pharmacist and the students I worked with were extremely generous with their time and knowledge. incentives for practitioners are simply not there. I feel that the experience of living in such a culturally diAlmost all medications in Turkey can be obtained without prescription. Those medications requiring a prescription are paid verse region has added tremendously to my outlook on my for almost entirely through government insurance. In Turkey, career and taught me the importance of tolerance in a pharmedications are mostly the same as those available in the United macy practice conducted among people of different cultures, States, but they are kept behind the counter and organized in beliefs, and expectations. glass cabinets according to disease state. All tablets and capsules come in unit-of-use boxes of varying amounts. In addition, al- Mike LaRosa is a third-year pharmacy student at Jefferson School most half the cabinet space is devoted to vitamin and herbal sup- of Pharmacy, Thomas Jefferson University, in Philadelphia. To read plements. Patients are received in the center of the pharmacy at more about his experience, visit http://istanbulpharmacy.blogspot. a waist-level counter that runs along the entire pharmacy. Many com. He can be reached at [email protected]. 16 DRUG TOPICS Februar y 2011 DrugTopics .c om tensive se ex Quality generics from the ground up. cy en ist y ilit ab eli dr an An ess en ctiv п¬Ђe st e Co s roducts Con 0p tion of 83 lec Actavis, the leader in п¬Ѓrst-class generics. Around the world, there’s a growing demand for high-quality, lower-cost alternatives to brand name pharmaceuticals. At Actavis, we’re at the forefront of meeting that need. From our rigorous research and development program, to our world-class manufacturing facilities, we’re committed to serving the global market – with quality generics from the ground up. To learn more, call Actavis customer service at 888.925.2342 or visit us at www.actavis.us Up front INDUSTRY NEWS & ANALYSIS Boutique focuses on needs of breast-cancer patients An independent drugstore recently expanded its boutique section for breast-cancer patients to include a wide variety of medical products and clothing. Lehan Drugs and Home Medical Equipment in DeKalb, Ill., now includes a 2,500-square-foot Women’s Health Department and Boutique that boasts 3 private dressing rooms and 3 certified lymphedema garment fitters. The Lehan family, which includes owners Tim and Ann Lehan; their daughter-in-law and pharmacist son; Tim’s brother, Patrick; and his sister, Terri Lehan Hettel, first added women’s health products to the drug- and medical-equipment store 7 or 8 years ago, after cancer patients visiting the store asked for lymphedema compression socks. “We wanted to be certified fitters in lymphedema garments, and it became obvious to us that we needed to start looking into being a mastectomy fitter,” said Lehan Hettel, who manages the store. Many specialized products followed. Today’s expanded Women’s Health Department and Boutique features products for all women. “We do bra fittings for everyone, and we have everything from вЂ�hot flash pajamas’ to scarves to hats with built-in sun protection,” Lehan Hettel said. More than 90 area doctors refer their breast-cancer patients to Lehan’s. And because it is the only drugstore in the community to offer this service, new patients consistently seek out Lehan Drugs. — Christine Blank, Contributing Editor A family affair: Four generations have served Lehan’s since the п¬Ѓrst store opened its doors in 1964. BIOTECHNOLOGY Flu vaccine patch to get 5-year test; beats traditional injection for effectiveness in animals A revolutionary flu vaccine patch is likely to be developed in the course of an upcoming 5-year clinical trial. The National Institutes of Health (NIH) recently awarded $10 million to the Georgia Institute of Technology, Emory University, and PATH, a nonproп¬Ѓt organization in Seattle, Wash., to test and reп¬Ѓne the influenza vaccine patch. The technology allows for the painless self-administration of flu vaccine by means of tiny microneedles that dissolve into the skin. The 5-year grant will advance the microneedle patch through a Phase 1 clinical trial and compare the effectiveness of traditional intramuscular injection of flu vaccine to that of microneedle patches. In animals, vaccination with the dissolving microneedles has been shown to have greater effectiveness than vaccination with hypodermic needles, according to researchers. “We have seen evidence that the vaccine works even better 18 DRUG TOPICS Februar y 2011 when administered to the skin because of the plethora of antigenpresenting cells which reside there. This study will allow us to determine how we can optimize the vaccine to take advantage of those cells that are important in generating the body’s immune response,” said Ioanna Skountzou, co-principal investigator for the project and assistant professor in Emory University’s Department of Microbiology and Immunology. The technology will also increase the number of people being vaccinated — especially susceptible populations such as children and the elderly — and reduce healthcare costs, according to Mark Prausnitz, the project’s principal investigator and a professor in the Georgia Tech School of Chemical and Biomolecular Engineering. “We believe a self-administered vaccine patch could reduce healthcare costs in 2 ways. First, self-administration removes the need to visit a clinic and use the precious time of a doctor or nurse. Second, the convenience of self-administration should increase the number of people getting vaccinated, which will reduce the number of people getting sick with influenza,” Prausnitz said. Although the patch would initially be available by prescription only, it could become over-the-counter at some point in the future, Prausnitz said. — Christine Blank, Contributing Editor Continued on pg. 20 DrugTopics .c om STOP LICE WITH COMPLETE CONFIDENCE В® 100% EFFECTIVE* 0% ACTIVE RESIDUE RID is 100% effective at killing lice, 100% effective at removing their eggs†Clinical studies show that, used as directed, RID is highly effective at killing lice and, with the RID comb, removing their eggs. Because it is vital that lice-killing products be used properly, RID provides parents with easy-to-follow directions in every package. If needed, they can also call the RID hotline or visit the RID website. Unlike NixВ®, RID leaves no active residue… a recognized factor in development of resistance‡ RID leaves no active residue that can lead to resistance. RID is designed to be applied and completely washed out. Any residue not washed out quickly degrades in sunlight. Therefore, lice are only exposed to the full lethal dose of the active ingredient and less likely to develop resistance. Recommend RID with confidence 1.800.RID.LICE www.ridlice.com В© 2010 Bayer HealthCare LLC Bayer, the Bayer Cross, RID, and the RID logo are registered trademarks of Bayer. * Based on clinical studies. Reapplication of RIDВ® shampoo and egg removal are required to ensure complete effectiveness. See label for important information. †Combing result demonstrated in laboratory studies performed by trained testers. ‡Other recognized factors in development of resistance include improper use of lice-killing treatments and misdiagnosis. Nix is a registered trademark of Insight Pharmaceuticals LLC. Up front U Continued from pg. 18 HANDS-ON LEARNING New pharmacy school offers unique 3-calendar-year PharmD program This fall, Saint Joseph College School of Pharmacy will open the doors of its new 35,000-square-foot facility in the heart of downtown Hartford, Conn., to its п¬Ѓrst class of students. With an expected enrollment of 68, the new school will offer a unique 3-calendar-year doctoral degree program in pharmacy (PharmD), which represents the п¬Ѓrst doctoral program in the college’s 78-year history. Modeled after curriculum employed at the University of Southern Nevada College of Pharmacy (Henderson), the program emphasizes a student-centered, active learning environment. The curriculum is organized in blocks, allowing students to concentrate on 1 course at a time through a variety of learning activities, rather than in the traditional lecture format. “We have student-centered, small-group learning. Professors are not expected to walk into a large lecture room and give a lecture where students learn passively. Instead, our classrooms are designed in the round, with the professor at the center, so that students are engaged and able to participate in the educational experience,” said Joseph R. Ofosu, PharmD, RPh, dean of Saint Joseph College School of Pharmacy. Joseph R. Ofosu Once a week, beginning in the п¬Ѓrst semester, pharmacy students will be introduced to practice experiences in community and institutional pharmacy settings. “Community sites range from small independent pharmacies to the largest chain pharmacies. Various institutional rotations include large medical centers, small community hospitals, longterm-care pharmacies, and home IV pharmacies. This will allow the students plenty of time to experience all that pharmacy has to offer. In the third year, the students will have an even larger choice of locations for more advanced rotations,” said John Parsi, RPh, CDE, the pharmacy school’s director of experiential education. The new pharmacy school provides students hands-on learning in patient care, dispensing, and all the other areas that a pharmacist can pursue. “Pharmacists have many career pathways open to them beyond dispensing, including health insurance, home-care services, government sectors, research, and teaching,” said Dr. Ofosu, who most recently served as associate dean for Academic Affairs at Howard University College of Pharmacy, Nursing and Allied Health Sciences. “This is a profession that will continue to do well. The need for drug or medication specialists is going to grow, due to the aging population and the new approach to healthcare. Nurses, pharmacists, and other healthcare professionals are going to play key roles. The new healthcare law and society are expecting more from the pharmacy profession,” Dr. Ofosu said. — Julia Talsma, Editor-in-Chief 20 DRUG TOPICS Februar y 2011 HEALTHY OPTIONS Walgreens brings fresh produce to “food deserts” In addition to its role as a pharmacy provider, Walgreens seems to be morphing into a supermarket in some U.S. cities. In 10 of its Chicago-area stores, Walgreens is piloting a program to provide healthy food options such as fresh fruits and vegetables, frozen meats and п¬Ѓsh, eggs, and whole-grain cereals and pastas in its stores. In fact, it is carrying 750 new food items in each of the 10 stores, which are primarily in the south and west sides of Chicago. Walgreens’ executives chose those locations to pilot food stores because they are in urban areas where there are no supermarkets or other retail locations selling healthy food, leaving neighborhood residents few options beyond high-calorie fast foods or processed food products sold by convenience stores. “Last year, we were approached by Chicago’s mayor, Richard M. Daley, about п¬Ѓnding ways to address вЂ�food deserts.’ Because we are the city’s most accessible retailer, we decided to look at how we could help in places where there was limited or no access to healthy food options,” said Don Whetstone, senior director, new format development, Walgreens. Walgreens started rolling out the redesigned Chicago stores last year. “We are focused on health and wellness, and this is one more way we can help improve the health outcomes of customers and patients in the area,” Whetstone said. In an increasingly competitive big-chain marAccording to Whetketplace, Walgreens’ act of social service may also help its bottom line. stone, the biggest chal(Photo courtesy of Walgreens) lenge connected with adding fresh and frozen food to drugstores is determining the right product mix to serve the community. “So far, we are hearing very positive feedback from customers about the offerings, and they are pretty vocal about letting our store managers know what items they would like to see more of,” Whetstone said. While Walgreens’ executives are considering adding the full line of “healthy foods” to other Walgreens’ stores, they have not yet announced locations in other cities. “The concept of a food desert is not exclusive to Chicago … [but] Chicago is the only city with this pilot at this time,” Whetstone said. However, that may soon change. According to a recent Reuters report, at the company’s annual meeting in January, Walgreens executives announced a plan to bring similar initiatives to some 300 to 500 stores in the company’s chain of more than 7,600. — Christine Blank, Contributing Editor DrugTopics .c om What makes a pharmacy KHUВїUVWFKRLFH" 2QWKHJRDFFHVV В® Customers are busy. QS/1 ’s IVR helps you provide on-demand service. 3URYLGHDQ\WLPHSKRQHUHВїOORUGHULQJDQGKHOSIXOVHUYLFHVOLNHWLPHO\UHВїOO UHPLQGHUVVRWKH\NQRZWKHLUKHDOWKLV\RXUВїUVWSULRULW\2XUHQGWRHQG SKDUPDF\V\VWHPDQGVHUYLFHVZRUNWRJHWKHUWRIUHHPRUHRI\RXUWLPH To provide exceptional service. To improve lives. To be her pharmacist. Every day. В© 2011, J M SMITH CORPORATION. QS/1 is a registered trademark of the J M Smith Corporation. 1.800.231.7776 www.qs1.com Issues & Trends Up front In Depth Fred Gebhart, Contributing Editor New report advocates replacing Medicaid FFS with managed pharmacy benefit A new report urges states to replace Medicaid fee-for-service pharmacy programs with the kind of managed drug beneп¬Ѓts used in Medicare Part D plans, Medicaid managed care organizations, and some commercial health plans. Why drop FFS? Optimal pharmacy benefit management could save $30 billion over the next decade, the report claimed. In the near term, savings of $12 per member per month in 2011 can be expected. The claim comes in an analysis of Medicaid drug spending commissioned by the Pharmaceutical Care Management Association (PCMA) and conducted by The Lewin Group, healthcare and human services consultants. The projected savings include a combination of reduced dispensing fees, reduced ingredient-cost reimbursement, increased generic use, and decreased drug utilization. The key message in the report is that pharmacy beneп¬Ѓt managers (PBMs) can cut Medicaid expenditures. PBMs can cut Medicaid costs “We, like every other health-related group, have been looking for ways to save money in Medicaid without cutting benefits or harming patients,” PCMA President and CEO Mark Merritt told Drug Topics. “Medicaid is not a traditional PBM space, but this is a space legislators are going to look into. This report is intended to spark discussion so policymakers don’t start slashing without seeing the larger picture.” Merritt said the key audience for the report is governors and state legislators around the nation. PCMA hit the same 22 DRUG TOPICS Februar y 2011 audience with a telephone survey of registered voters suggesting that respondents preferred to cut expenditures for prescription-drug coverage rather than cutting payments to physicians or hospitals. There was no immediate reaction from state ofп¬Ѓcials, but at least one pharmacy group said PCMA was using Medicaid spending to build support for its PBM membership. Flawed assumptions The National Community Pharmacists Association (NCPA) criticized the underlying policy assumptions in the Lewin report, starting with the lack of distinctions drawn between Medicaid and Medicare program requirements and populations as well as the lack of attention given to differences between state Medicaid programs and the п¬Ѓnancial dependence of PBMs on rebates from brand-name drug manufacturers. “The point we want to highlight is really the PBM track record when it comes to a serious cost-cutting mechanism — generic drugs — which is obviously undercut by their brand-name drug rebates,” said NCPA spokesman John Norton. Overlooked impact NCPA also said the report failed to recognize the potential impact of reduced reimbursement on pharmacy access, the pending expansion of the Medicaid population base, the likelihood that reducing drug utilization and drug treatments would boost overall medical expenditures, the lack of prescribing controls in the Lewin model, widely different generic dispensing rates among states, and controls on nongeneric products needed to reduce expenditures to the projected levels. Lewin analysts concluded that FFS programs account for 73% of all Medicaid pharmacy benefit spending. Dispensing fees, ingredient costs, and benefit management are directed by state ofп¬Ѓcials who are subject to local political pressures, Merritt said. Medicare Part D, Medicaid managed care organizations, and state employee plans typically use private-sector PBMs to set dispensing fees, ingredient reimbursement, and generic dispensing goals, and other plan parameters. “Medicaid is the last large unmanaged pharmacy beneп¬Ѓt in the country,” Merritt said. “Medicaid dispensing fees are double the fees paid under Medicare.” Merritt said PCMA wants to bring the same kind of management to Medicaid pharmacy benefits that Medicare and other drug programs employ. NCPA suggested that states could provide more effective care at lower cost by focusing on generic drug substitution and use than by bringing PBMs into Medicaid. Generics п¬Ѓrst “All plans, including state Medicaid FFS plans, will realize signiп¬Ѓcant savings by implementing a вЂ�generics п¬Ѓrst’ plan design,” NCPA said in a written statement. “PBMs are not a critical component of implementing these plan designs. Recent generic dispensing rates from the big 3 PBMs demonstrate that the retail channel effectively drives generics across all types of plans. In 2009, all of the PBMs had signiп¬Ѓcantly lower generic dispensing rates associated with their mail pharmacies where they were solely responsible for generic dispensing.” DrugTopics .c om See the effect of LEXAPRO Proven efп¬Ѓcacy in MDD in adolescents aged 12 to 17, and in MDD and GAD in adults1-5 In adolescents aged 12 to 17 with Major Depressive Disorder (MDD)*1 In adults with MDD and Generalized Anxiety Disorder (GAD)1 LEXAPRO and citalopram are not the same1,6,7 • LEXAPRO is approved for MDD and GAD1; citalopram is not approved for GAD.6 • LEXAPRO is approved for MDD in adolescents aged 12 to 17 years1; citalopram is not.6 There is no generic available for LEXAPRO *LEXAPRO is indicated as an integral part of a total treatment program for MDD. Drug treatment may not be indicated for all adolescents with this syndrome. WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Lexapro or any other antidepressant in a child, adolescent or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not approved for use in pediatric patients less than 12 years of age. Contraindications • Lexapro is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs). There have been reports of serious, sometimes fatal, reactions with some cases resembling neuroleptic malignant syndrome (NMS) and serotonin syndrome. Features may include hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on an MAOI. Serotonin syndrome was reported for two patients who were concomitantly receiving linezolid, an antibiotic which has MAOI activity. Lexapro should not be used in combination with an MAOI or within 14 days of discontinuing an MAOI. MAOIs should not be initiated within 14 days of discontinuing Lexapro. • Lexapro is contraindicated in patients taking pimozide or with hypersensitivity to escitalopram or citalopram. Please see additional Important Safety Information on adjacent page. Visit the LEXAPRO website at www.lexapro.com There is no generic available for LEXAPRO Lexapro (escitalopram oxalate) is indicated for the acute and maintenance treatment of major depressive disorder (MDD) in adults and adolescents aged 12-17 years. Lexapro is also indicated for the acute treatment of generalized anxiety disorder (GAD) in adults. IMPORTANT SAFETY INFORMATION Warnings and Precautions • All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality and unusual changes in behavior, especially within the п¬Ѓrst few months of treatment or when changing the dose. Consideration should be given to changing the therapeutic regimen, including discontinuing medication, in patients whose depression is persistently worse, who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Families and caregivers of patients treated with antidepressants should be alerted about the need to monitor patients daily for the emergence of agitation, irritability, unusual changes in behavior, or the emergence of suicidality, and report such symptoms immediately. Prescriptions for Lexapro should be written for the smallest quantity of tablets, consistent with good patient management, in order to reduce the risk of overdose. • A major depressive episode may be the initial presentation of bipolar disorder. In patients at risk for bipolar disorder, treating such an episode with an antidepressant alone may increase the likelihood of precipitating a mixed/manic episode. