Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics Oral Penicillin (Penicillin VK) Desensitization Protocol IV Penicillin (Ampicillin) Desensitization Protocol Dose Concentration Volume Dose Cumulative Dose Dose Concentration Volume Dose Cumulative No. (mg/ml) (ml) (mg) (mg) No. (mg/ml) (ml) (mg) Dose (mg) 1 0.0005 1 0.0005 0.0005 1 0.0625 1 0.0625 0.0625 2 0.005 1 0.005 0.0055 2 0.0625 2 0.125 0.188 3 0.25 1 0.25 0.44 3 0.1 0.4 0.04 0.0455 4 0.25 2 0.5 0.94 4 0.1 0.8 0.08 0.1255 5 0.25 4 1 1.94 5 1 0.15 0.15 0.2755 6 0.25 8 2 4 6 1 0.3 0.3 0.5755 7 4 1 4 8 7 1 0.6 0.6 1.1755 8 4 2 8 16 8 1 1 1 2.1755 9 4 4 16 32 9 1 2 2 4.1755 10 50 0.6 30 62 10 1 4 4 8.1755 11 50 1 50 112 11 1 8 8 16.1755 12 50 2 100 212 12 100 0.15 15 31.1755 13 50 4 200 412 13 100 0.3 30 61.1755 50 14 8 400 812 14 100 0.6 60 121.1755 Adapted from N Eng J Med. 1985;312(19):1229-32. 15 100 1 100 221 Preparation 16 100 2 200 421 Dilute penicillin (i.e., penicillin VK) 250 mg/5ml (50 mg/ml or 80,000 units/mL) as 17 100 4 400 821 directed to make a stock solution. Take 2.5 mL of penicillin VK solution and add 18* to 28.75 mL sterile water for irrigation and label this solution 4 mg/ml (6,400 100 8 800 1621 Adapted from DiPiro JT, Ownby DR, Schlesselman LS. Allergic and Pseudoallergic Drug Reactions. In: DiPiro JT (ed) Pharmacotherapy, a Pathophysiologic Approach (5th ed). New York, New York: Mcgraw-Hill; 2002:1585-97. Preparation Dilute 1 gram of penicillin (i.e., ampicillin) to 1,000 ml of 0.9% sodium chloride (normal saline or NS) to achieve the 1 mg/ml solution (expiration = 12 hours) Dose 1: Take 0.1 ml of the 1mg/ml solution and add to 200 ml of NS (0.0005 mg/mL) Dose 2: Take 1 ml of the 1 mg/ml solution and add to 200 ml of NS (0.005 m/mL) Dose 3 & 4: Take 1 ml of the 1 mg/ml solution and QS with NS to 10 ml (0.1 mg/ml) Doses 5 thru 11: Withdraw appropriate volume from 1mg/ml solution to make doses. For Doses 12 thru 18*: Dispense a sufficient number of 1 gram vials (not reconstituted). Administer doses every 15 minutes. Following final dose, observe patient for 15 to 30 minutes; administer full therapeutic dose intravenously. *Due to the short stability (1 hour) of the 100 mg/ml concentration, each vial must be reconstituted prior to administration. Each vial should be diluted with 9.4 ml of sterile water to provide a 10 ml volume (100 mg/ml). Sufficient volume should be withdrawn from each vial to make the respective dose. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. units/mL). Dilute drug volumes in 30 mL water prior to ingestion Administer doses every 15 minutes Doses 1-2: Take 1 mL of 4 mg/ml solution and add to 63 mL sterile water for irrigation to obtain a 0.0625 mg/ml (100 units/mL); Withdraw appropriate volumes to make doses. Doses 3-6: Take 2 mL of 4 mg/ml solution and add to 30 mL sterile water for irrigation to obtain a 0.25 mg/ml (400 units/mL). Withdraw appropriate volumes to make doses. Doses 7-9: Withdraw appropriate volumes from 4 mg/ml solution to make doses 7-9. Doses 10-14: Withdraw appropriate volumes from the stock solution (50 mg/ml or 80,000 units/mL) solution to make doses 10-14. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited. Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics IV Cephalosporin Desensitization Protocol Dose Concentration Volume Dose No. (mg/ml) (ml) (mg) 1 0.01 1.5 0.015 2 0.01 3 0.03 3 0.01 6 0.06 4 0.1 1.25 0.125 5 0.1 2.5 0.25 6 0.1 5 0.5 7 0.1 10 1 8 0.1 20 2 9 0.1 40 4 10 10 0.75 7.5 11 10 1.5 15 12 10 3 30 13 10 6.25 62.5 14 10 12.5 125 15 100 2.5 250 16 100 5 500 17 100 10 1000 Cumulative Dose (mg) 0.015 0.045 0.105 0.23 0.48 1 2 4 8 15 30 60 123 250 500 1000 2000 Adapted from Immunol Allergy Clin N Am. 2004;24:425-443. Preparation Dilute 1 gram of cephalosporin (i.e., ceftriaxone) in 9.6 ml of 0.9% sodium chloride (normal saline or NS) to achieve the 100 mg/ml solution, repeat for a total of 2 vials. Withdraw 2.5 mL from 100mg/mL solution and add to 22.5 mL NS (10 mg/mL). Doses 1-3: Take 0.1 mL of 10 mg/mL solution and add to 99.9 mL NS (0.01 mg/mL). Doses 4-9: Take 0.8 mL of 10 mg/mL solution and add to 79.2 mL NS (0.1 mg/mL). Doses 10-14: Withdraw 24 mL of 10 mg/mL solution. Use appropriate volume to make doses. Dose 15-16: Withdraw 7.5 mL of 100 mg/mL solution. Use appropriate volume to make doses. Dose 17: Take 10 mL of 100 mg/mL solution to make dose. *This protocol requires an infusion pump for administration. The interval between doses is 15 minutes. Following final dose, observe patient for 15 to 30 minutes; administer full therapeutic dose intravenously. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited. Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics IV Sulfamethoxazole/trimethoprim (SMX/TMP) Desensitization Protocol** Dose Volume Dose No. Time (minutes) (ml) (mg) 1 0 0.2* 0.8/0.16 2 20 2 8/1.6 3 40 10 40/8 4 60 20 80/16 5 80 100 400/80 6 100 170 680/136 7 120 300 1200/240 Adapted from Hospital Pharm. 1997;32(10):1362-9. Cumulative Dose (mg) 0.8/0.16 8.8/1.76 48.8/9.76 128.9/92 528.9/172 1208.9/308 2408/548 Preparation Dilute 30 ml of SMX/TMP (80 mg/16mg per ml) injection in 600 ml of diluent to obtain a concentration of 4mg/0.8 mg per ml. Administer each dose over 15 minutes.** The IV line should be flushed following each dose to ensure complete delivery of medication. *Further dilute the first dose to 10 ml for ease of administration. **This protocol requires an infusion pump for administration. The interval between doses is 20 minutes. Following final dose, therapeutic doses of SMX/TMP may be scheduled at normal intervals. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. Oral (Slow) Sulfamethoxazole/trimethoprim (SMX/TMP) Desensitization Protocol Day Dose Cumulative Dose (mg) Dosage Form: Suspension containing SMX 40 mg + TMP 8 mg per ml 1 1.25 ml once daily SMX 2 mg + TMP 0.4 mg 2 1.25 ml twice daily SMX 102 mg + TMP 20.4 mg 3 1.25 ml three times daily SMX 252 mg + TMP 50.4 mg 4 2.5 ml twice daily SMX 452 mg + TMP 90.4 mg 5 2.5 ml three times daily SMX 752 mg + TMP 150.4 mg Dosage Form: Single strength tablet (SMX 400 mg/TMP 80 mg) 6 1 tablet SMX 1152 mg + TMP 230.4mg Adapted from J Infect Dis. 2001 Oct 15;184:992-7. Preparation Use the commercially available SMX/TMP pediatric suspension (SMX 200 mg/TMP 40 mg per 5 ml) and dilute as directed. Following dose #6, therapeutic doses of SMX/TMP may be scheduled at normal intervals. Oral (Rapid) Sulfamethoxazole/trimethoprim (SMX/TMP) Desensitization Protocol Day Dose Cumulative Dose (mg) Dosage Form (doses 1-4): Suspension (1:20 dilution) containing SMX 2 mg + TMP 0.4 mg per ml 1 1 ml SMX 2 mg + TMP 0.4 mg 2 2 ml SMX 6 mg + TMP 1.2 mg 3 4 ml SMX 14 mg + TMP 2.8 mg 4 8 ml SMX 30 mg + TMP 6 mg Dosage Form (doses 5-8): Suspension containing SMX 40 mg + TMP 8 mg per ml 5 0.6 ml SMX 54 mg + TMP 10.8 mg 6 1.25 ml SMX 104 mg + TMP 20.8 mg 7 2.5 ml SMX 204 mg + TMP 40.8 mg 8 5 ml SMX 404 mg + TMP 80.8 mg Dosage Form (doses 9-19+): Double strength tablets containing SMX 800 mg + TMP 160 mg 9 0.5 tablet SMX 800 mg + TMP 160.8 mg 10 1 tablet SMX 1600 mg + TMP 320.8 mg 111 tablet twice daily SMX 3200 mg + TMP 640 mg 18 SMX 1600-3200 mg + TMP 32019+ 1-2 tablet(s) twice daily 640 mg Adapted from Ann Int Med. 1987;106:335. