Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
VOSEVI vs ZEPATIER
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
VOSEVI (sofosbuvir, velpatasvir, and voxilaprevir) is a fixed-dose combination of a nucleotide analog NS5B polymerase inhibitor (sofosbuvir), an NS5A inhibitor (velpatasvir), and a NS3/4A protease inhibitor (voxilaprevir). The combination inhibits hepatitis C virus replication by targeting multiple viral proteins.
ZEPATIER is a fixed-dose combination of elbasvir, an HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. Elbasvir inhibits HCV NS5A, disrupting viral replication and assembly. Grazoprevir inhibits the HCV NS3/4A serine protease, preventing cleavage of the HCV polyprotein into mature viral proteins.
Treatment of chronic hepatitis C virus genotype 1-6 infection in adults who have no prior treatment with a NS5A inhibitor and have been previously treated with a regimen containing sofosbuvir without a NS5A inhibitor,Treatment of chronic hepatitis C virus genotype 1-6 infection in adults who have prior treatment with a NS5A inhibitor-containing regimen
Treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults,Treatment of chronic HCV genotype 1 or 4 infection in pediatric patients 12 years of age and older or weighing at least 30 kg
One tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) orally once daily with food for 8 weeks.
One tablet (elbasvir 50 mg/grazoprevir 100 mg) orally once daily.
Sofosbuvir: 0.5 h (parent), 27 h (GS-331007 metabolite); Velpatasvir: 17 h; Voxilaprevir: 33 h. Terminal half-lives support once-daily dosing; metabolite GS-331007 accumulates but is less active.
Elbasvir: terminal half-life approximately 24 hours. Grazoprevir: terminal half-life approximately 31 hours. The prolonged half-lives support once-daily dosing and allow for sustained viral suppression.
Sofosbuvir is metabolized by cathepsin A and CES1 to the active metabolite GS-461203, followed by dephosphorylation. Velpatasvir and voxilaprevir are metabolized by CYP2B6, CYP2C8, CYP3A4 (minor). Voxilaprevir is also a substrate of OATP1B1/1B3.
Elbasvir is metabolized primarily by CYP3A. Grazoprevir is metabolized primarily by CYP3A. Mild oxidation and glucuronidation are minor pathways.
Sofosbuvir: 80% renal, 14% fecal; Velpatasvir: 94% fecal, 0.4% renal; Voxilaprevir: 40% renal, 47% fecal. VOSEVI components are eliminated primarily via biliary/fecal (velpatasvir, voxilaprevir) and renal (sofosbuvir) pathways.
Elbasvir: primarily biliary/fecal (≥90% as metabolites, <1% unchanged in urine). Grazoprevir: primarily biliary/fecal (≥90% as metabolites, <1% unchanged in urine). Renal elimination is negligible for both.
Sofosbuvir: ~85% bound; Velpatasvir: >99.5% bound; Voxilaprevir: >99% bound. Primarily to albumin.
Elbasvir: ≥99.9% bound, primarily to albumin and α1-acid glycoprotein. Grazoprevir: 98.8% bound, primarily to albumin and α1-acid glycoprotein.
Sofosbuvir: ~1.8 L/kg; Velpatasvir: ~4.9 L/kg; Voxilaprevir: ~3.9 L/kg. Large Vd indicates extensive tissue distribution, including liver (target organ).
Elbasvir: apparent Vd approximately 4.5 L/kg (high, indicating extensive tissue distribution). Grazoprevir: apparent Vd approximately 19 L/kg (very high, likely due to binding to plasma proteins and tissue uptake).
Oral: sofosbuvir ~92%, velpatasvir ~29%, voxilaprevir ~44% (fasted). Administer with food to increase absorption (especially voxilaprevir AUC 2- to 4-fold).
Elbasvir: absolute bioavailability not determined in humans; oral absorption is high. Grazoprevir: absolute bioavailability approximately 27% after oral administration; absorption is enhanced with food (high-fat meal increases AUC by 1.5-fold).
No dose adjustment required for mild to moderate renal impairment (e GFR ≥30 m L/min/1.73 m²). For severe renal impairment (e GFR <30 m L/min/1.73 m²) or end-stage renal disease, safety and efficacy not established; use not recommended.
No dose adjustment required for any degree of renal impairment including end-stage renal disease on dialysis.
Contraindicated in Child-Pugh class B or C decompensated cirrhosis due to increased voxilaprevir exposure. No dose adjustment required for Child-Pugh class A cirrhosis.
