[3-24-2015] The U.S. Food and Drug Administration (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 Harvoni (ledipasvir/sofosbuvir) or with Sovaldi (sofosbuvir) taken in combination with another direct acting antiviral for the treatment of hepatitis C infection. We are adding information about serious slowing of the heart rate, known as symptomatic bradycardia, to the Harvoni and Sovaldi labels. We are recommending that health care professionals should not prescribe either Harvoni or Sovaldi combined with another direct acting antiviral, such as the investigational drug daclatasvir or Olysio (simeprevir), with amiodarone. Patients should not stop taking any of their medicines without first talking to their health care professionals.
Harvoni and Sovaldi are used to treat chronic hepatitis C, a viral infection that can last a lifetime and lead to serious liver problems, including cirrhosis or liver cancer. These drugs reduce the amount of hepatitis C virus in the body by preventing the virus from multiplying within the body.
Our review of submitted postmarketing adverse event reports found that patients can develop a serious and life-threatening symptomatic bradycardia when either Harvoni or Sovaldi 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. Information about this serious risk of bradycardia has been added to the Warnings and Precautions, Drug Interactions, and Postmarketing Experience sections of the drug labels for Harvoni and Sovaldi. We will continue to monitor Harvoni and Sovaldi 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.
Health care professionals should not prescribe either Harvoni or Sovaldi combined with another direct-acting antiviral drug with amiodarone. However, in cases where alternative treatment options are unavailable, we recommend 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.
Patients taking either Harvoni or Sovaldi 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:
We urge health care professionals and patients to report side effects involving Harvoni, Sovaldi, or amiodarone to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.
FDA reviewed post-marketing reports of bradycardia submitted by the manufacturer Gilead Sciences and from the FDA Adverse Event Reporting System (FAERS) database. Reports included the use of amiodarone with either Harvoni (ledipasvir/sofosbuvir) or Sovaldi (sofosbuvir) in combination with other direct-acting antivirals, such as investigational drug daclatasvir or Olysio (simeprevir). Based on the reports, the concomitant administration of amiodarone with Harvoni, or with Sovaldi in combination with another direct-acting antiviral, may result in a severe or life-threatening bradycardia.
The postmarketing reports of serious symptomatic bradycardia are difficult to interpret because they occurred in patients with underlying cardiac disease, concomitant beta blocker therapy, and/or advanced liver disease. However, the following characteristics of these postmarketing cases suggest a causal association:
The mechanism of these events due to the coadministration of amiodarone with either Harvoni or with Sovaldi in combination with another direct-acting antiviral is unknown.
Nine patients receiving amiodarone reported symptomatic bradycardia during treatment with either Harvoni or with Sovaldi in combination with another direct-acting antiviral, such as daclatasvir, an investigational direct acting antiviral, or Olysio (simeprevir). Seven of the 9 patients were also receiving a beta blocker.
Six of the 9 patients experienced symptomatic bradycardia within the first 24 hours, and the remaining 3 patients experienced it within the first 2 to12 days following hepatitis C treatment initiation. One patient had a fatal outcome due to cardiac arrest, and 3 patients required pacemaker intervention.
In 3 of the patients, rechallenge with hepatitis C treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia. In one patient, discontinuation of amiodarone followed by rechallenge with hepatitis C treatment after 8 weeks did not result in recurrent bradycardia.
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Page Last Updated: 03/24/2015
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