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder. Lexapro should be used cautiously in patients with a history of mania or seizure disorder. Lexapro is not approved for use in treating bipolar depression. • The concomitant use of Lexapro with other SSRIs, SNRIs, triptans, tryptophan, antipsychotics or other dopamine antagonists is not recommended due to potential development of life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions. Reactions have been reported with SNRIs and SSRIs alone, including Lexapro, but particularly with drugs that impair metabolism of serotonin (including MAOIs). Management of these events should include immediate discontinuation of Lexapro and the concomitant agent and continued monitoring. • Patients should be monitored for adverse reactions when discontinuing treatment with Lexapro. During marketing of Lexapro and other SSRIs and SNRIs, there have been spontaneous reports of adverse events occurring upon discontinuation, including dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania. A gradual dose reduction rather than abrupt cessation is recommended whenever possible. • SSRIs and SNRIs have been associated with clinically signiп¬Ѓcant hyponatremia. Elderly patients and patients taking diuretics or who are otherwise volume-depleted appear to be at a greater risk. Discontinuation of Lexapro should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. • SSRIs (including Lexapro) and SNRIs may increase the risk of bleeding. Patients should be cautioned that concomitant use of aspirin, NSAIDs, warfarin or other anticoagulants may add to the risk. • Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Lexapro does not affect their ability to engage in such activities. • Lexapro should be used with caution in patients with severe renal impairment or with diseases or conditions that alter metabolism or hemodynamic responses. In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of Lexapro in hepatically impaired patients is 10 mg/day. • For pregnant or nursing mothers, Lexapro should be used only if the potential beneп¬Ѓt justiп¬Ѓes the potential risk to the fetus or child. Adverse Reactions • In clinical trials of MDD, the most common adverse reactions in adults treated with Lexapro (approximately 5% or greater and at least twice the incidence of placebo) were nausea (15% vs 7%), insomnia (9% vs 4%), ejaculation disorder (9% vs <1%), fatigue (5% vs 2%), somnolence (6% vs 2%), and increased sweating (5% vs 2%). In pediatric patients, the overall proп¬Ѓle of adverse reactions was similar to that seen in adults; however, the following additional adverse reactions were reported at an incidence of at least 2% for Lexapro and greater than placebo: back pain, urinary tract infection, vomiting, and nasal congestion. • In clinical trials of GAD, the most common adverse reactions in adults treated with Lexapro (approximately 5% or greater and at least twice the incidence of placebo) were nausea (18% vs 8%), ejaculation disorder (14% vs 2%), insomnia (12% vs 6%), fatigue (8% vs 2%), decreased libido (7% vs 2%) and anorgasmia (6% vs <1%). References: 1. LEXAPRO [package insert]. St. Louis, Mo: Forest Pharmaceuticals, Inc.; 2009. 2. Emslie GJ, Ventura D, Korotzer A, Tourkodimitris S. Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial. J Am Acad Child Adolesc Psychiatry. 2009;48:721-729. 3. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63:331-336. 4. Davidson JRT, Bose A, Korotzer A, Zheng H. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depress Anxiety. 2004;19:234240. 5. Wade A, Lemming OM, Hedegaard KB. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002;17:95-102. 6. Celexa [package insert]. St. Louis, Mo: Forest Pharmaceuticals, Inc.; 2009. 7. Mork A, Kreilgaard M, Sanchez C. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats. Neuropharmacology. 2003;45:167-173. Please see accompanying brief summary of Prescribing Information for LEXAPRO, including Boxed Warning. В© 2010 Forest Laboratories, Inc. Printed in U.S.A. 41-1017601r 5/10 Visit the LEXAPRO website at www.lexapro.com LEXAPROВ® (escitalopram oxalate) TABLETS/ORAL SOLUTION Brief Summary: For complete details, please see full Prescribing Information for Lexapro. Rx Only WARNINGS: SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Lexapro or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not approved for use in pediatric patients less than 12 years of age. [See Warnings and Precautions: Clinical Worsening and Suicide Risk, Patient Counseling Information: Information for Patients, and Used in Specific Populations: Pediatric Use]. INDICATIONS AND USAGE: Major Depressive Disorder-Lexapro (escitalopram) is indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [see Clinical Studies]. A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. Generalized Anxiety Disorder-Lexapro is indicated for the acute treatment of Generalized Anxiety Disorder (GAD) in adults [see Clinical Studies]. Generalized Anxiety Disorder (DSM-IV) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It must be associated with at least 3 of the following symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance. CONTRAINDICATIONS: Monoamine oxidase inhibitors (MAOIs)-Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated [see Warnings and Precautions]. Pimozide-Concomitant use in patients taking pimozide is contraindicated [see Drug Interactions]. Hypersensitivity to escitalopram or citalopram-Lexapro is contraindicated in patients with a hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in Lexapro. WARNINGS AND PRECAUTIONS: Clinical Worsening and Suicide Risk-Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. TABLE 1 Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18-24 5 additional cases Decreases Compared to Placebo 25-64 1 fewer case 65 6 fewer cases No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [see Dosage and Administration]. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers [see also Patient Counseling Information]. Prescriptions for Lexapro should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder-A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Lexapro is not approved for use in treating bipolar depression. Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions-The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including Lexapro treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms. The concomitant use of Lexapro with MAOIs intended to treat depression is contraindicated. If concomitant treatment of Lexapro with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Lexapro with serotonin precursors (such as tryptophan) is not recommended. Treatment with Lexapro and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. Discontinuation of Treatment with Lexapro-During marketing of Lexapro and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms. Patients should be monitored for these symptoms when discontinuing treatment with Lexapro. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate [see Dosage and Administration]. Seizures-Although anticonvulsant effects of racemic citalopram have been observed in animal studies, Lexapro has not been systematically evaluated in patients with a seizure disorder. These patients were excluded from clinical studies during the product’s premarketing testing. In clinical trials of Lexapro, cases of convulsion have been reported in association with Lexapro treatment. Like other drugs effective in the treatment of major depressive disorder, Lexapro should be introduced with care in patients with a history of seizure disorder. Activation of Mania/Hypomania-In placebocontrolled trials of Lexapro in major depressive disorder, activation of mania/hypomania was reported in one (0.1%) of 715 patients treated with Lexapro and in none of the 592 patients treated with placebo. One additional case of hypomania has been reported in association with Lexapro treatment. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorders treated with racemic citalopram and other marketed drugs effective in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, Lexapro should be used cautiously in patients with a history of mania. Hyponatremia-Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Lexapro. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when Lexapro was discontinued. Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk [see Geriatric Use]. Discontinuation of Lexapro should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Abnormal Bleeding-SSRIs and SNRIs, including Lexapro, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to the risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Patients should be cautioned about the risk of bleeding associated with the concomitant use of Lexapro and NSAIDs, aspirin, or other drugs that affect coagulation. Interference with Cognitive and Motor Performance-In a study in normal volunteers, Lexapro 10 mg/day did not produce impairment of intellectual function or psychomotor performance. Because any psychoactive drug may impair judgment, thinking, or motor skills, however, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Lexapro therapy does not affect their ability to engage in such activities. Use in Patients with Concomitant Illness-Clinical experience with Lexapro in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using Lexapro in patients with diseases or conditions that produce altered metabolism or hemodynamic responses. Lexapro has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were generally excluded from clinical studies during the product’s premarketing testing. In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of Lexapro in hepatically impaired patients is 10 mg/day [see Dosage and Administration]. Because escitalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimination. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with Lexapro, however, it should be used with caution in such patients [see Dosage and Administration]. Potential for Interaction with Monoamine Oxidase InhibitorsIn patients receiving serotonin reuptake inhibitor drugs in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Furthermore, limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that Lexapro should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping Lexapro before starting an MAOI. Serotonin syndrome has been reported in two patients who were concomitantly receiving linezolid, an antibiotic which is a reversible non-selective MAOI. ADVERSE REACTIONS: Clinical Trials Experience-Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Clinical Trial Data Sources; Pediatrics (6 -17 years)-Adverse events were collected in 576 pediatric patients (286 Lexapro, 290 placebo) with major depressive disorder in double-blind placebo-controlled studies. Safety and effectiveness of Lexapro in pediatric patients less than 12 years of age has not been established. Adults-Adverse events information for Lexapro was collected from 715 patients with major depressive disorder who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind, placebo-controlled trials. An additional 284 patients with major depressive disorder were newly exposed to escitalopram in open-label trials. The adverse event information for Lexapro in patients with GAD was collected from 429 patients exposed to escitalopram and from 427 patients exposed to placebo in double-blind, placebo-controlled trials. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Adverse Events Associated with Discontinuation of Treatment; Major Depressive Disorder; Pediatrics (6 -17 years)-Adverse events were associated with discontinuation of 3.5% of 286 patients receiving Lexapro and 1% of 290 patients receiving placebo. The most common adverse event (incidence at least 1% for Lexapro and greater than placebo) associated with discontinuation was insomnia (1% Lexapro, 0% placebo). Adults-Among the 715 depressed patients who received Lexapro in placebo-controlled trials, 6% discontinued treatment due to an adverse event, as compared to 2% of 592 patients receiving placebo. In two fixed-dose studies, the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro was not significantly different from the rate of discontinuation for adverse events in patients receiving placebo. The rate of discontinuation for adverse events in patients assigned to a fixed dose of 20 mg/day Lexapro was 10%, which was significantly different from the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro (4%) and placebo (3%). Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients). Generalized Anxiety Disorder; Adults-Among the 429 GAD patients who received Lexapro 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due to an adverse event, as compared to 4% of 427 patients receiving placebo. Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and fatigue (1%). Incidence of Adverse Reactions in Placebo-Controlled Clinical Trials; Major Depressive Disorder; Pediatrics (6 -17 years)-The overall profile of adverse reactions in pediatric patients was generally similar to that seen in adult studies, as shown in Table 2. However, the following adverse reactions (excluding those which appear in Table 2 and those for which the coded terms were uninformative or misleading) were reported at an incidence of at least 2% for Lexapro and greater than placebo: back pain, urinary tract infection, vomiting, and nasal congestion. Adults-The most commonly observed adverse reactions in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue, and somnolence. Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 715 depressed patients who received Lexapro at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients. TABLE 2 Treatment-Emergent Adverse Reactions Observed with a Frequency of 2% and Greater Than Placebo for Major Depressive Disorder Adverse Reaction Autonomic Nervous System Disorders Dry Mouth Sweating Increased Central & Peripheral Nervous System Disorders Dizziness Gastrointestinal Disorders Nausea Diarrhea Constipation Indigestion Abdominal Pain General Influenza-like Symptoms Fatigue Psychiatric Disorders Insomnia Somnolence Appetite Decreased Libido Decreased Respiratory System Disorders Rhinitis Sinusitis Urogenital Ejaculation Disorder1,2 Impotence2 Anorgasmia3 Lexapro (N=715) Placebo (N=592) 6% 5% 5% 2% 5% 3% 15% 8% 3% 3% 2% 7% 5% 1% 1% 1% 5% 5% 4% 2% 9% 6% 3% 3% 4% 2% 1% 1% 5% 3% 4% 2% 9% 3% 2% <1% <1% <1% 1Primarily ejaculatory delay. 2Denominator used was for males only (N=225 Lexapro; N=188 placebo). 3Denominator used was for females only (N=490 Lexapro; N=404 placebo). Generalized Anxiety Disorder; Adults-The most commonly observed adverse reactions in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay), insomnia, fatigue, decreased libido, and anorgasmia. Table 3 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse events that occurred among 429 GAD patients who received Lexapro 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients. TABLE 3 Treatment-Emergent Adverse Reactions Observed with a Frequency of 2% and Greater Than Placebo for Generalized Anxiety Disorder Adverse Reactions Lexapro Placebo (N=429) (N=427) Autonomic Nervous System Disorders Dry Mouth 9% 5% Sweating Increased 4% 1% Central & Peripheral Nervous System Disorders Headache 24% 17% Paresthesia 2% 1% Gastrointestinal Disorders Nausea 18% 8% Diarrhea 8% 6% Constipation 5% 4% Indigestion 3% 2% Vomiting 3% 1% Abdominal Pain 2% 1% Flatulence 2% 1% Toothache 2% 0% General Fatigue 8% 2% Influenza-like Symptoms 5% 4% Musculoskeletal System Disorder Neck/Shoulder Pain 3% 1% Psychiatric Disorders Somnolence 13% 7% Insomnia 12% 6% Libido Decreased 7% 2% Dreaming Abnormal 3% 2% Appetite Decreased 3% 1% Lethargy 3% 1% LEXAPROВ® (escitalopram oxalate) TABLETS/ORAL SOLUTION Adverse Reactions TABLE 3 Treatment-Emergent Adverse Reactions Observed with a Frequency of 2% and Greater Than Placebo for Generalized Anxiety Disorder (continued) Lexapro (N=429) Respiratory System Disorders Yawning Urogenital Ejaculation Disorder1,2 Anorgasmia3 Menstrual Disorder LEXAPROВ® (escitalopram oxalate) TABLETS/ORAL SOLUTION Placebo (N=427) 2% 1% 14% 6% 2% 2% <1% 1% 1Primarily ejaculatory delay. 2Denominator used was for males only (N=182 Lexapro; N=195 placebo). 3Denominator used was for females only (N=247 Lexapro; N=232 placebo). Dose Dependency of Adverse Reactions-The potential dose dependency of common adverse reactions (defined as an incidence rate of 5% in either the 10 mg or 20 mg Lexapro groups) was examined on the basis of the combined incidence of adverse events in two fixed-dose trials. The overall incidence rates of adverse events in 10 mg Lexapro-treated patients (66%) was similar to that of the placebo-treated patients (61%), while the incidence rate in 20 mg/day Lexapro-treated patients was greater (86%). Table 4 shows common adverse reactions that occurred in the 20 mg/day Lexapro group with an incidence that was approximately twice that of the 10 mg/day Lexapro group and approximately twice that of the placebo group. Adverse Reaction Insomnia Diarrhea Dry Mouth Somnolence Dizziness Sweating Increased Constipation Fatigue Indigestion TABLE 4 Incidence of Common Adverse Reactions in Patients with Major Depressive Disorder Placebo 10 mg/day (N=311) Lexapro (N=310) 4% 7% 5% 6% 3% 4% 1% 4% 2% 4% <1% 3% 1% 3% 2% 2% 1% 2% 20 mg/day Lexapro (N=125) 14% 14% 9% 9% 7% 8% 6% 6% 6% Male and Female Sexual Dysfunction with SSRIs-Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence. Adverse Event Ejaculation Disorder (primarily ejaculatory delay) Libido Decreased Impotence Libido Decreased Anorgasmia TABLE 5 Incidence of Sexual Side Effects in Placebo-Controlled Clinical Trials Lexapro In Males Only (N=407) 12% 6% 2% (N=737) 3% 3% In Females Only Placebo (N=383) 1% 2% <1% (N=636) 1% <1% There are no adequately designed studies examining sexual dysfunction with escitalopram treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects. Vital Sign Changes-Lexapro and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with Lexapro treatment. In addition, a comparison of supine and standing vital sign measures in subjects receiving Lexapro indicated that Lexapro treatment is not associated with orthostatic changes. Weight Changes-Patients treated with Lexapro in controlled trials did not differ from placebo-treated patients with regard to clinically important change in body weight. Laboratory Changes-Lexapro and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with Lexapro treatment. ECG Changes-Electrocardiograms from Lexapro (N=625), racemic citalopram (N=351), and placebo (N=527) groups were compared with respect to (1) mean change from baseline in various ECG parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed (1) a decrease in heart rate of 2.2 bpm for Lexapro and 2.7 bpm for racemic citalopram, compared to an increase of 0.3 bpm for placebo and (2) an increase in QTc interval of 3.9 msec for Lexapro and 3.7 msec for racemic citalopram, compared to 0.5 msec for placebo. Neither Lexapro nor racemic citalopram were associated with the development of clinically significant ECG abnormalities. Other Reactions Observed During the Premarketing Evaluation of Lexapro-Following is a list of treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by the 1428 patients treated with Lexapro for periods of up to one year in doubleblind or open-label clinical trials during its premarketing evaluation. The listing does not include those events already listed in Tables 2 & 3, those events for which a drug cause was remote and at a rate less than 1% or lower than placebo, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life threatening. Events are categorized by body system. Events of major clinical importance are described in the Warnings and Precautions section. Cardiovascular - hypertension, palpitation. Central and Peripheral Nervous System Disorders - light-headed feeling, migraine. Gastrointestinal Disorders - abdominal cramp, heartburn, gastroenteritis. General - allergy, chest pain, fever, hot flushes, pain in limb. Metabolic and Nutritional Disorders - increased weight. Musculoskeletal System Disorders - arthralgia, myalgia jaw stiffness. Psychiatric Disorders - appetite increased, concentration impaired, irritability. Reproductive Disorders/Female - menstrual cramps, menstrual disorder. Respiratory System Disorders - bronchitis, coughing, nasal congestion, sinus congestion, sinus headache. Skin and Appendages Disorders - rash. Special Senses - vision blurred, tinnitus. Urinary System Disorders - urinary frequency, urinary tract infection. Post-Marketing Experience; Adverse Reactions Reported Subsequent to the Marketing of Escitalopram-The following additional adverse reactions have been identified from spontaneous reports of escitalopram received worldwide. These adverse reactions have been chosen for inclusion because of a combination of seriousness, frequency of reporting, or potential causal connection to escitalopram and have not been listed elsewhere in labeling. However, because these adverse reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events include: Blood and Lymphatic System Disorders: anemia, agranulocytis, aplastic anemia, hemolytic anemia, idiopathic thrombocytopenia purpura, leukopenia, thrombocytopenia. Cardiac Disorders: atrial fibrillation, bradycardia, cardiac failure, myocardial infarction, tachycardia, torsade de pointes, ventricular arrhythmia, ventricular tachycardia. Ear and Labyrinth Disorders: vertigo Endocrine Disorders: diabetes mellitus, hyperprolactinemia, SIADH. Eye Disorders: diplopia, glaucoma, mydriasis, visual disturbance. Gastrointestinal Disorders: dysphagia, gastrointestinal hemorrhage, gastroesophageal reflux, pancreatitis, rectal hemorrhage. General Disorders and Administration Site Conditions: abnormal gait, asthenia, edema, fall, feeling abnormal, malaise. Hepatobiliary Disorders: fulminant hepatitis, hepatic failure, hepatic necrosis, hepatitis. Immune System Disorders: allergic reaction, anaphylaxis. Investigations: bilirubin increased, decreased weight, electrocardiogram QT prolongation, hepatic enzymes increased, hypercholesterolemia, INR increased, prothrombin decreased. Metabolism and Nutrition Disorders: hyperglycemia, hypoglycemia, hypokalemia, hyponatremia. Musculoskeletal and Connective Tissue Disorders: muscle cramp, muscle stiffness, muscle weakness, rhabdomyolysis. Nervous System Disorders: akathisia, amnesia, ataxia, choreoathetosis, cerebrovascular accident, dysarthria, dyskinesia, dystonia, extrapyramidal disorders, grand mal seizures (or convulsions), hypoaesthesia, myoclonus, nystagmus, Parkinsonism, restless legs, seizures, syncope, tardive dyskinesia, tremor. Pregnancy, Puerperium and Perinatal Conditions: spontaneous abortion. Psychiatric Disorders: acute psychosis, aggression, agitation, anger, anxiety, apathy, completed suicide, confusion, depersonalization, depression aggravated, delirium, delusion, disorientation, feeling unreal, hallucinations (visual and auditory), mood swings, nervousness, nightmare, panic reaction, paranoia, restlessness, self-harm or thoughts of self-harm, suicide attempt, suicidal ideation, suicidal tendency. Renal and Urinary Disorders: acute renal failure, dysuria, urinary retention. Reproductive System and Breast Disorders: menorrhagia, priapism. Respiratory, Thoracic and Mediastinal Disorders: dyspnea, epistaxis, pulmonary embolism, pulmonary hypertension of the newborn. Skin and Subcutaneous Tissue Disorders: alopecia, angioedema, dermatitis, ecchymosis, erythema multiforme, photosensitivity reaction, Stevens Johnson Syndrome, toxic epidermal necrolysis, urticaria. Vascular Disorders: deep vein thrombosis, flushing, hypertensive crisis, hypotension, orthostatic hypotension, phlebitis, thrombosis. DRUG INTERACTIONS: Serotonergic Drugs-Based on the mechanism of action of SNRIs and SSRIs including Lexapro, and the potential for serotonin syndrome, caution is advised when Lexapro is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John’s Wort [see Warnings and Precautions]. The concomitant use of Lexapro with other SSRIs, SNRIs or tryptophan is not recommended. Triptans-There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Lexapro with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see Warnings and Precautions]. CNS Drugs- Given the primary CNS effects of escitalopram, caution should be used when it is taken in combination with other centrally acting drugs. Alcohol-Although Lexapro did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as with other psychotropic medications, the use of alcohol by patients taking Lexapro is not recommended. Monoamine Oxidase Inhibitors (MAOIs)-[see Contraindications and Warnings and Precautions]. Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)-Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate the risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when Lexapro is initiated or discontinued. Cimetidine-In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400 mg/day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively. The clinical significance of these findings is unknown. Digoxin-In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin. Lithium-Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Lexapro and lithium are coadministered. Pimozide and Celexa-In a controlled study, a single dose of pimozide 2 mg coadministered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known. Sumatriptan-There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of an SSRI and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised. Theophylline-Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated. Warfarin-Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown. Carbamazepine-Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered. Triazolam-Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam. KetoconazoleCombined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram. Ritonavir-Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram. CYP3A4 and -2C19 Inhibitors-In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance. Drugs Metabolized by Cytochrome P4502D6-In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6. Metoprolol-Administration of 20 mg/day Lexapro for 21 days in healthy volunteers resulted in a 50% increase in Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Lexapro and metoprolol had no clinically significant effects on blood pressure or heart rate. Electroconvulsive Therapy (ECT)-There are no clinical studies of the combined use of ECT and escitalopram. USE IN SPECIFIC POPULATIONS: Pregnancy; Pregnancy Category C-In a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses (approximately 56 times the maximum recommended human dose [MRHD] of 20 mg/day on a body surface area [mg/m2] basis). Maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. The developmental no-effect dose of 56 mg/kg/day is approximately 28 times the MRHD on a mg/m2 basis. No teratogenicity was observed at any of the doses tested (as high as 75 times the MRHD on a mg/m2 basis). When female rats were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 24 times the MRHD on a mg/m2 basis. Slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose. Slightly increased offspring mortality was also seen at 24 mg/kg/day. The no-effect dose was 12 mg/kg/day which is approximately 6 times the MRHD on a mg/m2 basis. In animal reproduction studies, racemic citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects, when administered at doses greater than human therapeutic doses. In two rat embryo/fetal development studies, oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose. This dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). The developmental no-effect dose was 56 mg/kg/day. In a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day. Thus, teratogenic effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit. When female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose. The no-effect dose was 12.8 mg/kg/day. Similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses 24 mg/kg/day. A no-effect dose was not determined in that study. There are no adequate and well-controlled studies in pregnant women; therefore, escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pregnancy-Nonteratogenic Effects Neonates exposed to Lexapro and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions]. Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective, case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. There is currently no corroborative evidence regarding the risk for PPHN following exposure to SSRIs in pregnancy; this is the first study that has investigated the potential risk. The study did not include enough cases with exposure to individual SSRIs to determine if all SSRIs posed similar levels of PPHN risk. When treating a pregnant woman with Lexapro during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment [see Dosage and Administration]. Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication. Labor and Delivery-The effect of Lexapro on labor and delivery in humans is unknown. Nursing Mothers-Escitalopram is excreted in human breast milk. Limited data from women taking 10-20 mg escitalopram showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram. There were two reports of infants experiencing excessive somnolence, decreased feeding, and weight loss in association with breastfeeding from a racemic citalopram-treated mother; in one case, the infant was reported to recover completely upon discontinuation of racemic citalopram by its mother and, in the second case, no follow-up information was available. Caution should be exercised and breastfeeding infants should be observed for adverse reactions when Lexapro is administered to a nursing woman. Pediatric Use-Safety and effectiveness of Lexapro has not been established in pediatric patients (less than 12 years of age) with Major Depressive Disorder. Safety and effectiveness of Lexapro has been established in adolescents (12 to 17 years of age) for the treatment of major depressive disorder [see Clinical Studies]. Although maintenance efficacy in adolescent patients with Major Depressive Disorder has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients. Safety and effectiveness of Lexapro has not been established in pediatric patients less than 18 years of age with Generalized Anxiety Disorder. Geriatric Use-Approximately 6% of the 1144 patients receiving escitalopram in controlled trials of Lexapro in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of Lexapro between 10 and 20 mg. The number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. Nevertheless, greater sensitivity of some elderly individuals to effects of Lexapro cannot be ruled out. SSRIs and SNRIs, including Lexapro, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Hyponatremia]. In two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared to young subjects and Cmax was unchanged [see Clinical Pharmacology]. 10 mg/day is the recommended dose for elderly patients [see Dosage and Administration]. Of 4422 patients in clinical studies of racemic citalopram, 1357 were 60 and over, 1034 were 65 and over, and 457 were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out. DRUG ABUSE AND DEPENDENCE: Abuse and Dependence; Physical and Psychological Dependence-Animal studies suggest that the abuse liability of racemic citalopram is low. Lexapro has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. The premarketing clinical experience with Lexapro did not reveal any drug-seeking behavior. However, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate Lexapro patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior). OVERDOSAGE: Human Experience-In clinical trials of escitalopram, there were reports of escitalopram overdose, including overdoses of up to 600 mg, with no associated fatalities. During the postmarketing evaluation of escitalopram, Lexapro overdoses involving overdoses of over 1000 mg have been reported. As with other SSRIs, a fatal outcome in a patient who has taken an overdose of escitalopram has been rarely reported. Symptoms most often accompanying escitalopram overdose, alone or in combination with other drugs and/or alcohol, included convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose. Management of Overdose-Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for Lexapro. In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO 63045 USA Licensed from H. Lundbeck A/S В© 2009 Forest Laboratories, Inc. Rev. 05/09 Issues & Trends Up front In Depth Fred Gebhart, Contributing Editor Proposed Part D rules for short-cycle dispensing roil LTC P roposed rules designed to cut waste in Medicare Part D could create problems for long-termcare (LTC) pharmacy. LTC facilities and pharmacies that serve them will have to adjust their care and business models for short-cycle dispensing. Most LTC facilities currently dispense 30-day п¬Ѓlls. The proposed rules require 7-day or shorter п¬Ѓlls for Part D prescriptions. “The proposed rule requires LTC pharmacies to be up and running with shortcycle dispensing by January 1, 2012,” said Lynne Batshon, director of policy and advocacy, American Society of Consultant Pharmacists (ASCP). “We have some concerns about pharmacies’ ability to be in place within that time frame. We don’t have a sense of how many pharmacies might not be able to continue to provide services.” Short-cycle dispensing is designed to reduce the waste associated with 30-day п¬Ѓlls in the LTC setting. The Affordable Care Act of 2010 requires Part D plan sponsors to use speciп¬Ѓc, uniform dispensing techniques such as weekly, daily, or automated dose dispensing. The proposed rules cover all pharmacies that dispense to LTC facilities, including mail-order pharmacies, Batshon noted. And while the draft rules apply only to brand name products, many observers expect the Centers for Medicare and Medicaid Services to extend the same requirement to generic products. Tip of the iceberg Short-cycle dispensing is only the tip of the iceberg. Not only do LTC facilities and pharmacies have to work out the mechanics of a new dispensing cycle, they also have to work out financial details with Part D plans. Without some accommodation, pharmacies could be dispensing four 7-day scripts and getting paid for one 30-day п¬Ѓll. DrugTopics .c om Another provision requires unused medications dispensed short-cycle to be returned to the pharmacy. Some states allow redispensing of returned medications under some circumstances; some do not, said Marissa Schlaifer, director of pharmacy affairs, Academy of Managed Care Pharmacy. The Drug Enforcement Administration restricts returns of narcotics. Despite the conflicts, LTC facilities must return unused medications and LTC pharmacies must deal with the returns. Pharmacies must also report returns to Part D plans, which will report to CMS. Little thought has been given to the mechanics of handling returned medications, and the National Council for Prescription Drug Programs (NCPDP) is still developing the needed communication protocols. “These are pretty signiп¬Ѓcant changes,” Schlaifer said. “We need a new standard for electronic communications along with all the other details. A 1-year time frame is very short.” Not much time Pharmacy and LTC groups are discussing implementation dates with CMS, Schlaifer said, but pharmacy must proceed on the assumption that the new procedures will take effect as scheduled next January. The impact of short-cycle dispensing will be uneven, said Carla McFaddin, ASCP director of professional affairs. Larger facilities already using automated dispensing will have few problems adapting. Retail pharmacies serving only 1 or 2 LTC facilities can probably adjust to shorter п¬Ѓll cycles without major additional costs. “It is the in-between pharmacies that could have problems,” McFaddin said. “It comes down to what extent facilities are willing to share the costs involved.” The outlook could be clear in June, when Part D plans assemble bids for 2012. All parties, including LTC facilities, LTC pharmacies, NCPDP, and Part D plans, must agree to new dispensing cycles with the required hardware and software investments, new handling procedures and communications protocols for return of unused medications, and new fee structures to support the new programs. CMS could delay implementation of the medication-return requirement, Schlaifer added, but short-cycle dispensing is explicitly required by legislation and cannot be deferred. “CMS says the data show that shortcycle dispensing will save money overall,” she said. “I have not seen those numbers myself. Short-cycle dispensing may cut waste, but it may also increase the costs of dispensing. The jury is still out on the overall impact on patient care.” Extension requested CMS accepted comments on the proposed rules through January 21, 2011. In comments responding to the Federal Register notice of November 22, 2010, ASCP requested the extension of the proposed implementation date by 1 year to January 1, 2013. “Pharmacies, nursing homes, and prescription drug plans all need more time to implement short-cycle dispensing,” said ASCP President Albert Barber, PharmD, CGP, FASCP, in a released statement. “An additional year to create systems and invest in new technology and training gives pharmacists a chance to make this transition without negatively impacting care for seniors.” ASCP also requested that CMS consider adding controlled substances to its list of drugs exempted from the rule because of the stringent record-keeping associated with these substances. Also, there are high risks of diversion with controlled substances as the number of times a drug is handled increases. Februar y 2011 DRUG TOPICS 27 Chains & Business Fred Gebhart, Contributing Editor Technicians key to telepharmacy success in North Dakota Pharmacy technicians have emerged as key players in the growth of telepharmacy in both inpatient and outpatient settings. That’s the view from North Dakota, which relies heavily on telepharmacy to bring pharmacy services to communities and hospitals that don’t a pharmacist. d ’t have h Telepharmacy would never have been as successful as it has been without technicians,” said Barbara E. Lacher, BS, RPh Tech, CPhT, assistant program director, pharmacy technician program, and associate professor, North Dakota State College of Science. “Techs are key to everything we do.” The college regularly updates its tech training program to reflect current practice needs. One of the latest curriculum updates is additional information on overthe-counter medications. That helps techs answer basic patient questions and, more importantly, helps techs recognize when to bring the pharmacist into the loop. More education makes techs more effective, especially in telepharmacy sites where the pharmacist isn’t in the next room. No argument from the Pharmacy Technician Certiп¬Ѓcation Board (PTCB). PTCB has certiп¬Ѓed about 80,000 techs nationwide. Only the beginning “North Dakota is a good example to model,” said PTCB Executive Director and CEO Melissa M. Corrigan, RPh. “They are very forward-thinking. They are looking at Melissa Corrigan telepharmacy and technicians as a way to bring pharmacy services to rural communities. But that is only the beginning.” Pharmacy chains are using technicians to provide patient services by telephone, Corrigan said. The military is using telepharmacy to dispense around the 28 DRUG TOPICS Februar y 2011 world. Hospitals are using telepharmacy in sterile prep rooms and across large campus settings. Technicians are the common element keeping all these systems working. “Pharmacy techs are the people at the actual remote site,” said National Pharmacy Technician Association Chairman and CEO Mike Johnston, CPhT. “The telepharmacy role is very different from working as a tech in a traditional setting. You don’t have the in-person supervision. Telepharmacy techs are more independent and need to be better trained.” Licensing and cross-training North Dakota agrees. Technicians who want to work in telepharmacy must have at least 12 months of certiп¬Ѓcation in the state. The hands-on experience is a plus. “Technicians like telepharmacy,” Lacher said. “It gives them a little more scope than working with a pharmacist on-site, and telepharmacy wages are higher. We wouldn’t have telepharmacy without technicians.” North Dakota began licensing telepharmacies in 2001 to extend pharmacy services to rural areas. Some rural hospitals without a pharmacist are using telepharmacy to provide inpatient pharmacy services. A few are even crosstraining nurses as technicians. “If you don’t have a pharmacist and don’t have a tech, the nurses end up making a lot of decisions they aren’t trained for,” said Shelley Doherty-Johnsen, RPh, director, ePharmacist Direct, Fargo, N.D., which provides telepharmacy services to more than a dozen rural hospitals around the state from a central facility in Fargo. “If they can cross-train some of their nurses as techs, they can add pharmacy services without adding staff.” That makes sense from the commercial side of telepharmacy. “Pharmacy technicians are ideally suited to telepharmacy,” said Michael E. Coughlin, president and CEO of telepharmacy provider ScriptPro. “Nurses don’t have the experience in claims processing, inventory, and other areas. A pharmacy tech already knows that universe.” A variety of universes Technicians already know a variety of pharmacy universes. That’s why hospitals and health systems have emerged as key players in the telepharmacy world, Coughlin said. One of the newest wrinkles is sterile-preparation telepharmacy. Techs prepare chemotherapy and other IV medications in a typical sterile facility; the supervising is pharmacist linked electronically. “Even if the pharmacist is sitting in the next room, telepharmacy can give you a higher level of oversight than you have with a traditional sterile-prep situation,” he said. “Telepharmacy gives you clear, visual records of drugs, bar codes, syringes — every step of the preparation process.” That kind of remote veriп¬Ѓcation is also п¬Ѓnding favor with the Department of Defense. The U.S. Navy is using telepharmacy to verify dispensing by technicians around the globe, Coughlin said. “Telepharmacy allows pharmacies to provide expertise and oversight anywhere in the world with a video link,” he said. “We see huge growth in telepharmacy, with more technicians becoming involved in drug preparation, in dispensing, in working with patients. Telepharmacy allows you to bring the pharmacist into the loop at precisely the right moment.” DrugTopics .c om Cover Story Angela Watkins Medicare Part D Audits Is your pharmacy prepared? W ith the opening of the 112th Congress, there is considerable uncertainty on how healthcare reform will progress. However, there is one thing of which you can be certain: With Medicare Part D plan sponsors under scrutiny from the Centers for Medicare & Medicaid Services (CMS), which has oversight of all aspects of the program’s administration, pharmacy audits will continue and possibly even increase in the future. Is your pharmacy prepared? The Medicare program cost $509 billion in 2009 and had 46.3 million beneп¬Ѓciaries, according to the most recent Medicare Board of Trustees Report, issued on August 5, 2010. It is the nation’s largest federally funded healthinsurance program. Controlling the cost of the program is an ongoing concern of both the Obama administration and Congress. Therefore, any Medicare provider can expect an audit. According to statistics captured in 2009 and released in 2010, 44% of audits targeted hospital pharmacy records; 29% targeted long-term-care facilities; and 21% targeted community pharmacies. “All sponsors are required to have a comprehensive plan to detect, correct, and prevent fraud, waste, and abuse. Medicare Part D audits help ensure that procedures and reimbursement mechanisms are consistent with contractual and regulatory requirements,” said Daniel B. Frier, Esq., founding partner, Frier Levitt, LLC, located in New York and New Jersey. Different types of audits Pharmacies participating in the Medicare Part D program should be aware of 2 types of possible audits: Desk audits and п¬Ѓeld audits. Desk audits use automated means to review pharmacy claims and encounter data. This type of audit can include reviews of payment reports, drug utilization, physician prescribing patterns, and geographic prescribing reports. Field audits are performed onsite at the pharmacy and involve physical observations, prescription reviews, and checks for compliance with Part D regulations and procedures. Field