Epclusa (velpatasvir/sofosbuvir) is a prescription drug that’s used to treat hepatitis C. Epclusa can cause side effects that range from mild to serious. Examples include headache and skin rash.

Specifically, Epclusa is used in adults and certain children to treat hepatitis C virus (HCV).

The active ingredients in Epclusa are velpatasvir and sofosbuvir. (An active ingredient is what makes a drug work.) The drug comes as a tablet and pellets. You’ll take both forms by mouth.

Keep reading to learn about the common, mild, and serious side effects that Epclusa can cause. For a general overview of the drug, including details about its uses, see this article.

Some people may have mild or serious side effects while taking Epclusa. Some of the more commonly reported side effects may include:

This list doesn’t include all possible side effects. If you’re concerned about your risk for side effects of Epclusa, talk with your doctor.

Some people may experience mild side effects while taking Epclusa. Examples that have been reported include:

Epclusa may cause other mild side effects, too. See the drug’s prescribing information for more details.

In most cases, these side effects should be temporary, and some may be easy to manage. But if you have any symptoms that bother you or don’t go away, talk with your doctor or pharmacist. And do not stop using Epclusa unless your doctor recommends it.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks and reviews side effects of the medication. If you’d like to notify the FDA about a side effect you’ve had with Epclusa, visit MedWatch.

Serious side effects of Epclusa can occur, though they are less common. The list below includes some of the serious side effects that have been reported with Epclusa.

Call your doctor right away if you have serious side effects. Call 911 or your local emergency number if your symptoms feel life threatening or you might be having a medical emergency.

Serious side effects can include:

To learn more about both of these, see the “Side effects explained” section below. And if you have questions about your specific risk for serious side effects of Epclusa, talk with your doctor.

* An allergic reaction to Epclusa is possible. However, this side effect wasn’t reported in studies.
Epclusa has a boxed warning about the risk of this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Epclusa isn’t known to interact with alcohol. However, drinking alcohol may raise your risk for certain side effects of Epclusa. These may include:

Excessive alcohol use can lead to liver problems, such as inflammation (swelling) in the liver, cirrhosis (liver scarring), and liver failure. Hepatitis C can also cause these harmful effects. Therefore, drinking alcohol while being treated for hepatitis C raises your risk for liver problems.

In general, it’s best to avoid alcohol while you’re taking Epclusa to treat hepatitis C. If you drink alcohol and you have questions about how much may be safe for you to drink during Epclusa treatment, talk with your doctor.

Below, find answers to some commonly asked questions about Epclusa.

What will my life be like after Epclusa cures my hepatitis C?

After you’ve finished the 12-week Epclusa treatment, you won’t be cured of hepatitis C right away. You’ll be considered “cured” when the hepatitis C virus (HCV) is no longer detected in your blood. Three months after your treatment is completed, you will have a blood test to see if your treatment was effective.

In studies, Epclusa was successful at curing hepatitis C infection in most people who took the drug. But it’s possible to get a hepatitis C infection again. Having it once doesn’t make you immune to it.

After your infection is cured, avoid certain activities that may raise the risk of getting a hepatitis C infection again. Examples of these activities include:

  • sharing needles with someone who may have HCV
  • getting a tattoo or body piercing with unsanitary equipment
  • having sex without a condom or other barrier method with a partner who may have HCV

After HCV treatment, you may want to take certain steps to help you stay on track toward your health and wellness goals. These might include:

How long do side effects from Epclusa last?

Side effects of Epclusa should end when you stop using the drug. Side effects after treatment weren’t reported in studies of Epclusa. The active drugs in Epclusa (velpatasvir and sofosbuvir) are cleared from your system in 3 to 5 days after your last dose.

It may take your body a while to heal and recover from hepatitis C infection. If you’re experiencing symptoms that bother you or don’t go away, talk with your doctor.

Does Epclusa interact with any other drugs?

Yes, Epclusa can interact with many other medications. Before taking it, be sure to tell your doctor and pharmacist about all prescription and over-the-counter medications you take. Also let them know about any vitamins, herbs, or supplements you’re using. Sharing this information can help prevent potentially harmful interactions.

Some of the more common medications that can interact with Epclusa may include:

This list may not contain all interactions. Talk with your doctor to see if Epclusa could interact with any treatments you take.

It’s also important to note that Epclusa can interact with grapefruit, and with the herb St. John’s wort. You can see this article for more information about Epclusa’s interactions.

Does Epclusa have any long-term side effects?

No, long-term side effects haven’t been reported with Epclusa.

