MEDIHALER ERGOTAMINE
Clinical safety rating: avoid
Strong CYP3A4 inhibitors (eg clarithromycin) are contraindicated due to risk of ergotism Contraindicated in coronary artery disease and uncontrolled hypertension.
Ergotamine is a serotonin (5-HT1B/1D) receptor agonist with additional affinity for 5-HT2, dopamine D2, and alpha-adrenergic receptors. It causes vasoconstriction of cranial blood vessels and inhibits neurogenic inflammation.
| Metabolism | Hepatic, primarily via CYP3A4. Undergoes first-pass metabolism. |
| Excretion | Ergotamine is extensively metabolized in the liver. Approximately 90% of the dose is excreted as metabolites in the bile/feces, with less than 3% excreted unchanged in urine. |
| Half-life | The terminal elimination half-life is approximately 2 hours for the initial phase, followed by a prolonged terminal phase of 21-30 hours due to slow release from tissue binding sites. This long terminal half-life contributes to the risk of accumulation and toxicity with frequent dosing. |
| Protein binding | Protein binding: 90-95%, primarily to albumin and possibly to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution: approximately 1.9 L/kg (range 1.4-2.4 L/kg). This large Vd indicates extensive tissue distribution, including accumulation in peripheral tissues such as the lungs and liver, which explains the prolonged terminal half-life and risk of toxicity. |
| Bioavailability | Bioavailability via inhalation: approximately 25-40% (compared to IM route). Oral bioavailability is very low (<5%) due to extensive first-pass metabolism; thus, oral forms are not used. The inhalation route bypasses first-pass hepatic metabolism, providing higher systemic availability than oral. |
| Onset of Action | Inhalation via Medihaler: onset within 5-10 minutes for relief of migraine headache. |
| Duration of Action | Duration of action is 4-6 hours for relief of acute migraine. However, the drug's prolonged elimination half-life and tissue binding lead to potential cumulative effects with repeated use; clinical effect may be prolonged but with increased risk of ergotism. |
One inhalation (0.36 mg ergotamine) at onset of migraine; may repeat after 5 minutes if needed, up to 6 inhalations per attack and 15 per week.
| Dosage form | AEROSOL, METERED |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min). No specific dose adjustment for mild to moderate impairment; use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). Avoid use in moderate impairment (Child-Pugh B); no data for mild impairment (use with caution). |
| Pediatric use | Not recommended for use in children due to risk of toxicity and lack of safety data. |
| Geriatric use | Use with caution due to increased susceptibility to vasospasm and peripheral vascular disease; start with lower dose (e.g., 1 inhalation) and monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors (eg clarithromycin) are contraindicated due to risk of ergotism Contraindicated in coronary artery disease and uncontrolled hypertension.
| FDA category | Contraindicated |
| Breastfeeding | Ergotamine is excreted in breast milk with a milk-to-plasma ratio of approximately 0.8. It may cause ergotism (vomiting, diarrhea, seizures) in infants and suppress lactation. Use is contraindicated in breastfeeding due to potential toxicity. |
| Teratogenic Risk |
■ FDA Black Box Warning
Serious and/or life-threatening peripheral ischemia and vasospasm have been associated with ergotamine when coadministered with potent CYP3A4 inhibitors (including protease inhibitors, macrolide antibiotics, and azole antifungals). Concomitant use is contraindicated.
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to ergot alkaloids","Peripheral vascular disease","Coronary artery disease","Uncontrolled hypertension","Severe hepatic or renal impairment","Sepsis","Pregnancy (teratogenic; risk of uterine contractions)","Concurrent use with potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors, azole antifungals)","Prolonged use or exceeding recommended dosage"]
| Precautions | ["Vasospastic reactions: may cause prolonged vasoconstriction leading to ischemia or gangrene","Risk of ergotism: chronic use or overdose may lead to severe vasoconstriction and ischemia","Cardiac effects: may cause angina, myocardial infarction, or coronary vasospasm","Fibrotic complications: retroperitoneal, pleural, or cardiac valve fibrosis with long-term use","Cerebrovascular effects: may cause cerebral ischemia or stroke","Rebound headache: overuse may lead to medication-overuse headache"] |
Loading safety data…
| Ergotamine is contraindicated in pregnancy. First trimester: Increased risk of congenital malformations, including vascular disruption defects (e.g., limb reduction, gastroschisis). Second and third trimesters: Uterine hypertonicity, placental insufficiency, fetal distress, and increased risk of preterm labor and low birth weight. Ergotamine crosses the placenta. Category X. |
| Fetal Monitoring | Monitor maternal blood pressure (risk of hypertension), uterine activity (signs of hypertonicity or tetanic contractions), and fetal heart rate patterns (non-stress test/bioimpedance) for distress. Assess for signs of ergotism (nausea, vomiting, vasospasm, paresthesia). |
| Fertility Effects | Ergotamine may impair fertility in females by disrupting ovulatory function due to its dopamine agonist activity, potentially causing hyperprolactinemia. In males, no specific data; however, ergot alkaloids may affect fertility via vascular effects on reproductive organs. Use is not recommended for individuals seeking conception. |