Cases of severe bradycardia and heart block have been observed when Daklinza is used in combination with sofosbuvir and concomitant amiodarone with or without other drugs that lower heart rate. The mechanism is not established. The concomitant use of amiodarone was limited through the clinical development of sofosbuvir plus direct-acting antivirals (DAAs). Cases are potentially life threatening, therefore amiodarone should only be used in patients on Daklinza and sofosbuvir when other alternative antiarrhythmic treatments are not tolerated or are contraindicated. Should concomitant use of amiodarone be considered necessary it is recommended that patients are closely monitored when initiating Daklinza in combination with sofosbuvir. Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for 48 hours in an appropriate clinical setting. Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on Daklinza in combination with sofosbuvir. All patients receiving Daklinza and sofosbuvir in combination with amiodarone with or without other drugs that lower heart rate should also be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.

Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone was coadministered with a sofosbuvir-containing regimen. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (ledipasvir/sofosbuvir). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this bradycardia effect is unknown. Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options and who will be coadministered DAKLINZA and sofosbuvir: Counsel patients about the risk of serious symptomatic bradycardia. Cardiac monitoring in an inpatient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Patients who are taking sofosbuvir in combination with Daklinza who need to start amiodarone therapy due to no other alternative treatment options should undergo similar cardiac monitoring as outlined above. Due to amiodarone’s long elimination half-life, patients discontinuing amiodarone just prior to starting sofosbuvir in combination with Daklinza should also undergo similar cardiac monitoring as outlined above. Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, or memory problems.