The FDA warned 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. The agency is adding information about serious slowing of the heart rate, known as symptomatic bradycardia, to the Harvoni and Sovaldi labels. The FDA recommends 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.
Harvoni and Sovaldi, drugs that prevent the hepatitis C virus from multiplying in the body, 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. Hepatitis C is usually spread when blood from a person infected with the hepatitis C virus enters the body of someone who is not infected. Today, most people become infected with the Hepatitis C virus by sharing needles or other equipment to inject drugs. Before 1992, when widespread screening of the blood supply began in the United States, Hepatitis C was also commonly spread through blood transfusions and organ transplants.
A 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. The cause of these events could not be determined.
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: (1) short time to symptom onset from starting either Harvoni or Sovaldi in combination with other direct-acting antivirals, (2) resolution of symptoms upon dechallenge, and (3) recurrence of symptoms upon rechallenge
The FDA 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, the 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 two 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: near-fainting or fainting, dizziness or light-headedness, weakness or excessive tiredness, shortness of breath, chest pains or confusion or memory loss.
See the FDA Drug Safety Announcement
See also Medical Law Perspectives, September 2014 Report: Hepatitis: Provider Malpractice and Patient Injury
See also Medical Law Perspectives, May 2013 Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication
See also Medical Law Perspectives, November 2013 Report: Diagnosis and Treatment of Heart Attacks: Liability Issues
See the Medical Law Perspectives October 24, 2014 Blog: Expensive HCV Drug Price Going Up in U.S; Gilead Offers Cheaper Versions in Developing Nations