Contraindicated in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment required in mild (Child-Pugh A) hepatic impairment.
Safety and efficacy in pediatric patients <18 years have not been established; no specific dosing recommendations.
Not approved for use in pediatric patients; safety and efficacy not established.
No dose adjustment required based on age. Clinical studies included patients ≥65 years with no overall differences in safety or efficacy; consider renal function monitoring.
No dose adjustment required; however, clinical studies indicate similar safety and efficacy as in younger adults, but caution is warranted due to potential age-related comorbidities.
Risk of hepatitis B virus reactivation in patients coinfected with HCV and HBV. Test all patients for evidence of current or prior HBV infection before starting treatment. Monitor HCV/HBV coinfected patients for hepatitis B reactivation during treatment and post-treatment follow-up.
Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV, which may result in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection before initiating treatment.
Risk of HBV reactivation,Risk of bradycardia when coadministered with amiodarone; avoid use unless alternatives are not available,Decompensated hepatic impairment: not recommended for use in patients with moderate or severe hepatic impairment (Child-Pugh B or C),Drug interactions: potential for reduced therapeutic effect if given with P-gp inducers (e.g., rifampin) or moderate/strong CYP inducers
Risk of hepatitis B virus reactivation,Hepatic decompensation with use in patients with moderate or severe hepatic impairment (Child-Pugh B or C),Elevation of total bilirubin and/or ALT levels,Risk of adverse reactions due to drug interactions (e.g., strong CYP3A inducers/inhibitors)
Concomitant use with rifampin (CYP2B6 and P-gp inducer) due to significant decrease in voxilaprevir concentrations,Concomitant use with St. John's wort (Hypericum perforatum) due to decreased drug concentrations,Coadministration with rosuvastatin is contraindicated due to increased risk of myopathy/rhabdomyolysis,Severe hepatic impairment (Child-Pugh C)
Moderate or severe hepatic impairment (Child-Pugh B or C),Use with strong CYP3A inducers (e.g., rifampin, St. John's wort, carbamazepine, phenytoin),Use with certain HIV medications (e.g., efavirenz, etravirine, nevirapine, atazanavir/ritonavir, lopinavir/ritonavir, darunavir/ritonavir, tipranavir/ritonavir),Use with cyclosporine
VOSEVI should be taken with food to ensure adequate absorption. A high-fat meal (approximately 800–1000 calories, 50% fat) increases absorption of velpatasvir and voxilaprevir. Avoid concurrent use with St. John's wort, rifampin, and other P-glycoprotein inducers, as they may reduce VOSEVI efficacy.
ZEPATIER can be taken with or without food. No specific food restrictions are required. Grapefruit and grapefruit juice may increase exposure to grazoprevir; although not contraindicated, consider avoiding large quantities.
VOSEVI is contraindicated in pregnancy due to risk of fetal harm. No adequate human data; animal studies show developmental toxicity at clinically relevant exposures. Use effective contraception during treatment and for 6 months after completion.
ZEPATIER (grazoprevir/elbasvir) is contraindicated in pregnancy due to the ribavirin component in some regimens. Ribavirin is teratogenic in all trimesters, causing fetal malformations and embryolethality. Grazoprevir/elbasvir alone has no adequate human data, but animal studies show no teratogenicity. However, combination with ribavirin mandates avoidance in pregnancy.
No data on presence in human milk; animal studies indicate excretion. M/P ratio unknown. Risk of adverse effects in infant not excluded; advise against breastfeeding during therapy.
No data on human milk excretion. M/P ratio unknown. Ribavirin accumulates in breast milk and is contraindicated during breastfeeding. Grazoprevir/elbasvir: animal studies show excretion in milk; potential for adverse effects. Avoid breastfeeding during treatment and for 7 days after last dose.
No data on pharmacokinetic changes in pregnancy; dose adjustments not established. VOSEVI is not recommended in pregnancy; if inadvertent exposure occurs, consult specialist.
No dose adjustment studies in pregnancy. ZEPATIER is not recommended during pregnancy due to ribavirin component. If inadvertently used, no specific dose adjustment; consult maternal-fetal specialist.