However, hepatitis C can cause long-term harm to your liver, such as cirrhosis (liver scarring). This could last even after your hepatitis C infection is cured. Cirrhosis symptoms may include:

If you have cirrhosis, it’s important to keep up with blood tests and doctor appointments so your doctor can monitor your liver health.

Is depression a side effect of Epclusa?

Yes, depression may be a rare side effect of Epclusa. However, this condition is common in people managing illnesses such as hepatitis C.

If you experience depression, talk with your doctor about ways to manage your mood. It may also be helpful to connect with others who are coping with hepatitis C. For more information, visit help4hep.org or call 877-Help-4-Hep (877-435-7443).

Help is out there

If you or someone you know is in crisis and considering suicide or self-harm, please seek support:

If you’re calling on behalf of someone else, stay with them until help arrives. You may remove weapons or substances that can cause harm if you can do so safely.

If you are not in the same household, stay on the phone with them until help arrives.

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There are some precautions to know about before taking Epclusa.

Boxed warning: Risk of reactivation of hepatitis B virus

Epclusa has a boxed warning about the risk of reactivation of existing hepatitis B virus (HBV). A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

HBV can reactivate (flare up) in people who have both HBV and hepatitis C. This can happen during or after Epclusa treatment.

For more details, see the “Side effects explained” section below.

Other warnings

Epclusa may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before you take Epclusa. Factors to consider include those in the list below.

Slow heart rate when taken with amiodarone. Taking Epclusa with amiodarone can cause bradycardia (slow heart rate). For this reason, doctors typically don’t prescribe these drugs together. Some people who’ve taken Epclusa with amiodarone have needed pacemakers to maintain a regular heart rate. If you take amiodarone, talk with your doctor about treatment options other than Epclusa.

Allergic reaction. If you’ve had an allergic reaction to Epclusa or any of its ingredients, you shouldn’t take it. Ask your doctor what other medications are better options for you.

Use of other medications that interact with Epclusa. Some medications shouldn’t be taken with Epclusa. Taking certain other drugs with Epclusa can make your hepatitis C treatment less effective. Other interactions can raise your risk for side effects. To learn more, see “Does Epclusa interact with any other drugs?” in the “FAQ about Epclusa’s side effects” section above.

Liver problems other than hepatitis C. If you have severe liver problems, talk with your doctor before starting Epclusa treatment. Your doctor might prescribe a drug with Epclusa to help treat your hepatitis C.

Liver transplant. Epclusa has only been studied in people with certain types of hepatitis C virus who’ve had a liver transplant. Be sure to talk with your doctor about whether Epclusa treatment is right for you if you’ve had a liver transplant.

History of kidney disease. Talk with your doctor about any kidney diseases or problems you may have. A drug called ribavirin should not be used in people with a certain level of kidney disease. Ribavirin is sometimes prescribed with Epclusa for hepatitis C treatment. Studies in people with severe kidney disease, including people receiving dialysis, found Epclusa treatment to be safe and effective. But it’s still important to discuss any kidney problems with your doctor.

Pregnancy and breastfeeding while taking Epclusa

It’s not known whether it’s safe to take Epclusa during pregnancy. If you’re pregnant or planning to become pregnant, talk with your doctor before taking Epclusa. If you become pregnant while taking the drug, call your doctor right away.

If you take ribavirin with Epclusa and you or your partner could become pregnant, use birth control throughout your treatment and for 6 months after your last dose of ribavirin. Talk with your doctor to learn more.

It also isn’t known whether it’s safe to take Epclusa while breastfeeding. If you’re breastfeeding or planning to, talk with your doctor about the risks and possible benefits of taking Epclusa.

Learn more about some possible side effects of Epclusa.

Risk of reactivation of hepatitis B virus

Epclusa has a boxed warning about the risk of reactivation of the hepatitis B virus (HBV). A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about drug effects that may be dangerous.

The HBV can reactivate (flare up) in people who have both HBV and hepatitis C.

Infection with HBV causes swelling and damage to your liver. People diagnosed with it usually take medication to relieve the symptoms and manage the infection. But even if all of your symptoms improve with treatment, the virus doesn’t get completely cleared from the body.

The HBV could reactivate during or after your treatment with Epclusa. If this happens, hepatitis B symptoms could return, including:

  • fever
  • joint pain
  • fatigue (low energy)
  • nausea or vomiting
  • decreased appetite
  • abdominal pain
  • light-colored stool
  • jaundice (yellowing of the skin or whites of the eyes)

What might help

Before you start using Epclusa, your doctor will do a blood test to check for HBV. If the test confirms that you have HBV, your doctor will monitor you closely during your Epclusa treatment. They will continue to monitor you after the treatment.

