Direct Acting Antiviral Medications for Treatment of Hepatitis C
____________________________________________________________________________________
Policy Number:
MM.04.036
Lines of Business:
HMO; PPO; QUEST Integration
Section:
Prescription Drugs
Place(s) of Service:
Office; Outpatient
Original Effective Date:
06/01/2015
Current Effective Date:
02/01/2016
I. Description
The diagnosis of chronic hepatitis C virus (HCV) infection is based on the presence of both anti-HCV
antibodies, detected by enzyme immunoassays, and HCV RNA, detected by molecular amplification
(polymerase chain reaction). HCV RNA can be detected in blood within one to three weeks after
exposure, and anti-HCV seroconversion occurs by eight to nine weeks after exposure.
Progression of chronic hepatitis C infection to end stage liver disease most commonly occurs over
several decades. Early in the course of infection, serum or liver-related enzyme levels, such as
alanine aminotransferase, aspartate aminotransferase, and y-glutamyltranspeptidase may be
elevated but there are no signs of liver dysfunction. As the disease progresses, signs of liver fibrosis
may develop and fibrosis will often progress to cirrhosis. However, many patients may go decades
or a lifetime without substantial liver damage. Early damage to the liver (including fibrosis) is
generally reversible, while cirrhosis may not be reversible. Disease progression is accelerated in
the presence of co-factors such as alcohol consumption, diabetes mellitus, older age at acquisition,
HIV co-infection, and co-infection with other hepatic viruses.
An assessment of the severity of hepatic fibrosis is important for treatment and prognosis of
chronic HCV infection. A variety of fibrosis scoring systems are available that gauge the degree of
hepatic fibrosis with either direct observation of fibrosis through liver biopsy or noninvasive
measurement of a biological correlate of hepatic fibrosis (see Appendix A). The METAVIR fibrosis
scoring system is the most commonly used method to stage and grade hepatic fibrosis and it
assigns a score from F0 to F4 based on a liver biopsy. Several blood tests that detect serological
markers of hepatic fibrosis also produce scores that can be staged to estimate degree of fibrosis
(e.g., HepaScore, FibroSure, FibroSpect II). Another group of tests involve radiological imaging to
measure qualities about the liver without an invasive surgery; these include magnetic resonance
elastography (MRE), ultrasound transient elastography (e.g., FibroScan), and acoustic radiation
force impulse imaging (ARFI; e.g., Acuson S2000).
Direct Acting Antiviral Medications for Treatment of Hepatitis C
2
Direct acting antiviral (DAA) medications for hepatitis C specifically target proteins involved in the
HCV life cycle and disrupt viral replication. In patients with chronic hepatitis C, these medications
offer the potential to improve cure rates with lower toxicity compared to treatment regimens that
do not include DAAs.
DAA Medications for the Treatment of Hepatitis C
Simeprevir (Olysio) is indicated as a combination treatment with other antiviral drugs in patients
with chronic HCV genotype 1 with compensated liver disease (including cirrhosis). Refer to
Appendix C for the U.S. Food and Drug Administration (FDA) approved treatment regimen for
Olysio.
Sofosbuvir (Sovaldi) is indicated for the treatment of HCV infection as a component of a
combination antiviral treatment regimen. The efficacy of sofosbuvir has been established in
patients with HCV genotype 1, 2, 3, or 4 infection, including those with hepatocellular carcinoma
meeting Milan criteria (awaiting liver transplantation) (refer to Appendix B) and those with
HCV/HIV-1 co-infection. Results from early small-scale research suggest that combination antiviral
treatments containing sofosbuvir may be effective in treating patients with HCV genotype 5 or 6
infection. Refer to Appendix D for the FDA approved treatment regimen for Sovaldi.
Ledipasvir/Sofosbuvir (Harvoni) is the first all-oral, interferon (IFN)-free regimen indicated for the
treatment of patients with HCV genotype 1. Results from early small-scale research suggest that
ledipasvir/sofosbuvir may be an effective treatment for patients with HCV genotype 4 or 6
infection. Refer to Appendix E for the FDA approved treatment regimen for Harvoni.
Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir (Viekira Pak) is indicated for the treatment of patients
with HCV genotype 1, including those with cirrhosis. Refer to Appendix F for the FDA approved
treatment regimen for Viekira Pak.
Daclatasvir (Daklinza) is indicated for use in combination with sofosbuvir for the treatment of
patients with HCV genotype 3, although its effectiveness is decreased in patients with cirrhosis.
Results from clinical trials suggest that daclatasvir with sofosbuvir may be an effective treatment
for patients with HCV genotype 1 or 2. Refer to Appendix G for the FDA approved treatment
regimen for Daklinza.
Ombitasvir/Paritaprevir/Ritonavir (Technivie) is indicated for use in combination with ribavirin for
the treatment of patients with HCV genotype 4 without cirrhosis. Refer to Appendix H for the FDA
approved treatment regimen for Technivie.
Prioritizing Patients to Receive Treatment for Chronic Hepatitis C
The combined American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases
Society of America (IDSA) guidelines for the treatment of chronic hepatitis C are available at
http://www.hcvguidelines.org/. These guidelines are updated frequently, so providers should
Direct Acting Antiviral Medications for Treatment of Hepatitis C
3
check them periodically for the most up to date recommendations on patient care. The
recommendations in these guidelines are a valuable resource for this policy but do not alone form
a basis for approval of a particular course of treatment. To ensure that patients with the greatest
need receive treatment, patients must be prioritized so that those with liver-related complications
or severe extrahepatic hepatitis C complications are given the highest priority for treatment. In the
current policy, only for those patients considered the highest priority (e.g., those who have
advanced hepatic fibrosis, compensated cirrhosis, severe extrahepatic manifestations of hepatitis C
infection, or a transplanted organ) may treatment with DAA medications be covered.
