Extreme Bradycardia After First Doses of Sofosbuvir and Daclatasvir in Patients Receiving Amiodarone: 2 Cases Including a Rechallenge

Abstract

Sofosbuvir and daclatasvir are direct-acting antiviral drugs used to treat chronic hepatitis C virus infection. In 2015, the Food and Drug Administration and European Medical Agency warned that bradycardia could occur when amiodarone was administered in combination with sofosbuvir, but no case reports had been published. We report extreme bradycardia within 2 hrs after intake of sofosbuvir and daclatasvir by 2 patients receiving amiodarone. The first patient had a cardiac asystole 30 min after receiving sofosbuvir and daclatasvir. Amiodarone, sofosbuvir, and daclatasvir treatment were stopped; after 10 days, the cardiac evaluation was normal and patient was discharged. The second patient was taking amiodarone and propranolol; 2 hrs after receiving sofosbuvir and daclatasvir, he had an extreme sinus node dysfunction (heart rate of 27beats/min). Amiodarone and propranolol were stopped, but the patient continued receiving sofosbuvir and daclatasvir for 3 days and sinus bradycardia was recorded each day, 2 hrs after intake of these drugs. When he stopped taking the drugs, no bradycardia was observed. Administration of sofosbuvir and daclatasvir on day 13 induced bradycardia 2 hrs after intake. However, no bradycardia occurred following a rechallenge 8 weeks after the patient stopped taking amiodarone. These observations indicate that patients treated with amiodarone should be continuously monitored within the first 48 hrs following the initiation of sofosbuvir and daclatasvir.

Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis

“…This systematic review overviewed cardiac events, which are of concerning in patients treated with sofosbuvir according to the last reports 3,7 .…”

“…Second, there are events occurring in patients without amiodarone 7 . Third, the causality relationship between sofosbuvir (and amiodarone) and the onset of bradycardia in the case reports and case-series is methodologically doubtful 3,7 . Thus, a reasonable uncertainty exists regarding sofosbuvir and the risk of cardiac/arrhythmic/bradycardic events.…”

“…2 In this update, bradycardia events were said to occur generally within hours to days, and a safety recommendation was made for patients who receive amiodarone to undergo cardiac monitoring for 48 hours after first administration. 2 These warnings were based on anecdotal case reports or small case series 3,4 . However, uncertainty exists regarding the pathophysiological mechanisms underlying this putative association between sofosbuvir and cardiac/bradycardia events.…”

Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

“…[35] Another observation reported extreme bradycardia after first doses of sofosbuvir and daclatasvir and indicated that patients treated with amiodarone should be continuously monitored within the first 48 hours following the initiation of therapy with these DAAs. [36] Direct acting antiviral-related pharmacokinetic drug interactions Food increases the absorption of the all-oral paritaprevir/ ritonavir/ombitasvir plus dasabuvir, boceprevir and simeprevir, and so, it is recommended to take these medications with food. Fatty meals increase the absorption of telaprevir and asunaprevir.…”

Treatment of Chronic Hepatitis C: Efficacy, Side Effects and Complications

“…The combination of ethinylestradiol with glecaprevir/pibrentasvir and velpatasvir/sofosbuvir + voxilaprevir can lead to ALT elevation and is therefore contraindicated [56, 59]. Last but not least DDI with the following medications need also to be kept in mind when treating with DAA: (1) amiodarone, (2) St. John’s wort, (3) rifampicin, (4) antiepileptic drugs, (5) antiretroviral medications and (6) psychotropic drugs [50, 64, 65]. …”