Dihydroergotamine × Naratriptan

Both drugs constrict blood vessels. Naratriptan stimulates serotonin receptors in the walls of cranial vessels. Dihydroergotamine acts on the same serotonin receptors and also on alpha-adrenergic receptors. Ergot drugs cause prolonged vasospasm and triptans can cause coronary artery spasm, so the vasoconstrictor effects of the two drugs may add up. Data on the combination are limited. In these data, naratriptan with ergotamine, dihydroergotamine or sumatriptan did not change blood pressure, heart rate or the electrocardiogram, and did not affect naratriptan blood levels. Still, the combination may in theory raise the risk of coronary artery spasm.

Tightness, pain or pressure in the chest, throat, neck and jaw is common after naratriptan. 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, and also after dihydroergotamine. Spasm of other arteries causes numb, cold, pale or bluish fingers and toes, muscle pain, abdominal pain with bloody diarrhoea from bowel ischaemia, and sometimes splenic infarction. Both drugs can raise blood pressure sharply, and hypertensive crisis has been reported after triptans.

The naratriptan summary of product characteristics (SmPC) from the Spanish Agency of Medicines and Medical Devices (AEMPS) contraindicates ergotamine and its derivatives (sections 4.3 and 4.5). The naratriptan and dihydroergotamine labels from the US Food and Drug Administration (FDA) also contraindicate the combination. Keep at least 24 hours between the two drugs, in either order (naratriptan and dihydroergotamine labels, FDA). The Spanish naratriptan SmPC sets the same 24-hour interval in both directions for ergotamine preparations (AEMPS). If chest pain or tightness spreading to the throat appears after a naratriptan dose and suggests cardiac ischaemia, give no further doses and evaluate the patient (naratriptan SmPC, AEMPS). If signs of vasospasm appear, such as cold, pale or bluish fingers, muscle pain or abdominal pain with blood in the stool, stop dihydroergotamine at once (dihydroergotamine label, FDA). Rule out vasospasm before the next naratriptan dose (naratriptan label, FDA). Monitor blood pressure (naratriptan label, FDA). Both drugs are contraindicated in uncontrolled hypertension (naratriptan and dihydroergotamine labels, FDA), and naratriptan also in moderate or severe hypertension (naratriptan SmPC, AEMPS). Taking triptans and ergot drugs, alone or together, on 10 or more days a month can lead to medication overuse headache (naratriptan and dihydroergotamine labels, FDA).