Eletriptan × Ketoconazole

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and ketoconazole strongly inhibits this enzyme. In a clinical study, ketoconazole 400 mg raised the peak eletriptan concentration (Cmax) 2.7-fold and the area under the curve (AUC) 5.9-fold. It also lengthened the eletriptan half-life from 4.8 to 8.3 hours. According to the ketoconazole summary of product characteristics of the European Medicines Agency (EMA), ketoconazole interactions can be stronger with a higher dose or a shorter dosing interval. Like other triptans, eletriptan can cause coronary artery spasm. In clinical trials, doses of 60 mg or more caused short-lived rises in blood pressure. At clinical doses, eletriptan neither inhibits nor induces cytochrome P450 enzymes, so it does not affect ketoconazole.

Tightness, pain or pressure in the chest, throat, neck and jaw is common after eletriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, sometimes in people without known heart disease. Rarely, blood pressure rises sharply, even to a hypertensive crisis. Spasm of other arteries can cause Raynaud's syndrome or bowel ischaemia with abdominal pain and bloody diarrhoea. Stroke and brain haemorrhage have occurred after triptans.

The combination is contraindicated (eletriptan label, US Food and Drug Administration, FDA). The eletriptan summary of product characteristics (SmPC) says not to use eletriptan with ketoconazole or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). The ketoconazole SmPC also lists the combination as not recommended (European Medicines Agency, EMA). Wait at least 72 hours after the last dose of ketoconazole before giving eletriptan (eletriptan and ketoconazole tablet labels, FDA). This concerns oral ketoconazole. In the European Union, its tablets are indicated for endogenous Cushing's syndrome (ketoconazole SmPC, EMA). After a cream is applied to the skin, ketoconazole is not measurable in plasma and no systemic effects are expected (ketoconazole cream SmPC, AEMPS). If eletriptan has been taken during ketoconazole treatment and chest pain or tightness suggesting cardiac ischaemia appears, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop eletriptan if arrhythmias occur and monitor blood pressure during treatment (eletriptan label, FDA). If signs of spasm in other arteries appear, such as abdominal pain with blood in the stool or white, cold fingers, rule out vasospasm before the next dose (eletriptan label, FDA).