Epclusa (sofosbuvir, velpatasvir)

Reviewed by: HU Medical Review Board | Last reviewed: May 2023

Epclusa (sofosbuvir and velpatasvir) is a combination drug used to treat chronic hepatitis C genotype 1, 2, 3, 4, 5, or 6 infection in adults, as well as children age 3 and older. Epclusa is approved to treat these genotypes without cirrhosis or with compensated cirrhosis.1 For adults and children with decompensated cirrhosis, Epclusa can be used with ribavirin.1,2

What are the ingredients in Epclusa?

The active ingredients in Epclusa are sofosbuvir and velpatasvir.1

How does Epclusa work?

Epclusa is a combination of 2 direct-acting antivirals. The active ingredients work in different ways:1

  • Sofosbuvir blocks the HCV NS5B RNA-dependent RNA polymerase. This affects the virus’ ability to replicate, stopping its growth.
  • Velpatasvir blocks HCV NS5A. This is a protein made by the HCV virus that is important to its growth and reproduction. The exact ways NS5A works are unknown. The inhibitor eliminates NS5A, which the virus uses to replicate RNA and assemble virions.

By blocking these proteins, Epclusa prevents HCV from further growth and reproduction. Many direct-acting antivirals work in this way by targeting proteins and specific steps in the HCV life cycle.1

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What are the possible side effects?

The most common side effects of Epclusa are headache and tiredness. When taken with ribavirin, the most common side effects include:1,2

  • Headache
  • Tiredness
  • Anemia (low red blood cell count)
  • Nausea
  • Insomnia
  • Diarrhea

Epclusa has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because if you have a history of hepatitis B virus, Epclusa may cause HBV reactivation. Your doctor will give you a blood test before starting Epclusa to monitor your risk of HBV reactivation. Reactivation could cause serious liver problems including liver failure or death.1

These are not all the possible side effects of Epclusa. Talk to your doctor about what to expect when taking Epclusa. You also should call your doctor if you have any changes that concern you when taking Epclusa.

Things to know about Epclusa

Epclusa may cause an abnormally slow heart rate (bradycardia). This risk is higher in people taking amiodarone to treat heart conditions. Call 9-1-1- if you have signs of bradycardia, including:1

  • Weakness
  • Near-fainting or fainting
  • Chest pain
  • Dizziness
  • Confusion
  • Shortness of breath
  • Memory problems
  • Tiredness

Before starting Epclusa, tell your doctor if you have:1

  • Hepatitis B infection now or in the past
  • Liver problems other than those related to HCV now or in the past
  • Severe kidney problems or are on dialysis
  • HIV-1 infection

Epclusa plus ribavirin can harm an unborn baby. If you or your partner can become pregnant, you should use birth control during treatment and for some time after the last dose of Epclusa. You should also not breastfeed during treatment with Epclusa and for some time after the last dose. Talk to your doctor about your options for birth control and breastfeeding while taking Epclusa.1

Before beginning treatment for hepatitis C, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.

For more information, read the full prescribing information of Epclusa.