amiodarone and metoprolol

Amiodarone inhibits CYP2D6, the enzyme responsible for metabolising metoprolol, thereby increasing metoprolol plasma concentrations. Additionally, both drugs have additive negative chronotropic and dromotropic effects on the sinoatrial and atrioventricular nodes, and amiodarone can also have a negative inotropic effect. This combined action can lead to excessive slowing of heart rate and reduced cardiac conduction.

Patients may experience symptomatic bradycardia, hypotension, dizziness, fatigue, and in severe cases, heart block, syncope, or worsening of heart failure. The risk is particularly pronounced in patients with pre-existing conduction system disease, left ventricular dysfunction, or those taking other negative chronotropic agents.

Alternative beta-blockers with minimal CYP2D6 metabolism (e.g., atenolol or nadolol) may be considered, but always assess clinically.

Well-established in clinical guidelines and observational studies; amiodarone has been shown to increase metoprolol concentrations and additive effects on cardiac conduction are recognised. This interaction is documented in standard drug interaction databases and prescribing information.