Liverpool HEP Interactions

Do Not Coadminister

Sofosbuvir/Velpatasvir

Amiodarone

Summary:

Coadministration has not been studied and is not recommended. Coadministration of amiodarone and sofosbuvir combined with another direct acting antiviral such as velpatasvir may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. The effect on amiodarone, sofosbuvir, and velpatasvir concentrations unknown. If coadministration is required as no other alternative is available, cardiac monitoring is recommended.

Description:

In the postmarketing setting, cases of severe bradycardia and heart block have been observed when SOF-containing products are used in combination with amiodarone. Interaction not studied. Effect on amiodarone, velpatasvir, and sofosbuvir concentrations unknown but may result in serious symptomatic bradycardia. Use only if no other alternative is available. Close monitoring is recommended if this medicinal product is administered with Epclusa. Life-threatening cases of severe bradycardia and heart block have been observed when sofosbuvir-containing regimens are used in combination with amiodarone. Bradycardia has generally occurred within hours to days, but cases with a longer time to onset have been observed mostly up to 2 weeks after initiating HCV treatment. Amiodarone should only be used in patients on Epclusa when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated. Should concomitant use of amiodarone be considered necessary, it is recommended that patients undergo cardiac monitoring in an in-patient setting for the first 48 hours of coadministration, 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. Due to the long half-life of amiodarone, cardiac monitoring as outlined above should also be carried out for patients should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on Epclusa. All patients with concurrent or recent use of amiodarone should be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.

Epclusa Summary of Product Characteristics, Gilead Sciences Ltd., March 2021.

Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with a sofosbuvir-containing regimen. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir-containing regimen (HARVONI® [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 effect is unknown. Coadministration of amiodarone with sofosbuvir/velpatasvir is not recommended. For patients taking amiodarone who have no other alternative viable treatment options and who will be coadministered sofosbuvir/velpatasvir: Counsel patients about the risk of symptomatic bradycardia. Cardiac monitoring in an in-patient 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/velpatasvir who need to start amiodarone therapy due to no other alternative viable treatment options should undergo similar cardiac monitoring as outlined above. Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting sofosbuvir/velpatasvir 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 pains, confusion, or memory problems. Interaction not studied. Effect on amiodarone, velpatasvir, and sofosbuvir concentrations unknown.

Epclusa Prescribing Information, Gilead Science Inc., June 2021.

A case was reported of a man in his 70s who presented to the Emergency Department with transient loss of consciousness. He was taking amiodarone for atrial fibrillation and had prostatic hyperplasia and chronic hepatitis C, for which he had been started on sofosbuvir + ribavirin, a day prior to presentation. On examination, his only abnormal investigation was bradycardia, with a heart rate of 38 bpm. He was admitted for observation, and sofosbuvir, ribavirin, and amiodarone were stopped, after which he had no further episodes of bradycardia and was discharged on day nine. The authors hypothesise a drug interaction between amiodarone and sofosbuvir due to P-gp inhibition by amiodarone causing an increase in sofosbuvir exposure, and build-up of sofosbuvir in cardiomyocytes. The authors note two similar case reports in the literature.

Severe Bradycardia Induced by Sofosbuvir and Amiodarone which Resolved after the Discontinuation of Both Drugs. Monoe C, Shimizu H, Kitaguchi K, et al. Case Reports Intern Med,2020;59(20):2619-2622.

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