MIGERGOT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIGERGOT (MIGERGOT).
Ergotamine is a partial agonist at serotonin (5-HT) receptors, particularly 5-HT1B/1D, and also exhibits agonism at alpha-adrenergic and dopamine receptors. It causes vasoconstriction of cranial blood vessels and reduces central pain transmission.
| Metabolism | Primarily hepatic via CYP3A4; also undergoes first-pass metabolism. |
| Excretion | Primarily hepatic metabolism (ergotamine) with 90% biliary/fecal elimination as metabolites; less than 4% renal excretion unchanged. |
| Half-life | Ergotamine: 2 hours (initial) with terminal half-life 21-34 hours due to enterohepatic recirculation; caffeine: 3-6 hours. |
| Protein binding | Ergotamine: 90-99% bound to albumin; Caffeine: 25-36% bound to albumin. |
| Volume of Distribution | Ergotamine: 1.7 L/kg (large due to high tissue binding); caffeine: 0.5-0.7 L/kg. |
| Bioavailability | Oral: <5% (high first-pass); Sublingual: 15-25%; Rectal: 30-40%. |
| Onset of Action | Sublingual: 15-30 minutes; Oral: 30-60 minutes; Rectal: 15-30 minutes. |
| Duration of Action | Vasoconstrictor effects persist 6-12 hours; clinical migraine relief up to 24 hours with sustained action. |
1 mg ergotamine tartrate and 100 mg caffeine per rectal suppository, inserted rectally at onset of headache; may repeat after 1 hour if needed, maximum 2 suppositories per headache and 5 per week.
| Dosage form | SUPPOSITORY |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to risk of ergotism. |
| Liver impairment | Contraindicated in hepatic impairment; Child-Pugh A, B, C: avoid use due to reduced metabolism and risk of toxicity. |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Use with caution; lower doses recommended due to increased sensitivity and higher risk of adverse effects; avoid in elderly with cardiovascular disease. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIGERGOT (MIGERGOT).
| Breastfeeding | Contraindicated. Ergotamine excreted in breast milk; may cause ergotism (vomiting, diarrhea, seizures) in infants. M/P ratio not established. Discontinue nursing or drug. |
| Teratogenic Risk | Pregnancy Category X. First trimester: increased risk of congenital malformations, especially cardiovascular and CNS defects. Second and third trimesters: ergotamine-induced uterine contractions may cause preterm labor, fetal hypoxia, and low birth weight. Avoid in all trimesters. |
| Fetal Monitoring |
■ FDA Black Box Warning
Concomitant use with strong CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors, azole antifungals) has been associated with acute ergot toxicity (vasospasm, ischemia).
| Serious Effects |
Concurrent use of potent CYP3A4 inhibitors, peripheral vascular disease, coronary artery disease, uncontrolled hypertension, sepsis, hepatic or renal impairment, pregnancy, lactation, and hypersensitivity to ergot alkaloids.
| Precautions | ["Risk of ergotism (vasospasm, ischemia) especially with prolonged use or overdosage","Risk of fibrotic complications (retroperitoneal, pulmonary, cardiac) with chronic use","May cause nausea, vomiting, and drug dependence (headache rebound)"] |
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| Monitor fetal heart rate and uterine activity if inadvertent exposure. Assess for signs of ergotism (maternal: hypertension, peripheral ischemia; fetal: growth restriction, distress). |
| Fertility Effects | May impair fertility due to ergotamine-induced hyperprolactinemia and interference with ovulation. Data limited. |