II. Criteria/Guidelines
A. DAA medications are covered for the treatment of HCV infection (subject to Limitations and
Administrative Guidelines) when all of the following criteria are met:
1. The patient is at least 18 years of age;
2. The patient is infected with an HCV genotype (and subtype, when applicable) for which the
treatment being sought is indicated (refer to Appendix I);
3. The prescribing physician attests that the patient is at low risk for noncompliance with the
treatment regimen;
4. The patient has an HCV RNA positive diagnosis documented by a quantitative titer obtained
within the three months preceding treatment initiation;
5. The patient has no history of alcohol or substance abuse within the six months prior to
treatment initiation;
6. The patient presents with at least one of the following indications:
a. Liver biopsy with a METAVIR stage of F3 or F4;
b. Transient elastography (FibroScan) score greater than or equal to 9.5 kPa;
c. FibroSure (FibroTest) score of greater than or equal to 0.58;
d. Score from another blood test that detects serological markers of hepatic fibrosis that is
equivalent to a METAVIR stage of F3 or F4;
e. Radiological imaging consistent with cirrhosis (e.g., evidence of portal hypertension);
f. Clinical findings consistent with cirrhosis (i.e., ascites or esophageal varices);
g. Serious extrahepatic manifestations of hepatitis C, i.e., type 2 or 3 essential mixed
cryoglobulinemia with end-organ manifestations (e.g., vasculitis), proteinuria, nephrotic
syndrome, or membranoproliferative glomerulonephritis ;
h. Organ transplant; or
i. Liver biopsy with a METAVIR stage of F2 (or equivalent, i.e., FibroScan score of greater
than or equal to 7.0 or FibroSure score of greater than or equal to 0.48) and HIV coinfection.
7. The medication is being prescribed by, or in consultation with, one of the following
specialists:
a. Hepatologist;
b. Gastroenterologist; or
c. Infectious Disease Specialist.
8. The patient agrees to the following:
a. 100% medication compliance;
Direct Acting Antiviral Medications for Treatment of Hepatitis C
4
b. Regular follow-up with specialty pharmacist or treating provider;
c. No alcohol or illicit drug use during the course of treatment;
d. Drug testing, when recommended by the treating provider; and
e. Blood draws to measure HCV RNA, when ordered.
9. Treatment is in accordance with FDA approved treatment regimens unless otherwise noted
in Appendix I.
B. DAA medications are covered for the treatment of HCV infection (subject to Limitations and
Administrative Guidelines) regardless of the degree of liver fibrosis when the above criteria
(A.1-5, 7-9) are met for health care workers who are HCV positive and, because they perform
invasive procedures, are at significant risk of transmitting the infection to patients.
C. Patients who meet the above criteria for treatment and in whom previous treatment has failed
(i.e., relapse, non-response, partial response) may be retreated (subject to Limitations and
Administrative Guidelines). Relapse is defined as the reappearance of HCV RNA in plasma after
being undetectable at completion of therapy. Non-response is defined as a less than 2
logarithm reduction in HCV RNA after completion of a course of therapy. Partial response is
defined as at least a 2 logarithm reduction in HCV RNA during treatment, but a detectable level
of HCV RNA at the end of the course of treatment. Only patients who experienced prior
treatment failure in the following situations may be eligible for retreatment:
1. Patients in whom a previous interferon and ribavirin regimen has failed may be retreated
according to the appropriate section of Table 2 in Appendix I.
2. Patients in whom a previous sofosbuvir plus ribavirin or sofosbuvir plus ribavirin with
interferon regimen has failed may be retreated based on their HCV genotype and presence
of cirrhosis:
a. For patients with genotype 1 without cirrhosis, retreatment with ledipasvir/sofosbuvir
and weight-based ribavirin for 12 weeks is considered medically necessary;
b. For patients with genotype 1 with cirrhosis, retreatment with ledipasvir/sofosbuvir and
weight-based ribavirin for 24 weeks is considered medically necessary;
c. For patients with genotype 2 or 4, there is no retreatment regimen supported by
scientific evidence. These patients should defer antiviral therapy pending additional
data or consider treatment within a clinical trial setting;
d. For patients with genotype 3 regardless of cirrhosis status, retreatment with sofosbuvir
and weight-based ribavirin plus interferon for 12 weeks is considered medically
necessary; and
e. For patients with genotype 5 or 6, retreatment with sofosbuvir and weight-based
ribavirin plus interferon for 12 weeks is considered medically necessary.
3. Patients infected with HCV genotype 1, 5, or 6 in whom a previous HCV nonstructural
protein 3 (NS3) protease inhibitor (i.e., telaprevir, boceprevir, or simeprevir) with interferon
and weight-based ribavirin regimen has failed may be retreated according to the
appropriate section of Table 2 in Appendix I.
4. Patients in whom a previous HCV nonstructural protein 5A (NS5A) inhibitor regimen (i.e.,
daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir plus
dasabuvir) has failed may be retreated based on degree of liver disease:
Direct Acting Antiviral Medications for Treatment of Hepatitis C
5
a. For patients with minimal liver disease, retreatment is considered not medically
necessary. These patients should defer antiviral therapy pending additional data or
consider treatment within a clinical trial setting;
b. For patients with cirrhosis or who require urgent retreatment, a treatment regimen may
be considered medically necessary based on the results of testing for resistanceassociated variants (RAVs) that confer varying susceptibility to specific drugs:
1. For patients with no NS5A inhibitor RAVs detected retreatment with
ledipasvir/sofosbuvir and weight-based ribavirin for 24 weeks is considered
medically necessary.
2. For patients who have NS5A inhibitor RAVs detected and who do not have NS3
inhibitor RAVs detected, treatment with simeprevir, sofosbuvir, and weight-based
ribavirin for 24 weeks is considered medically necessary.
3. For patients who have both NS3 and NS5A inhibitor resistance-associated variants
(RAVs) detected, retreatment should be conducted in a clinical trial setting as there
is no appropriate treatment regimen at this time.
III. Limitations
A. Treatment of HCV with DAA medication is not covered when any of the criteria specified above
(II.A-C) are not met.
B. Treatment of HCV with DAA medication is not covered for patients with short life expectancies
due to comorbid conditions.
C. Treatment is contraindicated in patients with a known hypersensitivity or allergy to the
prescribed drug used to treat hepatitis C.
D. Treatment of HCV with a regimen containing sofosbuvir and simeprevir is contraindicated in
patients with genotype 1a who have the Q80K polymorphism.
E. Treatment of HCV with ombitasvir/paritaprevir/ritonavir/dasabuvir is contraindicated in
individuals who are taking drugs that have any of the following qualities:
1. Highly dependent on CYP3A for clearance;
2. Strong inducers of CYP3A and CYP2C8; or
3. Strong inhibitors of CYP2C8.
F. Treatment of HCV with daclatasvir is contraindicated in patients who are taking drugs that are
strong inducers of CYP3A, including phenytoin, carbamazepine, rifampin, and St. John’s wort.
