AUDIENCE: Infectious Disease, Gastroenterology, Patient
ISSUE: The FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death. HBV reactivation usually occurred within 4-8 weeks.
As a result, FDA is requiring a Boxed Warning, our most prominent warning, about the risk of HBV reactivation to be added to the drug labels of these DAAs directing health care professionals to screen and monitor for HBV in all patients receiving DAA treatment. This warning will also be included in the patient information leaflet or Medication Guides for these medicines.
BACKGROUND: Direct-acting antiviral medicines are used to treat chronic hepatitis C virus (HCV) infection, an infection that can last a lifetime. These medicines reduce the amount of HCV in the body by preventing HCV from multiplying, and in most cases, they cure HCV. Without treatment, HCV can lead to serious liver problems including cirrhosis, liver cancer, and death (see List of Direct-Acting Antivirals in the FDA Drug Safety Communication, available at: http://www.bit.ly/2dz6Fgd).
FDA identified 24 cases of HBV reactivation reported to FDA and from the published literature in HCV/HBV co-infected patients treated with DAAs during the 31 months from November 22, 2013 to July 18, 2016. This number includes only cases submitted to FDA, so there are likely additional cases about which FDA is unaware. Of the cases reported, two patients died and one required a liver transplant. HBV reactivation was not reported as an adverse event in the clinical trials submitted for the DAA approvals because patients with HBV co-infection were excluded from the trials. See the data summary section in the Drug Safety Communication, available at: http://www.bit.ly/2dz6Fgd, for more detailed information.
RECOMMENDATION: Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with DAAs, and monitor patients using blood tests for HBV flare-ups or reactivation during treatment and post-treatment follow-up.
Patients should tell your health care professional if you have a history of hepatitis B infection or other liver problems before being treated for hepatitis C. Do not stop taking your DAA medicine without first talking to your health care professional. Stopping treatment early could result in your virus becoming less responsive to certain hepatitis C medicines. Read the patient information leaflet or Medication Guide that comes with each new prescription because the information may have changed. Contact your health care professional immediately if you develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of serious liver problems.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
The combination of ledipasvir and sofosbuvir is used to treat chronic hepatitis C (an ongoing viral infection that damages the liver). Sofosbuvir is in a class of antiviral medications called nucleotide polymerase inhibitors. It works by decreasing the amount of hepatitis C virus (HCV) in the body. Ledipasvir 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.
How should this medicine be used?
The combination of ledipasvir and sofosbuvir comes as a tablet to take by mouth. It is usually taken with or without food once daily. Take ledipasvir and sofosbuvir 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 ledipasvir and sofosbuvir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Continue to take ledipasvir and sofosbuvir even if you feel well. The length of your treatment (8 to 24 weeks) depends on your condition, how well you respond to the medication, and whether you experience severe side effects. Do not stop taking ledipasvir and sofosbuvir without talking to your doctor.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
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 ledipasvir and sofosbuvir,
- tell your doctor and pharmacist if you are allergic to ledipasvir or sofosbuvir, any other medications, or any of the ingredients in ledipasvir and sofosbuvir tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- 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 (Cordarone, Nexterone, Pacerone), certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), oxcarbazepine (Oxtellar XR, Trileptal), phenobarbital, or phenytoin (Dilantin, Phenytek); digoxin (Lanoxin), medications for heartburn and ulcers; medications for HIV taken together such as efavirenz (Sustiva, in Atripla), emtricitabine (Emtriva, in Atripla) and tenofovir (Viread, in Atripla); elvitegravir (Sustiva, in Atripla), cobicistat (Tybost, in Stribild), emtricitabine (Emtriva, in Stribild), and tenofovir (Viread, in Stribild); tenofovir (Viread), atazanavir (Reyataz) and ritonavir (Norvir); tenofovir (Viread), darunavir (Prezista) and ritonavir (Norvir); tenofovir (Viread), lopinavir (in Kaletra), and ritonavir (Norvir, in Kaletra); or tipranavir (Aptivus) and ritonavir (Norvir); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); rifapentine (Priftin); rosuvastatin (Crestor); simeprevir (Olysio); and sofosbuvir (Solvaldi). Your doctor may tell you not to take ledipasvir and sofosbuvir if you are taking one or more of these medications or may monitor you carefully for side effects.
- if you are taking antacids containing aluminum hydroxide or magnesium hydroxide (Maalox, Mylanta, Tums, others), take them 4 hours before or 4 hours after taking ledipasvir and sofosbuvir.
- tell your doctor what herbal products you are taking, especially St. John's wort. You should not take St. John's wort during your treatment with ledipasvir and sofosbuvir.
- tell your doctor if you have or have ever had kidney disease or any type of liver disease other than hepatitis C.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking ledipasvir and sofosbuvir, 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 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 medication cause?
Ledipasvir and sofosbuvir 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
Ledipasvir and sofosbuvir 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 (http://www.fda.gov/Safety/MedWatch) 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. Do not use if the seal over bottle opening is broken or missing. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).
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 (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to ledipasvir and sofosbuvir.
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.