Azithromycin × Pimozide

Both drugs prolong the QT interval on the electrocardiogram (ECG). The pimozide label reports QT prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation at therapeutic doses. The azithromycin label reports QT prolongation and torsade de pointes. According to the US pimozide label, macrolide use in patients with a prolonged QT interval, such as pimozide can produce, has rarely been associated with ventricular arrhythmias. Two sudden deaths were reported when clarithromycin was added to pimozide. The pharmacokinetic contribution of azithromycin is small. Its label calls it a weak cytochrome P450 inhibitor and finds no clinically significant inhibition of the enzyme CYP3A4, one of the two main routes of pimozide breakdown. The label does not fully rule such inhibition out, though. Azithromycin stays in the body for a long time: its terminal half-life is about 68 hours, and low concentrations persist after the course ends (azithromycin label). The labels give no study of this pair.

QT interval prolongation itself causes no symptoms and shows only on the electrocardiogram (ECG). The danger is ventricular arrhythmia: torsade de pointes, ventricular tachycardia and ventricular fibrillation, up to cardiac arrest and sudden death (pimozide and azithromycin labels). An arrhythmia episode presents as palpitations, dizziness or fainting. The risk is higher in women and older people and with low potassium or magnesium, clinically relevant bradycardia, arrhythmias or severe heart failure (azithromycin and pimozide labels).

The combination is contraindicated. The US pimozide label names azithromycin among the macrolide antibiotics that must not be given with pimozide (pimozide label, US Food and Drug Administration, FDA). The Spanish pimozide summary of product characteristics (SmPC) contraindicates pimozide with any drug known to prolong the QT interval and with macrolide antibiotics (pimozide SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). Azithromycin's own label puts it in the QT-prolonging group: it reports QT prolongation and torsade de pointes (azithromycin SmPC, AEMPS). The azithromycin labels are softer. The Spanish one asks for caution with such drugs and gives pimozide as an example, and the US one asks prescribers to weigh benefits and risks (azithromycin labels, AEMPS and FDA). The strictest document applies. If a patient taking pimozide needs an antibiotic, do not prescribe azithromycin. Clarithromycin and erythromycin are also contraindicated, and the US pimozide label also rules out sparfloxacin, gatifloxacin and moxifloxacin with pimozide (pimozide label, FDA). If a patient already takes both drugs, stop one of them. For any pimozide treatment, record an electrocardiogram (ECG) before the start and repeat it during treatment. Keep potassium and magnesium in the normal range, and stop pimozide if the QT or corrected QT (QTc) interval exceeds 500 ms (pimozide labels, AEMPS and FDA).