title: 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, St Michael's Hospital, Toronto, ON, Canada. naccaratom@smh.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Naccarato
authors.forename: Deborah
authors.initials: D
authors.lastname: Yoong
authors.forename: Charles
authors.initials: C
authors.lastname: la Porte
authors.forename: Ignatius
authors.initials: I
authors.lastname: Fong
mesh_terms: D000369:Aged, 80 and over; D000638:Amiodarone / Q000494:pharmacology / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000188:drug therapy*; D003577:Cytochrome P-450 Enzyme System; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D044966:Anti-Retroviral Agents; D003577:Cytochrome P-450 Enzyme System; D000638:Amiodarone