G. Repeat treatments in any of the following situations will not be covered:
1. Inadequate compliance resulting in failure to achieve sustained viral response (SVR);
2. Reinfection;
3. Discontinuation of treatment secondary to harmful alcohol and/or drug abuse; or
4. A prior treatment failure when there is no recognized, effective retreatment regimen.
H. The plan will not cover replacement medication for pills that are lost or stolen.
IV. Administrative Guidelines
A. Precertification is required for the initial eight weeks of treatment with sofosbuvir,
ledipasvir/sofosbuvir, daclatasvir, ombitasvir/paritaprevir/ritonavir, or
Direct Acting Antiviral Medications for Treatment of Hepatitis C
B.
C.
D.
E.
F.
G.
H.
6
ombitasvir/paritaprevir/ritonavir/dasabuvir. To precertify, contact CVS Specialty Guideline
Management (SGM) at (808) 254-4414. Precertification is required for continuation of
treatment in a maximum of eight week increments.
Ledipasvir/sofosbuvir or a sofosbuvir-containing regimen is the preferred treatment for
hepatitis C for patients with HCV genotype 1. Treatment of HCV genotype 1 with
ombitasvir/paritaprevir/ritonavir/dasabuvir is non-preferred and may be covered (subject to
Limitations and Administrative Guidelines) only in certain situations, including but not limited
to:
1. Treatment with ledipasvir/sofosbuvir or sofosbuvir is contraindicated because of adverse
effects, harmful drug interaction, allergy to the drugs, or treatment failure;
2. Scientific evidence demonstrates that ombitasvir/paritaprevir/ritonavir/dasabuvir is a more
effective treatment for the patient’s specific condition;
3. A recognized professional society recommends treatment with
ombitasvir/paritaprevir/ritonavir/dasabuvir for the patient’s specific condition.
The following medical record documentation, as applicable to the patient, must be submitted
with the initial precertification request:
1. Written treatment plan from the requesting provider; and
2. Documentation that the member has been assessed for potential non-adherence to
treatment regimen.
Precertification requests for continuing treatment must include an attestation from the
requesting provider, stating that the patient has been compliant with the treatment regimen.
A specialty pharmacy will dispense no more than 28 days of medication at one time.
The HMSA Hepatitis C Treatment Checklist can be found in Appendix K. This checklist,
completed and signed by the patient, is required prior to initiation of treatment.
This policy is not applicable to Akamai Advantage members.
It is recommended that an HCV RNA test be performed 4 weeks after the initiation of treatment
and that treatment be discontinued if HCV RNA results are greater than 25 IU/mL and patient
has been observed to be noncompliant.
V. Scientific Background
NS3/4A Serine Protease Inhibitors
The first-generation direct acting antivirals (DAAs), boceprevir and telaprevir, are nonstructural
protein 3/4A (NS3/4A) serine protease inhibitors and have demonstrated superior SVR compared
to standard therapy with interferon/ribavirin. Treatment response, defined as an SVR at 12 or 24
weeks, was achieved in the 60% to 80% range across various trials of boceprevir and telaprevir.
Adverse events (AEs) occur at a relatively high rate with these agents. Serious adverse events
(SAEs) can involve skin reactions, and hematologic abnormalities such as anemia,
thrombocytopenia, and leukopenia. The second-generation NS3/4A protease inhibitor,
simeprevir, has demonstrated superior SVR compared with standard regimens of
interferon/ribavirin. In pooled analysis of two similar trials, the SVR was 80%, and in a third trial
the SVR was 79%. AEs occurred at rates higher than placebo for skin reactions,
hyperbilirubinemia, and dyspnea. Compared with first-generation protease inhibitors, response
Direct Acting Antiviral Medications for Treatment of Hepatitis C
7
rates for simeprevir may be higher and AE rates lower; however, direct comparisons of the
medications are not available.
Paritaprevir is a NS3/4A serine protease inhibitor that is administered with ribavirin to boost its
plasma levels and half-life. When paritaprevir and ribavirin are administered in combination with
polymerase inhibitors and protease inhibitors, SVR rates are significantly higher than those
observed for treatment consisting of paritaprevir and ribavirin alone. The most common adverse
events are fatigue, headache, nausea, and insomnia. Further discussion on the effectiveness of
paritaprevir can be found in the Combination Medications section below.
NS5B Polymerase Inhibitors
There are currently two FDA approved NS5B polymerase inhibitors: sofosbuvir and dasabuvir. The
evidence on sofosbuvir comes from a mix of randomized and nonrandomized trials. The range of
SVR12 in these studies is from 67% to 97%, with several trials reporting SVR rates that are higher
than with other DAAs. The safety profile of sofosbuvir is favorable compared to other DAAs. SAEs
were uncommon in the trials, and serious hematologic abnormalities occurred in four percent or
less of patients. Dasabuvir is administered in combination with protease inhibitors and
polymerase inhibitors; further discussion on the effectiveness of dasabuvir can be found in the
Combination Medications section below.
NS5A Polymerase Inhibitors
There are currently three FDA approved NS5A inhibitors: daclatasvir, ledipasvir and ombitasvir.
The evidence on these medications comes from a series of randomized trials. The safety profile of
these drugs is favorable compared to other DAAs; many patients in clinical trials experienced mildto-moderate AEs, but SAEs were uncommon. A phase 3, open-label trial found that 89% of
treatment-naïve and 87% of treatment-experienced patients with genotype 3 achieved SVR12
following 12 weeks of treatment with daclatasvir and sofosbuvir. This regimen is less effective in
patients with cirrhosis, with SVR rates ranging from 58% to 69%. Ledipasvir and ombitasvir are
administered in combination with other DAAs; further discussion on the effectiveness of these
drugs can be found in the Combination Medications section below.
Other Protease Inhibitors
Ritonavir is an HIV protease inhibitor that was originally developed as an antiretroviral drug to
treat HIV. It does not have any activity against HCV, but has been found to boost the activity of
other protease inhibitors, including paritaprevir.
Combination Medications
On October 10, 2014, ledipasvir/sofosbuvir became the first combination treatment to receive
FDA approval. Results from the trials of this drug report very high response rates—in the range of
94% to 99%.