If you notice any hepatitis B symptoms during your treatment, tell your doctor right away. If blood tests show that HBV has returned, your doctor will treat it.


Some people may experience headaches while using Epclusa. This is one of the most commonly reported side effects of the drug. For most people, headaches caused by Epclusa are mild.

What might help

If you experience headaches from Epclusa, several home care strategies may help. A few to try include:

  • Apply a cold or warm compress to the painful area of your head.
  • Massage the painful area.
  • Drink plenty of water each day.
  • Distract yourself with an enjoyable activity or change of scenery, even if this just involves going outside for some fresh air.

Over-the-counter pain medications can be another way to relieve headaches. Talk with your doctor about which are safe for you to take.


Fatigue (low energy) can occur with Epclusa, and this is one of the most commonly reported side effects of the drug. Fatigue caused by Epclusa is usually mild.

What might help

If you have low energy while taking the medication, making some changes to your daily routine may help. Here are some tips you can try:

If you’re still struggling with fatigue while taking Epclusa, talk with your doctor. They may have other suggestions.


Although it’s not common, Epclusa can cause a mild skin rash in some people. This can cause redness or other discoloration of the skin.

What might help

A mild skin rash from Epclusa usually goes away on its own. However, if a rash bothers you or doesn’t go away, consider trying these tips:

  • Take an oatmeal bath to soothe your skin.
  • Apply a fragrance-free anti-itch skin cream or lotion.
  • Check with your doctor or pharmacist whether it’s safe for you to try an over-the-counter hydrocortisone cream.

Try not to scratch the areas of your skin affected by a rash, as this may further irritate the skin and raise your risk for infections. If you have concerns about getting a skin rash from Epclusa, talk with your doctor.

Allergic reaction

Like most drugs, Epclusa can cause an allergic reaction in some people. However, this side effect wasn’t reported in studies of Epclusa.

Symptoms of an allergic reaction can be mild or serious and can include:

  • skin rash
  • itchiness
  • flushing (temporary warmth, redness, or deepening of skin color)
  • swelling under your skin, typically in your eyelids, lips, hands, or feet
  • swelling of your mouth, tongue, or throat, which can make it hard to breathe

What might help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. They may suggest an over-the-counter oral antihistamine, such as diphenhydramine (Benadryl), or a topical product, like hydrocortisone cream.

If your doctor confirms that you had a mild allergic reaction to Epclusa, they’ll decide whether you should continue using it.

If you have symptoms of a severe allergic reaction, such as swelling or difficulty breathing, call 911 or your local emergency number right away. These symptoms could be life threatening and require immediate medical care.

If your doctor confirms you had a serious allergic reaction to Epclusa, they’ll discuss your treatment options with you.

Keeping track of side effects

During your Epclusa treatment, consider keeping notes about any side effects you’re having and share this information with your doctor. This is especially helpful when you first start taking new drugs or using a combination of treatments.

Your side effect notes can include things like:

  • your dosage when you had the side effect
  • how soon after starting that dosage you had the side effect
  • the symptoms
  • how they affected your daily activities
  • what other medications you were taking
  • any other information you feel is important

Keeping notes and sharing them with your doctor will help them learn more about how Epclusa affects you. And your doctor can use this information to adjust your treatment plan if needed.

Epclusa can be an effective treatment for the hepatitis C virus, but it may cause side effects in some people. In most cases, these are usually mild, but serious side effects are possible. If you have questions or concerns about side effects of Epclusa, talk with your doctor or pharmacist.

Questions that you may want to ask your doctor include:

  • Do I have a high risk of side effects from Epclusa?
  • Do any of my medications raise my risk of these side effects?
  • If I’ve had hepatitis or a liver transplant in the past, will I have a higher chance of side effects with Epclusa?

For hepatitis C resources and support, visit help4hep.org or call 877-Help-4-Hep (877-435-7443).

To learn more about Epclusa, see these articles:

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.


If I have a special event coming up, such as a wedding or vacation, could I wait to start my Epclusa treatment so that side effects don’t affect my plans?



In general, starting treatment with Epclusa as soon as possible is the best choice for your health. The hepatitis C virus causes damage to your liver even if you can’t feel it. Over time, this damage can cause cirrhosis (liver scarring).

After cirrhosis develops, it’s not always possible to reverse the damage. That’s why it’s so important to take steps to prevent it. Starting treatment for your hepatitis C early may lower your risk for complications, including cirrhosis and liver cancer.

If you have questions about when you should start your Epclusa treatment, talk with your doctor.

The Healthline Pharmacist TeamAnswers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.
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Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.