Prior Auth Protocol

FDA Approved Indications:

For the treatment of genotype 1 or 4 chronic hepatitis C virus (HCV) infection with or without ribavirin in adults

Health Net Approved Indications and Usage Guidelines:

Diagnosis of chronic hepatitis C (CHC) confirmed by detectable serum HCV RNA by quantitative assay in patients with genotype 1 or 4. Genotype is required to determine length of approval.

AND

For genotype 1a, laboratory testing for the presence or absence of virus with NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93 [See General Information section]

AND

A trial of Harvoni is required (Member must meet prior authorization criteria for and use Harvoni unless contraindicated) unless the patients creatinine clearance is less than 30 mL/minute (Stage 4 or Stage 5 chronic kidney disease)

AND

Chart note documentation and copies of lab results are required

AND

Prescribed by or in consultation with a gastroenterologist, hepatologist or infectious disease physician.

AND

One of the following clinical states to identify candidates for treatment:
- Evidence of Stage 2 or greater hepatic fibrosis defined by one of the following:
  - Liver biopsy confirming a METAVIR score F2 or greater
  - Transient elastography (Fibroscan) score greater than or equal to 7.5 kPa
  - FibroSure (also known as FibroTest) score of greater than or equal to 0.48
  - APRI score greater than 0.7
  - FIB greater than 3.25
  - ARFI score of greater than 1.34 m/s
  - MRE score of greater than 3.20 kilopascals
  - HepaScore ≥0.55
  - FibroMeter ≥ 0.411
- Evidence of extra-hepatic manifestation of hepatitis C virus, such as type 2 or 3 essential mixed cryoglobulinemia with end- organ manifestations (e.g. vasculitis), or kidney disease (e.g. proteinuria, nephrotic syndrome or membranoproliferative glomerulonephritis).
- HIV-1 co-infection
- Hepatitis B co-infection
- Other coexistent liver disease (e.g. nonalcoholic steatohepatitis)
- Type 2 diabetes mellitus (insulin resistant)
- Porphyria cutanea tarda
- Debilitating fatigue impacting quality of life (e.g., secondary to extra-hepatic manifestations and/or liver disease) Fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest, and causes a substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months
- Men who have sex with men with high-risk sexual practices
- Patients with a current injectable substance abuse disorder and actively participating in treatment
- Persons on long-term hemodialysis
- Women of childbearing age who wish to become pregnant
- HCV-infected health care workers who perform exposure-prone procedures

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

For patients infected with HCV Genotype 1a: Testing for the presence of virus with NS5A resistance-associated polymorphisms is recommended. Clinical trial results show decreased efficacy of Zepatier in HCV genotype 1a with presence of NS5A polymorphisms. If baseline NS5A polymorphisms are present for genotype 1a, refer to Section VI on the longer recommended duration of therapy.
Zepatier is contraindicated with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors, strong inducers of cytochrome P450 3A (CYP3A), and efavirenz.
Zepatier is contraindicated for use in patients with moderate to severe hepatic impairment (Child-Pugh Class B or Class C) due to the expected significantly increased grazoprevir plasma concentration and the increased risk of alanine aminotransferase (ALT) elevations.
Child-Pugh Score:

	1 Point	2 Points	3 Points
Bilirubin	Less than 2 mg/dL Less than 34 umol/L	2-3 mg/dL 34-50 umol/L	Over 3 mg/dL Over 50 umol/L
Albumin	Over 3.5 g/dL Over 35 g/L	2.8-3.5 g/dL 28-35 g/L	Less than 2.8 g/dL Less than 28 g/L
INR	Less than 1.7	1.7 - 2.2	Over 2.2
Ascites	None	Mild / medically controlled	Moderate-severe / poorly controlled
Encephalopathy	None	Mild / medically controlled Grade I-II	Moderate-severe / poorly controlled Grade III-IV

Diagnostic criteria for chronic fatigue syndrome was developed by an expert committee convened by the Institute of Medicine on the basis of a comprehensive literature review and input from patient, advocacy, and research communities. These diagnostic criteria state that symptoms should persist for at least 6 months and be present at least half the time with moderate, substantial, or severe intensity to distinguish chronic fatigue syndrome from other diseases.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Harvoni* (sofosbuvir/ledipasvir)	1 tablet PO QD for 12 weeks	24 weeks
Epclusa*	Without cirrhosis or with compensated cirrhosis, treatment naive or treatment experienced: One tablet PO QD	12 weeks
Epclusa* plus ribavirin	With decompensated cirrhosis (Child-Pugh class B or C) treatment naive or treatment experienced: One tablet PO QD plus weight based ribavirin	12 weeks

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Zepatier	Genotype 1a: Treatment-naive or PegIFN/RBVexperienced without baseline NS5A polymorphisms at amino acid positions 28, 30, 31, or 93 One tablet PO QD	12 weeks
Zepatier	Genotype 1b: Treatment-naive or PegIFN/RBVexperienced One tablet PO QD	12 weeks
Zepatier	Genotype 4: Treatment-naive One tablet PO QD	12 weeks
Zepatier + ribavirin	Genotype 1a: Treatment-naive or PegIFN/RBVexperienced with baseline NS5A polymorphisms at amino acid positions 28, 30, 31, or 93 One tablet PO QD plus BID ribavirin	16 weeks
Zepatier + ribavirin	Genotype 1a or 1b: PegIFN/RBV/PI-experienced One tablet PO QD plus BID ribavirin	12 weeks
Zepatier + ribavirin	Genotype 4: PegIFN/RBV-experienced One tablet PO QD plus BID ribavirin	16 weeks

Product Availability:

Zepatier Tablets: grazoprevir 100 mg/elbasvir 50 mg

References:

1. Zepatier [Prescribing Information]. Whitehouse Station, NJ: Merck and Co.; January 2016.
2. Zeuzem SJ, Ghalib R, Reddy R, et al. Grazoprevir-elbasvir combination therapy for treatment naove cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4 or 6 infection. Annals of Int Med July 7, 2015;163;1:1-13.
3. American Association for the Study of Liver Disease Recommendations for Testing, Managing, and Treating Hepatitis C; December 2015. (accessed at: http://www.hcvguidelines.org).