title: 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.
authors.affiliation: AP-HP, Hôpital Antoine Béclère, Service de Pharmacie, DHU TORINO, Clamart, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Renet
authors.affiliation: AP-HP, Hôpital Antoine Béclère, Service de Pharmacie, DHU TORINO, Clamart, France; INSERM UMR-S 999, DHU TORINO, LabEx LERMIT, Le Plessis-Robinson, France; Univ. Paris-Sud, France.
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Chaumais
authors.affiliation: Univ. Paris-Sud, France; AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, DHU Hepatinov, France; INSERM UMR-S 1193, Villejuif, France.
authors.forename: Teresa
authors.initials: T
authors.lastname: Antonini
authors.affiliation: AP-HP, Hôpital Antoine Béclère, Service de Cardiologie, DHU TORINO, Clamart, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zhao
authors.affiliation: AP-HP, Centre Régional de Pharmacovigilance, Hôpital Henri Mondor, Créteil, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Cardiology department, Charles Nicolle University Hospital, Rouen, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Savoure
authors.affiliation: Univ. Paris-Sud, France; AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, DHU Hepatinov, France; INSERM UMR-S 1193, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Univ. Paris-Sud, France; AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, DHU Hepatinov, France; INSERM UMR-S 1193, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
authors.affiliation: Univ. Paris-Sud, France; AP-HP, Hôpital Antoine Béclère, Service de Cardiologie, DHU TORINO, Clamart, France; INSERM UMR-S 1180, TORINO, LabEx LERMIT, Chatenay Malabry, France. Electronic address: vincent.algalarrondo@u-psud.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Algalarrondo
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D001919:Bradycardia / Q000139:chemically induced* / Q000175:diagnosis; D002219:Carbamates; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014665:Vasodilator Agents; D014633:Valine; C549273:daclatasvir; D000638:Amiodarone; D000069474:Sofosbuvir
keywords: Cardiac Arrest; DAA; Drug Interactions; Side Effect