On December 19, 2014 ombitasvir/paritaprevir/ritonavir/dasabuvir was approved by the FDA and
became the only FDA approved regimen that contains three distinct mechanisms of action. It
consists of the fixed-dose combination of ombitasvir 25mg (an NS5A inhibitor), paritaprevir
150mg (an NS3/4A protease inhibitor), and ritonavir 100mg (an approved HIV-1 protease
Direct Acting Antiviral Medications for Treatment of Hepatitis C
8
inhibitor), dosed once daily with a meal, and dasabuvir 250mg (a non-nucleoside NS5B
polymerase inhibitor), dosed twice daily with a meal. A phase 2b trial found that
ombitasvir/paritaprevir/ritonavir/dasabuvir administered with ribavirin for 12 weeks to
treatment-naïve patients with genotype 1 resulted in SVR24 ranging from 90% to 97% based on
the dosage of each drug. In the same trial, administration of
ombitasvir/paritaprevir/ritonavir/dasabuvir administered with ribavirin for 24 weeks to
treatment-experienced patients with genotype 1 resulted in an SVR24 of 95%. When this
combination regimen was administered to patients with cirrhosis for 24 weeks in another trial,
observed SVR12 ranged from 92% to 96%. Ombitasvir/paritaprevir/ritonavir/dasabuvir is taken for
12 weeks, except in certain patients with genotype 1a and cirrhosis, who should take it for 24
weeks. Ribavirin should be co-administered in patients with genotype 1a, and in all patients who
have cirrhosis or who have received a liver transplant.
On July 24, 2015, the fixed-dose regimen of ombitasvir/paritaprevir/ritonavir received FDA
approval to be administered with ribavirin to patients with HCV genotype 4 since dasabuvir has no
activity against genotype 4. A randomized study found that 100% of treatment-naïve and
treatment-experienced patients with genotype 4 achieved SVR12 following 12 weeks of
ombitasvir/paritaprevir/ritonavir with ribavirin.
There is no direct evidence comparing outcomes of immediate versus delayed treatment with
DAAs. However, the degree of treatment benefit, and the implications of delaying treatment, can
be inferred from knowledge of the natural history of hepatitis C. The long interval between
chronic hepatitis C infection and the development of irreversible cirrhosis implies that patients
will not be harmed by a delay of treatment if they have an early stage of the disease and
treatment is initiated before the development of irreversible liver damage. For patients with
cirrhosis or who are at high risk for progression to cirrhosis in the near future, immediate
treatment is indicated and delay of treatment may result in worse outcomes. Other patients who
should be treated without delay include those with serious extrahepatic manifestations of
hepatitis C and those with hepatocellular carcinoma awaiting transplant.
Summary
The availability of direct acting antiviral medications (DAAs) represent a major advancement in the
treatment of hepatitis C, with the potential to dramatically improve cure rates with less toxicity
compared to standard treatment without DAAs. All of the DAAs that are currently FDA approved
have demonstrated treatment responses that are superior to standard care consisting of
interferon and ribavirin. Direct comparisons of the different agents are lacking, but differences in
treatment response and adverse effects are reported. The first-generation protease inhibitors,
boceprevir and telaprevir, have response rates in the 60% to 80% range and have a relatively high
incidence of serious adverse effects. Newer DAA treatment regimens have demonstrated higher
response rates and fewer adverse effects in treatment-naïve and treatment-experienced patients
than the first-generation protease inhibitors.
There is no direct evidence on immediate versus delayed treatment, but based on the natural
history of the disease, it is reasonable to conclude that some patients can delay treatment
without suffering adverse outcomes. These are generally patients with no fibrosis or early fibrosis.
Outcomes will not be adversely impacted if these patients have close monitoring and if treatment
Direct Acting Antiviral Medications for Treatment of Hepatitis C
9
is instituted prior to the onset of irreversible liver damage. For patients with more advanced
disease, immediate treatment should be given to avoid progression of irreversible liver damage.
Other patients who should be treated without delay include patients with serious extrahepatic
manifestations of hepatitis C and patients with hepatocellular carcinoma awaiting transplant.
Based on the available evidence, treatment with DAAs for patients with chronic hepatitis C
infection may be considered medically necessary. For patients with early disease, either
immediate or delayed treatment may be considered medically necessary. For patients with
advanced disease, patients with serious extrahepatic manifestations, and patients with
hepatocellular carcinoma awaiting transplant, only immediate treatment may be considered
medically necessary.
Various professional societies, governmental agencies and health plans have developed policies
and treatment regimens for HCV. Those of the Department of Veterans Affairs, American
Association for the Study of Liver Diseases, European Association for the Study of the Liver, and
others can be found in the References section. As research is constantly being conducted in this
field, this policy may not reflect the latest recommendations of the above associations, societies
and agencies.
VI. Important Reminder
The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not
intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is
intended to discourage or prohibit providing other medical advice or treatment deemed
appropriate by the treating physician.
Benefit determinations are subject to applicable member contract language. To the extent there
are any conflicts between these guidelines and the contract language, the contract language will
control.
This Medical Policy has been developed through consideration of the medical necessity criteria
under Hawaii’s Patients’ Bill of Rights and Responsibilities Act (Hawaii Revised Statutes §432E-1.4),
generally accepted standards of medical practice and review of medical literature and government
approval status. HMSA has determined that services not covered under this Medical Policy will not
be medically necessary under Hawaii law in most cases. If a treating physician disagrees with
HMSA’s determination as to medical necessity in a given case, the physician may request that
HMSA reconsider the application of the medical necessity criteria to the case at issue in light of any
supporting documentation.
VII. References
1. AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis
C. http://www.hcvguidelines.org. Accessed September 3, 2015.
2. BCBSA. Medical Policy Reference Manual. Direct Acting Antiviral Medications for Treatment of
Chronic Hepatitis C #5.01.25. Archived February 2015.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
10
3. Anthem. Clinical UM Guideline. Hepatitis C Pegylated Interferon Antiviral Therapy CG-DRUG07. Last reviewed February 5, 2015.
4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management
of hepatitis C virus infection. J Hepatol 2014; 60:392-420.
5. The French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in
liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994; 20(1 Pt 1):1520.
6. Department of Veterans Affairs. Treatment considerations from the Department of Veterans
Affairs National Hepatitis C Resource Center and the Office of Public Health. Revised February
17, 2015. Available online at: http://www.hepatitis.va.gov/pdf/treatment-considerations2015-02.pdf. Last accessed September 3, 2015.
7. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and Sofosbuvir for 8 or 12 weeks for
chronic HCV without cirrhosis. N Engl J Med 2014; 370: 1879-1888.
8. Afdhal N, Reddy, KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV
genotype 1 infection. N Engl J Med 2014; 370: 1483-1493.
9. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for
hepatitis C with cirrhosis. N Engl J Med 2014; 370: 1973-1982.
10. Olysio [package insert]. Titusville, NJ: Janssen Therapeutics; April 2015.
11. Sovaldi [package insert]. Foster City, CA: Gilead Sciences Inc.; August 2015.
12. Harvoni [package insert]. Foster City, CA: Gilead Sciences Inc.; March 2015.
13. Viekira Pak [package insert]. North Chicago, IL: AbbVie Inc.; July 2015.
14. Daklinza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; July 2015.
15. Technivie [package insert]. North Chicago, IL: Abbvie Inc.; July 2015.
16. Baranova A, Lal P, Birerdinc A, Younossi M. Non-Invasive markers for hepatic fibrosis. BMC
Gastroenterology, 2011; 11(91): 15.
17. Mayo Clinic. Hepatitis C Virus (HCV) FibroSURE. LabCorp Burlington. Accessed April 10, 2015.
18. Nudo CG, Jeffers LJ, Bejarano PA, Servin-Abad LA, Leibovici Z, De Medina M, et al. Correlation
of laparoscopic liver biopsy to elasticity measurements (FibroScan) in patients with chronic
liver disease. Gastroenterology & Hepatology, 2008; 4(12): 862-870.
19. Nelson DR, Cooper JN, Lalezari JP, Lawitz E, Pockros PJ, Gitlin N, et al. All-oral 12-week
treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3
infection: ALLY-3 phase III study. Hepatology 2015; 61(4): 1127-1135.
20. Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, et al. Daclatasvir
plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med 2015; 373: 714-725.
21. Reddy KR, Bourlière M, Sulkowski M, Omata M, Zeusem S, Feld JJ. Ledipasvir and sofosbuvir in
patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated
safety and efficacy analysis. Hepatology 2015; 62(1): 79-86.
22. Sulkowski MS, Eron JJ, Wyles D, Trinh R, Lalezari J, Wang C. Ombitasvir, paritaprevir co-dosed
with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: A
randomized trial. JAMA 2015; 313(12): 1223-1231.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
11
23. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A. Simeprevir
plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus
genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naïve
patients: the COSMOS randomized study. Lancet 2014; 384(9956): 1756-1765.
24. Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown Jr., RS. Ledipasvir and sofosbuvir
plus ribavirin for treatment of HCV infection in patients with advanced liver disease.
Gastroerentology 2015 Sep; 149(3) 649-659.
25. Sulkowsi MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I. Daclatasvir
plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014;
370L 211-221.
26. Hézode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, et al.
Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naïve and
treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a
randomized, open-label trial. Lancet 2015; 385(9986): 2502-2509.
27. Kowdley KV, Lawtiz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, et al. Phase 2b trial of
interferon-free therapy for hepatitis C virus genotype 1; N Engl J Med 2014; 370: 222-232.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
12
Appendix A
Meta-analysis of Histological Data in Viral Hepatitis (METAVIR)
Table 1 METAVIR Fibrosis Stage
0
No fibrosis
1
Portal fibrosis without septa (bridges)
2
Portal fibrosis with septa (bridges)
3
Numerous septa without cirrhosis
4
Cirrhosis
* Baranova A et al. Non-Invasive markers for hepatic fibrosis. BMC Gastroenterology, 2011; 11(91).
FibroSure Score Ranges
Table 2 Comparison Between FibroSure Score and METAVIR Stage
FibroSure Score METAVIR Stage Equivalent
< 0.21
Stage F0
0.21 – 0.27
Stage F0 – F1
0.27 – 0.31
Stage F1
0.31 – 0.48
Stage F1 – F2
0.48 – 0.58
Stage F2
0.58 – 0.72
Stage F3
0.72 – 0.74
Stage F3 – F4
> 0.74
Stage F4
* Mayo Clinic. Hepatitis C Virus (HCV) FibroSURE. LabCorp Burlington. Accessed April 10, 2015.
Transient Elastography Cutoff Values
Table 3 Comparison Between FibroScan Measurement and METAVIR Stage
FibroScan Measurement (kPa) METAVIR Stage Equivalent
7.0
Stage F2
9.5
Stage F3
11.8
Stage F4
* Nudo CG et al. Correlation of laparoscopic liver biopsy to elasticity measurements (FibroScan) in
patients with chronic liver disease. Gastroenterology & Hepatology, 2008; 4(12): 862-870.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
13
Appendix B
Milan Criteria
The Milan criteria are a generally accepted set of criteria to assess suitability in patients with cirrhosis
and hepatocellular carcinoma for liver transplantation.
According to the Milan criteria, in order to be suitable for liver transplantation one needs to have:
• no lesion larger than 5 cm
• ≤ 3 lesions with diameter ≤ 3 cm
• no extrahepatic involvement
• no major vessel involvement
Direct Acting Antiviral Medications for Treatment of Hepatitis C
14
Appendix C
FDA Approved Treatment Regimen for Olysio (Simeprevir)
The recommended dose of simeprevir is one 150 mg tablet, taken orally, once daily with food.
Simeprevir should be administered in combination with peginterferon alfa and ribavirin or in
combination with sofosbuvir for the treatment of chronic hepatitis C (CHC) in adults. The
recommended regimen and treatment duration for simeprevir, peginterferon alfa, and ribavirin
combination therapy is provided in Table 1. The recommended regimen and treatment duration for
simeprevir and sofosbuvir combination therapy is provided in Table 2.
Table 1
Recommended Regimens and Treatment Duration for Simeprevir, Peginterferon Alfa, and
Ribavirin Combination Therapy for Treatment of CHC Infection
Patient Population
Treatment Regimen and Duration
Treatment-naïve patients
12 weeks of simeprevir + peginterferon alfa + ribavirin, followed by
and prior relapsers*
an additional 12 weeks of peginterferon + ribavirin (total treatment
duration of 24 weeks)◊
Prior non-responders
12 weeks of simeprevir + peginterferon alfa + ribavirin, followed by
‡
(including partial and nonan additional 36 weeks of peginterferon alfa + ribavirin (total
§
responders )
treatment duration of 48 weeks)◊
* Prior relapser: HCV RNA not detected at the end of prior interferon-based therapy and HCV RNA
detected during follow-up.