auditors will typically review the following: • Prescription records • Computerized dispensing records 30 DRUG TOPICS Februar y 2011 • Patient signature logs • Quality control plans “In general, auditors are looking at the validity of a prescription for legal and regulatory compliance, and conп¬Ѓrming that the prescription corresponds with the claim submission,” said Rena Bielinski, PharmD, AHFI, Chief Pharmacy Ofп¬Ѓcer, National Audit, Miramar, Fla. National Audit (www.nationalaudit. com) works with various healthinsurance providers in performing audits nationwide. Bielinski said that onsite audits include general physical observations. Rena Bielinski Among other things, these observations check for and review: • Compliance with Health Insurance Portability and Accountability Act (HIPAA) guidelines • Display of Medicare Part D posters • General safety conditions and cleanliness • Security of controlled substances as required by law • Pharmacists’ licenses • Presence of nonpharmacy employees in pharmacy area • Refrigerator temperatures Bielinski noted a trend in some general п¬Ѓndings in recent years. These п¬Ѓndings include: • Incorrect use of DAW (“dispensed as written”) codes • Missing proof of drug deliveries • Unauthorized or undocumented reп¬Ѓlls • Absence of hard copies of prescriptions • Missing prescriber signatures Be audit-ready Each health-insurance provider or pharmacy beneп¬Ѓt manager (PBM) may have a different set of guidelines on how pharmacies in its network should ensure that Medicare Part D regulations are being met and on how they should comply with an audit. However, Timothy J. Davis, PharmD, owner of Beaver Health Mart Pharmacy in Beaver, Penn., noted that a successful audit begins before the letter conп¬Ѓrming an impending DrugTopics .c om GETTY IMAGES/PHOTOGRAPHER’S CHOICE RF/SNAP DECISION (PILL BOTTLE), GETTY IMAGES/PHOTODISC/ MEDIOIMAGES (NUMBERS, LEFT), GETTY IMAGES/THE IMAGE BANK/DAVID GOULD (REDLINE NUMBERS) audit even arrives. Employees at Beaver Health Mart have a clear roadmap that outlines their speciп¬Ѓc duties, especially for those employees who play a role during an audit. “Each employee knows what is expected of them even before an audit. We’ve taken the time to communicate expectations, deliverables, and time frames with all functional departments and employees managing a delegated function,” said Davis. “It takes a little extra effort to plan upfront. But the staff is better prepared with regard to their particular involvement in the audit process.” Davis said his pharmacy is “auditTimothy J. Davis ready” year-round. “We review materials regularly and monitor actions on an ongoing basis,” he said. “We are quick to take action in areas where we п¬Ѓnd noncompliance.” Software identiп¬Ѓes audit triggers Davis also uses technology as a quality-control mechanism. He said, “Technology that helps integrate workflow also helps staff proactively prepare for any audit.” A software program helps Beaver Health Mart Pharmacy staff track patient signatures, physician prescriptions, electronic notes that can flag speciп¬Ѓc item alerts, day supply calculations, and signature prompts. It can also generate reports sorted by total sales price, drug names, and drug serial numbers. “The right software can help identify audit triggers and provides safeguards to protect your bottom line,” Davis added. Davis extends use of that technology to his customers by allowing them to register online (www.BeaverHealthMart. com) for a variety of services, including prescription reп¬Ѓlls. Once a pharmacy has been through an audit, is the business exempt from another one? Bielinski warned pharmacists not to think that Medicare Part D audits are a one-time event. “Audits are an ongoing responsibility to ensure effective oversight and management,” he said. Keys to a successful audit Bielinski offered a number of tips for pharmacies faced with upcoming audits. Communicate and be forthright with the audit vendor. The vendor has some flexibility in rearranging audit dates, but, once a date is conп¬Ѓrmed, it is difп¬Ѓcult for the vendor to make another change. “Don’t be afraid to contact the audit vendor as many times as necessary to ask DrugTopics .c om any questions you might have about the audit,” she added. Bielinski also suggested that pharmacies: • Send requested materials to the vendor in a timely fashion. If you cannot meet the deadline, ask for an extension well in advance of the due date. Vendors use automation to manage from hundreds to thousands of pharmacies, so it is crucial that you respond by the due date. • Make sure that all the documents requested are in the п¬Ѓle and in chronological order. Proactively maintain records in organized п¬Ѓles so that when you are notiп¬Ѓed of an audit there will be less time needed for preparation. • Review the п¬Ѓle to make sure that you are aware of any deп¬Ѓciencies that CMS will discover. • Be familiar with the language regarding audits in your plan or PBM contract; this tells you what your rights are during an audit and what rights the plan or PBM has. Attorney Frier and his partner, Jonathan E. Levitt, add that receiving payment from CMS is no assurance that a provider has billed or coded correctly for a service. “CMS has the [right] to reopen any individual claim within 12 months of payment to the provider and may reopen a claim for an additional 36 months for good cause,” said Frier. The company website (www.frierlevitt.com) outlines various scenarios that might cause CMS to reopen a claim. Because contract language and standards set forth vary from contract to contract, Levitt and Frier suggest that pharmacists read those documents before signing them. In the п¬Ѓnal analysis, Davis said, while Medicare Part D audits can be time-consuming for pharmacies, audits are quality-control mechanisms that lead to improved customer care — the true bottom line. Angela Watkins is a freelance writer in Massillon, Ohio. Februar y 2011 DRUG TOPICS 31 Special Report Barbara Hesselgrave Partnership improves prescription delivery to American Indians 32 DRUG TOPICS Februar y 2011 ans and other IHS patients requesting the service in the Rapid City area.” The back story Michael A. Valentino, RPh, MHSA, chief consultant in Pharmacy Beneп¬Ѓts Management Services, Veterans Health Administration, Department of Veterans Affairs, said that the mail-order pharmacy program, which was conceived almost 2 decades ago, was the result of “some very insightful pharmacy leadership in the VA who understood manual processing was not a viable process in the long run.” The VA, he added, was probably the п¬Ѓrst to break ground and pioneer mail-order automation in both the public and private health-sector markets. “We were 2 years ahead of Kaiser.” In describing the considerations that led to CMOP, Valentino said that the lack of space and the cost and inefп¬Ѓciency of the labor-intensive process of п¬Ѓlling so many prescriptions manually “just wasn’t going to serve us.” He added, “We knew we’d never have enough pharmacists or space or technicians, so we built this highly costeffective, efп¬Ѓcient, and quality product.” With the fast turnaround time of CMOP’s electronic mail fulп¬Ѓllment, it takes only a few days from the time a prescription is entered until the patient receives the medication. According to Valentino, patients are very happy with the service, and pharmacy staffers have more time to spend with the patients. Creating the relationship Pamela Schweitzer, PharmD, BCPS, a pharmacy consultant with Phoenixarea IHS, is a former pharmacy director with the VA. Her experience with the VA was invaluable, she said, and she envisioned bringing the same efficiencies to IHS. But it was not until “all Pamela Schweitzer the stars were lined DrugTopics .c om GETTY IMAGES/DIGITAL VISION/STEFANO SALVETTI I magine a government health program that serves millions earning the highest excellence rating awarded by J.D. Power and Associates. Has it happened? Indeed it has. The 5-star-rated mailorder pharmacy program of the Department of Veteran Affairs (VA) was the п¬Ѓrst of its kind in this country to receive the rating. Today it continues to set a benchmark for innovation and efп¬Ѓciency, and now the VA is partnering with the Indian Health Services (IHS) to improve prescription delivery to the federally recognized tribes of IHS, a population of about 2 million people. On October 21, 2010, IHS announced a pilot program between its Rapid City PHS Indian Hospital in Rapid City, S.D., and the VA’s Consolidated Mail Outpatient Pharmacy (CMOP) program in Leavenworth, Kan. According to an agency statement, “The pilot program will improve safety and cost effectiveness by providing prescription reп¬Ѓlls by mail to support care for veter- Special Report up” that the transition from manual to centralized fulп¬Ѓllment could take place for IHS. “In the early 2000s new laws enabled us to bill a third party; then early in 2003 we had a big initiative for electronic health records,” said Schweitzer. But what really got the process going, she added, were high gas prices. Schweitzer noted that it was costly for patients to travel long distances to come to pharmacies every 30 days to п¬Ѓll prescriptions. Two years ago she began “planting the seeds of the idea,” talking personally with the tribes and promoting the idea within the ranks of IHS, and “all the negativity went away,” she said. She was able to sell the project to area leaders who recognized the potential beneп¬Ѓts and would help champion the idea of switching from a manual to centralized fulп¬Ѓllment system. Besides patient-access problems, Schweitzer said, the IHS pharmacists were burning out. They were spending most of their time п¬Ѓlling prescriptions rather than focusing on patients who needed counseling and extra care. Job retention and satisfaction were down. In the remote IHS service areas, she said, several facilities, including the Rapid City test site, were having a hard time recruiting pharmacists. Less restock, more patient time Todd Warren, PharmD, BCPS, director of pharmacy at Rapid City PHS Indian Hospital, said that his facility п¬Ѓlls approximatelly 900 prescriptions a day, of which “roughly 45% are reп¬Ѓlls, which can be mailed.” Warren said that all of Rapid City’s constituents were asked whether they wanted to participate in the mail-order program. Not surprisingly, some did not wish to receive mailed prescriptions. Several elders believed their medications would be stolen, he said. Other patients feared that they would DrugTopics .c om LCDR Peter Juve, PharmD (left), counsels a patient opting to obtain a prescription in person at the hospital pharmacy. Mail-order is also available for all patients. (Photo courtesy of Rapid City PHS Indian Hospital.) The CMOP program has given pharmacists such as LCDR Todd Campbell, PharmD (left), more time to spend with individual patients. (Photo courtesy of Rapid City PHS Indian Hospital.) not remember to call in for prescription reп¬Ѓlls, and some simply liked to come into the pharmacy. Since the August 2010 inception of Rapid City’s reп¬Ѓll service with CMOP, Warren said, the hospital has signed up about 50% of its constituents. The process begins when a patient visits the IHS provider, who asks which prescription needs reп¬Ѓlling. The provider then reviews and renews the prescription. The patient’s next stop is to the IHS pharmacist, who asks whether the patient would like to have the prescription mailed. If the patient agrees to mail-order, the pharmacist puts the prescription into a queue going to CMOP. The prescription is п¬Ѓlled and mailed to that patient from the Leavenworth facility. The total turnaround time is about 35 hours plus an additional 2.5 days in transit from Leavenworth to the Rapid City member. Continued on pg. 34 Februar y 2011 DRUG TOPICS 33 Special Report Continued from pg. 33 In addition to patients’ satisfaction, Warren said, the pharmacy staff is very pleased with the service. “The nice thing for us is that before, we were returning to stock a large number of prescriptions within the 7-day window; [now] once they’re gone, they’re out,” he said. Improved adherence Valentino said that medication adherence is a signiп¬Ѓcant issue for the VA, and CMOP plays an important role. “I can tell you, if you don’t have the drug in your possession, you can’t be adherent.” He added that the VA is trying to п¬Ѓnd additional ways to communicate with patients taking chronic medication and is in the process of designing an iPhone app and a system to send text messages to cell phones. Schweitzer is also pleased with the results of the partnership. She remembers how she wanted to institute this process for many years after her tenure at the VA, where she observed models that allowed pharmacists important interaction and clinical time with patients. Now, that her vision is becoming reality, Schweitzer said that she is seeing the real-time beneп¬Ѓts at Rapid City and couldn’t be more enthusiastic about the program. With centralized п¬Ѓlling and packaging of prescriptions, pharmacists gain time to interact more often with patients, said Schweitzer. This beneп¬Ѓts the hospital and medical staff, she pointed out. In 2011, the hospital will have its п¬Ѓrst pharmacy resident, she added. Future CMOP rollouts are planned for IHS facilities in Phoenix and Minnesota. Over the next few years, Schweitzer said, all of IHS will be included in the CMOP program. Barbara Hesselgrave is a freelance writer A short primer on First Nation healthcare The lands, education, health, and lives of the federally recognized people of the First Nation — their preferred nomenclature — are directly affected by the federal government. The distinction between federally recognized and state-recognized American Indians harks back to historical events of the late 1780s, when special government-to-government relationships between the federal government and Indian tribes were established by the U.S. Constitution. The federal government granted American Indians reservation land, under their sovereignty, to compensate for the lands taken from them. However, the lands “granted” as “Federal Reserves” were generally undesirable, being far removed from centers of commerce and unsuitable for productive farming and pasturage. Moreover, the forcible removal from traditional lands also meant a separation from the plants and animals that were an integral part of traditional practices and American Indian medicine. The BIA takeover In 1926, the Bureau of Indian Affairs (BIA) was formed. It is the oldest bureau of the U.S. Department of the Interior. The BIA’s mission concerns administration and management of American Indian land. This includes matters pertaining to natural resources, building, school funding, and social issues affecting the nearly 2 million people living on the reservations. Today, there are 565 federally recognized American Indian tribes and Alaska Natives in 35 states. The Indian Health Services (IHS) provides direct health services to American Indians. This agency, which was organized within the Department of Health and Human Services during the 1950s, arose from the national push for prevention in public health when vaccines for polio, diphtheria, and whooping cough emerged. The situation today With little or no access to public transportation and few opportunities to earn a living, most American Indians are at or below the federal poverty level and must often travel long distances to access an IHS facility. If patients require tests or services not available through their local IHS facility and must travel to other state-run facilities, despite their citizenship of that state they may be referred back to IHS and turned away, once they disclose that they are American Indian. This state of affairs contributes to an abysmal reality. A July 2003 report by the U.S. Commission on Civil Rights, “A Quiet Crisis: Federal Funding and Unmet Needs in Indian Country,” stated that American Indians have a lower life expectancy than any other racial/ethnic group. In addition, the commission found that American Indians experience some of the highest rates of chronic diseases such as diabetes, HIV, tuberculosis, and alcoholism. Permanent funding The Obama administration has made efforts to boost funding for IHS. In addition, when President Obama signed into law the Patient Protection and Affordable Care Act (PPACA), it permanently reauthorized the Indian Health Care Improvement Act (IHCIA), which created the framework for the IHS. Prior to PPACA, the continuation of IHCIA was dependent on an annual reauthorization. — Barbara Hesselgrave based in Virginia. 34 DRUG TOPICS Februar y 2011 DrugTopics .c om Clinical ANTICOAGULATION THERAPIES Anna D. Garrett, PharmD, BCPS Anticoagulation update Risk factors for VTE in HIV The frequency of venous thromboembolism (VTE) in patients with HIV ranges from 0.19% to 7.63% per year. This frequency correlates to an approximate 10-fold increase in risk over that of the general population. Despite this, national guidelines do not address VTE prevention and treatment for patients with HIV. According to the literature, a higher rate of VTE occurs in patients with HIV who are younger than 50 years (3.31% vs. 0.53% in age-matched healthy controls), have a CD4+ cell count less than 200 cells/mm3, or have a diagnosis of acquired immunodeп¬Ѓciency syndrome. Both protein S and C deп¬Ѓciencies are considered risk factors. These deп¬Ѓciencies are thought to be secondary to immunosuppression. In addition, the use of protease inhibitors (speciп¬Ѓcally indinavir and saquinavir) and the presence of active opportunistic infections or antiphospholipid antibodies may be associated with VTE in HIV. The mechanism of the increased risk relative to use of protease inhibitors is unclear but several hypotheses have been suggested. These include interference with hepatic metabolism, generation of endothelial or platelet dysfunction, or effects of fat redistribution on the coagulation proп¬Ѓle (although data have not supported this). Many cases of VTE are preventable. In light of the expense associated with VTE cases, it is imperative that all VTE risk factors be identiп¬Ѓed and incorporated into medical decision-making for high-risk patients, including those with HIV, in order to decrease the burden on the healthcare system. Risk factors associated with HIV are not well understood; therefore, long-term prospective studies assessing these are needed. Source: Kiser KL, Badowski ME. Risk factors for venous thromboembolism in patients with human immunodeп¬Ѓciency virus infection. Pharmacotherapy. 2010;30(12):1292–1302. Previous antiplatelet therapy results in poorer outcomes in cases of intracerebral hemorrhage A recent meta-analysis of patients with intracerebral hemorrhage who were taking antiplatelet drugs showed a modest but signiп¬Ѓcantly higher mortality rate in those who were receiving these agents. Researchers performed a meta-analysis of 25 cohort studies comprising 9,900 patients with intracerebral hemorrhage; 23% of patients had been taking antiplatelet drugs (usually aspirin) at the time of the hemorrhage. In a multivariable-adjusted pooled analysis, previous antiplatelet therapy was associated with signiп¬Ѓcantly higher mortality (odds ratio, 1.27; P=.001) but not worse functional outcomes (OR, 1.10). In this analysis, too few patients were taking nonaspirin antiplatelet drugs or dual antiplatelet therapies to allow conп¬Ѓdent DrugTopics .c om conclusions about different antiplatelet regimens. The authors commented that this report serves to remind us that antiplatelet drugs, including aspirin, are not necessarily benign and should be prescribed only if the beneп¬Ѓt outweighs the risk of treatment. Source: Thompson BB, BГ©jot Y, Caso V, et al. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: A systematic review. Neurology. 