Elbasvir
(in ZEPATIER)
What it isAn HCV NS5A replication-complex inhibitor, co-formulated with the NS3/4A protease inhibitor grazoprevir as Zepatier.
Why this oneProvides a once-daily oral regimen for chronic HCV genotypes 1 and 4, effective even in advanced chronic kidney disease including dialysis.
What limits itBaseline NS5A resistance-associated substitutions in genotype 1a reduce efficacy (guiding testing and ribavirin addition), and grazoprevir exposure-related ALT elevations require monitoring.
FDA label
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| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Chronic HCV GT1a, treatment-naive or PegIFN/RBV-experienced, WITHOUT baseline NS5A polymorphisms | adults & peds >=12 y or >=30 kg | 1 tablet (elbasvir 50 mg / grazoprevir 100 mg) QD x 12 wk | 1 tablet QD x 12 wk | 1 tablet QD |
| Chronic HCV GT1a WITH baseline NS5A polymorphisms (positions 28/30/31/93) | adults & peds >=12 y or >=30 kg | 1 tablet QD + weight-based ribavirin x 16 wk | 1 tablet QD + RBV x 16 wk | 1 tablet QD |
| Chronic HCV GT1b, treatment-naive or PegIFN/RBV-experienced | adults & peds >=12 y or >=30 kg | 1 tablet QD x 12 wk | 1 tablet QD x 12 wk | 1 tablet QD |
| Chronic HCV GT1a or 1b, PegIFN/RBV/protease-inhibitor-experienced | adults & peds >=12 y or >=30 kg | 1 tablet QD + ribavirin x 12 wk | 1 tablet QD + RBV x 12 wk | 1 tablet QD |
| Chronic HCV GT4, treatment-naive | adults & peds >=12 y or >=30 kg | 1 tablet QD x 12 wk | 1 tablet QD x 12 wk | 1 tablet QD |
| Chronic HCV GT4, PegIFN/RBV-experienced | adults & peds >=12 y or >=30 kg | 1 tablet QD + ribavirin x 16 wk | 1 tablet QD + RBV x 16 wk | 1 tablet QD |
Renal No adjustment needed (any degree of renal impairment, incl. hemodialysis); adjust ribavirin per its label if CrCl <=50 mL/min
Hepatic Mild (Child-Pugh A): no adjustment. Moderate/severe (Child-Pugh B/C) or any prior hepatic decompensation: CONTRAINDICATED
Ribavirin co-administration required in some regimens (see table); ribavirin contraindications/warnings then also apply
Instructions
- Take with or without food
- Before starting: test all patients for HBV (HBsAg + anti-HBc)
- GT1a: test for baseline NS5A resistance-associated polymorphisms to set regimen/duration
- Hepatic labs before treatment, at week 8 (and week 12 if 16-wk course), and as indicated
- HCV/HIV-1 co-infection: same regimens as mono-infection
Contraindications
- Moderate or severe hepatic impairment (Child-Pugh B/C) or any history of hepatic decompensation
- OATP1B1/3 inhibitors that significantly raise grazoprevir levels (atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine) — ALT-elevation risk
- Strong CYP3A inducers (phenytoin, carbamazepine, rifampin, St. John's wort) and efavirenz — loss of virologic response
- If given with ribavirin, all ribavirin contraindications apply (incl. pregnancy)
Cautions
- HBV reactivation in HCV/HBV co-infected patients — can cause fulminant hepatitis, hepatic failure, death; test and monitor (boxed)
- Late ALT elevations (~1%, at/after wk 8; higher in females, Asians, age >=65) — monitor hepatic labs; discontinue if ALT >10x ULN persists or with signs of liver inflammation
- Hepatic decompensation/failure (incl. fatal) reported with NS3/4A protease-inhibitor regimens — monitor; discontinue if decompensation develops
- Significant drug interactions via CYP3A/OATP1B1/3 — review co-medications
Adverse reactions
- ZEPATIER x12 wk: fatigue, headache, nausea (>=5%)
- With ribavirin x16 wk: anemia, headache (moderate/severe >=5%)
- Late ALT elevations ~1%; bilirubin elevation and hemoglobin decline mainly with ribavirin
- Postmarketing: angioedema, hepatic decompensation/failure
Pregnancy No adequate human data (animal studies: no adverse developmental effects); if given with ribavirin, regimen is CONTRAINDICATED in pregnancy and in men whose partners are pregnant
Lactation Unknown if present in human milk (present in rat milk, no pup effects); weigh benefit vs risk; with ribavirin, ribavirin lactation guidance applies
⚠ BOXED WARNING
- Hepatitis B virus reactivation in patients coinfected with HCV and HBV
Principal riskBoxed warning (Zepatier): risk of hepatitis B virus reactivation in patients coinfected with HCV and HBV.
Classes and tags
Clinical profile
Mechanism of action: Elbasvir ballicule
