What to Know About Vosevi (Sofosbuvir, Velpatasvir, Voxilaprevir)

Offering hepatitis C cure rates of up to 98% in just 12 weeks

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Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) is a fixed-dose combination drug used to treat chronic hepatitis C infection. It is comprised of three different drugs that prevent the replication of the hepatitis C virus (HCV).

Approved for use by the U.S. Food and Drug Administration (FDA) on July 19, 2017, Vosevi is among a newer class of drugs known as direct-acting antivirals (DAAs). Compared to previous-generation medications, DAAs offer higher cure rates, shorter treatment courses, and fewer side effects. Vosevi is used in adults previously treated for hepatitis C, including those with early-stage cirrhosis.

Even after multiple past treatment failures, Vosevi offers cure rates of between 96% and 98%, according to clinical trials published in the New England Journal of Medicine.

Man and his wife meeting with a doctor
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Vosevi is currently approved for use in some adults with HCV genotypes 1, 2, 3, 4, 5, and 6 who were previously treated for chronic HCV infection but failed to achieve sustained virologic response, the general definition of a cure.

This drug works by interfering with stages in the virus' life cycle. It is not cytotoxic like chemotherapy drugs used to kill cancer; rather, it blocks biological processes that the virus needs to replicate. Each of the drugs in Vosevi target different and distinct stages:

  • Sofosbuvir, a nucleotide inhibitor, attaches itself to RNA to block the genetic coding needed to make viral copies.
  • Velpatasvir, an NS5a protease inhibitor, blocks the protease enzyme from chopping proteins into the building blocks of the virus. It does so by binding to a specific enzyme known as NS5A.
  • Voxilapravir, an NS3/4a protease inhibitor, targets a different protease enzyme known as NS3/4a.

The combination of drugs is more effective than the individual drug agents alone. This is because HCV is not just one virus. Rather, it consists of six major genetic strains (known as genotypes), over 50 subtypes, and thousands upon thousands of variants, each with their own unique shape and structural configuration.

While an HCV variant may be able to elude one drug or maybe two, it is rare for it to elude all three. This "tag-team" approach has proven effective in not only curing hepatitis C but also preventing the escape of variants that can later multiply and cause drug resistance.

Before Taking

Treatment recommendations vary by the HCV genotype:

  • Vosevi can be used in adults who have been previously treated with the NS5a inhibitor Daklinza (daclatasvir), velpatasvir (used in the combination drug Epclusa), ledipasvir (used in the combination drug Harvoni), or elbasvir (used in the combination drug Zepatier).
  • Vosevi can also be used in adults with genotypes 1a and 3 who have been previously treated with sofosbuvir without an NS5a inhibitor.

Although the practice has yet to be officially endorsed, the FDA concedes that Vosevi may be effective in adults with all other HCV genotypes who have previously been treated with sofosbuvir without an NS5a inhibitor.

Vosevi can be used in adults with compensated cirrhosis (in which the liver is damaged but still functional), but not those with decompensated cirrhosis (in which the liver is non-functional).

Precautions and Contraindications

The only absolute contraindication for people on Vosevi therapy is the concurrent use of the tuberculosis drug rifampin. While similar medications like rifabutin and rifapentine may have an effect on Vosevi concentrations, rifampin appears to do so immediately, consistently, and profoundly.

Taking Vosevi and rifampin together will greatly reduce the concentration of sofosbuvir, velpatasvir, and voxilaprevir in the blood, leading to treatment failure.

Although there have been no human studies on the effects of Vosevi during pregnancy, animal studies have not shown any evidence of fetal harm at doses well in excess of those given to humans.

It is not known if sofosbuvir, velpatasvir, or voxilaprevir can be transmitted in breast milk or what effect they may have on nursing babies. Animal studies have found no evidence of harm, although long-term studies in humans have not been conducted.


Vosevi is available in a beige, film-coated tablet embossed with "GSI" on one side and "3" on the other. Each tablet contains 400 milligrams (mg) of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir. There are no generic formulations.

The recommended dosage of Vosevi is one tablet taken daily with food. Take this medication at the same time each day to keep the amount of drug in your body at a constant level and allow it to work most effectively.

The treatment duration is 12 weeks irrespective of HCV genotype or treatment history. Even if your symptoms disappear during treatment, continue to take this medication for the full length of time prescribed. If you stop taking the medication, your infection may return.

Side Effects

Like all medications, Vosevi may cause side effects. The side effects tend to be manageable and often resolve on their own without treatment.


The most common side effects (affecting at least 5% of users) include:

  • Headache (affecting up to 23% of users)
  • Fatigue (affecting up to 19% of users)
  • Diarrhea (affecting up to 14% of users)
  • Nausea (affecting up to 13% of users)
  • Abnormal weakness (affecting up to 6% of users)
  • Insomnia (affecting up to 6% of users)

Less common side effects (affecting less than 1% of users) include a rash, usually mild and self-limiting, and mild to moderate depression.