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited. Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics IV Imipenem/cilastatin (Rapid) Desensitization Protocol Imipenem Infusion Concentration Rate (mg/ml) (ml/min) Infusion Rate (mg/min) Dose/ 30 min Cumulative Dose (mg) 1 0.0001 0.003 0.003 0.0001 2 0.0002 0.006 0.009 0.001 1 0.001 0.03 0.039 2 0.001 2 0.002 0.06 0.099 5 3 0.01 1 0.01 0.3 0.399 150 6 3 0.01 2 0.02 0.6 0.999 180 7 4 0.1 1 0.1 3 3.999 190 8 4 0.1 2 0.2 6 9.999 200 9 4 0.1 3 0.3 9 18.999 210 9 5 2 1 2 60 69.999 240 10 5 2 2 4 120 189.999 Time (min) Dose # Bag # 0 1 1 0.0001 30 2 1 60 3 2 90 4 120 250 11 5 2 3 6 180* 500 Developed from similar protocols in Ann Pharmacother. 2003 Apr;37:513-6. & Allergy. 1997;52:683-4. Oral Linezolid Desensitization Protocol (using IV formulation) Final Preparation Volume Doses 1-12 were compounded from a (ml) premixed intravenous solution of linezolid 600 mg/300 ml. For each dose, sterile water for 1 0.366 2 injection was added in sufficient quantity ot 2 0.732 2 attain a final volume of at least 2 ml. 3 0.146 2 4 0.293 2 Following dose #14, the full therapeutic 5 0.586 2 dosage was administered as linezolid 600 mg 6 1.17 2 (one tablet) every 12 hours. 7 2.34 3 8 4.69 5 *For palatability, 1 ml of simple syrup was 9 9.38 10 added to doses 10-12. 10* 18.8 15 11* 37.5 25 12* 75 50 13 200 1/3 tablet 14 400 2/3 tablet Adapted from Pharmacother. 2006;26(4)563-8. Dose # Dose (mg) Preparation 1. Bag #5 is prepared first. Remove the overfill from a 250 ml bag of 0.9% sodium chloride (NS) and add 500 mg of imipenem to obtain a 2 mg/ml concentration. Label Bag #5 (2 mg/ml). 2. Bag#4: Remove 10 ml of the 2 mg/ml solution from Bag#5 and add it to 200 ml of NS. Label Bag #4 (0.1 mg/ml) 3. Bag#3: Remove 10 ml of the 0.1 mg/ml solution from Bag#4 and add it to 100 ml of NS. Label Bag #3 (0.01 mg/ml). 4. Bag#2: Remove 10 ml of the 0.01 mg/ml solution from Bag#3 and add it to 100 ml of NS. Label Bag #2 (0.001 mg/ml). 5. Bag#1: Remove 10 ml of the 0.001 mg/ml solution from Bag#2 and add it to 100 ml of NS. Label Bag #1 (0.0001 mg/ml). Administration Bags #1 - #3 (doses #1-6) are administered over a one hour period. The rate of each bag should be doubled after 30 minutes. Bag #4 (doses7-9) is administered over 1.5 hours. The rate of infusion should increase every 30 minutes. Bag #5 (doses 9-11) is administered over ~2 hours. The rate of infusion is increased every 30 minutes. *Dose #11 should infuse until the bag is empty to obtain a cumulative dose of 500 mg. Following successful desensitization, standard doses of imipenem may be administered at the normal interval. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited. Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics IV Vancomycin (Rapid) Desensitization Protocol Dose Concentration Vancomycin Dilution # (mg/ml) Dose (mg) 1 1:10,000 0.0002 0.02 2 1:1000 0.002 0.2 3 1:100 0.02 2 4 1:10 0.2 20 5 Standard 2 500 Adapted from Ann Intern Med.1984;100:157 & Ann Pharmacother. 