Voxilaprevir

VOSEVI is a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir which are DAA agents against the hepatitis C virus [see Microbiology (12.4) ].

• VOSEVI is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have [see Dosage and Administration (2.2) and Clinical Studies (14) ]: genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor. genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.ICD-10: B18.2

• VOSEVI is contraindicated with rifampin [see Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ]. Coadministration with rifampin.contraindicated

Testing: Prior to initiating VOSEVI, test all patients for HBV infection by measuring HBsAg and anti-HBc. ( 2.1 ) Recommended dosage: One tablet (400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir) taken orally once daily with food. ( 2.2 ) See recommended treatment regimen and duration in table below ( 2.2 ): Genotype Patients Previously Treated with an HCV Regimen Containing: VOSEVI Duration 1, 2, 3, 4, 5, or 6 An NS5A inhibitor In clinical trials, prior NS5A inhibitor experience included daclatasvir, elbasvir, ledipasvir, ombitasvir, or velpatasvir. 12 weeks 1a or 3 Sofosbuvir without an NS5A inhibitor In clinical trials, prior treatment experience included sofosbuvir with or without any of the following: peginterferon alfa/ribavirin, ribavirin, HCV NS3/4A protease inhibitor (boceprevir, simeprevir, or telaprevir). 12 weeks For patients with renal impairment including end stage renal disease on dialysis, follow the dosage recommendations in the table above. ( 2.3 ) VOSEVI is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C). ( 2.4 , 5.2 ) 2.1 Testing Prior to the Initiation of Therapy Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with VOSEVI [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage The recommended dosage of VOSEVI is one tablet, taken orally, once daily with food [see Clinical Pharmacology (12.3) ].

Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. Monitor HCV/HBV coinfected patients for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. ( 5.1 ) Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease: Hepatic decompensation/failure, including fatal outcomes, have been reported mostly in patients with cirrhosis and baseline moderate or severe liver impairment (Child-Pugh B or C) treated with HCV NS3/4A protease inhibitor-containing regimens. Monitor for clinical and laboratory evidence of hepatic decompensation. Discontinue VOSEVI in patients who develop evidence of hepatic decompensation/failure. ( 5.2 ) Bradycardia with Amiodarone Coadministration: Serious symptomatic bradycardia may occur in patients taking amiodarone with VOSEVI, a sofosbuvir-containing regimen, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with VOSEVI is not recommended. In patients without alternative viable treatment options, cardiac monitoring is recommended.

The following serious adverse reactions are described below and elsewhere in labeling: Serious Symptomatic Bradycardia When Coadministered with Amiodarone [see Warnings and Precautions (5.3) ]. The most common adverse reactions (incidence greater than or equal to 10%, all grades) observed with treatment with VOSEVI for 12 weeks were headache, fatigue, diarrhea, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in HCV-Infected Subjects without Cirrhosis or with Compensated Cirrhosis The adverse reactions data for VOSEVI were derived from two Phase 3 clinical trials (POLARIS-1 and POLARIS-4) that evaluated a total of 445 subjects infected with genotype 1, 2, 3, 4, 5, or 6 HCV, without cirrhosis or with compensated cirrhosis (Child-Pugh A), who received VOSEVI for 12 weeks. VOSEVI was studied in placebo- and active-controlled (sofosbuvir/velpatasvir) trials [see Clinical Studies (14.1 and 14.2) ]. The proportion of subjects who permanently discontinued treatment due to adverse events was 0.2% for subjects who received VOSEVI for 12 weeks.

8.1 Pregnancy Risk Summary No adequate human data are available to establish whether or not VOSEVI poses a risk to pregnancy outcomes. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with the components of VOSEVI (sofosbuvir, velpatasvir, or voxilaprevir) at exposures greater than those in humans at the recommended human dose (RHD) [see Data ] . During organogenesis in the mouse, rat, and rabbit, systemic exposures (AUC) of velpatasvir were approximately 23 (mice), 4 (rats), and 0.5 (rabbits) times the exposure in humans at the RHD, while exposures of voxilaprevir were approximately 141 (rats) and 4 (rabbits) times the exposure in humans at the RHD. Exposures of the predominant circulating metabolite of sofosbuvir (GS-331007) were approximately 6 (rats) and 16 (rabbits) times the exposure in humans at the RHD. In rat pre/postnatal development studies, maternal systemic exposures (AUC) for each component of VOSEVI were approximately 7 (sofosbuvir metabolite GS-331007), 3 (velpatasvir), and 238 (voxilaprevir) times the exposure in humans at the RHD. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Metabolism

The pharmacokinetic properties of the components of VOSEVI are provided in Table 4. The multiple dose pharmacokinetic parameters of sofosbuvir and its metabolite GS-331007, velpatasvir, and voxilaprevir are provided in Table 5.

