[Posted 03/24/2015] ISSUE: FDA is warning that serious slowing of the heart rate can occur when the antiarrhythmic drug amiodarone is taken together with either the hepatitis C drug ledipasvir/sofosbuvir (Harvoni) or with sofosbuvir (Sovaldi) taken in combination with another direct acting antiviral for the treatment of hepatitis C infection. FDA is adding information about serious slowing of the heart rate, known as symptomatic bradycardia, to the ledipasvir/sofosbuvir and sofosbuvir labels. FDA is recommending that health care professionals should not prescribe either ledipasvir/sofosbuvir or sofosbuvir combined with another direct acting antiviral, such as the investigational drug daclatasvir or simeprevir (Olysio), with amiodarone.
FDA review of submitted postmarketing adverse event reports found that patients can develop a serious and life-threatening symptomatic bradycardia when either ledipasvir/sofosbuvir or sofosbuvir combined with another direct-acting antiviral is taken together with amiodarone. The reports included the death of one patient due to cardiac arrest and three patients requiring placement of a pacemaker to regulate their heart rhythms. The other patients recovered after discontinuing either the hepatitis C drugs or amiodarone, or both (see Data Summary). The cause of these events could not be determined. FDA will continue to monitor ledipasvir/sofosbuvir and sofosbuvir for risks of serious symptomatic bradycardia and further investigate the reason why the use of amiodarone with these hepatitis C drugs led to the heart-related events.
BACKGROUND: For a Data Summary and additional recommendations for health professionals and patients, see the FDA Drug Safety Communication at: http://www.fda.gov/Drugs/DrugSafety/ucm439484.htm.
RECOMMENDATION: Health care professionals should not prescribe either ledipasvir/sofosbuvir or sofosbuvir combined with another direct-acting antiviral drug with amiodarone. However, in cases where alternative treatment options are unavailable, FDA recommends heart monitoring in an inpatient hospital setting for the first 48 hours. Subsequently, monitoring in a doctor’s office or self-monitoring of the heart rate should be done every day through at least the first 2 weeks of treatment.
Due to the long half-life of amiodarone, patients discontinuing amiodarone just prior to starting ledipasvir/sofosbuvir, or sofosbuvir in combination with another direct-acting antiviral, should also undergo similar cardiac monitoring as outlined above.
Patients taking either ledipasvir/sofosbuvir or sofosbuvir combined with another direct-acting antiviral drug with amiodarone should seek medical attention right away if they experience signs or symptoms of symptomatic bradycardia such as:
- Near-fainting or fainting
- Dizziness or light-headedness
- Excessive tiredness
- Shortness of breath
- Chest pains
- Confusion or memory 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?
Simeprevir is used along with ribavirin (Copegus, Rebetol) and peginterferon alfa (Pegasys) to treat chronic hepatitis C (an ongoing viral infection that damages the liver). Simeprevir is in a class of medications called protease inhibitors. It works by decreasing the amount of hepatitis C virus (HCV) in the body. Simeprevir may not prevent the spread of hepatitis C to other people.
How should this medicine be used?
Simeprevir comes as a capsule to take by mouth. It is usually taken with food once a day. Take simeprevir 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 simeprevir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the capsules whole; do not split, chew, or crush them.
You will take simeprevir with peginterferon alfa and ribavirin for 12 weeks. Then you will stop taking simeprevir and will take peginterferon and ribavirin for an additional 12 or 36 weeks. The length of your treatment depends on whether you have received prior treatment for hepatitis C, how you responded to prior treatment, how you respond to the medications, and whether you experience severe side effects. Continue to take simeprevir, peginterferon alfa, and ribavirin as long as they are prescribed by your doctor. Do not stop taking any of these medications without talking to your doctor even if you are feeling well.
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 simeprevir,
- tell your doctor and pharmacist if you are allergic to simeprevir, sulfa drugs, any other medications, or any of the ingredients in simeprevir capsules. Ask your pharmacist or check the manufacturer's patient information for a list of the ingredients.
- tell your doctor if you are taking any of the following medications: antifungal medications such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), or voriconazole (Vfend); certain medications for HIV such as atazanavir (Reyataz), darunavir (Prezista), delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir (Kaletra), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir), saquinavir (Invirase), or tipranavir (Aptivus); certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), oxcarbazepine (Trileptal), phenobarbital, or phenytoin (Dilantin, Phenytek); cisapride (Propulsid) (not available in the U.S.); clarithromycin (Biaxin, in Prevpac); dexamethasone; erythromycin (E.E.S., Eryc, Ery-tab, others); medication containing cobicistat (Stribild); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); rifapentine (Priftin); or telithromycin (Ketek). Your doctor will probably tell you not to take simeprevir if you are taking one or more of these medications. Also tell your doctor if you have ever taken boceprevir (Victrelis) or telaprevir (Incivek).
- 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: calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor XR, Tiazac), felodipine (Plendil), nicardipine (Cardene), nifedipine (Adalat, Procardia), nisoldipine (Sular), or verapamil (Calan, Covera HS, Isoptin); certain medications for high cholesterol such as atorvastatin (Lipitor, in Caduet), lovastatin (Altoprev, Mevacor, in Advicor), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), or simvastatin (Zocor, in Simcor, in Vytorin); certain medications for irregular heartbeat such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), flecainide (Tambocor), mexiletine (Mexitil), propafenone (Rhythmol SR), or quinidine; cyclosporine (Neoral, Sandimmune); digoxin (Lanoxin); midazolam taken by mouth; sildenafil (only Revatio brand used for lung disease); sirolimus (Rapamune); tacrolimus (Prograf); tadalafil (only Adcirca brand used for lung disease); triazolam (Halcion) taken by mouth; or warfarin (Coumadin). 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 simeprevir, 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 what herbal products you are taking, especially milk thistle or St. John's wort. You should not take milk thistle or St. John's wort during your treatment with simeprevir.
- tell your doctor if you have had a liver transplant, if you are receiving phototherapy, if you are of East Asian descent, and if you have or have ever had any type of liver disease other than hepatitis C.
- tell your doctor if you are pregnant, plan to become pregnant, or can possibly become pregnant. If you are male, tell your doctor if your partner is pregnant, plans to become pregnant, or can possibly become pregnant. Simeprevir must be taken with ribavirin which can seriously harm the fetus. You must use two methods of birth control to prevent pregnancy in you or your partner during treatment with these medications and for 6 months after your treatment. Talk to your doctor about which methods you should use; hormonal contraceptives (birth control pills, patches, implants, rings, or injections) may not work well in women who are taking these medications. You or your partner must be tested for pregnancy prior to treatment, every month during your treatment, and for 6 months after your treatment. If you or your partner becomes pregnant while taking these medications, call your doctor immediately.
- tell your doctor if you are breast-feeding.
- plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, a hat, and sunscreen. Also avoid the use of tanning beds, sunlamps, or other types of light therapy during your treatment. Simeprevir may make your skin sensitive to sunlight. Call your doctor right away if you experience a severe sunburn or burning, redness, swelling, or blisters on your skin.
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 with food as soon as you remember it. However, if it is less than 12 hours before the scheduled time for your 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?
Simeprevir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- muscle pain
Some side effects can be serious. If you experience any of these symptoms or those listed in the SPECIAL PRECAUTIONS section, call your doctor immediately or get emergency medical treatment:
- difficulty breathing
- mouth sores or ulcers
- red or swollen eyes ("pink eye")
Simeprevir 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 [at 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. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
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 will order certain lab tests to check your body's response to simeprevir.
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.