The makers of the hepatitis C drugs Harvoni and Sovaldi are warning that users may face an increased risk of heart problems or death if they combine the medications with the heart drug amiodarone and another direct acting antiviral medication.
Gilead Inc. sent out a “Dear Health Care Provider” letter (DOCX) on March 20, warning about at least nine reported cases of bradycardia, including one fatal cardiac arrest, linked to the combined use of the hepatitis C and heart drugs. In addition to the one patient death, three of the patients required pacemakers.
According to the Gilead letter, six of the cases involving symptomatic bradycardia, which causes abnormally slow heartbeats, occurred within the first 24 hours of treatment. The other three cases happened within the first two to 12 days. In three of the incidents, the patients were taking Harvoni in combination with amiodarone. Five of the cases involved a combination of Sovaldi with the hepatitis C drug Bristol-Myers Squibb drug Daklinza and amiodarone; and there was one case involving a combination of Sovaldi, amiodarone and Johnson & Johnson’s hepatitis C drug Olysio.
The warning indicates that Gilead believes the combinations to avoid are Harvoni together with amiodarone, and Solvadi together with amiodarone and other hepatitis C drugs belonging to a class of medications known as direct acting antiviral (DAA) drugs.
“Coadministration of amiodarone with either Harvoni or with Sovaldi in combination with another DAA is not recommended,” the letter warns. “The mechanism of the potential interaction between amiodarone and Harvoni, or Sovaldi in combination with another DAA is unknonw. Because the number of patients taking amiodarone who have been exposed to Harvoni or Sovaldi in combination with another DAA is unknown, it is not possible to estimate the incidence of occurrence of these events.”
Both Harvoni and Sovaldi are blockbuster drugs for Gilead, making up more than half the company’s annual revenue. Harvoni raked in $2.11 billion in sales in the last quarter of 2014 alone, and Sovaldi generated $1.73 billion in sales in the same quarter.
The drugs are extremely expensive, with a standard two-week Sovaldi treatment course costing $84,000.
In a report published on January 28, the Institute for Safe Medication Practices (ISMP) warned that Gilead has a poor track record of filing complete adverse event reports to the FDA in cases involving Sovaldi (sofosbuvir). According to the report, only 39% of Sovaldi incident reports were reasonably complete.
“With limited pre-approval testing and weak adverse event reporting, the safety profile of sofosbuvir remains uncertain,” the ISMP warned at the time.