◊ Recommended duration of treatment if patient does not meet stopping rules (see Table 3).
‡ Prior partial responder: prior on-treatment ≥ 2 log10 IU/mL reduction in HCV RNA from baseline at
Week 12 and HCV RNA detected at end of prior interferon-based therapy.
§ Prior non-responder: prior on-treatment < 2 log10 reduction in HCV RNA from baseline at Week 12
during prior interferon-based therapy.
Table 2
Recommended Regimens and Treatment Duration for Simeprevir and Sofosbuvir
Combination Therapy for Treatment of CHC Infection
Patient Population
Treatment Regimen
Treatment Duration
Treatment-naïve and treatment-experienced*
simeprevir + sofosbuvir 12 weeks
patients without cirrhosis
Treatment-naïve and treatment-experienced*
simeprevir + sofosbuvir 24 weeks
patients with cirrhosis
* Treatment-experienced patients include prior relapsers, prior partial responders, and prior nonresponders who failed prior interferon-based therapy.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
Table 3
Treatment Stopping Rules in Patients Receiving Simeprevir in Combination with
Peginterferon Alfa and Ribavirin with Inadequate On-Treatment Virologic Response
Treatment Week HCV RNA
Action
Week 4
Week 12
Week 24
≥ 25 IU/mL
Discontinue simeprevir, peginterferon alfa, and ribavirin
Discontinue peginterferon alfa and ribavirin (treatment with
simeprevir is complete at week 12)
Discontinue peginterferon alfa and ribavirin (treatment with
simeprevir is complete at week 12)
Use with Sofosbuvir
No treatment stopping rules apply to the combination of simeprevir and sofosbuvir.
15
Direct Acting Antiviral Medications for Treatment of Hepatitis C
16
Appendix D
FDA Approved Treatment Regimen for Sovaldi (Sofosbuvir)
The recommended dose of sofosbuvir is one 400 mg tablet, taken orally, once daily with or without
food. Sofosbuvir should be used in combination with ribavirin or in combination with pegylated
interferon and ribavirin for the treatment of chronic hepatitis C (CHC) in adults. The recommended
regimen and treatment duration for sofosbuvir combination therapy is provided in Table 1.
For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in Table 1.
Table 1
Recommended Regimens and Treatment Duration for Sofosbuvir Combination Therapy in
HCV Mono-infected and HCV/HIV-1 Co-infected Patients
Patient Population
Treatment
Duration
Patients with genotype 1 or 4 CHC
sofosbuvir + peginterferon alfa + ribavirin
12 weeks
Patients with genotype 2 CHC
sofosbuvir + ribavirin
12 weeks
Patients with genotype 3 CHC
sofosbuvir + ribavirin
24 weeks
Sofosbuvir in combination with ribavirin for 24 weeks can be considered as a therapeutic option for
CHC patients with genotype 1 infection who are ineligible to receive an interferon-based regimen.
Treatment decision should be guided by an assessment of the potential benefits and risks for the
individual patient.
Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation
Sofosbuvir in combination with ribavirin is recommended for up to 48 weeks or until the time of liver
transplantation, whichever occurs first, to prevent post-transplant HCV reinfection.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
17
Appendix E
FDA-Approved Treatment Regimen for Harvoni (Ledipasvir/Sofosbuvir)
The recommended dose of ledipasvir/sofosbuvir is one tablet (90 mg of ledipasvir and 400 mg of
sofosbuvir), taken orally, daily with or without food. The recommended regimen and treatment
duration for ledipasvir/sofosbuvir is provided in Table 1.
Table 1 Recommended Regimens and Treatment Duration for Ledipasvir/Sofosbuvir
Patient Population
Recommended Treatment Duration
Treatment-naïve with or without cirrhosis
12 weeks*
◊
Treatment-experienced without cirrhosis
12 weeks
◊
Treatment-experienced with cirrhosis
24 weeks
*
Ledipasvir/sofosbuvir for 8 weeks can be considered in treatment-naïve patients without cirrhosis
who have pre-treatment HCV RNA less than 6 million IU/mL.
◊ Treatment-experienced patients who have failed treatment with either peginterferon alfa +
ribavirin or an HCV protease inhibitor + peginterferon alfa + ribavirin.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
18
Appendix F
FDA Approved Treatment Regimen for Viekira Pak (Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir)
The recommended dose of Viekira Pak is two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets
once daily (in the morning) and one dasabuvir 250 mg tablet twice daily (morning and evening) with a
meal without regard to fat or calorie count.
The recommended regimen and treatment duration for ombitasvir/paritaprevir/ritonavir/dasabuvir is
provided in Table 1.
Table 1
Recommended Regimens and Treatment Duration for
Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir
Patient Population
Treatment*
Genotype 1a, without cirrhosis
ombitasvir/paritaprevir/ritonavir/dasabuvir
+ ribavirin
Genotype 1a, with cirrhosis
ombitasvir/paritaprevir/ritonavir/dasabuvir
+ ribavirin
Genotype 1b, without cirrhosis
ombitasvir/paritaprevir/ritonavir/dasabuvir
Genotype 1b, with cirrhosis
ombitasvir/paritaprevir/ritonavir/dasabuvir
+ ribavirin
Duration
12 weeks
24 weeks◊
12 weeks
12 weeks
*
Note: Follow the genotype 1a dosing recommendations in patients with an unknown genotype 1
subtype or with mixed genotype 1 infection.
◊ Ombitasvir/paritaprevir/ritonavir/dasabuvir administered with ribavirin for 12 weeks may be
considered for some patients based on prior treatment history.
HCV/HIV-1 co-infection: For patients with HCV/HIV-1 co-infection, follow the dosage recommendations
in the table above.
Liver Transplant Recipients: In liver transplant recipients with normal hepatic function and mild fibrosis
(Metavir stage ≤ F2), the recommended duration of ombitasvir/paritaprevir/ritonavir/dasabuvir with
ribavirin is 24 weeks, irrespective of HCV genotype 1 subtype.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
19
Appendix G
FDA Approved Treatment Regimen for Daklinza (Daclatasvir)
The recommended dosage of Daklinza is 60 mg, taken orally, once daily in combination with sofosbuvir
for 12 weeks. Daklinza may be taken with or without food. The optimal duration of Daklinza and
sofosbuvir for patients with cirrhosis has not been established. For specific dosage recommendations
for sofosbuvir, refer to the respective prescribing information.
