Warning against use of new hepatitis C drugs with amiodarone

Safety warnings | messages in brief | 28/04/2015

The Federal Office informs about recommendations of the European Medicines Agency EMA regarding a restriction of the use of new hepatitis C drugs together with amiodarone.

Measures at EU level

The European Medicines Agency (EMA) has confirmed that there is an increased risk of severe bradycardia (abnormally slowed heartbeat) or cardiac conduction disorders if hepatitis C patients receiving therapy with the combination drug Harvoni (sofosbuvir and ledipasvir) or Sovaldi (sofosbuvir) together with Daklinza (daclatasvir) also use the antiarrhythmic drug amiodarone, which is used to treat cardiac arrhythmias. To minimize the risk, it is recommended that amiodarone be used only in those patients taking these new hepatitis C drugs who cannot tolerate other antiarrhythmic drugs. In any case, if amiodarone use cannot be avoided, patients must be monitored closely. Because of the long residence time of amiodarone in the body, this monitoring must be performed even if it has been several months since amiodarone was taken. The possible mechanism behind these interactions is currently unknown. However, a causal relationship is considered possible. A total of eight such reports have been received to date. Of these, one case was fatal. In six patients, the bradycardia occurred within 24 hours of starting hepatitis C treatment, in the other two patients within two to twelve days.

Situation in Austria

The following drug products are approved in Austria:

Harvoni 90 mg/400 mg film-coated tablets.

Sovaldi 400 mg film-coated tablets

Daklinza 30 mg film-coated tablets

Recommendations of the BASG

Recommendations for prescribers:

Severe cardiac bradycardia or conduction disturbances have been reported when hepatitis C patients on therapy with Harvoni or on Sovaldi along with Daklinza are also taking the antiarrhythmic drug amiodarone concomitantly. Of eight cases reported through April 2015, one was fatal and two others required the use of pacemakers.
In six patients, bradycardia occurred within 24 hours of starting hepatitis C treatment, and in the other two within two to 12 days.

Attempts to re-administer (re-challenge) the combination of these drugs resulted in recurrence of symptoms in 2 cases. New symptoms were still observed 8 days after discontinuation of amiodarone therapy.
Amiodarone should be used only in those patients treated with Harvoni, or Sovaldi together with Daklinza, when other antiarrhythmic drugs are not tolerated or are contraindicated.

If amiodarone administration cannot be avoided, patients must be monitored closely, especially during the first weeks of treatment. In patients at high risk for bradycardia, monitoring in an appropriate clinical setting for 48 hours after initiation of therapy is recommended.

Because of the long half-life of amiodarone, monitoring should be performed even if the patient has been taking amiodarone for several months.

Patients receiving this combination should be advised of the possible symptoms of bradycardia. They should also be instructed to seek prompt medical attention if they observe such symptoms. Symptoms of bradycardia, as well as cardiac conduction disturbance, include slow heartbeat, lightheadedness, feeling of weakness, unusual fatigue, shortness of breath, and chest pain.

Recommendations for patients:

Some cases of severely slowed heartbeat or cardiac electrical conduction disturbances have been reported when patients on hepatitis C therapy with either Harvoni or Sovaldi and Daklinza together, also received a concomitant drug containing the active ingredient amidarone for cardiac arrhythmias.

Most cases occurred within 24 hours of starting hepatitis C treatment, but some occurred up to 12 days later. Two patients required treatment with a pacemaker, and one patient died.

Patients being treated with Harvoni or Sovaldi along with Daklinza should not take amiodarone unless there is no other suitable alternative.

If amiodarone administration cannot be avoided, patients must be monitored closely by their physician. This may require monitoring in an inpatient facility for a period of 48 hours after initiation of therapy.

Because amiodarone has a very long residence time in the body, monitoring may be necessary even if it has been several months since the last dose of amiodarone.

It is advised to watch for symptoms such as slow heartbeat, lightheadedness, feeling of weakness, unusual fatigue, shortness of breath, and chest pain. If any of these symptoms are present, medical attention must be sought immediately.