Clarithromycin × Disopyramide

Disopyramide is broken down in the liver by CYP3A4, and clarithromycin inhibits this enzyme, so disopyramide blood levels rise. Both drugs prolong the QT interval, and their effects on the heart add up.

QT prolongation on the ECG, palpitations, fainting, torsades de pointes. Post-marketing reports also describe hypoglycemia with this combination: sweating, tremor, hunger, confusion.

Avoid the combination. The disopyramide label lists macrolides that inhibit CYP3A4 among combinations that are not recommended (disopyramide label). The US Food and Drug Administration (FDA) advises against clarithromycin in patients on class IA antiarrhythmics, including disopyramide (clarithromycin FDA label). Clarithromycin is contraindicated in patients with a history of QT prolongation or ventricular arrhythmia and in those with low potassium or magnesium (clarithromycin label). If the combination cannot be avoided, monitor the ECG, disopyramide blood levels and blood glucose during co-administration (clarithromycin label). Stop disopyramide if the QT interval or QRS duration lengthens by more than 25% (disopyramide label). Check potassium and correct it if needed (disopyramide label).