CurrentCentenePolicy HIM.PA.SP62

Elbasvir/Grazoprevir (Zepatier) (PDF)

Clinical coverage policy defining medical necessity criteria, prior authorization requirements, dosing limits, contraindications, and continuity/renewal criteria for Zepatier (elbasvir/grazoprevir) across Centene HIM lines of business (with state exceptions noted).

Policy Summary

PayerCentene

PolicyElbasvir/Grazoprevir (Zepatier) (PDF)

Policy CodePolicy HIM.PA.SP62

Change TypeMultiple updates (material and clarifying)

Effective DateAug 1, 2020

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that member meets all approval criteria; genotype confirmation and HCV RNA quantitative within last 6 months required.

SourceLink

POLICY UPDATE CHANGES

Added step therapy bypass for IL HIM per IL HB 5395.

For continued therapy criteria, revised option for treatment duration minimum from 60 days to 28 days and removed requirement for specific confirmed genotype.

Added prescriber exception for HIM Georgia.

Clarified that coadministration with omeprazole up to 20 mg is not acceptable justification to bypass Epclusa.

Removed qualifier of 'chronic' from HCV criteria.

Added Appendix G guidance on incomplete adherence and management of treatment interruptions per AASLD-IDSA recommendations.

1 & 4Covered HCV Genotypes

Age ≥12 or weight ≥30 kgCovered patient population

Maximum approval duration

1 tab/dayMaximum daily dose

Coverage Summary

Zepatier is a fixed‑dose combination of elbasvir (an NS5A inhibitor) and grazoprevir (an NS3/4A protease inhibitor) indicated for treatment of HCV genotype 1 or 4 in patients aged ≥ 12 years or weighing ≥ 30 kg. Coverage is covered_with_criteria with requirements including specialist prescriber (with state exceptions), documentation of HCV RNA and genotype, and NS5A resistance testing for genotype 1a when applicable. High‑level constraints include a maximum of 1 tablet/day (elbasvir 50 mg / grazoprevir 100 mg) and approval durations of up to 16 weeks (consistent with Section V dosing guidance).

Thresholds

Age>= 12 years or weight >= 30 kg

HCV RNA test recencyDetectable quantitative HCV RNA within last 6 months

Minimum treatment exposure for continued therapy>= 28 days

Maximum daily doseelbasvir/grazoprevir 50 mg/100 mg (1 tablet) per day

Approval durationUp to a total of 16 weeks

Child-Pugh A requirementIf cirrhosis present, confirmation of Child-Pugh A (5-6 points) required

Initial Therapy Criteria - Hepatitis C Infection

Initial Approval Criteria - Hepatitis C Infection

Covered when ALL of the following are met:

ALL of the following

Diagnosis of HCV infection as evidenced by detectable serum HCV RNA levels by quantitative assay in the last 6 months
Prescribed by or in consultation with a gastroenterologist, hepatologist, infectious disease specialist, or provider who has expertise in treating HCV based on a certified training program (Appendix F)
Prescriber requirement does not apply to HIM Georgia
Age ≥ 12 years or weight ≥ 30 kg
Confirmed HCV genotype is 1 or 4
Chart note documentation and copies of lab results are required

Initial Therapy Criteria - Other diagnoses/indications

Initial Approval Criteria - Other diagnoses/indications

Covered when ALL of the following are met:

ALL of the following

Member must use sofosbuvir-velpatasvir (Epclusa authorized generic), if applicable for the requested indication, unless contraindicated or clinically significant adverse effects are experienced
Coadministration with omeprazole up to 20 mg is NOT acceptable justification for inability to use Epclusa
ONE of the following
- If this drug has recently (within the last 6 months) undergone a label change that is not yet reflected in this policy, refer to the no coverage or non-formulary policies as applicable: HIM.PA.33 (formulary) or HIM.PA.103 (non-formulary)
- If the requested use is NOT specifically listed under section III AND criterion 2a does not apply, refer to off-label use policy HIM.PA.154

Continuation Therapy Criteria - Hepatitis C Infection

Continued Therapy - Hepatitis C Infection

Covered when ALL of the following are met:

ALL of the following

Member must meet ONE of
- Currently receiving medication via Centene benefit or previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (refer to state addendums CC.PHARM.03A and CC.PHARM.03B)
- Documentation supports member is currently receiving Zepatier and has recently completed at least 28 days of treatment with Zepatier

Continuation Therapy Criteria - Other diagnoses/indications

Diagnoses / Indications Not Authorized

Applicable Codes

Product availability (NDC not specified in policy text)NDC

No codes listed

Relevant billing/diagnosis codes (populate if available)mixed

No codes listed

Provider Actions & Requirements

Prior Authorization

Prior authorization and documentation

Provider must submit documentation (office chart notes, lab results, or other clinical information) supporting that the member meets all approval criteria. Required documentation includes confirmation of HCV genotype and a quantitative HCV RNA result obtained within the last 6 months.

