Amiodarone and Concurrent Antiretroviral Therapy: A Case Report and Review of the Literature

Abstract

Therapy for HIV often can make pharmacologic management of comorbidities challenging since many antiretroviral agents significantly modulate drug metabolism pathways. Amiodarone is commonly used to control cardiac arrhythmias; however, it is recognized as having a narrow therapeutic window with potential for significant drug toxicity. Amiodarone is metabolized by CYP3A4, CYP2C8 and CYP1A1 to an active metabolite and therefore may be affected by comedications that modulate these isoenzymes. Since amiodarone is frequently associated with toxicity, the Heart Rhythm Society (formerly the North American Society of Pacing and Electrophysiology) developed guidelines to minimize the potential for adverse events. However, recommendations for the management of situations where amiodarone must be given with a drug that significantly affects its metabolism are lacking. This paper will discuss our experience with a case of concurrent amiodarone and antiretroviral therapy, as well as provide a review of interactions that may lead to toxicity or potential treatment failure with amiodarone. Primary literature was identified through Medline (1946 to May 2013) and Embase (1980 to May 2013), using the following terms: amiodarone, antiretroviral, HIV, cytochrome P450 and drug interaction. Case reports, studies of xenobiotic interactions with amiodarone in healthy volunteers, and in vitro studies that investigated metabolic pathways of amiodarone were reviewed. Although clinical data was limited, several cases support the finding that potent inhibitors or inducers of cytochrome P450 may lead to amiodarone toxicity or lack of therapeutic effect, respectively. As well, several case reports, in vitro data and clinical investigations have associated some of the antiretrovirals with QT prolongation, which may result in additive cardiotoxicity in patients also receiving amiodarone. Therefore, to manage situations where amiodarone must be used with concurrent interacting antiretrovirals, we recommend a monitoring plan that follows the Heart Rhythm Society guidelines, however with the addition of serial therapeutic drug level monitoring and frequent electrocardiography to minimize potential toxicity and successfully manage both conditions.

New‐onset postoperative atrial fibrillation after heart surgery

“…78 Similar results were reported in another double-blind study on 601 patients where only one oral prophylactic dose was administered. 80 Amiodarone is extensively metabolized in the liver via CYP3A4, CYP2C8 and CYP1A1 iso-enzymes 81 and awareness of drug interactions is essential. 82 Furthermore, the metabolism of amiodarone may be inhibited by dietary products, such as grapefruit juice 83 and green tea.…”

Atrial fibrillation and human immunodeficiency virus type‐1 infection: a systematic review. Implications for anticoagulant and antiarrhythmic therapy

“…A significant increase of serum amiodarone concentrations has been described in a patient taking indinavir, which is, however, no longer widely used . Another case report described a progressive accumulation of amiodarone 200 mg daily after the initiation of atazanavir , reinforcing the evidence that co‐administration of amiodarone with PIs should be closely monitored.…”

Cardiovascular Disease and HIV: Pathophysiology, Treatment Considerations, and Nursing Implications

“…22 Further, inhibition of metabolism via the cytochrome P450 pathway by antiretroviral agents (specifically, atazanavir and emtricitabine) leads to increased serum levels of amiodarone, resulting in the potential for hypotension, bradycardia, and more cardiac arrhythmias. 41 Because of increased serum levels of amiodarone, the risks of toxic effects due to amiodarone outweigh the benefits of managing the atrial fibrillation with this drug. Further, because of previous nonadherence to medications that resulted in HIV genotypic resistance to some antiretroviral agents, Elmer must maintain his current antiretroviral therapy regimen because few other options for treating HIV infection exist.…”