ERGOMAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERGOMAR (ERGOMAR).
Ergotamine acts as a partial agonist at serotonin 5-HT1B and 5-HT1D receptors, causing vasoconstriction of cranial blood vessels. It also inhibits norepinephrine reuptake and has alpha-adrenergic blocking activity.
| Metabolism | Primarily hepatic via CYP3A4; minor contributions from CYP2D6. Undergoes extensive first-pass metabolism. |
| Excretion | Primarily hepatic metabolism with extensive biliary excretion; less than 5% excreted unchanged in urine. Fecal elimination accounts for approximately 30-40% of the dose as metabolites. |
| Half-life | Terminal elimination half-life is approximately 2-3 hours for ergotamine, but clinical effects may persist longer due to active metabolites (e.g., ergotamine's half-life is 2.4 hours; metabolites have half-lives up to 10 hours). |
| Protein binding | 90-95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.4 L/kg (16-18 L in adults), indicating moderate tissue distribution. |
| Bioavailability | Sublingual: ~40-50%; Oral: <10% due to extensive first-pass metabolism; Rectal: ~25-30%. |
| Onset of Action | Sublingual: 15-30 minutes; Oral: 30-60 minutes; Rectal: 20-30 minutes; Intramuscular: 10-20 minutes. |
| Duration of Action | Sublingual/Oral: 4-6 hours; Rectal: 6-8 hours; Intramuscular: 8-12 hours. Clinical note: Vasoconstrictive effects may persist longer than analgesic effect. |
| Molecular Weight | 581.67 Da (ergotamine tartrate) |
Ergotamine tartrate 1-2 mg sublingually or orally at onset of migraine, then 1-2 mg every 30 minutes as needed, maximum 6 mg per attack and 10 mg per week.
| Dosage form | TABLET |
| Renal impairment | GFR > 30 mL/min: No adjustment. GFR 10-30 mL/min: Caution; reduce dose by 50%. GFR < 10 mL/min: Contraindicated. |
| Liver impairment | Child-Pugh A: Caution; reduce dose by 50%. Child-Pugh B: Contraindicated. Child-Pugh C: Contraindicated. |
| Pediatric use | Not recommended for children under 12 years. Pediatric use not established; avoid use. |
| Geriatric use | Elderly patients are more sensitive to vasoconstriction; use lower initial dose (e.g., 1 mg) and monitor for adverse effects. |
| 1st trimester | Contraindicated; ergotamine derivatives have uterine stimulant effects and may cause fetal hypoxia, growth retardation, and malformations. |
| 2nd trimester | Contraindicated; risk of uterine hypertonus and reduced placental blood flow leading to fetal distress. |
| 3rd trimester | Contraindicated; may induce premature labor and cause neonatal ergotism. |
Clinical note
Comprehensive clinical and safety monograph for ERGOMAR (ERGOMAR).
| Placental transfer | Rapid placental transfer demonstrated; ergotamine crosses placenta and can achieve fetal concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk; may cause ergotism in the infant (vomiting, diarrhea, convulsions). Avoid breastfeeding during therapy and for at least 48 hours after last dose. |
■ FDA Black Box Warning
Serious and/or life-threatening peripheral ischemia and vasospasm have been associated with the concomitant use of ergotamine with potent CYP3A4 inhibitors including protease inhibitors, macrolide antibiotics, and azole antifungals.
| Serious Effects |
PregnancyLactationPeripheral or coronary vascular diseaseHypertension (severe or uncontrolled)SepsisRenal or hepatic impairmentConcurrent use of potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors)
| Precautions | Risk of ischemic events (peripheral, cardiac, cerebral), fibrosis (retroperitoneal, pulmonary, cardiac), elderly patients (more sensitive to adverse effects), ergotism, drug interactions with CYP3A4 inhibitors, and prolonged use leading to medication-overuse headache. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4, increasing ergotamine levels and risk of toxicity. No other significant food interactions. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | Ergotamine (ERGOMAR) is contraindicated in pregnancy due to its oxytocic properties and potential for uterine hyperstimulation, fetal hypoxia, and congenital anomalies. First trimester: Increased risk of spontaneous abortion and major malformations (e.g., limb defects, CNS abnormalities) based on case reports. Second and third trimesters: Uterine hypertonicity and decreased placental perfusion leading to fetal distress, preterm labor, and low birth weight. Use only if benefit outweighs risk and no alternative; avoid in all trimesters. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, signs of ergotism (nausea, peripheral ischemia, paresthesias), uterine tone, and fetal heart rate via electronic fetal monitoring. Fetal: Ultrasound for growth and anomalies if exposed in first trimester; non-stress test or biophysical profile for uterine hyperstimulation or fetal distress. |
| Fertility Effects | Ergotamine may impair fertility due to hyperprolactinemia inhibition (dopamine agonist activity) and potential vascular effects on reproductive organs. In animal studies, reduced conception rates and implantation. Human data limited; discontinuation recommended for women attempting conception. |
| Clinical Pearls | Ergomar (ergotamine tartrate sublingual tablets) is a first-line abortive therapy for acute migraine attacks, but its use is limited by vasoconstrictive risks. Avoid in patients with coronary artery disease, hypertension, peripheral vascular disease, or pregnancy. Administer at the first sign of migraine; sublingual route offers rapid absorption. Concomitant use with potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors) is contraindicated due to risk of ergotism. Limit total dose to 6 mg per attack and 10 mg per week. |
| Patient Advice | Take one sublingual tablet at the first sign of migraine, placing it under the tongue to dissolve, and do not swallow. · Do not exceed 3 tablets per attack or 5 tablets per week; overuse can lead to serious side effects. · Seek immediate medical attention if you experience symptoms of ergotism like severe coldness, numbness, or pain in hands/feet, muscle cramps, chest pain, or rapid heartbeat. · Avoid grapefruit and grapefruit juice during treatment as it may increase the risk of side effects. · Inform your doctor if you are pregnant, breastfeeding, or have any history of heart disease, high blood pressure, or peripheral artery disease. |