title: A metoprolol-terbinafine combination induced bradycardia.
abstract: To report a sinus bradycardia induced by metoprolol and terbinafine drug-drug interaction and its management. A 63 year-old Caucasian man on metoprolol 200 mg/day for stable coronary artery disease was prescribed a 90-day course of oral terbinafine 250 mg/day for onychomycosis. On the 49th day of terbinafine therapy, he was brought to the emergency room for a decrease of his global health status, confusion and falls. The electrocardiogram revealed a 37 beats/min sinus bradycardia. A score of 7 on the Naranjo adverse drug reaction probability scale indicates a probable relationship between the patient's sinus bradycardia and the drug interaction between metoprolol and terbinafine. The heart rate ameliorated first with a decrease in the dose of metoprolol. It was subsequently changed to bisoprolol and the heart rate remained normal. By inhibiting the cytochrome P450 2D6, terbinafine had decreased metoprolol's clearance, leading in metoprolol accumulation which has resulted in clinically significant sinus bradycardia.
authors.affiliation: Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, 5400 Boul. Gouin Ouest, Montreal, QC, H4J 1C5, Canada, emmanuel.bebawi@umontreal.ca.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bebawi
authors.forename: Suhail S
authors.initials: SS
authors.lastname: Jouni
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Tessier
authors.forename: Anne Julie
authors.initials: AJ
authors.lastname: Frenette
authors.forename: Dave
authors.initials: D
authors.lastname: Brindamour
authors.forename: Maxime
authors.initials: M
authors.lastname: Doré
mesh_terms: D001919:Bradycardia / Q000139:chemically induced*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology*; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000009:adverse effects*; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects*; D000077291:Terbinafine
chemical_list: D009281:Naphthalenes; D019389:Cytochrome P-450 CYP2D6; D000077291:Terbinafine; D008790:Metoprolol