2010;75:1333–1342. Risk of combination therapy with warfarin/ antiplatelet agents may not outweigh beneп¬Ѓt Many patients with new-onset atrial п¬Ѓbrillation receive anticoagulation with warfarin to decrease their risk of ischemic stroke. They may also have co-existing vascular conditions that may require platelet inhibition with aspirin or clopidogrel in addition to warfarin. A Danish study of 119,000 patients hospitalized with atrial п¬Ѓbrillation examined the safety of these therapies relative to the decrease in stroke risk. Nearly 83,000 patients were discharged on warfarin, aspirin, clopidogrel, or a combination of these agents. The most common therapies were warfarin alone (43%), aspirin alone (40%), or warfarin plus aspirin (16%). Nonfatal bleeding occurred in 12,191 patients (10%) and fatal bleeding occurred in 1,381 patients (1.2%). The risk for fatal or serious nonfatal bleeding was 3.7 times higher for patients who received triple therapy (warfarin plus clopidogrel plus aspirin) versus warfarin alone; 3.1 times higher for patients who received warfarin plus clopidogrel; and 1.7 to 1.8 times higher for patients who had aspirin added to either of the other 2 drugs (clopidogrel or warfarin). The most common location of bleeding was in the gastrointestinal system. Stroke risk was not lowered for patients receiving triple therapy or warfarin plus clopidogrel. The outcome of this analysis makes a strong argument for much greater care in the use of antiplatelet drugs with warfarin even when there is a strong indication for both. For example, if a patient receiving warfarin requires one or more stents, the baremetal type may be preferable to the drug-eluting type in order to decrease the required duration of therapy with clopidogrel. If possible, combination therapy should be avoided since the risks of bleeding outweigh the beneп¬Ѓts of reduced stroke incidence. Source: Hansen ML, SГёrensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433–1441. Anna D. Garrett is manager, Outpatient Clinical Pharmacy Programs, Mission Hospital, Asheville, N.C., and president and founder of the National Association of Women in Health Care (www.nawhc.com). She also is a Drug Topics board member. She can be reached at anna. [email protected]. Februar y 2011 DRUG TOPICS 35 Continuing Education AN ONGOING CE PROGRAM OF THE UNIVERSITY OF FLORIDA COLLEGE OF PHARMACY AND DRUG TOPICS Medication errors: Causes, prevention, liability, and the apology Virgil Van Dusen, RPh, JD REGIONAL DEAN TTUHSC SCHOOL OF PHARMACY TEXAS TECH UNIVERSITY — ABILENE, TEXAS W. Steven Pray, PhD, DPh BERNHARDT PROFESSOR COLLEGE OF PHARMACY SOUTHWESTERN OKLAHOMA STATE UNIVERSITY M edication errors are a serious problem for pharmacists and society. Pharmacists п¬Ѓll the vast majority of prescriptions or drug orders correctly, but even in the best-managed pharmacies errors still occur. Although medication errors are small in number, they may have a devastating effect on the patient and pharmacist. Fortunately, policies can be implemented and technology used to reduce the error rate. This article explores the common causes of medication errors, error-prevention strategies, and possible liability, as well as how the pharmacist should respond to the patient after an error. Medication error deп¬Ѓned and identiп¬Ѓed Medication errors are caused by a number of “wrongs.” The wrong drug may have been prescribed or dispensed, the wrong strength dispensed, or wrong directions placed on the label. A provider may fail to give a medication or the patient may be noncompliant, failing to take a medication when prescribed. The deп¬Ѓnition of an error is any incorrect event occurring during the process of medication use.1 The National Coordinating Council for Medication Error Reporting and Prevention deп¬Ѓnes a medication error as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient, or consumer. Such events may be related to professional practice; healthcare products, procedures, and systems, including prescribing; order communication; product labeling; packaging; nomenclature; compounding; dispensing; distribution; administration; education or monitoring; and use.”2 36 DRUG TOPICS Februar y 2011 GETTY IMAGES/BLEND IMAGES/TERRY VINE (SENIOR HISPANIC WOMAN LOOKING AT MEDICATION BOTTLE); OJO IMAGES/ TOM MERTON (MAN READING INSTRUCTIONS ON PILL BOTTLE); PHOTODISC/SETH JOEL (MEDICINE CABINET WITH PRESCRIPTION BOTTLES) WEATHERFORD, OKLAHOMA W W W.D R U GTO P I C S .C O M CREDIT: 2.0 EARN CE CREDIT FOR THIS ACTIVITY AT WWW.DRUGTOPICS.COM EDUCATIONAL OBJECTIVES Goal: To educate pharmacists and pharmacy technicians on medication errors, including causes, mitigation techniques, and how to address the patient after the error. After participating in this activity, pharmacists and pharmacy technicians should be able to: в—Џ Relate the history of medication errors and current rates of errors в—Џ Identify causes of medication errors in pharmacy practice and costs associated with those errors в—Џ List speciп¬Ѓc methods for reducing medication errors в—Џ Explain how pharmacists should respond to a patient who has experienced medication error The University of Florida College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. ACPE # 0012-9999-10-147-H05-P (K) ACPE # 0012-9999-10-147-H05-T (K) This lesson is not valid for CE credit after 02/28/2013. To obtain immediate CE credit, take the test online at www.drugtopics.com. Click on the “Continuing Education” box on the Drug Topics home page, which will take you to the CE site. Log in, find and click on this lesson, and follow the three simple steps. Test results will be displayed immediately and you can print the certificate showing your earned CE credits. For questions concerning PRINT CEs, call 352-273-6275. For questions concerning ONLINE CEs, call 877-252-7711. W W W.D R U GTO P I C S .C O M Month 2011 DRUG TOPICS 37 MEDICATION ERRORS Continuing Education TABLE 1 Adverse drug event. In contrast, an adverse drug event (ADE) is a medication-induced injury. Some ADEs are not Sixth Canon, 1848 Code of Ethics medication errors (e.g., an allergic reaction in a patient with Philadelphia College of Pharmacy no history of allergy is an ADE). Other ADEs, however, are Apothecaries are likewise liable to commit errors in caused by errors.3 ADEs are common in hospitals, nursing compounding prescriptions: homes, and outpatient/community settings. Firstly — from the imperfect handwriting of the physicians; Experts estimate that 1.5 million preventable ADEs occur Secondly — owing to the various synonyms of drugs in use, and 4 yearly in the United States. A recent report from the Departtheir imperfect abbreviations; ment of Health and Human Services indicates that among Thirdly — from the confusion which even in the best-regulated hospitalized Medicare beneп¬Ѓciaries, adverse events related to establishments may sometimes occur, arising from the press of medication account for 31% of total events.5 In these patients, business; and events involving temporary harm were related to medication Fourthly — from deficient knowledge or ability of one or more of the assistants in the shop, or of the proprietor. most commonly at 42%. Finally, medication-related preventable events were assessed at 50%.5 Source: Ref 7 Audit methods. Audits of completed pharmacy orders can identify medication errors. Researchers conduct random thorized a new and separate incentive program for eligible inspections of prescriptions in community pharmacies awaitprofessionals who are electronic prescribers.8 ing patient pickup. The actual contents of the vial are comeRx. The Electronic Prescribing (eRx) Incentive Program pared with the drug and strength listed on the label to discover went into effect on January 1, 2009. Electronic prescribers whether an incorrect medication or an incould earn a 2% incentive payment during correct strength of the correct medication 2010. Paying physicians to prescribe elecwas wrongly dispensed. Researchers also tronically on their Medicare Part B claims Medication errors compare the patient’s name on the label may encourage them to also prescribe and have always plagued to the identifying information on the outer transmit non-Medicare prescriptions elecpharmacy.The 1848 bag to help detect wrong-patient errors. tronically, thereby reducing errors caused Code of Ethics of Comparing information entered into by handwriting. E-prescribing participation the Philadelphia the computer with the vial label using is now voluntary for physicians and pharthese methods is a powerful tool for deCollege of Pharmacy macies, but a penalty may begin in 2012 termining the accuracy with which pharfor prescribers who do not e-prescribe for identifed 4 specific macist and technician enter data and for Medicare and Medicaid patients.8 errors often still reducing errors. When these investigative Abbreviations. Finally, errors can ocsignificant today. methods were employed in an outpatient cur through the use of abbreviations. Bemedication-error prevention program at a cause of this problem, most abbreviations Veteran’s Administration outpatient pharshould be avoided. macy, the error rate decreased from 0.6% to 0.1% in just 12 Certain abbreviations are misinterpreted today as easily as months.6 they were 150 years ago. The Institute for Safe Medication Practice (ISMP) has identiп¬Ѓed several easily misinterpreted History of errors abbreviations, some of which have resulted in patient harm.9 The Institute of Medicine (IOM) has lately focused much attention on medication errors, but medication errors have Automation and dispensing systems always plagued pharmacy. The 1848 Code of Ethics of the The pressure to п¬Ѓnish one’s tasks in a busy pharmacy has alPhiladelphia College of Pharmacy identiп¬Ѓed 4 speciп¬Ѓc reasons ways been a source of errors. New dispensing systems and for errors (e.g., bad handwriting) often still signiп¬Ѓcant today automated prescription-п¬Ѓlling technologies can increase ef(Table 1).7 To combat bad handwriting, a 2007 IOM study п¬Ѓciency, however, and can provide several error-prevention checkpoints. suggested that individual “states should enact legislation consistent with and complementary to the Medicare ModernizaCommunicating with patients to prevent errors tion Act’s electronic prescribing provisions and remove existing Pharmacists must understand the purpose of each prescription, barriers to such prescribing.”4 its route of administration, and its frequency of use. DiscussHandwriting vs. e-prescribing. In 2005, the Centers for ing these points with the patient can prevent possible errors. Medicare and Medicaid Services (CMS) published regulations Communication discouraged. As recently as 3 decades establishing standards to discourage handwritten prescriptions ago (before passage of the Omnibus Budget Reconciliation Act and encourage e-prescribing.8 of 1990 [OBRA-90]), pharmacists rarely discussed medication MIPPA. Addressing the issue of handwriting from a feduse with patients, and patients seldom knew the purpose for eral perspective, legislation known as the Medicare Improvewhich the medication was prescribed. It was considered unments for Patients and Providers Act of 2008 (MIPPA) au- 38 DRUG TOPICS Februar y 2011 DrugTopics .c om CONTINUING EDUCATION seemly for patients to know too much about the medicines Error rates their physicians prescribed.10 Estimates of error rates vary widely across a variety of pharmacy-care settings. The 1952 American Pharmaceutical Association Code of Methods. Exact error rates often disagree because of the Ethics stated, “The pharmacist does not discuss the therapeutic different methodologies used to identify and quantify them. effect or composition of a prescription with a patient. When Four studies examining dispensing errors in community pharsuch questions are asked, he suggests that the qualiп¬Ѓed pracmacies employed the same method of error detection, п¬Ѓnding titioner is the proper person with whom such matters should errors rates of 1.7% to 24%.13 be discussed.”10 Projections. Extrapolating error rates to potential daily By suppressing patient interaction, APhA prevented pharprescription volumes provides projections of the numbers of macists from understanding patient needs, concerns, and other patients who are potentially affected. For instance, an error issues related to medication use or misuse. However, patient rate of 1.7% equals approximately 4 errors per 250 prescripinteraction is now mandatory. Pharmacists who understand tions per pharmacy per day. On a national scale, perhaps 51.5 patients’ medical conditions and medications will more easily million errors occur during the п¬Ѓlling of 3 billion prescriptions recognize inappropriate drug therapy. annually in the United States.13 A better process. The pharmacist’s routine could include conп¬Ѓrming patient knowledge of their medication regimens; Deп¬Ѓnitions. The fundamental deп¬Ѓnition of an error also checking for appropriate individualized dosing for the patient determines error rates. One investigator may deп¬Ѓne an error based on age, weight, and drug elimination; and conductas any inappropriate use of a drug, regardless of whether ing follow-up after new medications are added to a patient’s harm resulted. Another researcher may deп¬Ѓne an error as regimen. This approach to therapy would only those situations with the potential to also help avoid several common types of cause harm or to be viewed as “clinically medication errors.11 An error rate of 1.7% signiп¬Ѓcant.”14 Error reporting may also be limited in Case law. Evidence of the magnitude equals approximately some studies to speciп¬Ѓc types of errors or of medication errors over a century ago is 4 errors per 250 to errors occurring at 1 or more speciп¬Ѓc unavailable. Case law does provide some prescriptions per locations in the dispensing process.15 evidence of the history of errors, however, pharmacy per day. Telephone prescriptions. For examand their effect on the public. In the 1932 case of Jones v. Walgreen Co., Perhaps 51.5 million ple, a 2003 study focused on errors created as a result of telephoned prescriptions. In a physician-signed prescription for “Stronerrors occur during that study, 12.4% of all telephoned pretium Salicylate four ounces (Wyatt), teathe filling of 3 billion scriptions contained an error in the inforspoonful in water four times a day” was prescriptions per year. mation provided by the person calling in presented to a graduate pharmacist.12 The the prescription.16 pharmacist п¬Ѓlled it with pure Parke-Davis Children. Another area of research strontium salicylate powder rather than the focuses on errors in children. Children are particularly vuleffervescent “Wyatt” (actually Wyeth) brand. nerable to medication errors because their smaller body size The plaintiff suffered severe injury from the adverse effects and incomplete/immature organ function affect medication of the overdose. The pure strontium provided 720 grains in distribution and metabolism. Further, children seldom if ever 16 hours when the usual oral dose of the medication should double-check their caregiver’s procedure for errors. One study have been between 60 and 100 grains daily. found that approximately 15% of children were dispensed A judgment was rendered in favor of the patient in the a medication with a potential dosing error.17 Another study amount of $20,000. The pharmacy appealed, but the judgment was afп¬Ѓrmed on appeal. The court ruled that a phardiscovered that 22% of acetaminophen doses ordered for macist who does not consult with a physician regarding an children were outside the 10 to 15 mg/kg safe dosage recobvious overdose may be guilty of negligence. ommendation.18 The court stated that “in applying his knowledge and exVenues. Other medication error studies have focused on ercising care and diligence, the druggist is bound to give his speciп¬Ѓc venues, such as nursing homes, psychiatric facilities, patrons the beneп¬Ѓt of his best judgment…” In this case the chemotherapy units, and hemodialysis units. The multitude court referenced the pharmacist’s responsibility to use “ordiof factors used in identiп¬Ѓcation of medication error and the nary skill and care” toward patients, deп¬Ѓning such care as “the uniqueness of areas investigated cause serious challenges in highest degree of prudence, thoughtfulness, and diligence, and accurate error-rate determination. is proportioned to the danger involved.”12 Cost of errors Thus, dispensing a poisonous dosage would be viewed as Medication errors can be п¬Ѓnancially and emotionally devasa breach of the duty owed the patient and as negligence on tating. Errors that cause patient harm can generate п¬Ѓnancially the part of the pharmacist, rendering the pharmacist liable for crippling malpractice actions and affect pharmacy goodwill the resulting injuries. DrugTopics .c om Februar y 2011 DRUG TOPICS 39 MEDICATION ERRORS Continuing Education TABLE 2 Sources of pharmacist medication errors • • • • • • • • • • • Wrong drug dispensed Wrong strength dispensed Calculation error Abbreviation or symbol misinterpreted Illegible handwriting Disruption in workflow Sound-alike drug names Look-alike drug names Failure to verify verbal orders Ambiguous orders Lack of drug knowledge errors per year, each creating approximately 20 minutes of extra work for the healthcare workers (mainly nurses and pharmacists), thus diverting hundreds of hours from direct patient care.1 Causes of errors Errors may occur at any step of the medication-use process (Table 2).24 Overdose. Dispensing an overdose is among the most serious medication errors. Overdoses can result from the administration of excessive single doses or the too-frequent administration of correct doses. Many medications are available in a variety of dosage forms and strengths. When it is not clear which is intended, the prescriber must be consulted Source: Ref 24 for clariп¬Ѓcation. Even dispensing the wrong form of the drug can have serious consequences. when adverse publicity escalates. Costs include additional Errors may be mechanical or intellectual.25 healthcare expenditures to care for the injured patient, which can be overwhelming. A 2000 study estimated the national Mechanical. Mechanical errors occur when the pharmaannual cost of preventable outpatient pharmacy ADEs for cist errs with respect to the prescription itself, e.g., dispensing Medicare enrollees aged ≥65 years at $887 million ($1,983 the wrong drug or the wrong strength, or labeling incorrectly. per ADE).19 Intellectual. An intellectual error occurs when the pharHospital costs. Hospital-based errors are even more macist fails to act in a manner to prevent harm in connection costly. The cost of additional inpatient care for a preventwith the medication, dosage, frequency, or any other use of able ADE incurred while in the hospital the medication by the patient that would is $5,857.20 This study, published in 1997, be foreseeable based on the pharmacist’s One study found training and/or professional background. reflected п¬Ѓgures for 1993 that excluded that 28% of patients any healthcare costs outside of the hosError prevention pital. If one assumes an annual incidence who presented Error prevention (risk management) is of 400,000 in-hospital preventable ADEs to an emergency a set of activities designed to reduce the (each incurring extra hospital costs of department did so incidence of errors. Errors cannot be com$5,857), however, the annual cost of hosbecause of an ADE. pletely eliminated, as the risk of a misп¬Ѓll pital errors is $2.3 billion in 1993 dollars More than 70% of will always be present. (almost $4 billion in 2010 dollars). Methods. Pharmacies must develop ER visits. Another method used to essuch ADEs were and maintain appropriate methods for entimate medication-error costs is to exampreventable. tering orders and п¬Ѓlling prescriptions. ine emergency-room visits and subsequent Risk management. Every pharmacist hospitalizations. One study made in a tershould view his/her role as that of a risk tiary care hospital determined that 1.4% manager, because every pharmacist action is subject to postof admissions were due to an ADE, perhaps preventable in hoc review. 28% of cases.21 The estimated cost per ADE was $10,375, Communication. Verbal communication and written with an estimated annual hospital cost of $1.2 million for all documentation are important in reducing risk. Adequate preventable ADEs. Another study found that 28% of patients patient communication is critical. presenting to an emergency department did so because of Documentation. Documenting events or interventions an ADE, and over 70% of such ADEs were preventable. The is equally important in demonstrating due diligence on the average institutional cost was approximately $1,444 for each part of the pharmacist to prevent errors. preventable medication-related visit.22 Counseling. Although it is time-consuming, establishing Nursing homes. Nursing homes also experience costs a pattern of counseling patients about medications demonassociated with medication errors, which is highly signiп¬Ѓcant strates compliance with OBRA-90, thereby allowing pharmain light of the number of medications taken by nursing-home cists to discover and address medication errors. residents. The U.S. General Accounting Ofп¬Ѓce reported in Common errors. Pharmacists should also identify com2000 that preventable errors in a single nursing home cost mon medication errors, taking action to prevent these errors up to $340,942 over a 2-year period.23 before they can occur. The ISMP’s Medication Safety Alert newsDiverted work hours. Addressing medication errors letter, the US Pharmacopeia (USP) MedMARx data reports, creates extra work, and the costs may be substantial. For and case studies from the Agency for Healthcare Research example, a 700-bed hospital may have 300,000 medication 40 DRUG TOPICS Februar y 2011 DrugTopics .c om CONTINUING EDUCATION TABLE 3 Examples of error-prone abbreviations Term Mistaken for: AD, AS, AU (right ear, left ear, each ear) OD, OS, OU (right eye, left eye, each eye) BT (bedtime) BID (twice a day) HS (half-strength) BT (bedtime) o.d., OD (once daily) OD (right eye) OJ (orange juice) OD or OS (right eye, left eye) Per os (orally) OS (left eye) q.d. or QD (daily) qid or QID (four times daily) especially if the period after the “q” or tail of the “q” appears to be an “i” qhs (each bedtime) qhr (every hour) qn (each night) qh (every hour) q.o.d. or QOD (every other day) mistaken for q.d. (daily) or QID (four times daily) q1d (daily) qid (four times daily) U or u (unit) the numerals 0 or 4, causing a 10-fold overdose or more (e.g., “4U” seen as “40” or “4u” seen as “44”) U or u (unit) cc, so dose is given in volume instead of units (e.g., “4u” seen as “4cc”) Source: Ref 26 and Quality’s web M&M (http://www.webmm.ahrq.gov) are excellent resources in understanding issues associated with medication errors.4 ISMP list. FDA and ISMP have launched a campaign to eliminate use of ambiguous medical abbreviations that are frequently misinterpreted and lead to mistakes that result in patient harm. As part of the campaign, FDA recommended that healthcare professionals consider ISMP’s “List of ErrorProne Abbreviations, Symbols, and Dose Designations” whenever medical information is communicated. Table 3 provides some examples.26 Toolkit. In addition, FDA and ISMP have provided a toolkit of resource materials, known as “ISMP and FDA Campaign to Eliminate Use of Error-Prone Abbreviations.”27 Technology. Technology may help reduce errors. Barcode technology and automated medication-dispensing devices help personnel choose the correct medications. Mindfulness. Nontechnological interventions may also provide an opportunity for reduced errors. Examples of such practices include improved communication practices (e.g., always resolving medication discrepancies), creating a culture of safety, and reducing fatigue in the workplace through careful scheduling. DrugTopics .c om Patient education Patients and family play an integral role in preventing medication errors if they have the necessary information. • Pharmacists should provide the name of each medication when counseling patients. • Pharmacists should allow patients to visualize the medications and explain that the medication should always look the same. • Patients should be encouraged to speak to the pharmacist if the prescription’s color differs to ensure that it is a different generic rather than the wrong medication. • Patients should be instructed on storage requirements and special instructions to ensure correct use. • Patients should be encouraged to question any discrepancy (e.g., the label name differs, the directions differ, the medication appears different). • Patients should be informed about possible side effects, the risk of their occurrence, what action to take if they occur, short- and long-term side effects of taking the medication (including the risk of dependency), and the importance of self-observation in assessing these effects. • The effects of the medication, both minor and more profound, should be discussed, including how each will affect day-to-day functioning, what to do if they occur, and when a pharmacist or physician should be consulted. Counseling patients on the use of their medications can also prevent medication errors related to the time of administration, route of administration, and noncompliance. Obra-90. OBRA-90 greatly changed pharmacists’ responsibilities regarding patient counseling and the associated potential for errors.28 Pharmacists must “offer to discuss” with each patient or caregiver matters that in the pharmacist’s professional judgment are signiп¬Ѓcant, including the name and description of the medication, its dosage form, route of administration, and duration of therapy. Providing patients information, as required under this federal provision for Medicaid patients, may conceivably result in better therapeutic outcomes, fewer medication-error problems, and patients’ greater understanding of their medications. State provisions. In recognition of its beneп¬Ѓts, every state has extended counseling provisions to all patients (not just Medicaid patients) thereby giving more patients the opportunity to have better understanding of medication usage. Reporting of errors Pharmacy organizations. Pharmacy organizations often monitor self-reported medication errors. This system detects only a small percentage of errors, but it is one of the few options available. Pharmacy organizations should pursue a better method to identify error patterns and allow for early intervention when an error has occurred. Self-reporting and prevention. Error reporting and review may also provide valuable information regarding error trends so that prevention efforts may achieve maximum Februar y 2011 DRUG TOPICS 41 MEDICATION ERRORS Continuing Education TABLE 4 ISMP error reporting form 1. Describe the error or preventable adverse drug reaction. What went wrong? 