Ergot Derivatives

Ergot derivatives are alkaloids that act as agonists at 5HT1B and 5HT1D receptors and at alpha-adrenergic and dopamine receptors, causing cranial vasoconstriction and inhibiting trigeminal nerve activation. They are used for acute migraine and cluster headache when triptans fail.

Classification. Ergotamine, dihydroergotamine and, for postpartum haemorrhage, ergometrine.

Pharmacokinetics. Ergotamine has poor and erratic oral absorption and a long duration of action. Both are metabolised by CYP3A4, so inhibitors cause serious toxicity.

• Ergotamine 2 mg orally or sublingually at the start of a migraine; 1 mg may be repeated every 30 minutes if needed; maximum 6 mg in 24 hours and 10 mg in a week.
• Dihydroergotamine 1 mg subcutaneously, intramuscularly or intravenously, repeated after 1 hour; maximum 3 mg in 24 hours and 6 mg in a week. Intravenous 0.5 to 1 mg with an antiemetic for status migrainosus. Nasal 0.5 mg in each nostril, repeated after 15 minutes.

Differences. Dihydroergotamine causes less nausea and less vasoconstriction than ergotamine.

• Acute migraine: only if triptans have failed or are not tolerated; use on no more than 2 days a week.
• Status migrainosus: dihydroergotamine intravenously with metoclopramide, in hospital.
• Cluster headache: dihydroergotamine as an alternative.
• Postpartum haemorrhage: ergometrine is used by obstetric teams as a uterotonic, with the same vasoconstrictor contraindications.

Selection. Avoid regular use; medication overuse headache develops at 10 or more days a month.

Contraindications. Pregnancy, breastfeeding, coronary artery disease, peripheral vascular disease, uncontrolled hypertension, stroke, sepsis, and severe liver or kidney impairment. Strong CYP3A4 inhibitors (macrolides, azole antifungals, ritonavir- or cobicistat-boosted antiretrovirals). Triptans within 24 hours.

Adverse effects. Nausea, vomiting, abdominal cramps, paraesthesia, muscle pains, chest tightness, medication overuse headache. Ergotism with cold painful limbs, claudication and gangrene. Chronic use causes fibrosis of the heart valves, lungs and retroperitoneum.

Interactions. Strong CYP3A4 inhibitors raise ergot levels and can cause limb ischaemia and stroke. Beta blockers and other vasoconstrictors add risk.

Special groups.

• Pregnancy: contraindicated; uterine contraction.
• Breastfeeding: contraindicated.
• Children: not used.
• Older adults: avoid.
• Kidney and liver impairment: contraindicated in severe disease.

Monitoring. Peripheral pulses, blood pressure, days of use each month.

Referral and escalation. Cold, blue or painful limbs, chest pain, or visual or neurological symptoms need emergency care and stopping the drug.