Documentation Required

Prescriber qualification

Prescriptions must be written by or in consultation with a gastroenterologist, hepatologist, or infectious disease specialist, or by a provider with documented expertise in treating HCV based on an acceptable certified training program (see Appendix F). The prescriber requirement does not apply to HIM Georgia.

Clinical Evidence & References

Key references: Zepatier Prescribing Information (May 2022); AASLD‑IDSA HCV guidance (updated Dec 19, 2023); CDC Clinical Overview (Jan 31, 2025).

Background

Mechanism: elbasvir = NS5A inhibitor; grazoprevir = NS3/4A protease inhibitor. Indication: treatment of HCV genotype 1 or 4 in patients aged ≥ 12 years or weighing ≥ 30 kg. Recommended regimen and duration vary by genotype, prior treatment history, presence of baseline NS5A resistance‑associated polymorphisms (positions 28, 30, 31, or 93 for genotype 1a), and cirrhosis/Child‑Pugh status; see Section V Dosage and Administration for specific regimens (e.g., generally one tablet once daily for 12 weeks, with extensions to 16 weeks and/or addition of ribavirin in certain scenarios).

Definitions

Child-Pugh A definitionChild-Pugh class A = 5-6 points (see Appendix E for scoring criteria: bilirubin, albumin, INR, ascites, encephalopathy)

NS5A RAS definitionMutations at amino acid positions 28, 30, 31, or 93 (NS5A resistance-associated polymorphisms) that reduce efficacy in genotype 1a

Revision History

07.15.25addedLatest

Added step therapy bypass for Illinois HIM per IL HB 5395 (step therapy requirements do not apply for Illinois HIM requests as of 1/1/2026).

07.15.25revised

Continued therapy criteria revised: changed minimum treatment exposure option from 60 days to 28 days and removed requirement for specific confirmed genotype; also added requirement that the prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen.

05.30.24revised

Policy Summary

PayerCentene

PolicyElbasvir/Grazoprevir (Zepatier) (PDF)

Policy CodePolicy HIM.PA.SP62

Change TypeMultiple updates (material and clarifying)

Effective DateAug 1, 2020

Next Review Date

SourceLink

On This Page

For genotype 1a, laboratory testing for presence or absence of virus with NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93

Documentation of treatment status (treatment-naive or treatment-experienced)

If cirrhosis is present, confirmation of Child-Pugh A status

Member must use sofosbuvir-velpatasvir (Epclusa authorized generic), unless contraindicated or clinically significant adverse effects are experienced

Coadministration with omeprazole up to 20 mg is NOT acceptable justification for inability to use Epclusa; For Illinois HIM requests, the step therapy requirements do not apply as of 1/1/2026 per IL HB 5395

Life expectancy ≥ 12 months with HCV treatment

Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen

See Section V Dosage and Administration

Dose does not exceed elbasvir/grazoprevir 50 mg/100 mg (1 tablet) per day

Approval duration: up to a total of 16 weeks

Approved duration should be consistent with a regimen in Section V

Member is responding positively to therapy

Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen

See Section V

Dose does not exceed elbasvir/grazoprevir 50 mg/100 mg (1 tablet) per day

Approval duration: up to a total of 16 weeks

Approved duration should be consistent with a regimen in Section V

Step Therapy

Step therapy redirection to Epclusa authorized generic

Member must use sofosbuvir‑velpatasvir (Epclusa authorized generic) for the applicable indication unless it is contraindicated or the member experiences clinically significant adverse effects. Coadministration with omeprazole up to 20 mg is NOT considered acceptable medical justification to bypass Epclusa.

Denial Risk

Contraindications and warnings

Do not approve Zepatier for patients with moderate or severe hepatic impairment (Child‑Pugh B or C) or any history of hepatic decompensation. Zepatier is contraindicated with inhibitors of OATP1B1/3 that significantly increase grazoprevir concentrations, with strong CYP3A inducers, and with efavirenz. Monitor patients for HBV reactivation during and after HCV treatment.

Do‑not‑approve conditions: Child‑Pugh B or C; history of hepatic decompensation
Major contraindicated coadministrations: strong OATP1B1/3 inhibitors; strong CYP3A inducers; efavirenz
Warning: monitor for HBV reactivation (boxed warning)

Documentation Required

NS5A resistance testing for genotype 1a

For genotype 1a requests, baseline laboratory testing for NS5A resistance‑associated polymorphisms at amino acid positions 28, 30, 31, and 93 is required. Presence of baseline NS5A polymorphisms for genotype 1a affects the recommended regimen and typically requires adjustment to the regimen and/or longer duration (see Section V Dosage and Administration).

Added prescriber exception for HIM Georgia (prescriber requirement does not apply to HIM Georgia).

07.20.22clarified

Clarified that coadministration with omeprazole up to 20 mg is not acceptable justification to bypass Epclusa (Appendix E unacceptable justification).

05.30.24clarified

Added Appendix G guidance on incomplete adherence and AASLD-IDSA recommended management of treatment interruptions describing missed-dose management and thresholds for restarting, extending, or stopping therapy.