Dosage Modification Due to Drug Interactions
Strong inhibitors of cytochrome P450 enzyme 3A (CYP3A): Reduce the dosage of Daklinza to 30 mg
once daily when co-administered with strong CYP3A inhibitors using the 30 mg tablet.
Moderate CYP3A inducers: Increase the dosage of Daklinza to 90 mg once daily using an appropriate
combination of tablets (three 30 mg tablets or one 60 mg and one 30 mg tablet) when coadministered
with moderate CYP3A inducers.
Strong CYP3A inducers: Daklinza is contraindicated in combination with strong CYP3A inducers.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
20
Appendix H
FDA Approved Treatment Regimen for Technivie (Ombitasvir/Paritaprevir/Ritonavir)
The recommended dosage of Technivie is two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets
once daily (in the morning) with a meal without regard to fat or calorie content. Technivie is
recommended to be administered in combination with ribavirin.
Patient Population
Treatment
Duration
Genotype 4 without cirrhosis
Technivie + ribavirin*
12 weeks
*Technivie administered without ribavirin for 12 weeks may be considered for treatment-naïve
patients who cannot take or tolerate ribavirin.
Hepatic impairment: Technivie is not recommended in patients with moderate hepatic impairment
(Child-Pugh B). Technivie is contraindicated in patients with severe hepatic impairment (Child-Pugh C).
Direct Acting Antiviral Medications for Treatment of Hepatitis C
21
Appendix I
Table 1
Genotype
Recommended Regimens for Treatment-Naïve Patients (Based on AASLD/IDSA Current
Guidelines and/or Product Label)
Recommended Regimens*
Drugs
Daklinza (DCV)/Sovaldi (SOF)
1a (no
cirrhosis)
1a (cirrhosis)
1b (no
cirrhosis)
Treatment
Duration
12 weeks
Δ
Harvoni (LED/SOF)
Viral load < 6,000,000
Viral load ≥ 6,000,000
Viekira Pak (OMB/PTV/RTV/DSV)/RBV
Sovaldi (SOF)/Olysio (SMV) ± RBV
12 weeks
◊
□
Daklinza (DCV)/Sovaldi (SOF) ± RBV
Harvoni (LED/SOF)
Δ
24 weeks
Viekira Pak (OBV/PTV/RTV/DSV)/RBV
12 weeks
24 weeks
Sovaldi (SOF)/Olysio (SMV) ± RBV
24 weeks
◊
□
Δ
12 weeks
2 (cirrhosis)
3 (no
cirrhosis)
3 (cirrhosis)
◊
Δ
24 weeks
◊
Viekira Pak (OBV/PTV/RTV/DSV) ± RBV
Sovaldi (SOF)/Olysio (SMV) ± RBV
Δ
Daklinza (DCV)/Sovaldi (SOF)
Sovaldi (SOF)/RBV
Δ
Daklinza (DCV)/Sovaldi (SOF)
Sovaldi (SOF)/RBV
Daklinza (DCV)/Sovaldi (SOF)
Sovaldi (SOF)/PEG/RBV
Daklinza (DCV)/Sovaldi (SOF) ± RBV
Sovaldi (SOF)/PEG/RBV
4
Harvoni (LED/SOF)
Technivie (OBV/PTV/RTV) /RBV
Sovaldi (SOF)/RBV
5
Harvoni (LEF/SOF)
6
Harvoni (LEF/SOF)
Δ
Δ
None
12 weeks
Daklinza (DCV)/Sovaldi (SOF) ± RBV
Harvoni (LED/SOF)
Δ
None
‡
Sovaldi (SOF)/Olysio (SMV)
2 (no
cirrhosis)
None
8 weeks
12 weeks
12 weeks
Viekira Pak (OBV/PTV/RTV/DSV)
1b (cirrhosis)
Treatment
Duration
‡
8 weeks
12 weeks
12 weeks
Daklinza (DCV)/Sovaldi (SOF)
Harvoni (LED/SOF)
Viral load < 6,000,000
Viral load ≥ 6,000,000
Alternative Regimens*
Drugs
None
12 weeks
24 weeks
24 weeks
12 weeks
None
12 weeks
24 weeks
None
16 weeks
12 weeks
12 weeks
24 weeks
12 weeks
12 weeks
Sovaldi (SOF)/RBV
24 weeks
Sovaldi (SOF)/RBV
24 weeks
Sovaldi (SOF)/PEG/RBV
12 weeks
12 weeks
24 weeks
12 weeks
Sovaldi (SOF)/PEG/RBV
12 weeks
12 weeks
Sovaldi (SOF)/PEG/RBV
12 weeks
Direct Acting Antiviral Medications for Treatment of Hepatitis C
Table 2
Recommended Regimens for Patients in Whom Previous Treatment Has Failed (Based
on AASLD/IDSA Current Guidelines and/or Product Label)
Genotype
Recommended Regimens*
Patients in whom previous PEG/RBV has failed
Drugs
Daklinza (DCV)/Sovaldi (SOF)
1a (no
cirrhosis)
Alternative Regimens*
Treatment
Duration
12 weeks
Δ
Harvoni (LED/SOF)
Viekira Pak (OBV/PTV/RTV/DSV)/RBV
◊
Sovaldi (SOF)/Olysio (SMV)
Daklinza (DCV)/Sovaldi (SOF) ± RBV
1a (cirrhosis)
Harvoni (LED/SOF)
Harvoni (LED/SOF)/RBV
Sovaldi (SOF)/Olysio (SMV) ± RBV
Daklinza (DCV)/Sovaldi (SOF)
◊
□
Harvoni (LED/SOF)
2
3 (no
cirrhosis)
3 (cirrhosis)
5
6
◊
Sovaldi (SOF)/Olysio (SMV) ± RBV
Sovaldi (SOF)/RBV
Daklinza (DCV)/Sovaldi (SOF)
Sovaldi (SOF)/PEG/RBV
Daklinza (DCV)/Sovaldi (SOF)/RBV
Sovaldi (SOF)/PEG/RBV
Harvoni (LED/SOF)
4
Δ
Harvoni (LED/SOF)
Harvoni (LED/SOF)/RBV
Viekira Pak (OBV/PTV/RTV/DSV)
Δ
Δ
None
None
12 weeks
12 weeks
◊
Sovaldi (SOF)/Olysio (SMV)
1b (cirrhosis)
None
24 weeks
12 weeks
24 weeks
12 weeks
Daklinza (DCV)/Sovaldi (SOF) ± RBV
Treatment
Duration
24 weeks
Δ
Viekira Pak (OBV/PTV/RTV/DSV)
Drugs
12 weeks
12 weeks
12 weeks
24 weeks
Δ
Viekira Pak (OBV/PTV/RTV/DSV) /RBV
1b (no
cirrhosis)
22
12 weeks
24 weeks
None
24 weeks
12 weeks
12 weeks
24 weeks
16-24 weeks
12 weeks
12 weeks
24 weeks
12 weeks
12 weeks
Sovaldi (SOF)/PEG/RBV
12 weeks
None
None
None
Technivie (OBV/PTV/RTV)/RBV (no cirrhosis)
12 weeks
Sovaldi (SOF)/PEG/RBV
Sovaldi (SOF)/RBV
12 weeks
24 weeks
12 weeks
Sovaldi (SOF)/PEG/RBV
