Clarithromycin × Digoxin

Digoxin is cleared with the help of the P-glycoprotein (P-gp) transporter, and clarithromycin inhibits it, so digoxin blood levels rise (clarithromycin SmPC). The US Food and Drug Administration (FDA) reports a 70% increase in the area under the digoxin concentration curve (digoxin FDA label). Digoxin has a narrow therapeutic index, and older age, low body weight, impaired kidney function, low potassium or magnesium and high calcium predispose to toxicity (digoxin FDA label).

Loss of appetite, nausea, vomiting, visual changes and heart rhythm disorders: bradycardia, heart block, ventricular extrasystoles, ventricular tachycardia and ventricular fibrillation. Life-threatening arrhythmias have been reported with this combination after marketing.

The US Food and Drug Administration (FDA) lists clarithromycin among drugs that raise digoxin levels by more than 50% and for them recommends measuring serum digoxin before starting, reducing the digoxin dose by about 30–50% or giving it less often, and continuing to monitor (digoxin FDA label). Monitor digoxin levels carefully throughout the clarithromycin course (clarithromycin SmPC): after marketing, some patients on this combination showed signs of digoxin toxicity, including life-threatening arrhythmias (clarithromycin SmPC). Monitor more closely when clarithromycin is started and stopped (digoxin FDA label). If signs of toxicity appear, measure the digoxin level and interrupt or adjust the dose (digoxin FDA label).