Sofosbuvir, Velpatasvir, and Voxilaprevir

Sofosbuvir, velpatasvir, and voxilaprevir — sold as Vosevi — is a fixed-dose combination antiviral tablet approved to treat chronic hepatitis C virus (HCV) infection in adults who have previously received HCV treatment.

• Vosevi is approved for adults with HCV genotype 1, 2, 3, 4, 5, or 6 who were previously treated with a regimen containing an NS5A inhibitor
• Vosevi is approved for adults with HCV genotype 1a or 3 who were previously treated with sofosbuvir but without an NS5A inhibitor
• All eligible patients must have no cirrhosis or only compensated cirrhosis (Child-Pugh A — meaning the liver is still functioning adequately)
• Vosevi has not shown additional benefit over sofosbuvir/velpatasvir in adults with genotype 1b, 2, 4, 5, or 6 who previously took sofosbuvir without an NS5A inhibitor

Vosevi targets the hepatitis C virus from three different angles at once. Sofosbuvir blocks the NS5B polymerase — an enzyme the virus uses to copy its genetic material. Velpatasvir blocks the NS5A protein, which the virus needs to replicate and assemble. Voxilaprevir blocks the NS3/4A protease, an enzyme the virus uses to build functional proteins. By hitting three separate steps in the viral life cycle simultaneously, Vosevi makes it extremely difficult for HCV to reproduce and survive.

Because it attacks multiple viral targets, this combination is effective even against HCV strains that have developed resistance to earlier treatments — which is why it is specifically designed for people who have tried other HCV regimens before.

Vosevi is taken as one tablet by mouth once daily. It must always be taken with food, because eating a meal significantly increases how much of each ingredient your body absorbs — especially voxilaprevir, which is absorbed far better with food. The standard treatment duration is 12 weeks; your prescriber will confirm the right schedule for you based on your HCV genotype and treatment history.

• Take Vosevi at the same time each day with a meal
• No dose adjustment is needed for kidney disease, including dialysis
• Vosevi is not recommended for people with moderate or severe liver impairment (Child-Pugh B or C)
• If you take antacids, separate them from Vosevi by at least 4 hours

Most people taking Vosevi tolerate it well — the large majority of side effects reported in clinical trials were mild to moderate.

Seek medical attention right away if you develop a slow or irregular heartbeat, signs of liver problems (yellowing skin, belly swelling, confusion), a severe or blistering rash, or signs of hepatitis B flare-up (see warnings).

• Hepatitis B reactivation: The biggest risk — HBV can flare up dangerously in people coinfected with HBV and HCV. All patients must be tested for HBV before starting. Those with HBV infection must be monitored during and after treatment. Some cases have led to liver failure and death.
• Liver decompensation/failure: People with advanced liver disease or cirrhosis can experience sudden liver worsening. Vosevi is not recommended in moderate-to-severe liver impairment (Child-Pugh B or C). Watch for jaundice, belly swelling, confusion, or vomiting blood.
• Dangerous slow heartbeat with amiodarone: Combining Vosevi with the heart drug amiodarone is not recommended. If unavoidable, close cardiac monitoring is required. Symptoms to watch for include fainting, dizziness, shortness of breath, or chest pain.
• Reduced effectiveness with certain drugs: Medicines that speed up liver enzyme activity (like rifampin, St. John's Wort, or certain seizure drugs) can lower Vosevi levels enough to make treatment fail. These combinations should be avoided.

Vosevi has several important drug interactions — always share your full medication list with your prescriber before starting.

• Rifampin (antibiotic): Contraindicated — must never be taken with Vosevi
• Amiodarone (heart rhythm drug): Not recommended — risk of severe, potentially fatal slow heartbeat
• St. John's Wort (herbal supplement): Not recommended — lowers levels of all three Vosevi ingredients
• Carbamazepine, phenytoin, phenobarbital (seizure drugs): Not recommended — reduce Vosevi drug levels significantly
• Certain HIV drugs (atazanavir, lopinavir, efavirenz, tipranavir/ritonavir): Not recommended due to significant interaction risks
• Statins (cholesterol drugs): Vosevi raises statin levels, increasing risk of muscle damage (myopathy/rhabdomyolysis); rosuvastatin and pitavastatin should be avoided; others require dose limits
• Cyclosporine (immunosuppressant): Not recommended — greatly increases voxilaprevir exposure
• Digoxin and dabigatran: Vosevi raises their levels — monitoring required
• Acid reducers (antacids, H2 blockers, proton pump inhibitors): Timing adjustments needed to avoid reducing velpatasvir absorption
• Diabetes medications: Clearing HCV may change blood sugar control — monitor closely and adjust as needed

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Hepatitis B testing required: Every patient must be tested for HBV before starting Vosevi — including people who think they have already cleared HBV
• Prior liver problems: Vosevi is not recommended for people with moderate or severe liver impairment (Child-Pugh B or C) or any history of liver decompensation
• Children: Safety and effectiveness have not been established in pediatric patients
• Older adults (65+): No dose adjustment needed — clinical trial data showed similar safety and effectiveness in older and younger adults
• Kidney disease/dialysis: No dose adjustment needed for any degree of renal impairment, including dialysis
• Pregnancy: There are no adequate human data on safety in pregnancy — discuss risks and benefits with your doctor before taking Vosevi
• Breastfeeding: It is unknown whether Vosevi passes into human breast milk; discuss with your doctor
• All medications and supplements: Tell your doctor everything you take, including herbal products — many interact with Vosevi

There is no specific antidote for a Vosevi overdose. If an overdose occurs, the patient should be monitored for signs of toxicity and treated with supportive care, including monitoring of vital signs and clinical condition. Hemodialysis can remove a significant portion of sofosbuvir's main metabolite (GS-331007), but is unlikely to meaningfully remove velpatasvir or voxilaprevir because they are so strongly bound to blood proteins.

Studies have confirmed that none of the three ingredients in Vosevi — sofosbuvir, velpatasvir, or voxilaprevir — cause meaningful changes to the heart's electrical activity (QTc interval prolongation) at doses well above the recommended amounts. This means Vosevi is not expected to cause the type of heart rhythm abnormality associated with some other medications. However, it is important to note that combining Vosevi with amiodarone — a separate heart drug — can cause a dangerous slowing of the heart rate through a mechanism that is not yet fully understood.

Each of the three components in Vosevi reaches peak blood levels within 2 to 4 hours of an oral dose, and all three are absorbed significantly better when taken with food. Sofosbuvir is mainly cleared through the kidneys (excreted in urine), while velpatasvir and voxilaprevir are primarily cleared through the liver and excreted in feces. Velpatasvir and voxilaprevir are both highly bound to plasma proteins (over 99%), which is why hemodialysis cannot remove them effectively. The body processes voxilaprevir primarily through the CYP3A4 liver enzyme system, which is why drugs that affect this enzyme can significantly alter voxilaprevir levels.

Store below 30 °C (86 °F).