Eletriptan × Itraconazole

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and itraconazole strongly inhibits this enzyme. No study has looked at this pair directly, but according to the itraconazole label, itraconazole is likely to raise eletriptan concentrations. The closest guide is data on other strong CYP3A4 inhibitors. Ketoconazole 400 mg raised the eletriptan area under the curve (AUC) 5.9-fold and lengthened its half-life from 4.8 to 8.3 hours. Erythromycin 1000 mg raised the AUC 3.6-fold. After itraconazole is stopped, its plasma levels take 7–14 days to become almost undetectable. 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.

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 itraconazole or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). The itraconazole SmPC also lists eletriptan as not recommended: avoid it during itraconazole treatment and for 2 weeks after stopping itraconazole (itraconazole SmPC, AEMPS). The FDA eletriptan label requires a gap of at least 72 hours after a strong inhibitor. Yet after itraconazole is stopped, its plasma levels take 7–14 days to become almost undetectable, and even longer in liver cirrhosis or with other CYP3A4 inhibitors (itraconazole SmPC, AEMPS). If eletriptan has been taken during itraconazole 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).