2. Was this an actual medication error (reached the patient) or are you expressing concern about a potential error or writing about an error that was discovered before it reached the patient? 3. Patient outcome. 4. Type of practice site (hospital, private office, retail pharmacy, drug company, long-term care facility, etc.) 5. The generic name (INN or official name) of all products involved. 6. The brand name of all products involved. 7. The dosage form, concentration, strength, etc. 8. How was the error discovered/intercepted? 9. Please state your recommendations for error prevention. boards have legal authority to address errors, however, and can take appropriate action. In recent years boards have become more vigilant in addressing medication errors. Pharmacy boards have included regulations stating that misп¬Ѓlling a prescription may be considered unprofessional conduct and subject to board oversight. For example, the Oklahoma State Board of Pharmacy included in its regulations: “Violations of the rules of professional conduct … include … [the] 1) failure to establish and maintain effective controls to prevent prescription errors or misп¬Ѓlls, or 2) misп¬Ѓlling of a prescription that departs from the standards of care ordinarily exercised by a pharmacist with proof of actual injury not having to be established.”32 Pharmacy boards can employ similar regulations to take action against a pharmacy and/or pharmacy involved in a medication error. Liability associated with errors Pharmacists who act in a careless manner or who are inattentive to detail can be considered legally negligent, even if their actions result in unintended patient harm. (This is in impact. If pharmacists refuse to voluntarily report medication contrast to a criminal event, which typically requires intent errors, important epidemiologic and preventive information on the part of the responsible party.) is unavailable to the medical community. Four factors. In malpractice actions, 4 elements must Medwatch. The MedWatch program is the FDA’s sysbe met for the pharmacist to be legally liable: a duty owed tem for reporting errors and ADEs.29 It is composed of volby the pharmacist, a breach of that duty, untary reports from medical professioncausation, and damages. If any of these als and mandatory reports submitted by Pharmacists who elements cannot be proven, the court can manufacturers (i.e., reports received by dismiss the case. It is important to review the manufacturer from patients and cliact in a careless these elements in detail: nicians). About 250,000 such reports are manner or who are Duty. Responsible, ethical pharmacists received annually via FDA Form 3500. inattentive to detail have always attempted to provide the best Unfortunately, it is believed that many ercan be considered possible care. Caring for patients may be rors and ADEs are not reported, owing to natural, but the pharmacist/patient relaa combination of time pressures, fear of lilegally negligent, tionship establishes the legal duty. Once a ability, and lack of perceived beneп¬Ѓt from even if their actions pharmacist provides patient care, the ensureporting the incident.30 result in unintended ing relationship requires that care to meet MERP. ISMP is a federally certified patient harm. professional pharmacy practice standards. patient-safety organization that provides Many courts have addressed the stanlegal protection and confidentiality for dards of care owed to patients. In French any submitted report. Identity, afп¬Ѓliation, Drug Co. v. Jones, the court stated, “All courts have held that and location remain conп¬Ѓdential in any reports submitted to a druggist is required to use a high standard of care in disgovernment agencies or manufacturers. pensing drugs on prescriptions of physicians, and when he The ISMP Medication Errors Reporting Program (MERP) negligently supplies a drug other than the drug requested, he is a conп¬Ѓdential national voluntary reporting program similar is liable for resulting harm to the purchaser.”33 to MedWatch. MERP provides an expert analysis of the causes of medication errors, subsequently disseminating recomIn the case of Speevy v. United States, the court held, “In mendations for their prevention. Published case studies alert п¬Ѓlling and reп¬Ѓlling prescriptions, a pharmacist is required to healthcare professionals and others about recommendations exercise that high degree of care which a very prudent and to prevent errors. ISMP notiп¬Ѓes manufacturers and regulacautious person would exercise under the same or similar tory agencies (eg, FDA) of recommended changes to increase circumstances.”34 From these and other cases it is clear that safety. In addition to actual errors, near-errors and hazardous courts have high expectations of pharmacists when it comes conditions may also be reported. Completion of the form is to care provided to patients. simple and it can be submitted electronically (Table 4).31 Breach of duty. Once a plaintiff establishes that a speciп¬Ѓc duty of care existed, the next element in the negligence claim State boards of pharmacy. Reporting medication eris determining whether that duty was breached. rors to state pharmacy boards is generally not required. These Abbreviation: INN, international nonproprietary name Source: Ref 31 42 DRUG TOPICS Februar y 2011 DrugTopics .c om CONTINUING EDUCATION Medication error: Case study A highly agitated physician enters your clinic pharmacy. Her ofп¬Ѓce is a few doors down the hall from your pharmacy. She asks to speak to you privately. She has a bottle from your pharmacy in her hand. It was п¬Ѓlled 4 days ago, and your label states that it contains tramadol 50 mg, to be taken 3 times daily. The patient, currently in her ofп¬Ѓce, complained of nausea and anorexia beginning 3 days ago. He also noticed dizziness, sleepiness, malaise, and tremor. He was afraid he had the flu, even though it was not flu season. In taking his history, the physician asked to see his current medications. Your prescription is the only medication he is currently taking. She used a search engine to investigate whether the correct strength had been dispensed and discovered that the product in the container is trazodone 50 mg. Out of a sense of professional respect, she is asking how the error occurred and what you expect her to tell the patient. Several courses of action are open to you, including: в—Џ Ask her to give the bottle to you and send the patient to you. Empty the bottle and place tramadol in the bottle, telling the patient to continue taking it 3 times daily. Do not inform the patient about the misп¬Ѓll. в—Џ Substitute tramadol 50 mg for the trazodone, and ask her to give it to the patient, telling the patient A breach of duty is typically based on some established standard of practice with which the pharmacist failed to comply. Applicable standards are found in provisions of national organizations, state or federal laws or regulations, or even the pharmacy’s own standards as published in its policy and/or procedure manual. A common breach of duty is failure to place the right medication in the right container. This breach is fairly simple to establish, as any evidence of a misп¬Ѓlling is virtually sufп¬Ѓcient for a presumption of negligence.35 Expert testimony may establish a breach of duty, but the obviousness of the error in a misп¬Ѓll may make expert testimony unnecessary. State provisions (e.g., laws or regulations) regarding errors as unprofessional conduct establish the duty for accuracy and the resulting breach when the lack of accuracy is shown. This is why many pharmacy malpractice actions never reach a jury verdict. Out-of-court settlements are common if it is clear that there was a breach of duty owed by the pharmacist and no defense against the liability is present. Causation. Pharmacists owe patients a duty to follow set standards; the element of causation requires proof that the pharmacist’s action or inaction caused the alleged patient damage. Causation provides a means of connecting conduct with a resulting effect, typically an injury. DrugTopics .c om в—Џ в—Џ that you made an error, but that you have corrected the situation. Request that she send the patient to you, discard the old bottle, п¬Ѓll the prescription correctly, and give the patient a full refund. Do not describe the misп¬Ѓll. Request that she send the patient to you, apologize to the patient, and п¬Ѓll the prescription correctly. Consider the potential consequences of each and decide which is best for the patient and yourself: в—Џ Correcting the misп¬Ѓll is commendable, but refusing to inform the patient about the misп¬Ѓll is deceptive, compounding the problem. Either the physician or the patient may discover the misп¬Ѓll. в—Џ Correcting the misп¬Ѓll and asking the physician to explain the situation allows the pharmacist to give the patient the correct medication and also to avoid a confrontation, but avoids the opportunity to accept responsibility and tender an apology. The patient may п¬Ѓle a lawsuit out of lingering resentment and mistrust. в—Џ Correcting the misп¬Ѓll and refunding the purchase price are both commendable, but not informing the patient about the misп¬Ѓll is deceptive, compounding the problem. Either the physician or the patient may discover the misп¬Ѓll. в—Џ Of the options presented, this apology and reп¬Ѓlling the prescription correctly appears best. It allows you to accept blame, while correcting the misп¬Ѓll. The pharmacist may be held responsible if no new intervening act severs the link between the pharmacist’s action and the patient’s injury. For example, if a pharmacist dispenses 5 mg of warfarin when the physician prescribed 1 mg of warfarin and the patient immediately suffers a stroke, causation is readily apparent. However, suppose in the same misп¬Ѓll situation the patient ingested the incorrect warfarin 5 mg for only 2 days before noticing the error and obtaining the correct 1-mg tablets. In this case, if the patient suffered a stroke 2 months later, establishing the causal link between the original breach and the injury would be very difп¬Ѓcult. Damages. The п¬Ѓnal element requiring proof in a malpractice action is that of damages. Without some form of damages no recovery is permitted. Damages fall into the categories of actual damages and punitive damages. • Actual damages compensate injured patients for any direct loss based on the pharmacist’s negligence. The intent of payment for actual injuries is to restore the patient to the condition he or she experienced before the negligent action of the pharmacist. Some are easily calculated, such as medical costs or lost wages as a result of time away from work. Other actual damages are more difп¬Ѓcult to calculate, such as loss of vision or hearing, emotional injuries, pain and sufFebruar y 2011 DRUG TOPICS 43 MEDICATION ERRORS Continuing Education fering, and other physical injuries. The п¬Ѓnancial payment may not fully restore the patient, but it does help ease the pain and make the harm more bearable. Tort reform in some states limits п¬Ѓnancial compensation by capping the award at a preset п¬Ѓgure, thereby preventing excessively large awards and giving insurance companies the ability to better estimate losses. • Punitive damages, in contrast to actual damages, are intended to punish the individual causing the harm. They have no connection with actual damages. Typically, punitive damages can be assessed if it is found that the pharmacist acted with reckless disregard for the patient’s life. Examples include the pharmacist allowing technicians to п¬Ѓll prescriptions without oversight, watching television while filling prescriptions, or attempting to cover up a prescription error. Failure to follow stated manufacturer guidelines addressing the need to observe automated equipment might also result in punitive damages.36 If pharmacists fail to admit an error or to express sorrow out of fear of litigation, it limits their ability to manage or mitigate harm caused by the error. Medication errors may be discovered by the patient, a physician, a poison center, the pharmacist who made the error, or another pharmacist.39 Once an error is discovered, the pharmacist must determine what, if anything, will be said to the patient. Unfortunately, pharmacy educators often fail to address this inevitable patient interaction, thereby leaving the pharmacist little direction in formulating an appropriate response. Apology laws. In order to allow medical professionals, including pharmacists, to apologize without fear of it being construed as an admission of guilt, many states have enacted relevant legislation. As of 2008, 34 states had passed laws banning the introduction of some forms of apologies in litigation.38 Partial apology. Approximately two-thirds of existing state apology laws protect only the expression of regret, not accompanying information related to fault. This type of legislation Defenses to liability provides for partial apology protection. Even if an injured patient can prove all 4 Thus, if the pharmacist says, “I am sorry elements, defenses for the pharmacist may for your pain,” no liability arises. If, however, An authentic exist. For instance, if the patient could have the pharmacist says, “I am sorry for misп¬Ѓllapology has the avoided harm caused by the pharmacist’s ing your prescription and your pain,” liability capacity to inspire negligence, liability may be partly or tocould occur based on that statement.40 tally avoided under a legal theory known These п¬Ѓne-line distinctions between a a unique kind of as contributory negligence. manifestation of sympathy and an admishealing, both for the Contributory negligence. Patients sion of fault are confusing; pharmacists party who inп¬Ѓicted may contribute to their harm by failure to should clearly understand the distinction the harm and the comply with directions, follow the pharand determine what protection may be patient who suffered provided by their individual states. macist’s instructions, or recognize apparent risks and take action. Healing effect. An apology may mitithe harm. For example, if the pharmacist instructgate potential damages, but it also provides ed the patient to always expect to receive a emotional healing, both for the party who green capsule, yet the patient consumed a prescription misinflicted harm and the patient who suffered harm. п¬Ѓlled with a white tablet, contributory negligence could be The apology acts as a healing agent for the party who has attributed to the patient. Thus, pharmacist counseling can erred because giving an apology demonstrates moral courage make patients more responsible for recognizing risks and takby speaking a truth that carries potentially grave consequencing action to minimize those risks. es.40 It also provides the opportunity to demonstrate moral Comparative negligence. Statutes or doctrines concernintegrity and to restore the relationship with the harmed paing comparative negligence have replaced contributory neglitient. Finally, offering an apology allows the pharmacist to gence in many jurisdictions. In this case, negligence is measured regain self-respect in light of the pharmacist’s imperfection as a percentage, and damages are diminished in proportion to and failure that resulted in the medication error. the amount of negligence attributable to the person for whose Studies have shown that in the aftermath of an error, injury, damage, or death recovery is sought. Juries can make “….professionals often feel shame, humiliation, agony, anthe determination of percentage of negligence. guish, devastation, panic, guilt, remorse, sadness, anger, self-doubt, and self-blame.”40 Yet the authentic apology has Importance of issuing an apology the capacity to inspire a unique kind of healing and has the The purpose of an apology is to recognize responsibility for potential to bring emotional healing to both the pharmacist an act that may have had negative consequences and allow and the patient. the responsible party to express remorse. Psychologists have discovered that one of the most sigThe professional pharmacist has many opportunities to say niп¬Ѓcant factors influencing the granting of forgiveness is re“I’m sorry” or “I apologize,” yet may never do so.37 Patients pentance by the party who has erred. Thus, a heartfelt and have a right to know what went wrong when an error ocsincere apology may reduce liability by invoking the patient’s curs, and pharmacy practitioners should be able to disclose forgiveness. A culture of disclosure and apology may be benerrors without fear of repercussion.38 eп¬Ѓcial in mitigating liability. 44 DRUG TOPICS Februar y 2011 DrugTopics .c om CONTINUING EDUCATION Conclusion Patients expect safe, error-free medication distribution by pharmacists. However, pharmacists involved with medication distribution occasionally misп¬Ѓll or mislabel a prescription. Systems can be created to greatly decrease the risk of errors and injuries to a patient. Pharmacists must be mindful of the possibility of errors and continue to take steps to identify errors and correct them before they reach the patient. References 1. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med. 1995;10:199–205. 2. National Coordinating Council for Medication Error Reporting and Prevention. NCC MERP: The First Ten Years. December 2005. http://www.nccmerp.org/pdf/reportFinal2005-11-29.pdf. Accessed January 20, 2011. 3. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA. 1995;274:29–34. 4. Institute of Medicine. Preventing Medication Errors. Quality Chasm Series. Washington, DC: National Academies Press; 2007. 5. Department of Health and Human Services. Ofп¬Ѓce of Inspector General. Adverse events in hospitals: National incidence among Medicare beneп¬Ѓciaries. November 2010. http://oig.hhs.gov/oei/reports/oei-0609-00090.pdf. Accessed January 20, 2011. 6. Boneberg RF, Kellick KA, Pudhorodsky TG, Vitell SJ, Jones GE. Results of a retrospective outpatient medication error prevention program at a Department of Veterans Affairs Medical Center. ASHP Midyear Clinical Meeting. 1991;26:325E. 7. Smith DB, Ellis C, Troth SF. A code of ethics adopted by the Philadelphia College of Pharmacy. Am J Pharm. 1848;20:148–151. 8. U.S. Department of Health and Human Services. Centers for Medicare and Medicaid Services. Electronic Prescribing (eRx) Incentive Program. http://www.cms.gov/ERXincentive/. Accessed January 20, 2011. 9. Institute for Safe Medication Practices (ISMP). ISMP’s list of errorprone abbreviations, symbols, and dose designations. ISMP Medication Safety Alert! Washington, DC: ISMP;2001:6. 10. Buerki RA, Vottero LD. Ethical Responsibility in Pharmacy Practice. 2nd ed. Madison, WI: American Institute of the History of Pharmacy;2002. 11. Cohen MR. Causes of medication errors. In: Cohen MR, ed. Medication Errors. Washington, DC: American Pharmaceutical Association;1999:1.1–1.8. 