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.

The burden and management of cytochrome P450 2D6 (CYP2D6)‐mediated drug–drug interaction (DDI): co‐medication of metoprolol and paroxetine or fluoxetine in the elderly

“…The beta‐1 selective metoprolol is one of the most efficacious beta‐blockers . An important limitation is, however, that metoprolol can induce bradycardia . Metoprolol is extensively metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme, which is associated with an interindividual variation including the absence of activity due to genetic polymorphism .…”

Expert consensus on management of dermatophytosis in elderly patients, patients with comorbidities, and immunocompromised status: an Indian perspective

“…2 Azole drugs have significant potential of drug-drug interactions with a wide range of medications for various clinical indications (Table 1). 2,14,[16][17][18] Azoles are known to interact with antiepileptic drugs like phenytoin, carbamazepine, and phenobarbital which leads to reduction in the efficacy of azole drugs due to stimulation of CYP3A4. 2 They are contraindicated with most of the drugs including quinidine (antimalarial and antiarrhythmic drug), benzodiazepines (alprazolam, chlordiazepoxide, clonazepam, diazepam, estazolam, flurazepam, halazepam, quazepam, and triazolam for anxiety), and statins (lovastatin, simvastatin, atorvastatin for hypertension, heart disease).…”

Cardiodermatology in the physician’s practice

“…Terbinafine is an inhibitor of CYP2D6 isoenzyme affecting the metabolism of a number of commonly used cardiac drugs such as propafenone or β-blockers [31]. The concomitant use of terbinafine and metoprolol may induce sinus bradycardia [35].…”

“…Terbinafina jest inhibitorem izoenzymu CYP2D6 i wpływa na metabolizm wielu powszechnie stosowanych leków kardiologicznych, takich jak propafenon czy β-adrenolityki [31]. Jednoczesne stosowanie terbinafiny i metoprololu może wywołać bradykardię zatokową [35].…”