2001 Nov;35:1458-64. Premedication Diphenhydramine 50 mg IV and hydrocortisone 100 mg IV 15 minutes prior to initiation of protocol, then every 6 hours throughout protocol. Preparation 1. Prepare a standard bag of 500 mg vancomycin in 250 ml of normal saline [0.9% sodium chloride (NS)] or dextrose 5% in water (D5W); label as infusion #5, vancomycin 2 mg/ml. 2. Draw up 10 ml of the 2 mg/ml vancomycin preparation and place in 100 ml bag of NS or D5W; label as infusion #4, vancomycin 0.2 mg/ml. 3. Draw up 10 ml of the 0.2 mg/ml vancomycin preparation and place in 100 ml bag of NS or D5W; label as infusion #3, vancomycin 0.02 mg/ml. 4. Draw up 10 ml of the 0.02 mg/ml vancomycin preparation and place in 100 ml bag of NS or D5W; label as infusion #2, vancomycin 0.002 mg/ml. 5. Draw up 10 ml of the 0.002 mg/ml vancomycin preparation and place in 100 ml bag of NS or D5W; label as infusion #1, vancomycin 0.0002 mg/ml. IV Vancomycin (Slow) Desensitization Protocol (Lin) Concentration Vancomycin How Provided (mg/ml) Dose (mg) 1 1 0.001 0.5 0.5 mg in 500 ml 2 2 0.01 5 5 mg in 500 ml 3 3 0.02 10 10 mg in 500 ml 4 4 0.10 50 50 mg in 500 ml 5 4 0.10 50 50 mg in 500 ml 6 5 0.2 100 100 mg in 500 ml 7* 6 0.4 200 100 mg in 250 ml x 2 8 7 0.6 300 150 mg in 250 ml x 2 9 8 1 500 250 mg in 250 ml x 2 10 9 2 1000 500 mg in 250 ml x 2 11 9 2 1000 500 mg in 250 ml x 2 12 9 2 1000 500 mg in 250 ml x 2 13 10 4 1000 1000 mg in 250 ml x 2 Adapted from Ann Pharmacother. 2001 Nov;35:1458-64. Day Dose # *Beginning on day 7, the doses are infused consecutively. Infusion Directions Infuse each dose over 5 hours. If pruritus, hypotension, rash, or difficulty breathing occurs, stop the infusion and reinfuse the previously tolerated infusion. On day 14, administer the required dose of vancomycin in the usual dilution of NS or D5W (e.g., 1000 mg in 250 ml ) at a rate of 100 ml/hour. Decrease the rate if the patient becomes symptomatic or, alternatively, increase the rate if the patient tolerates the dose. Consider premedicating with oral antihistamines prior to each dose. Infusion Directions Initiate infusion at 0.5 ml/min (30 ml/hour) and increase by 0.5 ml/min (30 ml/hour) as tolerated every 5 minutes to a maximum rate of 5 ml/min (300 ml/hour). If pruritus, hypotension, rash, or difficulty breathing occurs, stop infusion and reinfuse the previously tolerated infusion at the highest tolerated rate. This step may be repeated up to three times for any given concentration. Upon completion of infusion #5, immediately administer the required dose of vancomycin in the usual dilution of NS or D5W over 2 hours. Decrease the rate if the patient becomes symptomatic or, alternatively, increase the rate if the patient tolerates the dose. Administer diphenhydramine 50 mg by mouth 1 hour prior to each standard dose. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited. Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics IV Tobramycin Desensitization Protocol Dose Elapsed Time Dose (mg) # (hours) 1 0 0.001 2 0.5 0.002 3 1 0.004 4 1.5 0.008 5 2 0.016 6 2.5 0.032 7 3 0.364 8 3.5 0.128 9 4 0.256 10 4.5 0.512 11 5 1 12 5.5 2 13 6 4 14 6.5 8 15 7 16 16 7.5 32 17 8 16 Cumulative (Dose) 0.001 0.003 0.007 0.015 0.031 0.063 0.127 0.255 0.511 1.023 2.023 4.023 8.023 16.023 32.023 64.023 80.023 TOBI® (Tobramycin Preservative-free Solution for Nebulization) Desensitization Protocol Doses were administered every 2 Dose # Dose (mg) hours with continuous pulse oximetry 1 0.3 and vital signs being followed every 2 2 0.6 hours. 