No specific antidote is available for overdose with VOSEVI. If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with VOSEVI consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Hemodialysis can efficiently remove the predominant circulating metabolite of sofosbuvir, GS-331007, with an extraction ratio of 53%. Hemodialysis is unlikely to result in significant removal of velpatasvir or voxilaprevir since velpatasvir and voxilaprevir are highly bound to plasma protein.

• Jul 18, 2017NDANDA209195Gilead Sciences Inc

1. 1Fatigue19718%
2. 2Headache13412%
3. 3Treatment Failure11411%
4. 4Drug Ineffective1069.9%
5. 5Nausea1049.7%
6. 6Hepatitis C898.3%
7. 7Diarrhoea868.0%
8. 8Vomiting363.3%
9. 9Insomnia292.7%
10. 10Abdominal Discomfort232.1%
11. 11Hepatocellular Carcinoma222.0%
12. 12Product Dose Omission201.9%
13. 13Intentional Dose Omission191.8%
14. 14Asthenia181.7%
15. 15Decreased Appetite181.7%

The 10 most recently updated of 33 ClinicalTrials.gov registrations naming Voxilaprevir as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Sofosbuvir/Velpatasvir/Voxilaprevir Salvage Therapy in Hepatitis C Patients Who Relapsed After DAA Treatment
  Active not recruiting · Observational · 200 enrolled · Xiangya Hospital of Central South University
  NCT07565948updated 2026-05-04
• Access to Hepatitis C Treatment in Cameroon: Comparison of a Simplified Test and Treat Strategy to a Standard Strategy
  Not yet recruiting · Phase 4 · Interventional · 576 enrolled · ANRS, Emerging Infectious Diseases
  NCT07098481updated 2025-08-01
• Impact of Direct-acting Antiviral Drugs on The Patterns of Gut Microbiota in Patients With HCV Related Chronic Liver Diseases
  Completed · Observational · 30 enrolled · Assiut University
  NCT06829966updated 2025-02-17
• Improving Response to Immunotherapy in Patients With Advanced Hepatocellular Carcinoma and Chronic Hepatitis C Virus Infection With Direct-Acting Antiviral Therapy
  Terminated · Phase 4 · Interventional · 2 enrolled · M.D. Anderson Cancer Center
  NCT05717400updated 2024-12-31
• The Efficacy of Vosevi in Treating DAA-experienced Patients
  Recruiting · Observational · 200 enrolled · The Third Affiliated Hospital of Guangzhou Medical University
  NCT06180590updated 2024-03-13
• A Registry for Participants With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With a Sofosbuvir-Based Regimen Without Interferon for Chronic Hepatitis C Infection
  Terminated · Observational · 1,609 enrolled · Gilead Sciences
  NCT02292706updated 2023-10-04
• Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication
  Completed · Phase 4 · Interventional · 87 enrolled · University of Maryland, Baltimore
  NCT03823911updated 2023-05-22
• A Registry for Adolescent and Pediatric Participants Who Received a Gilead Hepatitis C Virus Direct Acting Antiviral (DAA) in Gilead-Sponsored Chronic Hepatitis C Infection Trials
  Terminated · Observational · 461 enrolled · Gilead Sciences
  NCT02510300updated 2023-01-27
• Combined Ribavirin With Sofosbuvir/Velpatasvir/Voxilaprevir in Retreatment of Chronic Hepatitis C Non-responders
  Completed · Phase 4 · Interventional · 281 enrolled · Helwan University
  NCT04695769updated 2022-09-02
• Efficacy and Safety of SOF/VEL + RBV and SOF/VEL/VOX for 12 Weeks in HCV Subjects With GT3b and Compensated Cirrhosis
  Unknown · Phase 4 · Interventional · 100 enrolled · Peking University People's Hospital
  NCT05467826updated 2022-07-21

Frequently asked questions

How does Voxilaprevir work?

VOSEVI is a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir which are DAA agents against the hepatitis C virus [see Microbiology (12.4) ].

What is Voxilaprevir used for?

According to FDA labeling, Voxilaprevir carries indications including: VOSEVI is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have [see Dosage and Administration (2.2) and Clinical Studies (14) ]: genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor. genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Voxilaprevir?

Voxilaprevir is classified as Hepatitis C Virus NS3/4A Protease Inhibitor, Breast Cancer Resistance Protein Inhibitors, HCV NS3/4A Protease Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, P-Glycoprotein Inhibitors, Decreased RNA Replication.

What are the brand names for Voxilaprevir?

Voxilaprevir is marketed under brand names including Vosevi.

What are the contraindications for Voxilaprevir?

Voxilaprevir labeling lists contraindications including: VOSEVI is contraindicated with rifampin [see Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ]. Coadministration with rifampin.. Always consult the full prescribing information and a clinician.