Erythromycin × Fluconazole

Fluconazole prolongs the QT interval on its own by directly inhibiting the delayed rectifier potassium current (IKr) in heart cells. Erythromycin also prolongs the QT interval, and the enzyme CYP3A4 breaks it down. Fluconazole moderately inhibits this enzyme. Its prescribing information warns that this can increase QT prolongation caused by drugs broken down by CYP3A4. Because fluconazole has a long half-life, its effect on the enzyme lasts 4 to 5 days after the last dose. The documents give no figures for the rise in erythromycin levels.

The electrocardiogram (ECG) shows a prolonged QT interval and ventricular extrasystoles, and the person may notice palpitations or skipped beats. The most dangerous rhythm disorders, listed in the erythromycin documents, are torsade de pointes, ventricular fibrillation and cardiac arrest. The fluconazole documents name sudden cardiac death as the risk of this combination. The risk is higher with low potassium or magnesium, advanced heart failure, a slow heart rate and in older people.

The combination is contraindicated (fluconazole prescribing information from the Spanish Agency of Medicines and Medical Devices, AEMPS, and the US Food and Drug Administration, FDA). Fluconazole keeps inhibiting the enzyme CYP3A4 for 4 to 5 days after the last dose (fluconazole documents, AEMPS and FDA). Take this time into account if erythromycin is needed right after a course of fluconazole. Do not give erythromycin to people with a history of QT interval prolongation or ventricular arrhythmias, including torsade de pointes, or with low potassium or magnesium (erythromycin prescribing information, AEMPS). Use fluconazole with caution in conditions that predispose to arrhythmias. The risk is higher with low potassium and advanced heart failure (fluconazole prescribing information, AEMPS). If something may disturb electrolytes, such as diuretics, laxatives, vomiting, diarrhoea or kidney disease, check electrolyte levels (erythromycin prescribing information, AEMPS).