Brand Name(s):

  • Zepatier®


[Posted 08/28/2019]

Reason for Announcement:FDA Drug Safety Communication - rare occurrence of serious liver injury with use of hepatitis C medicines in patients with advanced liver disease

Company Name:Multiple

Product Description:Mavyret (glecaprevir and pibrentasvir), Zepatier (elbasvir and grazoprevir), and Vosevi (sofosbuvir, velpatasvir, and voxilaprevir)

Link to Original MedWatch: Web Site

AUDIENCE:Gastroenterology, Infectious Disease, Health Professional, Patient, Pharmacy

ISSUE:FDA has received reports that the use of Mavyret, Zepatier, or Vosevi to treat chronic Hepatitis C in patients with moderate to severe liver impairment has resulted in rare cases of worsening liver function or liver failure.

FDA identified 63 cases of worsening liver function called liver decompensation with regimens Mavyret, Zepatier, and Vosevi to treat Hepatitis C. Some of these cases led to liver failure and death. Most of these patients had moderate to severe liver impairment and should not have been prescribed these medicines.

RECOMMENDATION:Health professionals should continue to prescribe Mavyret, Zepatier, or Vosevi as indicated in the prescribing information for patients without liver impairment or with mild liver impairment (Child-Pugh A).

Mavyret and Zepatier should not be prescribed in patients with any history of prior hepatic decompensation. Vosevi is indicated for patients who have previously failed certain other Hepatitis C Virus treatments and is not recommended in patients with any history of hepatic decompensation unless the benefits outweigh the risk of liver injury, liver failure or death.

Patients should be aware that the risk of serious liver injury is rare. However, patients should contact a health professional right away if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools as these may be signs of liver injury.

For more information visit the FDA website at: Web Siteand Web Site.


You may already be infected with hepatitis B (a virus that infects the liver and may cause severe liver damage) but not have any symptoms of the disease. In this case, taking the combination of elbasvir and grazoprevir may increase the risk that your infection will become more serious or life-threatening and you will develop symptoms. Tell your doctor if you have or ever had a hepatitis B virus infection. Your doctor will order a blood test to see if you have or have ever had hepatitis B infection. Your doctor will also monitor you for signs of hepatitis B infection during and for several months after your treatment. If necessary, your doctor may give you medication to treat this infection before and during your treatment with the combination of elbasvir and grazoprevir. If you experience any of the following symptoms during or after your treatment, call your doctor immediately: excessive tiredness, yellowing of the skin or eyes, loss of appetite, nausea or vomiting, pale stools, stomach pain, or dark urine.

Keep all appointments with your doctor and the laboratory. Your doctor may order certain tests before, during, and after your treatment to check your body's response to the combination of elbasvir and grazoprevir.

Talk to your doctor about the risk(s) of taking the combination of elbasvir and grazoprevir.

WHY is this medicine prescribed?

The combination of elbasvir and grazoprevir is used alone or in combination with ribavirin (Copegus, Rebetol, Ribasphere, Virazole) to treat a certain type of chronic (long-term) hepatitis C infection (swelling of the liver caused by a virus). Elbasvir is in a class of antiviral medications called HCV NS5A inhibitors. It works by stopping the virus that causes hepatitis C from spreading inside the body. Grazoprevir is in a class of medications called protease inhibitors. It works by decreasing the amount of hepatitis C virus (HCV) in the body. It is not known if elbasvir and grazoprevir prevent the spread of hepatitis C to other people.

HOW should this medicine be used?

The combination of elbasvir and grazoprevir comes as a tablet to take by mouth. It is usually taken with or without food once daily for 12 to 16 weeks. Take elbasvir and grazoprevir at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take elbasvir and grazoprevir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take elbasvir and grazoprevir even if you feel well. The length of your treatment depends on your condition, how well you respond to the medication, and whether you experience severe side effects. Do not stop taking elbasvir and grazoprevir without talking to your doctor.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What SPECIAL PRECAUTIONS should I follow?

Before taking elbasvir and grazoprevir,

  • tell your doctor and pharmacist if you are allergic to elbasvir, grazoprevir, any other medications, or any of the ingredients in elbasvir and grazoprevir tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you are taking atazanavir (Reyataz), carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), cyclosporine (Gengraf, Neoral, Sandimmune), darunavir (Prezista, in Prezcobix), efavirenz (Sustiva, in Atripla), lopinavir (in Kaletra), phenytoin (Dilantin, Phenytek), rifampin (Rifadin, Rimactane, in Rifamate, in Rifater), saquinavir (Invirase), St. John's wort, or tipranavir (Aptivus). Your doctor will probably tell you not to take elbasvir and grazoprevir if you are taking one or more of these medications.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: bosentan (Tracleer); cobicistat taken along with elvitegravir, emtricitabine, and tenofovir (Genvoya, Stribild); etravirine (Intelence); medications to treat high cholesterol such as atorvastatin (Lipitor, in Caduet), fluvastatin (Lescol XL), lovastatin (Altoprev), rosuvastatin (Crestor), and simvastatin (Zocor, in Vytorin); ketoconazole; modafinil (Provigil); nafcillin; tacrolimus (Astagraf, Envarsus, Prograf, others); and warfarin (Coumadin, Jantoven). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with elbasvir and grazoprevir, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
  • tell your doctor if you have any type of liver disease other than hepatitis C. Your doctor may tell you not to take elbasvir and grazoprevir.
  • tell your doctor if you have had or are waiting for a liver transplant or if you have human immunodeficiency virus (HIV).
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking elbasvir and grazoprevir, call your doctor.

What SPECIAL DIETARY instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do IF I FORGET to take a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

Elbasvir and grazoprevir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • diarrhea
  • headache
  • difficulty falling asleep or staying asleep

Some side effects can be serious. If you experience any of these symptoms or those in the IMPORTANT WARNING section, call your doctor immediately:

  • weakness

Elbasvir and grazoprevir may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( Web Site ) or by phone (1-800-332-1088).

What should I know about STORAGE and DISPOSAL of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not remove tablets from the packaging until just before use.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. Web Site

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( Web Site) for more information if you do not have access to a take-back program.

What should I do in case of OVERDOSE?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at Web Site. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

What OTHER INFORMATION should I know?

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.

Selected Revisions: September 15, 2019.