March 23rd, 2015

Dangerous Interaction: New Hepatitis C Drug and Old Arrhythmia Drug

Late last week Gilead Sciences issued a warning about a rare but potentially fatal interaction between its stellar new hepatitis C drug sofosbuvir and amiodarone, a potent but tricky antiarrhythmic agent. Sofosbuvir is marketed as Sovaldi and, in combination with another antiviral agent, as Harvoni. Amiodarone is a class III antiarrhythmic with a number of different side effects and an extremely long half-life. Its use is generally reserved for difficult cases.

The company reported nine cases of symptomatic bradycardia. One patient died of a cardiac arrest and three patients received a pacemaker. Six cases occurred during the first day of treatment with sofosbuvir. Several patients were taking additional antiviral agents and seven patients were also taking a beta blocker. The company said the mechanism of action for the interaction is unknown.

Paul Sax, an infectious diseases specialist at the Brigham and Women’s Hospital, said that “this is a very uncommon drug-drug interaction. In the short-term, I anticipate it will have almost no effect on prescribing practices.”

A Baird analyst also said it is unlikely that the news will have a significant impact on the use of sofosbuvir. He estimated that there were about 1,000 patients taking amiodarone among the more than 200,000 patients who have received sofosbuvir so far. He noted that the baseline bradycardia risk for amiodarone by itself is about 2.5% per year.

The company said that the co-administration of sofosbuvir and amiodarone is not recommended. In cases where there is no alternative to co-adminstration, Gilead recommends close cardiac monitoring of patients, including monitoring in the hospital for the first 48 hours of treatment.

One Response to “Dangerous Interaction: New Hepatitis C Drug and Old Arrhythmia Drug”

  1. Tariq Ahmad, MD, MPH says:

    There appear to be further reports that these adverse effects might be occuring in other novel Hep C therapies. Per the FDA release they have seen cardiac issues in sofosbuvir (Sovaldi, Gilead Sciences), Daklinza, Briston-Myers Squibb), and simeprevir (Olysio, Johnson & Johnson).

    We reported the only case study of severe cardiac dysfunction in 14 patients with one of these novel therapies developed by BMS:

    Prior preclinical studies had shown cardiac dysfunction in at least one agents in this group of therapies (Ciluprevir developed by Boehringer Ingelheim).

    We noted that HF appeared to occur in patients with cardiac risk factors. Of note, patients with significant cardiac disease were generally excluded from the trials that led to approval of these medications.

    We surmised:
    “To date, we are unaware of unexpected cardiac events in patients treated with other investigational therapies with a similar chemical/molecular structure to BMS-986094. Nevertheless, ongoing studies are limited in size and, without the appropriate monitoring for cardiac safety signals, an agent presumed to have less cardiotoxicity
    could potentially yield increased cardiac dysfunction when used in a larger population of patients—particularly in those with underlying heart disease or who are older and at risk for cardiovascular disease. Notably, 75% of U.S. patients with HCV were born between 1945 and
    1965, which is the demographic with the highest prevalence of cardiovascular disease.

    It is difficult to say without looking at the data, but I wonder if betablockers and amiodarone are acting as signals for underlying cardiac dysfunction that is exacerbated by novel Hep C agents.