MIGRANAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIGRANAL (MIGRANAL).
MIGRANAL (dihydroergotamine mesylate) is an ergot alkaloid with agonist activity at serotonin 5-HT1D and 5-HT1B receptors, leading to vasoconstriction of cranial blood vessels and inhibition of trigeminal nerve transmission, thereby aborting migraine attacks.
| Metabolism | Hepatic metabolism primarily via CYP3A4; also undergoes non-CYP pathways. |
| Excretion | Primarily hepatic metabolism followed by renal excretion. Approximately 10% excreted unchanged in urine; fecal excretion accounts for <1%. |
| Half-life | Terminal elimination half-life ranges from 7 to 10 hours (mean 8.5 hours). Prolonged in renal impairment. |
| Protein binding | Approximately 14% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Approximately 2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Nasal spray: approximately 17% (relative to intravenous administration). |
| Onset of Action | Nasal spray: 15–30 minutes. |
| Duration of Action | Relief of migraine headache typically lasts 4–24 hours; may require repeat dosing after 1 hour (maximum 3 doses in 24 hours). |
1 mg intramuscularly at onset of migraine headache; may repeat after 1 hour if needed. Maximum: 2 mg per day and 4 mg per week.
| Dosage form | SPRAY, METERED |
| Renal impairment | No specific dose adjustment guidelines available; use with caution in renal impairment due to potential for reduced clearance. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose reduction recommended. |
| Pediatric use | Safety and efficacy not established in children under 18 years; no recommended dosing. |
| Geriatric use | No specific dose adjustment; use with caution due to increased risk of coronary artery disease and hypertension in elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIGRANAL (MIGRANAL).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Ergot alkaloids can reduce prolactin and cause ergotism in infants (vomiting, diarrhea, seizures). Contraindicated during breastfeeding due to risk of infant toxicity and potential decreased milk production. |
| Teratogenic Risk | Contraindicated in pregnancy due to ergot alkaloid activity (oxytocic effects, uterine hypertonicity). First trimester: no adequate studies, potential for teratogenicity based on animal data (skeletal malformations). Second trimester: uterine contractions may reduce placental perfusion. Third trimester: risk of preterm labor, fetal distress, low birth weight. Avoid throughout pregnancy. |
■ FDA Black Box Warning
Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of MIGRANAL with potent CYP3A4 inhibitors (including protease inhibitors and macrolide antibiotics). Because of this risk, concomitant use is contraindicated.
| Serious Effects |
["Hypersensitivity to dihydroergotamine or other ergot alkaloids","Concurrent use with potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors)","Uncontrolled hypertension","Ischemic heart disease (including angina, history of MI)","Coronary artery vasospasm (e.g., Prinzmetal's angina)","Peripheral vascular disease","Cerebrovascular disease (including stroke)","Severe hepatic or renal impairment","Sepsis","During or within 24 hours of treatment with another 5-HT1 agonist","During pregnancy (Category X)"]
| Precautions | ["Risk of serious cardiac events (e.g., myocardial ischemia, infarction) in patients with risk factors for coronary artery disease","Risk of cerebrovascular events including stroke","Risk of peripheral vascular ischemia","Risk of fibrosis (e.g., cardiac valvular, retroperitoneal, pulmonary)","May cause serotonin syndrome when used with serotonergic drugs","Do not use within 24 hours of another 5-HT1 agonist","Overuse may lead to medication-overuse headache"] |
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| Fetal Monitoring | Monitor uterine tone and fetal heart rate during use (if used inadvertently near term). Avoid use in pregnancy; if exposure occurs, assess fetal wellbeing via ultrasound, fetal heart rate monitoring, and growth scans due to risk of uteroplacental insufficiency. |
| Fertility Effects | Ergot alkaloids may inhibit prolactin secretion, potentially affecting ovulation and implantation. No formal human fertility studies; animal studies show reduced fertility at high doses. Clinical relevance uncertain. |