Ranolazine × Ritonavir

The liver breaks down ranolazine mainly through the enzyme CYP3A4, and ritonavir strongly inhibits this enzyme. The labels give no figures for this exact pair. The closest guide is ketoconazole, another strong CYP3A4 inhibitor, which raised the ranolazine area under the curve 3.0–3.9-fold. As ranolazine levels rise, so do its dose-dependent adverse effects and QT interval prolongation.

Excess ranolazine causes dizziness, nausea and vomiting. At high concentrations, double vision, lethargy and fainting are possible. In ranolazine overdose, low blood pressure, slow heart rate, QT prolongation on the electrocardiogram, severe tremor, unsteady gait and hallucinations have been reported.

The combination is contraindicated (ritonavir and ranolazine SmPCs, European Medicines Agency, EMA; US labels of both drugs, US Food and Drug Administration, FDA). The contraindication includes low-dose ritonavir used to boost other human immunodeficiency virus (HIV) protease inhibitors. All HIV protease inhibitors are on the ranolazine contraindication list (ranolazine SmPC, EMA), and the ritonavir documents contraindicate ranolazine at any ritonavir dose (ritonavir SmPC, EMA; ritonavir label, FDA). When ritonavir boosts another protease inhibitor, check that drug's prescribing information for contraindications as well (ritonavir SmPC, EMA). If a patient has taken both 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).