Posaconazole × Quinidine

Posaconazole strongly inhibits the liver enzyme CYP3A4 (posaconazole label), and the liver clears quinidine mainly through this enzyme (US quinidine label). As a result, posaconazole raises quinidine plasma levels, which prolongs the QT interval on the electrocardiogram and can cause torsade de pointes (posaconazole labels). Quinidine itself prolongs the QT interval in a dose-related way, and cases of torsade de pointes have been reported with posaconazole. The posaconazole label also lists quinidine among drugs that inhibit posaconazole clearance and may raise its levels. The documents give no numbers for this pair. The US quinidine label reports that quinidine levels rise with ketoconazole, another azole antifungal.

The main danger is QT interval prolongation on the electrocardiogram, torsade de pointes and other ventricular arrhythmias up to ventricular fibrillation (posaconazole and quinidine labels). The risk is higher with a slow heart rate, low potassium, magnesium or calcium and high quinidine levels, but the arrhythmia can occur without any of these (US quinidine label). Excess quinidine causes low blood pressure, vomiting, diarrhoea, tinnitus, hearing loss, vertigo, blurred or double vision, headache and confusion (US quinidine label). An arrhythmia attack shows as sudden strong palpitations, dizziness or fainting.

The combination is contraindicated (posaconazole label, European Medicines Agency, EMA; posaconazole label, US Food and Drug Administration, FDA). Quinidine is named in the contraindications, including in the generic posaconazole label (Spanish Agency of Medicines and Medical Devices, AEMPS). The FDA posaconazole label contraindicates posaconazole with all drugs that are broken down by the enzyme CYP3A4 and prolong the QT interval. Use posaconazole with caution in people with a prolonged QT interval, cardiomyopathy (especially with heart failure), sinus bradycardia or existing symptomatic arrhythmias (posaconazole label, EMA). Check potassium, magnesium and calcium and correct them as needed before and during posaconazole treatment (posaconazole labels, EMA and FDA). The QT interval on the electrocardiogram is a better guide to quinidine safety than its blood level (quinidine label, FDA). In haemodynamically unstable torsade de pointes, stop quinidine and perform immediate cardioversion or overdrive pacing, and actively correct low potassium, magnesium and calcium (quinidine label, FDA).