Patient Death Leads to Warning Label Change for Hepatitis C Drug

Co-administration of amiodarone with simeprevir and sofosbuvir combination is not recommended.

Co-administration of amiodarone with simeprevir and sofosbuvir combination is not recommended.

The FDA today approved changes to the package insert for simeprevir (Olysio), warning against the co-administration of the hepatitis C drug with a heart medication after a patient died last month.

Gilead Sciences announced a label change on March 20, 2015, for its blockbuster hepatitis C drugs, sofosbuvir (Sovaldi) and ledipasvir and sofosbuvir (Harvoni), after a patient suffered a fatal cardiac arrest from taking the drugs in combination with amiodarone.

Gilead sent an e-mail warning to health care professionals indicating 6 cases of symptomatic bradycardia that occurred within the first 24 hours of treatment, with 3 additional cases reported within the first 2 to 12 days of treatment. All of the patients were taking amiodarone, while 3 were using Harvoni, 5 were receiving Sovaldi with daclatasvir, and 1 was taking Sovaldi with Olysio.

In addition to the patient who died, 3 others required pacemaker intervention.

Now, the FDA has approved changes to Olysio’s package insert to include 2 new Warnings and Precautions:

  • Serious symptomatic bradycardia when co-administered with sofosbuvir and amiodarone
  • Gepatic decompensation and hepatic failure.

For pharmacists counseling patients prescribed amiodarone who have no viable alternative hepatitis C treatment options other than Olysio and sofosbuvir, the FDA recommends educating patients about the risk for serious symptomatic bradycardia and then suggesting they receive cardiac monitoring in an inpatient setting for the first 48 hours of co-administration. Following these steps, daily outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

As a result of amiodarone’s long elimination half-life, patients who discontinue amiodarone prior to starting sofosbuvir in combination with Olysio should receive cardiac monitoring. Patients taking Harvoni or Sovaldi in combination with another direct-acting antiviral who need to start amiodarone therapy are recommended to undergo similar monitoring.

The risk factors for symptomatic bradycardia in patients taking amiodarone may include the co-administration of a beta-blocker or underlying cardiac comorbidities and/or advanced liver disease.

There have not been any reports of similar cases occurring in patients receiving the heart drug plus Sovaldi with ribavirin or with pegylated interferon and ribavirin.