3 0.9 4 1.2 Dilutions were made from TOBI® 5 1.5 using preservative-free diluent to make up a 5 ml nebulized mist 6 3 treatment solution. 7 6 8 12 Anaphylaxis emergency treatment kits 9 24 and intubation supplies were present 10 48 at bedside throughout the entire 11 96 protocol and beyond. 12 150 13 200 14 250 15 300 Adapted from Pediatr Pulmonol. 2002;33:311-4. Adapted from J Allergy Clin Immunol. 1987;79:477-83. No premedications were administered Each dose is diluted in 10 ml of normal saline (0.9% sodium chloride) and delivered in 20 minute intervals with a delay of 10 minutes between doses. The final dose is decreased to 16 mg to ensure that a total of 80 mg is received. Heart rate, blood pressure and oxygen saturations should be monitored throughout. Persistent tachycardia (>120 bpm) or a fall in blood pressure (>20 mmHg) should halt further dose escalation. After dose #17, a regimen of 80 mg every 6 hours was instituted. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited. Marquette General Health System Pharmacy and Therapeutics Committee Medication Guideline Desensitization Protocols for Commonly Used Antibiotics IV Meropenem Desensitization Protocol Dose # 1 2 3 4 5 6 7 8 9 Meropenem Concentration (mg) 0.004 0.02 0.1 0.6 3 15 30 62 125 10 250 11 500 12 1000 Preparation Instructions Add 2 ml from bag 3 Add 1.67 ml from bag 4 Add 1.67 ml from bag 5 Add 0.2 ml from bag 6 Add 0.15 ml from bag 12 Add 0.313 ml of stock solution to minibag Add 0.625 ml of stock solution to minibag Add 1.25 ml of stock solution to minibag Add 2.5 ml of stock solution to minibag Remove 15 ml of NS from minibag (5 ml for amount being added and 10 ml overfill). Add 5 ml of stock solution to minibag. Remove 20 ml of NS from minibag (10 ml for amount being added and 10 ml overfill). Add 10 ml of stock solution to minibag Remove 30 ml from of NS from minibag (20 ml for amount being added and 10 ml overfill). Add 20 ml of stock solution to minibag. Final Concentration (mg/ml) 0.00008 0.0004 0.002 0.012 0.06 0.3 0.625 1.25 2.5 5 10 20 Adapted from Ann Pharmacother. 2003 Oct;37:1424-8. Preparation A stock solution was prepared from two 1 gram vials of meropenem by adding 20 ml of sterile water for injection into each vial with the resulting concentration of 50 mg/ml. Each dose was prepared in a 50 ml minibag of 0.9% sodium chloride (NS) and infused over 20 minutes. The IV line should be flushed between doses. The overfill volume should be removed from each minibag prior to adding medication. In addition, if greater than 2 ml of drug are added to the minibag (doses #9-12), that amount of volume should also be removed from the minibag prior to adding medication. Doses 1-5 were made from previously prepared doses. Doses 6-11 are made from the second stock solution vial (1 gram vial). One of the stock solutions is used completely to make dose 12. Document created: 07/12. Revised: None. Cross Reference: August 2012 P&T Committee Newsletter. Marquette General Health System Marquette General Hospital Marquette, MI 49855 This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL 330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
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