Clarithromycin × Ranolazine

The gut and liver break down ranolazine mainly through the enzyme CYP3A4, and clarithromycin strongly inhibits this enzyme. The labels give no figures for this exact pair. The closest guide is ketoconazole 200 mg twice daily, another strong CYP3A4 inhibitor. It raised the ranolazine area under the curve (AUC) 3.0–3.9-fold. As ranolazine levels rise, so do its dose-dependent adverse effects and QT interval prolongation on the electrocardiogram. Clarithromycin prolongs the QT interval on its own. The ranolazine prescribing information warns that combining ranolazine with such drugs may in theory raise the risk of ventricular arrhythmias.

Excess ranolazine causes dizziness, nausea and vomiting, and at high concentrations double vision, lethargy, confusion and fainting. Reported effects of oral ranolazine overdose include low blood pressure, slow heart rate, QT interval prolongation on the electrocardiogram, severe tremor, unsteady gait and hallucinations. Clarithromycin also prolongs the QT interval. Torsade de pointes and deaths have been reported in patients taking it.

The combination is contraindicated (clarithromycin summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS; ranolazine SmPC, European Medicines Agency, EMA; ranolazine label, US Food and Drug Administration, FDA). None of these documents sets a dose condition, so the contraindication covers any dose of either drug. Ranolazine is used for stable angina (ranolazine SmPC, EMA). In coronary artery disease, weigh the benefit of clarithromycin against a rare risk of arrhythmia, myocardial infarction and cardiovascular death (clarithromycin SmPC, AEMPS). Also weigh it against higher all-cause mortality one year or more after the course (clarithromycin label, FDA). Clarithromycin is contraindicated in patients with low blood potassium or magnesium and in those with a history of QT interval prolongation or ventricular arrhythmia (clarithromycin SmPC, AEMPS). If a patient has taken both drugs and develops dizziness, vomiting, double vision or fainting, observe the patient closely and give symptomatic and supportive care (ranolazine SmPC, EMA). Monitor the electrocardiogram continuously if needed (ranolazine label, FDA).