FDA Warns of Serious Slowing of Heart Rate with Hepatitis C Drugs and Amiodarone

The FDA approved label warning changes for two Gilead Sciences hepatitis C drugs after one person died and nine others had serious reactions when the drugs were coadministered with amiodarone, a drug used to treat irregular heartbeat.

The changes add information about serious and life-threatening cases of symptomatic bradycardia as well as one fatal cardiac arrest, notes a statement from the FDA. It updates the patient package insert and label for both Harvoni (ledipasvir and sofosbuvir) and Sovaldi (sofosbuvir) in the Warnings and Precautions, Adverse Reactions and Drug Interactions section.

“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,” states a safety alert posted on FDA’s website.

The postmarketing cases of symptomatic bradycardia that occurred when amidarone was coadministered with Harvoni include a fatal cardiac arrest and 3 cases requiring pacemakers to regulate the patient heart rhythms, according to the FDA. The bradycardia generally occurred within hours to days but there were also reported cases up to two weeks after treatment for hepatitis C was initiated.

Sovaldi and later Harvoni received FDA approval in the past two years for treatment of chronic hepatitis C, a condition that can cause serious damage to the liver including liver cancer. Both are direct-acting antiviral drugs that have demonstrated high cure rates in clinical trials.

Gilead Sciences, which makes both hepatitis C drugs, also issued a letter to healthcare providers with a warning about the potential for slower than normal heart rate called symptomatic bradycardia when Harvoni or Sovaldi are used with amiodarone. Postmarketing adverse events reports include nine cases of symptomatic bradycardia in patients who took amidarone with either Harvoni, or Sovaldi in combination with another direct acting antiviral, the experimental drug daclatasvir or Olysio.

The FDA also advised patients to seek medical attention right away if they experience signs of symptomatic bradycardia while taking either Harvoni or Sovaldi combined with another direct-acting antiviral drug with amiodarone. Symptoms may include near-fainting, dizziness or light headedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems, according the package insert.

Exactly what caused the events has not been determined but FDA officials said health professionals should not prescribe either Harvoni or Sovaldi combined with another direct-acting antiviral drug with amiodarone. If it is administered because no alternative is available, then cardiac monitoring in an in-patient setting for the first 48 hours is advised. Since the drug amidarone has a long half life, cardiac monitoring is also advised for patients who discontinue the drug just before starting treatment with Sovaldi.

In its letter to health care providers, Gilead warns that risk factors for the development of symptomatic bradycardia in patients taking amidarone may include “coadministration of beta blocker, or those with underlying cardiac comorbidities and/or advanced liver disease.”