12. Jones v. Walgreen Co. 265 Ill. App. 308 (Ill. App. 1932). 13. Flynn EA, Barker KN, Carnahan BJ. National observational study of prescription dispensing accuracy and safety in 50 pharmacies. J Am Pharm Assoc. 2003;43:191–200. 14. Allan EL, Barker KN, Malloy MJ, Heller WM. Dispensing errors and counseling in community practice. Am Pharm. 1995;NS35:25–33. 15. Lesar TS, Lomaestro BM, Pohl H. Medication-prescribing errors in a teaching hospital. A 9-year experience. Arch Intern Med. 1997;157:1569–1576. 16. Camp SC, Hailemeskel B, Rogers TL. Telephone prescription errors in DrugTopics .c om two community pharmacies. Am J Health Syst Pharm. 2003;60:613–614. 17. McPhillips HA, Stille CJ, Smith D, et al. Potential medication dosing errors in outpatient pediatrics. J Pediatr. 2005;147:761–767. 18. Losek JD. Acetaminophen dose accuracy and pediatric emergency care. Pediatr Emerg Care. 2004;20:285–288. 19. Field TS, Gilman BH, Subramanian S, Fuller JC, Bates DW, Gurwitz JH. The costs associated with adverse drug events among older adults in the ambulatory setting. Med Care. 2005;43:1171–1176. 20. Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA. 1997;277:307–311. 21. Jha AK, Kuperman GJ, Rittenberg E, Teich JM, Bates DW. Identifying hospital admissions due to adverse drug events using a computer-based monitor. Pharmacoepidemiol Drug Saf. 2001;10:113–119. 22. Tafreshi MJ, Melby MJ, Kaback KR, Nord TC. Medication-related visits to the emergency department: A prospective study. Ann Pharmacother. 1999;33:1252–1257. 23. GAO. Adverse drug events: The magnitude of health risk is uncertain because of limited incidence data. Washington, DC: US General Accounting Ofп¬Ѓce;2000. 24. Chisholm-Burns MA, Vaillancourt AM, Shepherd M, eds. Pharmacy Management, Leadership, Marketing, and Finance. Sudbury, MA: Jones & Bartlett;2011:122. 25. Fink JL, Vivian JC, Keller Reid K, eds. Pharmacy Law Digest. 35th ed. St. Louis, MO: Facts and Comparisons;2000;265. 26. Institute for Safe Medication Practices. ISMP’s list of error-prone abbreviations, symbols, and dose designations. http://www.ismp.org/ tools/errorproneabbreviations.pdf. Accessed January 20, 2011. 27. Institute for Safe Medication Practices. ISMP and FDA campaign to eliminate use of error-prone abbreviations. http://www.ismp.org/tools/ abbreviations/. Accessed January 20, 2011. 28. Omnibus Reconciliation Act of 1990. 42 U.S.C. В§1396r–8(g)(2) (A)(ii)(I). 29. FDA. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. http://www.fda.gov/Safety/MedWatch/default.htm. Accessed January 20, 2011. 30. Fontanarosa PB, Rennie D, DeAngelis CD. Postmarketing surveillance — lack of vigilance, lack of trust. JAMA. 2004;292:2647–2650. 31. Institute for Safe Medication Practices. ISMP Medication Errors Reporting Program (MERP). https://www.ismp.org/orderForms/reporterrortoISMP.asp. Accessed January 20, 2011. 32. Oklahoma Administrative Code. В§535: 10–3–1.2 (17), (18). 33. French Drug Co. v. Jones, 367 So.2d 431 (Miss. 1978). 34. Speevy v. United States, 512 F.Supp. 670 (N.D. Texas 1981). 35. Abood RR. Pharmacy Practice and the Law. 6th ed. Sudbury, MA: Jones & Bartlett;2011:372. 36. Schroeder v. Lester E. Cox Medical Ctr., Inc. 833 S.W.2d 411 (Mo. App. S.D. 1992). 37. Van Dusen V, Spies A. Professional apology: dilemma or opportunity? Am J Pharm Educ. 2003;67:813-818. 38. Vivian JC. Legal effect of an apology. US Pharm. 2008;33:68–72. 39. Van Dusen V. Legal and practical aspects of the professional’s apology. Pharmacy Times. 2008;74:82–92. 40. McCormick DW. Whatever you do, don’t say you’re sorry. Okla Bar J. 2001;72:2357. Februar y 2011 DRUG TOPICS 45 MEDICATION ERRORS Continuing Education TE ST QU E S TIO NS Write your answers on the form appearing on page 47 (photocopies of the answer form are acceptable) or on a separate sheet of paper. Mark the most appropriate answer. 1. A medication error would include which of the following? a. Wrong date on label c. Child-resistant container utilized b. Wrong drug dispensed d. Failure to counsel 2. An adverse drug event (ADE) is considered to be: a. A state board of pharmacy (BOP) action taken because a drug was dispensed by the pharmacy without the pharmacist’s п¬Ѓnal check b. The loss of a medication in transit between origination site and destination c. An injury due to medication, which can include an error d. A recall implemented by the manufacturer at the request of the FDA 3. It is estimated that at least ________preventable ADEs occur each year. a. 400,000 b. 1.5 million c. 51.5 billion d. 3 billion 4. When community pharmacies are audited for prescription errors, which of the following is appropriate? a. Comparing vial contents to the drug and strength listed on the label b. Comparing physician name to authorization date c. Comparing pharmacist’s initials on label to work schedule d. Calling patients at home to verify vial contents 5. The 1848 Philadelphia College of Pharmacy Code of Ethics identiп¬Ѓed which of the following reasons for medication errors? a. Lack of manufacturer-provided medications c. Lack of oversight by state BOPs b. Inferior quality of compounding ingredients d. Busy nature of the pharmacy 6. What legislation has been used as an incentive to encourage physicians to e-prescribe for medications? a. Omnibus Reconciliation Act b. The Robinson-Patman Act c. The FDA Modernization Act d. Medicare Improvements for Patients and Providers Act 7. Historically (pre-1990) the counseling of patients on the use of the medication was performed by the: a. Pharmacist b. Physician c. Physician’s nurse d. Pharmacy clerk 8. Pharmacy medication error rates in the community pharmacy setting: a. Routinely range from 0.1%-0.5%. c. Routinely range from 1%-5%. b. Routinely range from 0.5%-1%. d. Vary greatly due to differing research methods 9. If a pharmacy has a medication error rate of 1.7% and п¬Ѓlls 250 prescriptions per day, 6 days per week, approximately how many errors would occur annually? a. 42 b. 130 c. 420 d. 1300 10. Errors resulting from the telephoning of prescriptions to the pharmacy have been reported at a rate of: a. 1.3% b. 5.9% c. 12.4% d. 18.1% 11. Preventable ADEs in hospitalized patients are generally: a. Almost 3 times as costly as outpatient errors b. Less costly than outpatient errors, because the institution provides care at no cost to the patient c. Less costly than outpatient errors, because errors can be detected more quickly and resolved before injury d. As costly as outpatient errors, because both require signiп¬Ѓcant intervention 12. Errors resulting in medication overdoses may be caused by: a. Administration of an excessive single dose b. Omission of regularly scheduled medications c. Mislabeling of a prescription dosing schedule from 3 times daily to twice daily d. Providing a drug strength less than that prescribed by the physician 46 DRUG TOPICS Februar y 2011 13. Which of the following is an example of an intellectual error? a. Dispensing trazodone 150 mg when the prescription was for trazodone 50 mg, but labeling the prescription correctly b. Dispensing trazodone 150 mg when the prescription was for trazodone 50 mg, and also labeling the prescription incorrectly c. Filling an amantadine prescription as ordered for a child, knowing that the dose falls within the toxic range d. Filling 2 prescriptions at once and accidentally switching the labels 14. A pharmacist receives a prescription for the following: “Rx: Combigan Ophth. Drops 0.2%/0.5% 10 mL, Sig: 1 drop OD daily in am; 1 drop OU daily in pm.” According to the ISMP, which element of this prescription is most likely to cause a medication error? a. The percentage strengths of the ingredients c. Using “OD” and “OU” b. Using “mL” to designate volume d. Using “am” and “pm” 15. Pharmacists informing ISMP about an error can be assured that: a. Their names will remain conп¬Ѓdential b. The pharmacy for which they work will be disciplined for factors such as not hiring sufп¬Ѓcient help c. The state’s board of pharmacy will be informed d. Local news sources will receive information for creation of a public alert 16. State BOP regulations often include language stating that misп¬Ѓlling a prescription may be considered: a. Part of the normal press of business and subject to board oversight b. Unprofessional conduct and subject to board oversight c. Human error and not subject to board oversight d. Regrettable, but only subject to board oversight if the patient suffers harm 17. A pharmacist п¬Ѓlling a prescription for doxazosin accidentally placed doxepin in the bottle. Which element of liability has he created before the product even reaches the patient? a. Intentional infliction of harm b. Breach of duty c. Causation d. Damages 18. A pharmacist came to work hung over and told his technicians to п¬Ѓll Rxs and only bother him if they had a “bad problem.” He slept in the break room for 4 hours while the technicians п¬Ѓlled 250 prescriptions. A misп¬Ѓll occurred and a patient was hospitalized. In this case, the pharmacist will probably incur: a. Punitive damages only c. Neither punitive nor actual damages b. Actual damages only d. Both punitive and actual damages 19. After receiving a prescription for eyedrops, a patient noticed that the bottle had a green cap and was opaque. Previous prescriptions had always had an orange cap, with a milky suspension visible in the bottle. He used the product and suffered damage. What can be said about this situation? a. The pharmacist may be somewhat protected under the concept of contributory negligence b. The pharmacist has no defense to liability as the product is clearly misп¬Ѓlled c. Damages incurred as a result of a misп¬Ѓll in such situations are always attributed to the patient d. Damages will be split between the patient and the pharmacist, and are virtually always given a 50/50 division by a judge 20. Which of the following apologies made to a patient for a misп¬Ѓlled prescription could incur liability? a. “I regret deeply that your child was admitted to the hospital last night.” b. “I’m sorry that you were forced to visit the emergency room to deal with the vomiting.” c. “We were so busy, I made a mistake, but I am most sincere in my sympathy for your distress.” d. “When you are free, please come by and I’ll let you know how bad I feel.” DrugTopics .c om CONTINUING EDUCATION EVALUATION OF CE Drug Topics is conducting an evaluation of this CE article. Please check the box that best reflects your opinion of the evaluation questions. Please keep this evaluation attached to your answer form. Strongly Agree Agree Disagree Strongly Disagree 1. The objectives listed on page 37 were met. If not, please describe: 2. 3. 4. 5. 6. The author wrote an article of value. The information was clear and presented well. The learning activity (quiz) was effective. The article content was useful and relevant. The article was educational and not promotional. 2011 CEU CREDIT REQUEST To obtain immediate CE credit, take the test online at www.drugtopics.com. Just click on the “Continuing Education” box on the Drug Topics home page, which will take you to the CE site. Log in, find and click on this lesson, and follow the three simple steps. Test results will be displayed immediately and you can print the certificate showing your earned CE credits. The cost of the online test for this lesson is $6. ANSWER FORM ACPE # 0012-9999-10-147-H05-P (K) ACPE # 0012-9999-10-147-H05-T (K) Medication errors CE quiz answers February 2011 1. 2. 3. 4. a. a. a. a. b. b. b. b. c. c. c. c. d. d. d. d. 5. 6. 7. 8. a. a. a. a. b. b. b. b. c. c. c. c. d. d. d. d. 9. 10. 11. 12. a. a. a. a. b. b. b. b. c. c. c. c. d. d. d. d. 13. 14. 15. 16. Test questions start on page 46 a. a. a. a. b. b. b. b. c. c. c. c. d. d. d. d. 17. 18. 19. 20. a. a. a. a. b. b. b. b. c. c. c. c. d. d. d. d. Not valid for CE credit after 02/28/2013 Amount enclosed: в–Ў $6.00 for this lesson в–Ў $54.00 for any 12 lessons you take over the next year, starting from the date you sign up в–Ў Already series-enrolled for 2011 For questions concerning PRINT CEs, call 352-273-6275. For questions concerning ONLINE CEs, call 877-252-7711. Are you employed by a chain? If so, which one? Submit your check (payable to The University of Florida) and form to: University of Florida College of Pharmacy P.O. Box 113195, Gainesville, FL 32611-3195 E-mail address: [email protected] Fees not refundable or transferable REGISTRANT INFORMATION Name: (Last) Address: (First) (M.I.) Phone E-mail address: (Street) City: State: ZIP: Florida pharmacists: Please provide your license number DrugTopics .c om Februar y 2011 DRUG TOPICS 47 Regulatory & Legal RISK MANAGEMENT AND CQI Kenneth R. Baker, BS Pharm, JD Is it working? Monthly Rx safety audits A few years ago I was asked to participate in what was at that time a unique study to determine the effect on medication errors if telepharmacy were introduced in the state of North Dakota. The project was conducted in cooperation with the North Dakota Board of Pharmacy, The North Dakota Pharmacists Association, and North Dakota State University College of Pharmacy. These 3 pharmacy organizations were pioneers in telepharmacy. The question was whether there would be more medication errors if telepharmacy were made a permanent part of the practice. I was asked to participate in training pharmacy personnel in medication safety and continuous quality improvement (CQI). In addition, we were to institute a method of measuring quality in participating pharmacies and telepharmacy sites. Is it working? In essence, we wanted to know whether the CQI plan we instituted at each of these sites was working. If a pharmacy, be it community, longterm care, or hospital, cannot answer that question, its CQI program of medication error reduction is not complete. The п¬Ѓnal step in continuous quality improvement is to monitor progress and use that information to analyze and look for lingering vulnerabilities in its workflow. No matter how sophisticated a pharmacy’s quality system is, risk of error will still exist. There will always be vulnerabilities to п¬Ѓx and there will always be changes that need to be made to further reп¬Ѓne the system. While the goal in a CQI system is “perfection,” it will never be reached. The system will never be complete. 48 DRUG TOPICS Februar y 2011 Measuring success There are 2 measures of success every pharmacy should post on its wall. I refer to these measurements collectively as “Monthly Safety Audits.” Both should be posted each month and compared with results for prior months. The best way to compare is to draw a month-to-month graph using error and near-miss information as the graph point for each month. It should be a simple graph and, hopefully, the line of success should be going up. Quality-related events The first graph develops its point each month by subtracting the number of quality-related events (QRE: a combination of all near-misses and errors) from the number of prescriptions п¬Ѓlled for the month. This gives the number of prescriptions п¬Ѓlled correctly, which is divided by the total number of prescriptions п¬Ѓlled. This п¬Ѓgure is converted into a percentage. This percentage of prescriptions free of error (even one that was corrected before it reached the patient — i.e., 98%) is plotted on the vertical (y) axis. Time in months is on the horizontal (x) axis. QRE is a better measurement than errors, because nearmisses can expose a problem before it becomes an error or a claim. The best way to prevent errors is to prevent the mistakes that can lead to them. Effectiveness of CQI The second graph is a measurement of the percentage of QREs that are caught before reaching the patient. While the п¬Ѓrst graph shows success in avoiding mistakes, this second graph shows how successful the CQI system is at catching mistakes before they become errors. The hope is that every month both graphs will have lines that go up, meaning that the system is working and improving. In the North Dakota study, it was determined that by implementing a CQI system along with adequate training and measures of success, medication errors could be reduced, although not eliminated, in both the telepharmacy locations and the central pharmacies. The study did not show a signiп¬Ѓcant difference in the number of errors in the 2 workplaces. The systems used, although not perfect, were working. The combination of the 2 graphs outlined here helps in efforts to constantly improve the workflow. Posting both graphs emphasizes to staff the pharmacy’s commitment to success and quality. They give answers to essential questions: “How are we doing quality-wise?” and “Is the system working?” How do you track your pharmacy’s success, errors, and near-misses? How do you use the information collected? To see the Quality Manager system, visit www.pqc.net, the website of the Alliance for Patient Medication Safety. This article is not intended as legal advice and should not be used as such. When legal questions arise, pharmacists should consult with attorneys familiar with pharmacy law in their states. Ken Baker is a pharmacist and an attorney. He consults in the areas of pharmacy error reduction, communication, and risk management. Mr. Baker is an attorney of counsel with the Arizona law п¬Ѓrm of Renaud Cook Drury Mesaros, Pa. Contact him by e-mail at [email protected]. DrugTopics .c om Regulatory & Legal LEGAL COMPLIANCE Ned Milenkovich, PharmD, JD Telepharmacy opportunities: New horizons in patient care T echnology is providing ever-greater convenience in the pharmacy marketplace, so it should come as no surprise that one of the next new frontiers available to pharmacists, in their expansion of patient care, will be telepharmacy. Technology systems for telepharmacy, using bar-coding and other secure automation, have been in the works for quite some time now. Telepharmacy relates to the operation of a remote site located at a significant distance from the “home pharmacy.” The remote site is staffed by trained nonpharmacist personnel and serves as a pharmacy and a convenient meeting point for patients in isolated areas who do not have easy access to a pharmacist. In other words, the remote site serves as a surrogate for the home pharmacy, while the pharmacist is still able to interact with the patient and provide healthcare. How it works The remote site contains medication and electronic systems in the same way that a traditional pharmacy does. Ideally, the remote site should be staffed by a welltrained nonpharmacist who is able to serve a patient’s needs under the supervision of a remote pharmacist. When a patient comes to the remote site, a prescription is processed using technology that provides the pharmacist with visual access to the prescription itself as well as to the drug product as it moves through the fulп¬Ѓllment process. Once the prescription has been п¬Ѓlled, the pharmacist communicates with the patient by video feed and provides appropriate clinical counseling. The trained nonpharmacist DrugTopics .c om staffer assists the process by ensuring that the technology supporting the fulп¬Ѓllment of the prescription is functioning properly. In addition, the staffer assists the pharmacist and patient by enabling the communication through the video feed at the remote site. Through telepharmacy, a pharmacist is able to serve segments of a population that would otherwise not have ready access to such a healthcare provider. State laws lag Technology systems achieve near flawless accounting and accuracy, and they provide the pharmacist with tools never before available to simultaneously enhance patient care and increase business opportunity. Through implementation of telepharmacy, a pharmacist is able to serve segments of a population that would otherwise not have ready access to such a healthcare provider. Nevertheless, many state pharmacy laws and regulations are devoid of language regulating this area. Telepharmacy is still a novelty, and there is a lag in implementation of new laws after professional and technological innovations are deployed. Moreover, in the few states where telepharmacy laws exist, there is a lack of uniformity among the various states’ measures. Implementation of comprehensive and uniform state laws and regulations would provide a more certain medium for telepharmacy for the marketplace and patient population. With regard to state laws and regulations in the telepharmacy arena, establishing requirements that any technology used must be able to electronically link drug product at the remote site back to the original packaging from the drug manufacturer would ensure patient safety and offer a de minimus chance of medication dispensing error. By electronically sending the drug product’s bar-code information from the remote site back for comparison with the manufacturer’s bar code, the electronic indicia of the drug can be conп¬Ѓrmed without human intervention. Similarly, laws and regulations should require that captured images of the drug product and prescription that are labeled and dispensed at the remote site must be retrievable and reviewable by the pharmacy and pharmacist at all times. Finally, telepharmacy laws and regulations should provide for proper counseling by means of video technology that enables pharmacist and patient to interact directly. Technology in telepharmacy is making dramatic gains. It is incumbent on the states to ensure that its safe and effective use enables patient care to move forward. This article is not intended as legal advice and should not be used as such. When legal questions arise, pharmacists should consult with attorneys familiar with pharmacy law in their states. Ned Milenkovich is a member at McDonald Hopkins, LLC, and chairs its drug and pharmacy practice group. He is also a member of the Illinois State Board of Pharmacy. Ned can be reached at 312-642-1480 or at [email protected]. Februar y 2011 DRUG TOPICS 49 FEATURED THIS MONTH: FOOT CARE Product Updates O’Keeffe’s for Healthy Feet foot cream provides