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Epclusa (sofosbuvir, velpatasvir)

How is Epclusa used to treat HCV?

Epclusa (sofosbuvir and velpatasvir) is a combination medication indicated for chronic hepatitis C genotype 1, 2, 3, 4, 5, or 6 infection in adults.1 Specifically, Epclusa is indicated for treatment of these genotypes without cirrhosis or with compensated cirrhosis. In addition, Epclusa can be used with ribavirin in individuals with decompensated cirrhosis. Epclusa is a combination of two direct-acting antiviral medications, one being a nucleotide analog NS5B (nonstructural protein 5B) polymerase inhibitor (sofosbuvir) and the other being an HCV NS5A (nonstructural protein 5A) inhibitor (velpatasvir). There is a potential for hepatitis B reactivation in individuals taking Epclusa who have a history of HBV. Prior to taking Epclusa, your provider should test you for HBV and note any history you have with the condition. It is important to also consult the prescribing information for any medications you are also taking in combination with Epclusa, including ribavirin.2

What are the ingredients in Epclusa?

The active ingredients in Epclusa are sofosbuvir and velpatasvir.

How does Epclusa work?

Epclusa is a combination of two direct-acting antivirals, with one active ingredient, sofosbuvir, inhibiting the HCV NS5B RNA-dependent RNA polymerase. Essentially, this inhibitor affects the virus’ ability to replicate, thus, stopping its reproduction. The other active ingredient, velpatasvir acts as an inhibitor of HCV NS5A. NS5A is a nonstructural protein made by the HCV virus that is important to the virus’ growth and replication. The exact mechanism by which NS5A works is unknown. The inhibitor works to eliminate these crucial proteins made by the virus utilized for RNA replication and virion assembly. In theory, by inhibiting these proteins the virus will be prevented from further growth and reproduction. Many direct-acting antivirals work in this manner, targeting proteins and specific steps in the HCV life cycle.

What are the possible side effects of Epclusa?

Multiple clinical trials evaluated the safety and efficacy of Epclusa. The most common side effects of Epclusa are headache and tiredness. When taken with ribavirin, the most common side effects are:

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

This is not an exhaustive list of all potential side effects of Epclusa. Talk to your healthcare provider or pharmacist for further information.

Things to note about Epclusa

There is a possibility of HBV reactivation while taking Epclusa if you have a history of HBV. Your provider will administer a blood test before starting Epclusa to monitor your risk of HBV reactivation. Reactivation of HBV could cause serious liver problems including liver failure or death.

When taking Epclusa there is a chance of developing bradycardia, or abnormally slow heart rate. This risk is especially prevalent in those taking amiodarone, a medicine used to treat heart conditions. Seek immediate help if you experience any of the following related to bradycardia:

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

Before staring Epclusa talk to your provider if you:

  • Have or have had hepatitis B infection
  • Have or have had liver problems other than those related to HCV
  • Have severe kidney problems or are on dialysis
  • Have any other medical conditions
  • Are taking any other medications, supplements, or vitamins
  • Are pregnant or are planning to become pregnant. It is not known if Epclusa will affect an unborn baby.
  • Are breastfeeding or planning to breastfeed. It is not known if Epclusa can pass through breast milk.

Dosing information

Epclusa is a once-daily oral medication. A typical dose of Epclusa contains 400mg of sofosbuvir and 100mg of velpatasvir, and can be taken with or without food. Do not start taking any medications without alerting your provider while on Epclusa. Do not stop taking Epclusa or change the dose of Epclusa without talking to your provider. If you miss a dose, call your healthcare provider or pharmacist. If you take too much Epclusa, seek help at your local emergency room immediately.

Written by: Casey Hribar | Last reviewed: June 2019
  1. Epclusa Prescribing Information. Gilead Sciences, Inc. Feb 2017. Available from:
  2. Copegus (ribavirin) Prescribing Information. Aug 2011. Available from: