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
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 sofosbuvir, velpatasvir, and voxilaprevir 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 sofosbuvir, velpatasvir, and voxilaprevir. 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 will order certain tests before, during, and after your treatment to check your body's response to the combination of sofosbuvir, velpatasvir, and voxilaprevir.
Talk to your doctor about the risk(s) of taking sofosbuvir, velpatasvir, and voxilaprevir.
WHY is this medicine prescribed?
The combination of sofosbuvir, velpatasvir, and voxilaprevir is used to treat chronic (long-term) hepatitis C infection (swelling of the liver caused by a virus) in adults who have already received other HCV treatments. Sofosbuvir is a non-nucleoside NS5B polymerase inhibitor. It works by decreasing the amount of hepatitis C virus in the body. Velpatasvir is a hepatitis C virus (HCV) NS5A inhibitor. It works by stopping the virus that causes hepatitis C from spreading inside the body. Voxilaprevir is in a class of medications called HCV NS3/4A protease inhibitors. It works by decreasing the amount of HCV in the body.
HOW should this medicine be used?
The combination of sofosbuvir, velpatasvir, and voxilaprevir comes as a tablet to take by mouth. It is usually taken with food once daily for 12 weeks. Take sofosbuvir, velpatasvir, and voxilaprevir 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 sofosbuvir, velpatasvir, and voxilaprevir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Continue to take sofosbuvir, velpatasvir, and voxilaprevir 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 sofosbuvir, velpatasvir, and voxilaprevir 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 sofosbuvir, velpatasvir, and voxilaprevir,
- tell your doctor and pharmacist if you are allergic to sofosbuvir, velpatasvir, and voxilaprevir, any other medications, or any of the ingredients in the combination of sofosbuvir, velpatasvir, and voxilaprevir tablets. Ask your pharmacist for a list of the ingredients.
- tell your doctor if you are taking rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). Your doctor will probably tell you not to take sofosbuvir, velpatasvir, and voxilaprevir if you are taking rifampin.
- 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: amiodarone (Nexterone, Pacerone); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor, in Caduet), fluvastatin (Lescol), lovastatin (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), simvastatin (Flolipid, Zocor, in Vytorin); cyclosporine (Gengraf, Neoral, Sandimmune); dabigatran (Pradaxa); digoxin (Lanoxin); H2 blockers such as cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac); certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) including atazanavir (Reyataz), efavirenz (Sustiva, in Atripla), lopinavir (in Kaletra), tenofovir (Viread, in Atripla, Complera, Stribild, Truvada, others), and tipranavir (Aptivus) when taken with ritonavir (Norvir); imatinib (Gleevec); irinotecan (Camptosar); lapatinib (Tykerb); methotrexate (Otrexup, Rasuvo, Xatmep); mitoxantrone; rifabutin (Mycobutin); rifapentine (Priftin); certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), oxcarbazepine (Trileptal), phenobarbital, or phenytoin (Dilantin, Phenytek); sulfasalazine (Azulfidine); topotecan (Hycamtin); 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 sofosbuvir and velpatasvir, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- if you are taking aluminum or magnesium containing antacids (Maalox, Mylanta), take them 4 hours before or 4 hours after sofosbuvir, velpatasvir, and voxilaprevir.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you have or have ever had any type of liver disease other than hepatitis C or kidney disease or if you are currently on dialysis.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking sofosbuvir, velpatasvir, and voxilaprevir, 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 with food 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?
Sofosbuvir, velpatasvir, and voxilaprevir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- difficulty falling asleep or staying asleep
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:
Sofosbuvir, velpatasvir, and voxilaprevir 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).
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.