12 weeks
12 weeks
Sovaldi (SOF)/PEG/RBV
12 weeks
Harvoni (LED/SOF)
Δ
Harvoni (LED/SOF)
Δ
Patients in whom previous sofosbuvir plus RBV with or without PEG regimen has failed
Drugs
Treatment
Drugs
Duration
1 (no
Harvoni (LED/SOF)/RBV
12 weeks
None
cirrhosis)
1 (cirrhosis)
Harvoni (LED/SOF)/RBV
24 weeks
None
Treatment
Duration
Direct Acting Antiviral Medications for Treatment of Hepatitis C
Daklinza (DCV)/Sovaldi (SOF) ± RBV
24 weeks
None
Sovaldi (SOF)/PEG/RBV
12 weeks
Daklinza (DCV)/Sovaldi (SOF)/RBV
24 weeks
None
3
Sovaldi (SOF)/PEG/RBV
12 weeks
AASLD does not specify a preferred
Sovaldi (SOF)/RBV/PEG
5 or 6
treatment regimen
Patients in whom previous HCV NS3 protease inhibitor plus PEG and RBV regimen has failed
Drugs
Treatment
Drugs
Duration
Daklinza (DCV)/Sovaldi (SOF)
12 weeks
None
1 (no cirrhosis)
Harvoni (LED/SOF)
12 weeks
Daklinza (DCV)/Sovaldi (SOF) ± RBV
24 weeks
1 (cirrhosis)
Harvoni (LED/SOF)
24 weeks
None
Harvoni (LED/SOF)/RBV
12 weeks
AASLD does not specify a preferred
Sovaldi (SOF)/RBV/PEG
5 or 6
treatment regimen
Patients in whom previous SMV/SOF regimen has failed
Drugs
Treatment
Drugs
Duration
Daklinza (DCV)/Sovaldi (SOF)
12 weeks
None
1 (no cirrhosis)
Harvoni (LED/SOF)/RBV
12 weeks
Daklinza (DCV)/Sovaldi (SOF) ± RBV
24 weeks
None
1 (cirrhosis)
Harvoni (LED/SOF)/RBV
24 weeks
AASLD does not specify a preferred
Sovaldi (SOF)/RBV/PEG
5 or 6
treatment regimen
23
2
12 weeks
Treatment
Duration
12 weeks
Treatment
Duration
12 weeks
*
Abbreviations: SOF = sofosbuvir, SMV = simeprevir, LED = ledipasvir, RBV = ribavirin, PEG =
pegylated alfa interferon, OBV = ombitasvir, PTV = paritaprevir, RTV = ritonavir, DSV = dasabuvir;
DCV = daclatasvir
◊ Viekira Pak approval requires failure, intolerance, or contraindication to Harvoni and Sovaldi.
‡ Harvoni has been FDA approved as a 12-week treatment regimen but may be considered in
treatment-naïve patients without cirrhosis who have pre-treatment HCV RNA less than 6 million
IU/mL.
Δ This regimen does not have FDA approval for this indication, but its use is recommended by the
current AASLD/IDSA guidelines and is supported by research.
□ This regimen is not recommended for individuals with genotype 1a and the Q80K polymorphism.
As additional DAA agents are approved by the FDA, these may be considered medically necessary when
used according to their labeled indications until this policy is updated.
Direct Acting Antiviral Medications for Treatment of Hepatitis C
24
Appendix J
HMSA Hepatitis C Treatment Checklist
HMSA HEPATITIS C TREATMENT CHECKLIST
Coverage of Direct Acting Antiviral medications for the treatment of Hepatitis C is covered only if you
meet HMSA policies and guidelines related to the treatment. You must comply with all instructions
given to you by your physician and pharmacy, and agree to avoid all activities that may worsen your
liver disease or infect yourself or others with the hepatitis C virus or other bloodborne pathogens. By
initialing 1 through 8 and signing below where indicated you promise to comply with the requirements
of this checklist.
Please initial in the space provided next to each statement below. By initialing you agree to comply
with each statement.
1. I agree to comply with all instructions from my physician and dispensing pharmacy
related to the medication prescribed and dispensed to me.
2.
I agree to keep all appointments scheduled with my physician.
3.
I agree to not use alcohol or illicit drugs for the 6 months preceding and during
treatment for hepatitis C.
4.
I agree to attend Alcoholics Anonymous (AA), Narcotics Anonymous (NA) or a similar
program for substance abuse, if recommended by my physician.
5. I agree to use only the medications prescribed by my physician.
6. I agree to random drug and alcohol testing, if requested by my physician.
7. I agree to routine blood testing for the hepatitis C virus when ordered by my physician.
8. I understand that this treatment for hepatitis C is intended to be a once per lifetime
treatment.
By signing below I am indicating that I will comply with 1 through 8 above. I have had an opportunity
to ask questions about this form and my questions have been answered to my satisfaction. I
understand that payment by HMSA of the medication prescribed by my physician to treat hepatitis C is
dependent upon my compliance with the statements above. I further understand that HMSA will
discontinue payment for treatment with my medication to treat hepatitis C if at any time I am not
compliant with 1 through 8 above. I further understand that HMSA will not pay to replace the
medication prescribed if the medication is lost, stolen, destroyed or otherwise not available to me.
Patient Name:
Patient Signature:
Date: