Ergotamine × Frovatriptan

Frovatriptan constricts cranial vessels through serotonin receptors. Ergotamine also constricts arteries, and the effects of the two drugs add up. The Spanish frovatriptan summary of product characteristics (SmPC) warns of high blood pressure and coronary artery spasm when both drugs are taken for the same migraine attack. Ergotamine on its own can cause myocardial ischaemia, or rarely infarction, even in people with no known heart disease. Vasospasm after ergot drugs can be prolonged. The risk comes from the effect on vessels, not from drug levels. With ergotamine, the area under the curve and peak concentration of frovatriptan actually fell, by about 25%.

Coronary artery spasm causes chest pain, pressure or tightness, sometimes severe and spreading to the throat, neck or jaw, and can lead to myocardial infarction. Serious arrhythmias such as ventricular tachycardia and ventricular fibrillation have been reported within a few hours of taking drugs of this group. Vasospasm from ergotamine causes numbness and tingling in the fingers and toes, headache and pain over the heart. With severe spasm, the limbs turn blue and their pulses disappear. Spasm of other arteries causes Raynaud's syndrome and bowel ischaemia with abdominal pain and bloody diarrhoea. Splenic infarction has also been reported. In rare cases, blood pressure rises to a hypertensive crisis.

The frovatriptan documents of the Spanish Agency of Medicines and Medical Devices (AEMPS) and the US Food and Drug Administration (FDA) contraindicate the combination. The Spanish summary of product characteristics (SmPC) for ergotamine with caffeine contraindicates all triptans (AEMPS). Keep at least 24 hours between the two drugs, in either order (frovatriptan SmPC, AEMPS, and label, FDA). If ergotamine has not stopped the attack, do not add a triptan for the same attack (ergotamine with caffeine SmPC, AEMPS). If chest pain or tightness suggesting cardiac ischaemia appears after a frovatriptan dose, give no further doses and examine the patient further (frovatriptan SmPC, AEMPS). Stop ergotamine at once if numbness or tingling in the fingers, pain over the heart or other signs of vasospasm appear (ergotamine with caffeine SmPC, AEMPS). Stop frovatriptan if arrhythmias occur, and monitor blood pressure during treatment (frovatriptan label, FDA). If abdominal pain with blood in the stool or white fingers appear, rule out vasospasm before the patient takes frovatriptan again (frovatriptan label, FDA). Taking ergotamine, triptans or both on 10 or more days a month can cause medication overuse headache, with more frequent attacks (frovatriptan label, FDA).