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. |
| Molecular Weight | 547.7 |
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 | Contraindicated due to teratogenic effects including vascular disruption and increased risk of congenital malformations. |
| 2nd trimester | Contraindicated; may cause uterine contractions and reduced placental blood flow leading to fetal hypoxia. |
| 3rd trimester | Contraindicated; can induce premature labor and cause neonatal ergotism with potential for seizures and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for MIGERGOT (MIGERGOT).
| Placental transfer | Crosses placenta rapidly; achieves fetal serum concentrations 32-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk and may cause ergotism in infants (vomiting, diarrhea, convulsions). Avoid breastfeeding during therapy and for at least 12 hours after last dose. |
■ 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 |
PregnancyLactationCoronary artery diseaseUncontrolled hypertensionPeripheral vascular diseaseSepsisSevere hepatic or renal impairmentConcurrent use of potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors)
| 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) |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to inhibition of CYP3A4, which may increase ergotamine levels and risk of ergotism. No other specific food interactions; however, tyramine-rich foods (aged cheese, cured meats) may theoretically precipitate migraine in susceptible individuals, but this is not a direct drug interaction. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| 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 | 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. |
| Clinical Pearls | Rectal administration avoids first-pass metabolism and can be used when oral therapy is not tolerated. Do not use within 24 hours of triptans or other ergot alkaloids due to additive vasospasm risk. Ergotism risk increases with hepatic impairment, renal impairment, or concurrent use of potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors). Monitor for signs of ischemia: cool, pale, painful extremities. Abrupt discontinuation after prolonged use may cause rebound headache. |
| Patient Advice | Use exactly as prescribed; do not exceed 4 mg per migraine attack or 6 mg per week. · Insert suppository rectally; do not swallow or cut. · Do not take within 24 hours of sumatriptan, rizatriptan, or other migraine medications unless directed by your doctor. · Avoid grapefruit juice and grapefruit products while taking this medication. · Seek immediate medical attention if you experience severe abdominal pain, muscle cramps, chest pain, or numbness/tingling in extremities. |