As much as people fear hepatitis C treatment—mainly due to older generation drugs like peginterferon and ribavirin—there are many who report feeling better once treatment is started, due largely to the reduction of chronic inflammation caused by an HCV infection.


One possible hazard of Vosevi use is the reactivation of the hepatitis B virus (HBV) in people co-infected with HBV and HCV. The reactivation can occur during or after HCV treatment. Some cases have been especially severe, resulting in fulminant hepatitis (the massive death of liver tissues), liver failure, and death.

When to Call Your Doctor

Call your doctor immediately if you develop any signs of HBV reactivation, including:

  • Extreme fatigue
  • A general feeling of unwellness
  • Pain in the right abdomen under the ribs
  • Abdominal swelling
  • Jaundice (yellowing of the skin and/or eyes)
  • Cola-colored urine
  • Chalk-colored stools

Prior to the start of Vosevi, blood tests should be performed to identify past or current HBV infections. Anyone co-infected with HBV and HCV should be closely monitored during treatment and for up to 12 weeks following the completion of therapy to check for reactivation.

While serious, HBV reactivation is relatively uncommon, affecting roughly 0.6% of users, according to a 2017 review of studies in the World Journal of Gastroenterology. With that being said, people with active, untreated HBV infection may have as much as a 21% risk of reactivation.

Warnings and Interactions

There are a number of drugs that rely on the same enzymes for metabolization—called cytochromes—as Vosevi. If taken together, the drugs will compete for the available enzymes in the blood and liver. In some cases, this will cause an increase in a drug's concentration (raising the risk of toxicity); in others, it will cause a decrease (reducing the drug's efficacy).

There are several drug-drug interactions that may require interventions.

Vosevi Drug Interactions
Drug Type Interaction Recommendation
Acid-reducing drugs like antacids, H2 blockers, and proton pump inhibitors Reduces velpatasvir concentration Separate doses by 4 hours
Anticonvulsants like Dilantin (phenytoin) and Tegretol (carbamazepine) Reduces sofosbuvir, velpatasvir, and voxilaprevir concentrations Combined use is not recommended
Cyclosporine used to prevent organ rejection Increases voxilaprevir concentration Combined use is not recommended
HIV drugs Reyataz (atazanavir) and lopinavir Increases voxilaprevir concentration Combined use is not recommended
HIV drug Sustiva (efavirenz) Reduces velpatasvir and voxilaprevir concentrations Combined use is not recommended
Statin drugs like Lipitor (atorvastatin) and Zocor (simvastatin) Increases statin drug concentration Use the lowest statin dose needed to maintain cholesterol control
St. John's wort Reduces sofosbuvir, velpatasvir, and voxilaprevir concentrations Avoid St. John's wort
Tuberculosis drugs rifabutin and rifapentine Reduces sofosbuvir, velpatasvir, and voxilaprevir concentrations Combined use is not recommended

Cardiac Risk

Of special concern is the drug amiodarone (marketed under the brand names Cordarone, Pacerone, and others), which is used to treat heart rhythm disorders. Taking Vosevi and amiodarone together may cause severe bradycardia, a seriously slowed heartbeat. Some cases have resulted in death or the need for a heart transplant.

While not contraindicated for use, amiodarone should be never be used with Vosevi unless no other treatment options are available. Continuous cardiac monitoring should be performed for the first 48 hours of treatment, with repeat cardiac evaluations conducted every two weeks thereafter.

Call 911 or go to your nearest emergency room if you experience symptoms of bradycardia while on Vosevi, including lightheadedness, fainting, shortness of breath, chest pains, and confusion.

A Word From Verywell

As with all DAAs used to treat hepatitis C, Vosevi is extremely expensive. The average wholesale price (AWP) of Vosevi is $1,068 per tablet or $89,712 for a 12-week course. This does not include the cost of lab tests, doctor visits, and imaging studies.

The price tag is even higher than that of Mavyret (glecapravir/pibrentasvir), a DAA whose AWP is $439 per tablet, or $26,400 for an 8-week course.

Most insurance companies and Medicare cover Vosevi, but you may have to meet certain criteria. You should always check with your insurance company and physician before getting a prescription, since there could be a copayment or coinsurance cost that may be prohibitive.

In such instances, you may be able to enroll in a copay assistance program, in which part or all of your copay costs are covered, or a patient assistance program, in which all costs may be covered for eligible individuals.

To find which drug assistance programs you qualify for, contact Vosevi Support Path at 855-7-MYPATH (855-769-7824).

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  1. Bourlière M, Gordon S, Flamm S, et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017 Jun 1;376(22):2134-2146. doi:10.1056/NEJMoa1613512.

  2. Jiang X, Ye J, Li Y, et al. Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C: A systematic review and meta-analysis. World J Gastroenterol. 2018;24(28):3181-91. doi:10.3748/wjg.v24.i28.3181

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