Ergot alkaloid, 5-HT1B/1D and alpha-adrenoceptor agonist
ATC code: N02CA02 (Ergotamine)
Brand names
Ergomar, Cafergot
Activates 5-HT1B/1D receptors on intracranial vessels, causing vasoconstriction that blocks pulsatile pain afferents in migraine. Also activates peripheral vascular alpha-adrenoceptors, dopamine receptors at the chemotrigger zone (hence nausea) and weakly coronary 5-HT2 receptors. Metabolised exclusively by CYP3A4 – any CYP3A4 inhibitor (macrolides, azoles, ritonavir, cobicistat) raises concentration manifold and risks fatal ergotism: peripheral ischaemia, myocardial infarction, stroke.
Third line
Ergotamine is a third-line option for acute migraine attacks. SEN reserves it for patients in whom triptans failed or are contraindicated. Onset takes 2–4 hours; effect lasts 6–8 hours. Max 6 mg/day and 10 mg/week; exceeding this causes rebound headache and ergotism risk. Vasoconstrictor action contraindicates use in ischemic heart disease, uncontrolled hypertension and peripheral vascular disease.
11 pairs found. Sorted from critical to minor.
Mechanism
CYP3A4 inhibition – fatal ergotism. Fatal cases reported.
Symptoms
Limb ischaemia, stroke.
Management
Combination contraindicated.
Mechanism
Clarithromycin inhibits CYP3A4. Ergotamine is metabolised exclusively by CYP3A4; concentration rises 10+ fold. Fatal ergotism: digital ischaemia, MI, stroke. boxed warning.
Symptoms
Within 1–3 days: digital numbness, pallor, limb pain; in severe cases gangrene. Fatal cases reported.
Management
Combination contraindicated. For migraine in a clarithromycin patient – switch ergotamine to triptan after course completion, or use paracetamol for acute attack.
Mechanism
Cobicistat is a strong CYP3A4 inhibitor. Tybost Section 4.3 strict contraindication with ergot alkaloids.
Symptoms
Fatal ergotism.
Management
Combination contraindicated.
Mechanism
CYP3A4 inhibition – fatal ergotism.
Symptoms
Limb ischaemia, stroke.
Management
Combination contraindicated.
Mechanism
Erythromycin is a CYP3A4 inhibitor. Ergotamine rises 5–10 fold, fatal ergotism. Ergomar Section 4.
Symptoms
Digital ischaemia, MI within 1–5 days.
Management
Combination contraindicated.
Mechanism
Itraconazole is the strongest CYP3A4 inhibitor. Ergotamine rises 20+ fold, fatal ergotism with gangrene. Ergomar Section 4.
Symptoms
Digital ischaemia, gangrene, stroke within hours.
Management
Combination contraindicated.
Mechanism
Ketoconazole is a strong CYP3A4 inhibitor. Ergotamine rises 15-fold, fatal ergotism.
Symptoms
Limb ischaemia within 24 hours.
Management
Combination contraindicated.
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Noxafil Section 4.3 strict contraindication.
Symptoms
Fatal ergotism.
Management
Combination contraindicated.
Mechanism
Ritonavir is the strongest CYP3A4 inhibitor. Fatal ergotism. Ergomar Section 4.
Symptoms
Digital ischaemia, MI, stroke.
Management
Combination contraindicated.
Mechanism
Both drugs are 5-HT1B/1D vasoconstrictors. Additive effect on coronary and peripheral arteries. requires at least 24-hour separation.
Symptoms
Myocardial ischaemia, stroke, digital ischaemia within hours.
Management
Combination contraindicated. At least 24 hours between ergotamine and any triptan.
Mechanism
Voriconazole is a strong CYP3A4 inhibitor. Ergotamine rises 10+ fold. Vfend Section 4.3.
Symptoms
Fatal ergotism.
Management
Combination contraindicated.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Contraindicated in pregnancy: ergotamine triggers uterine contraction and reduces uteroplacental blood flow – risk of miscarriage, preterm birth and fetal hypoxia.
Passes into breast milk; may cause vomiting, diarrhea and reduced lactation. Breastfeeding during use is not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Ergotamine is evaluated for the following indications with varying evidence strength: Acute migraine attack (evidence tier C). See the full indication matrix with dosing and citations above on this page.
Common side effects of Ergotamine (≥ 1 in 100): Nausea and vomiting, Paresthesia, Leg weakness, Muscle cramps, Dizziness. See the Safety section for uncommon and serious reactions.
FDA category X. Contraindicated in pregnancy: ergotamine triggers uterine contraction and reduces uteroplacental blood flow – risk of miscarriage, preterm birth and fetal hypoxia.
Passes into breast milk; may cause vomiting, diarrhea and reduced lactation. Breastfeeding during use is not recommended.
Ergotamine is contraindicated in: Pregnancy, breastfeeding; Strong CYP3A4 inhibitors (clarithromycin, erythromycin, itraconazole, ketoconazole, voriconazole, posaconazole, ritonavir, cobicistat) – fatal ergotism; Other vasoconstrictors – triptans, dihydroergotamine, ergot alkaloids within 24 hours; Ischemic heart disease, prior myocardial infarction, unstable angina; Uncontrolled hypertension. Full list in the Safety section.