VOSEVI is a fixed-dose combination of sofosbuvir (NS5B inhibitor), velpatasvir (NS5A inhibitor), and voxilaprevir (NS3/4A protease inhibitor) indicated for treatment-naive and treatment-experienced patients with chronic HCV genotype 1–6 without cirrhosis or with compensated cirrhosis. It is particularly useful for patients who have failed prior NS5A inhibitor-containing regimens, including those with genotype 3 and compensated cirrhosis. Monitor for hepatitis B reactivation in HBV co-infected patients. Dose adjustment not required for mild or moderate renal impairment, but safety not established in severe renal impairment or ESRD. Caution with amiodarone due to risk of serious bradycardia. Check for drug interactions with P-gp inducers, CYP2B6, CYP2C8, and CYP3A4 substrates.
ZEPATIER (elbasvir/grazoprevir) is indicated for chronic HCV genotypes 1 or 4. Prior to initiation, test for NS5A resistance-associated substitutions (RASs) in genotype 1a. In patients with genotype 1a and baseline NS5A RASs, treatment duration is 16 weeks with ribavirin. Avoid in moderate to severe hepatic impairment (Child-Pugh B or C). Monitor hepatic function closely. Coadministration with strong CYP3A4 inducers (e.g., rifampin, carbamazepine) is contraindicated. Also contraindicated with OATP1B1/3 inhibitors (e.g., cyclosporine) and certain HIV protease inhibitors (e.g., atazanavir, darunavir, lopinavir). Grazoprevir increases serum creatinine due to OATP2B1 inhibition, but this does not reflect true renal function decline.
Take VOSEVI exactly as prescribed, usually one tablet once daily with food.,Do not skip doses or stop taking VOSEVI without talking to your doctor.,If you have hepatitis B co-infection, your doctor will monitor you for HBV reactivation during and after treatment.,Tell your doctor about all medications, including over-the-counter drugs, herbal supplements, and vitamins, as VOSEVI may interact with them.,Common side effects include headache, fatigue, diarrhea, and nausea. Contact your doctor if you experience severe abdominal pain, jaundice, or signs of liver injury.,VOSEVI does not prevent transmission of HCV. Practice safe sex and avoid sharing needles to reduce the risk of spreading the virus.
Take ZEPATIER exactly as prescribed, one tablet once daily with or without food.,Do not stop or skip doses without consulting your healthcare provider.,Inform your doctor of all medications you take, including over-the-counter drugs and herbal supplements, to avoid serious interactions.,Notify your healthcare provider immediately if you experience symptoms of liver problems: yellowing of skin or eyes, dark urine, pale stools, nausea, vomiting, or right upper abdominal pain.,ZEPATIER may elevate creatinine levels without reflecting kidney damage; your doctor will monitor appropriately.,If you have genotype 1a HCV, your doctor will test for specific resistance mutations to determine the correct treatment duration.,Avoid alcohol during treatment as it can exacerbate liver injury.,Use effective contraception during treatment and for 2 weeks after the last dose if you or your partner can become pregnant.
No interactions on record
No interactions on record
Common clinical questions about VOSEVI vs ZEPATIER, answered by our medical review team.
VOSEVI is a Direct-Acting Antiviral Combination that works by VOSEVI (sofosbuvir, velpatasvir, and voxilaprevir) is a fixed-dose combination of a nucleotide analog NS5B polymerase inhibitor (sofosbuvir), an NS5A inhibitor (velpatasvir), and a NS3/4A protease inhibitor (voxilaprevir). The combination inhibits hepatitis C virus replication by targeting multiple viral proteins.. ZEPATIER is a Direct-Acting Antiviral (HCV) that works by ZEPATIER is a fixed-dose combination of elbasvir, an HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. Elbasvir inhibits HCV NS5A, disrupting viral replication and assembly. Grazoprevir inhibits the HCV NS3/4A serine protease, preventing cleavage of the HCV polyprotein into mature viral proteins.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between VOSEVI and ZEPATIER depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of VOSEVI is: One tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) orally once daily with food for 8 weeks.. The standard adult dose of ZEPATIER is: One tablet (elbasvir 50 mg/grazoprevir 100 mg) orally once daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between VOSEVI and ZEPATIER in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. VOSEVI is classified as Category C. VOSEVI is contraindicated in pregnancy due to risk of fetal harm. No adequate human data; animal studies show developmental toxicity at clinically relevant exposures. Use effective. ZEPATIER is classified as Category C. ZEPATIER (grazoprevir/elbasvir) is contraindicated in pregnancy due to the ribavirin component in some regimens. Ribavirin is teratogenic in all trimesters, causing fetal malformat. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.