relief for dry feet that crack and split. Micatin Antifungal Cream now features drug facts and packaging in both English and Spanish. Topricin Foot Therapy Cream soothes diabetic nerve pain and treats dry, cracked skin. OTC Something afoot F rom arthritis to blisters to ingrown toenails, hurting feet present a huge public health concern, according to the American Academy of Orthopaedic Surgeons (AAOS), which states that 43.1 million U.S. residents suffer from foot problems — 1 in every 6 people. The National Institute on Aging also warns us to be kind to our feet: “Years of wear and tear can be hard on them. So can disease, bad circulation, poorly trimmed toenails, and wearing shoes that don’t fit.” To prevent problems or to soothe already aching feet, many will welcome these new or repackaged foot-care aids. Moisture support Winter weather can be especially tough on feet, causing cracked heels and split skin. To introduce its foot cream to a national audience, the O’Keeffe’s Company recently instituted several changes. New packaging, a more user-friendly website, and a nationwide advertising campaign will tell customers that O’Keeffe’s for Healthy Feet provides guaranteed relief for dry feet that crack and split. The special formulation penetrates the rough, thick skin 50 DRUG TOPICS Februar y 2011 of soles and heels, bringing in moisture to begin the skin’s natural healing process. Antifungal WellSpring Pharmaceutical Corp. is now shipping a rebranded Micatin Antifungal Cream carton that features English/ Spanish text and full Spanish drug facts inside, in a move to support compliance and education for the fastest-growing segment of the U.S. population. “The UPC will not change as it is a rolling change from our current package,” a company spokesperson told Drug Topics. Nerve-pain relief Topical BioMedics recently expanded distribution to include The Vitamin Shoppe and Pharmaca Integrative Pharmacy stores. The all-natural Topricin Foot Therapy Cream now comes in 2 sizes — a convenient 4-oz. jar and a 2-oz. tube. Completely safe for diabetics, Topricin soothes the burning, throbbing nerve pain in the feet, as well as treating dry, cracking skin of the feet. In addition to relieving foot and ankle pain, Topricin Foot Therapy Cream helps to prevent damage resulting from use of high heels. It is used pre- and post-performance by professional dancers who really have to “stay on their toes.” Ceremides Kao Brands Co. has reformulated its CurГ©l lotions and repackaged them into white bottles, a change from the original blue bottles. With the addition of ceremides complex, CurГ©l lotions replenish the ceremides lost to the elements. These lipid molecules are crucial to maintaining the skin’s protective barrier and locking in moisture. Shea butter CurГ©l Foot Therapy Cream is formulated with shea butter to deeply moisturize dry skin, healing cracked heels and smoothing tough soles. Urea helps to remove the thickened, callused skin that can develop on dry feet in the cold winter months, while vitamin E helps reduce dryness and flaking. Coconut milk, known for its anti-inflammatory beneп¬Ѓts, soothes and softens. Continued on pg. 52 DrugTopics .c om PHOTOS COURTESY OF THE O’KEEFFE’S COMPANY/WELLSPRLING PHARMACEUTICAL/TOPICAL BIOMEDICS DANA K. CASSELL Use as directed. FOR YOUR PATIENTS WITH HYPERTENSION RECOMMEND COLD MEDICINE WITH A HEART. Tell your patients about the only cold brand that won’t raise their blood pressure: CoricidinВ® HBP. Like many of your patients, S. Epatha Merkerson has hypertension. Since decongestants are contraindicated for hypertensive patients, they need to be careful when they get a cold. So assure your patients that Coricidin HBP is the smart choice because it’s decongestant-free and specially made to relieve cold symptoms without raising blood pressure. Recommend the full line of products from Coricidin HBP. Powerful cold medicine with a heart. В® Schering-Plough, maker of Coricidin HBP, sponsors the AHA High Blood Pressure website. В©2011 Schering-Plough HealthCare Products, Inc. FOOT CARE Continued from pg. 50 Healthifeet has added several new products to its line of footcare treatments. Collagen Available through Wound Care Innovations, LLC, CellerateRX activated collagen products are now being sold in retail pharmacies. The products previously had been used in healthcare settings such as the Veterans Health Administration. In addition to providing the skin structural support, collagen can actively assist in wound-healing processes — especially in diabetic foot ulcers and skin tears. Collagen has been proven to trigger every critical process involved in the body’s healing of diabetic wounds and helps establish balance in the patient’s wound bed. The patented collagen in CellerateRX products immediately provides the properties of activated collagen to the body. Although the RX in the name may be a bit disconcerting, CellerateRX is an OTC product line, available in powder and gel forms, and FDA-cleared for all wound types except for third-degree burns. The transparency of the GlacierGel dressing enables monitoring of the healing process without the necessity of removing the dressing, avoiding unnecessary wastage and preventing possible external contamination. The GlacierGel plasters can also be used in the prevention of blisters when placed on hotspots or areas of the foot where blisters typically develop. Featuring an enhanced adhesive, the GlacierGel dressings will stay in place for 3 to 4 days. Gel dressings One of 6 new products Tender Corp. is adding to its HealthiFeet brand of footcare treatments in 2011, HealthiFeet GlacierGel Advanced Blister & Burn Dressings give consumers the ability to eliminate the nagging pain of blisters and burns on contact. Soft, cooling, and absorbent, the oval-shaped dressings contain 50% water (hydrogel) and provide an immediate and highly effective cushion against friction to sensitive skin. 52 DRUG TOPICS Februar y 2011 Moleskin HealthiFeet’s new softer and more adhesive Moleskin blister treatment is also easier for consumers to use, with pre-cut shapes and sizes eliminating the need for scissors. A Moleskin pack includes 22 dressings with 5 unique anatomical shapes for easy application on hard-to-п¬Ѓt areas. The new Moleskin is useful for applying on hot spots to prevent further rubbing or as protection and pain relief from a fully developed blister. Blister kit HealthiFeet’s Blister Medic combines GlacierGel, Moleskin, antiseptic towelettes, and alcohol wipes into one complete ultralight foot care kit. Packages include 13 dressings and 15 wipes. Corn salve The new HealthiFeet Corn Salve safely removes unsightly corns overnight. The 24/7 Plantar Fasciitis Support offers a brace for day and a splint for night use. company says to “Apply the topical treatment to the affected area at night and wake up corn-free!” Heel balm HealthiFeet Heel Balm is formulated to moisturize severely dry cracked skin occurring in and around the heel area. Exfoliation HealthiFeet Exfoliating Moisturizer offers a one-step therapy for treating dry skin. The Exfoliating Moisturizer’s dual action formula acts to smooth and hydrate the skin. Tea tree oil Among several package changes for 2011, Health Enterprises is repackaging its 100% Tea Tree Oil, an antifungal product for toenails and athlete’s foot. Spa therapy Health Enterprises is also launching a line of new spa therapy items for feet, including the new TheraPED and TheraTOES, which help pamper and soothe sore feet. Plantar relief The 24/7 Plantar Fasciitis from Health Enterprises is the only product offering day (arch brace) and night (night splint) treatment for painful plantar fasciitis. Dana K. Cassell, a frequent contributor to Drug Topics, lives in North Stratford, N.H. DrugTopics .c om PHOTOS COURTESY OF WOUND CARE INNOVATIONS/TENDER CORP./HEALTH ENTERPRISES CellerateRX activated collagen products are now available in retail drugstores. Product Updates RX & OTC New indication FDA has approved a once-daily dose of Tibotec Therapeutics’ Prezista (darunavir) to be used in combination with ritonavir for treating HIV-1 in treatment-experienced adults with no darunavir resistance-associated mutations. Dosing recommendations are the same as those already approved for treatment-naive patients. (www.prezista.com / 877-732-2488) 2 1 3 RX CARE New drugs Available from Meridian Medical: Alsuma (6 mg/0.5 mL sumatriptan) 2-pack singledose preп¬Ѓlled auto-injector for acute treatment of migraine and cluster headaches. (www.alsuma.com / 877-770-8796) Novartis has announced FDA approval of Amturnide (aliskiren/amlodipine/hydrochlorothiazide tablets in 5 dosage strengths: 150/5/12.5 mg, 300/5/12.5 mg, 300/5/25 mg, 300/10/12.5 mg, 300/10/2 mg), a п¬Ѓxed-dose combination hypertension therapy for patients not adequately controlled by any 2 drugs in the following classes: direct renin inhibitors, calcium channel blockers, and diuretics. (www.pharma. us.novartis.com / 800-693-9993) FDA approved Bayer HealthCare’s 21/7-day Safyral (drospirenone 3 mg/ ethinyl estradiol 30 Ојg/levomefolate calcium 451-Ојg tablets plus levomefolate calcium 451-Ојg tablets), an oral contraceptive that raises folate levels in women. (www.safyral.com / 800-288-8371). FDA approved Watson’s Ella (ulipristal acetate 30 mg), an oral emergency contraceptive tablet available by prescription for the prevention of unintended pregnancy for up to 5 days after unprotected intercourse or a known contraceptive failure. (www.ella-rx.com / 800-272-5525) FDA has approved Endo Pharmaceuticals’ Fortesta, a Schedule III controlled substance. The clear, odorless gel delivered by metered-dose pump treats hypogonadDrugTopics .c om ism (low testosterone) in men ≥18 years. (www.endo.com / 800-462-ENDO) FDA approved Warner Chilcott’s Lo Loestrin FE (norethindrone acetate and ethinyl estradiol tablets, ethinyl estradiol tablets, and ferrous fumarate tablets) for the prevention of pregnancy. With 10 Ојg of estrogen, Loestrin FE offers the lowest estrogen dose of any oral contraceptive on the U.S. market. (973-442-3200) OTC Wyeth Consumer Healthcare has expanded the Caltrate product line with the launch of Caltrate Soft Chews in chocolate truffle and vanilla crГЁme flavors. Each supplement contains 600 mg of calcium carbonate and 400 IU of Vitamin D3. (www.caltrate.com / 888-797-5638) From TriDerma MD: 2 new skin-care/ repair products. TriDerma MD Spot and Wrinkle Erasing Cream Anti-Aging Complex helps to reduce the appearance of brown spots, age spots, and scars, while smoothing out п¬Ѓne lines and wrinkles. TriDerma MD Pore Reducing Anti-Age Serum helps to hide imperfections while improving the overall appearance of pores and skin texture. (www.triderma.com) From Valeant: Dr. LeWinn by Kinerase [2], a line of 10 cleansers, moisturizers, and daily treatments designed to extend skin’s youth by improving cell health. (drlewinnbykinerase.com) From Perio: Pure Silk Moisturizing Shave Cream Sensitive Skin Formula [3], infused with aloe, papaya, thyme, and willow bark. (www.pure-silk.com) New generics Glenmark Generics received п¬Ѓnal FDA approval for 2 products, indomethacin capsules in 25-mg and 50-mg strengths and sulfamethoxazole and trimethoprim tablets in double and single strengths. Indomethacin is used in treating arthritis; sufamethoxazole and trimethoprim tablets are Advertiser indicated for urinary tract BUDESONIDE infections. (Fax: +91-22COLCRYS 4018-9988) CORICIDIN HBP Perrigo announced CORPORATE that its licensor and supplier Synthon has received CORPORATE п¬Ѓnal FDA approval for leCORPORATE vocetirizine [1] tablets (geCORPORATE neric for Xyza, UCB/SeCORPORATE pracor), marketed in the LEXAPRO United States by SanofiMETFORMIN Aventis and indicated for PRADAXA the treatment of indoor PRILOSEC and outdoor allergies. RID (www.perrigo.com) Index Teva Pharmaceuticals CV2-2 URL Pharma Inc. 11-12 Schering-Plough 51 QS/1 Data Systems Inc. 21 Takeda Pharmaceuticals 5 Actavis Inc. Mylan Pharmaceuticals Inc. Roxane Laboratories Forest Laboratories Inc. 17 CV4 CV3 23-26 Mylan Pharmaceuticals Inc. 7-9 Boehringer Ingelheim Ltd. 15 Proctor & Gamble 29 Bayer Corporation 19 PHOTOS COURTESY OF PERRIGO/VALEANT/PERIO New products MARKETPLACE Products & Services Books/Publications Business For Sale A Step Ahead... Beneп¬Ѓts Design Consultants/Stafп¬Ѓng Making Thousands of $$$ at Your SECOND JOB and Keeping More of it The FIRST eBook of its kind directed toward the Licensed Health Care professionals working a SECOND JOB! Who should consider reading this book? • Any licensed healthcare professional working or wanting to work a second job! • Any licensed healthcare professional now working for a “staffing agency” as a second job! • Any licensed healthcare professional wanting to start their own “staffing agency” as a second job! • Corporate America looking for ways to help mitigate their number one expense...overtime and labor cost! • Those providing insight along with integrity looking to network and join an association to lend their expertise in the health care industry. www.TIMEBANDITSRX.com Kirkland, Washington COMPOUNDING PHARMACY FOR SALE All cash customers. No insurance plan hassles. Also DME and cards/gifts. No weekends. Priced for quick sale. Contact [email protected] Continuing Education PHARMACY VACATION SEMINARS ACPE ACCREDITED PROVIDER 2011 Live 15 Credit Hour Seminars Las Vegas at Harrah’s-February 23-25 Caribbean Cruise-March 13-20-Allure of the Seas-NEW SHIP! Naples Grande Beach Resort, Florida-April 27-29 Las Vegas at Planet Hollywood-June 8-10 Alaska-Voyage of the Glaciers-June 11-18 Antlers Hilton-Colorado Springs July 27-29 Las Vegas at Harrah’s-September 14-16 Westin Maui Resort & Spa-October 26-28 Caribbean Cruise-November 6-13-Ruby Princess Las Vegas at Harrah’s-December 7-9 New Drug Update DVD-10 Credit Hours-Anytime-Anywhere! Brokers CALL FOR FREE BROCHURE 1-800-940-5860 www.universitylearning.com Make a plan. See More Brokers on next page MA R KE TP LACE ADVE RTIS ING How your family reacts in an emergency can make all the difference. To make your family disaster plan, contact your local American Red Cross chapter or For Products and Services Advertising: Heather Schlosser at (800) 225-4569 x2779 E-mail: [email protected] 54 DRUG TOPICS Februar y 2011 For Recruitment Advertising: Jacqueline Moran at (800) 225-4569 x2762 E-mail: [email protected] visit www.redcross.org W W W.D R U GTO P I C S .C O M MARKETPLACE Products & Services Brokers Education SELLING YOUR PHARMACY? Need to Pass NAPLEX ? В® Do the NAPLEX Common Mistakes Sellers Make: в– Not using a licensed broker specializing in pharmacies в– Not knowing your true current market value в– Not effectively advertising to reach enough qualiп¬Ѓed buyers 3 Step with 2 В® 1 3 Call me before sharing information about your pharmacy with ANY buyer. NAPLEXВ® Review Call me today at 888-808-4RPH (4774) Daniel J. Lannon, RPh, VP Senior Pharmacy Broker Consulting Broker Services Prudential’s proprietary selling process will enable you to get the highest price for your pharmacy! QUICKCARDSВ® with MemoronicsВ® plus Posters, Audio CD, Math Practice, Telephone quizzing, and Patient Proп¬Ѓles. Using Memory Techniques of: Visual Auditory Repetition Self Testing www.prudentialcbs.com Financing and it’s * For details, please visit our website. Pharmacy Owners: Keep your pharmacy open! www.prontopass.com Legal Services Cash flow problems? Too much short-term debt? We can access long-term financing and reduce your monthly debt service. Up to $2 million available per pharmacy! If you are looking to sell, we can also provide financing to your buyer of up to $2 million for a terms of 10-25 years. LEGAL PROBLEMS With Medicare/Medicaid, Licensing Boards, Data Bank, DEA? Impaired Status, Compliance, Business Structuring. Whistle Blower. Call Kenneth Haber Over 30 years experience Former Assistant US Attorney Former Senior OIG Attorney 301.670.0016 • www.haberslaw.com No Obligation Visit shbconsultants.com or call 800-603-2519 Your message could be here! Reach thousands of industry professionals every month W W W.D R U GTO P I C S .C O M Repeating an ad ENSURES it will be seen and remembered! Februar y 2011 DRUG TOPICS 55 Final Word VIEWPOINT Dennis Miller, RPh When efп¬Ѓciency is all that matters W When I was in college, I used to think “efп¬Ѓciency” was an unequivocal good. I was attracted by the chain w drugstore model because I bought into the concept d thatt chains th h i are efп¬Ѓcient. Even though I am often critical of chains today, I admit that they try hard to cut their unit cost for п¬Ѓlling each prescription. A bald-faced lie The chains enthusiastically embrace the latest technology to improve efп¬Ѓciency. Very few pharmacists would elect to go back to using typewriters, п¬Ѓguring clerk timecards by hand, or using a bulky order book for the weekly Rx order. But technology can have a downside. For example, many pharmacy computers now have the ability to transmit data to our bosses about our speed and efп¬Ѓciency in п¬Ѓlling prescriptions. Many pharmacists feel that the chains care more about their technology than they do their employees. Pharmacists have been told routinely that improvements in technology will allow us more time to spend with customers. This has always been a bald-faced lie. The fundamental reason the chains introduce the latest technology is to cut stafп¬Ѓng. Stafп¬Ѓng levels are cut commensurate with each technological advance. A major drag Efп¬Ѓciency is what the chains are all about. The chain concept is meant to facilitate economies of scale. Mass purchasing of products allows lower unit costs. Chainwide computerization means that stores can be run more efп¬Ѓciently. Conversely, the foundation of the independent drugstore is customer service. The chains want the public to think that they offer customer service that’s as good as that of the independents, but that’s very often untrue. I’ve had bosses who ridicule pharmacists behind their backs for spending too much time talking with customers. The chains say they want us to speak with customers, but most pharmacists realize quickly that the chains don’t really mean it. The chains have always viewed patient counseling as a major drag on productivity that adds nothing to the bottom line. Huge cost The chains’ narrow focus on efп¬Ѓciency comes at a huge cost to customers, to employees, and to society. Equating health 56 DRUG TOPICS Februar y 2011 with the efп¬Ѓcient delivery of products comes at a tremendous price that the chains don’t want to discuss. Search Google for “pharmacy mistakes” for one illustration of the many costs of placing speed and efп¬Ѓciency above everything else. Many pharmacists feel that the chains have made the cold calculation that it is more proп¬Ѓtable to sling out prescriptions at lightning speed and pay customers harmed by mistakes than it is to provide adequate stafп¬Ѓng so that mistakes are a rarity rather than a predictable occurrence. I’d love to see a study that compares the per store error rate at chains versus independents. Employees as robots When efп¬Ѓciency is all that matters, employees are viewed as machines rather than human beings and as a necessary evil to be barely tolerated until the chain can п¬Ѓgure out a way to automate their jobs. Chain management is endlessly disappointed that it can’t remake the genomes of store employees so that those employees are robots. Employees may resent this and take their resentment out on customers. Thus rudeness toward customers is not surprising in the chain model. The narrow focus on efп¬Ѓciency carries a cost far beyond that of disillusioned employees. Pharmacists don’t have time to do much more than throw a few words at customers. Our customers end up not understanding their medications. The consequences of this can be grave. Assembly-line model Our entire healthcare system is based on quantity rather than quality. Society pays a heavy price for this assembly-line model, which says that human health is directly proportional to the per capita consumption of products. In this model of healthcare, the concept of prevention becomes a quaint dream of the distant past. Americans remain ignorant of the nonpharmacological determinants of human health. This model based on efficiency promotes a quick-fix pill for every ill rather than a fundamental understanding of those lifestyle choices that can have a profound effect on one’s health. Dennis Miller is a retired chain store pharmacist living in Delray Beach, Fla. He is working on a book about pharmacy practice “in the real world” and welcomes feedback sent to [email protected]. DrugTopics .c om Innovation at Work Right Now at Roxane, our extensive pharmaceutical offering is made up of one-third sole source and sole generic products. We continue to provide patients with drugs that help improve their quality of life – many of which are only available at Roxane. Providing the necessary drugs for your patients – Roxane Now for a greater tomorrow. years of innovation 125 Years of Impacting Tomorrow Right Now View our complete list of products at www.roxane.com. GROWTH INNOVATION QUALITY AFFORDABILITY Impacting Tomorrow Right Now. Pharmacy Essentials FREE 2011 GBR... with our compliments! As part of our ongoing commitment to pharmacy professionals, we are pleased to provide pharmacists and pharmacy technicians with the 2011 Generic Brand Reference (GBR В®) ... FREE. It is our way of saying “Thank You” for supporting Mylan products. The GBR is a handbook that contains a cross-referenced listing of generic and brand pharmaceuticals as well as a color identification section that includes photographs and NDC numbers for all products in the Mylan product portfolio. To receive your FREE 2011 GBR, go to www.mylanpharms.com and click “FREE GBR Offer.” 800.RX.MYLAN • 800.796.9526 • www.mylanpharms.com В©2011 Mylan Pharmaceuticals Inc. MYNMKT445A
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