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). |
| Molecular Weight | 591.7 |
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 | Contraindicated due to ergotamine derivative properties and risk of teratogenicity; use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; may cause uterine contractions and reduce placental blood flow, but risk of fetal harm is lower than in t1. |
| 3rd trimester | Contraindicated near term due to potent oxytocic effects and risk of uterine tetany, fetal distress, or neonatal ergotism. |
Clinical note
Comprehensive clinical and safety monograph for MIGRANAL (MIGRANAL).
| Placental transfer | Crosses placenta; ergotamine derivatives can constrict uteroplacental vessels, reducing fetal oxygenation. |
| Breastfeeding | Excreted into breast milk; may cause ergotism in infants (vomiting, diarrhea, seizures). Avoid breastfeeding; if necessary, discard milk for 48 hours after dose. |
■ 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 ergot alkaloidsCoronary artery diseasePeripheral vascular diseaseHypertension (severe or uncontrolled)SepsisHepatic or renal impairmentPregnancy (especially t1 and t3)Concurrent use with potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors)
| 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 |
| Food/Dietary | Avoid grapefruit juice as it may increase dihydroergotamine levels via CYP3A4 inhibition. No other significant food restrictions. |
Loading safety data…
| Lactation Rating |
| L5 |
| 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. |
| 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. |
| Clinical Pearls | MIGRANAL (dihydroergotamine mesylate) is a 5-HT1B/1D receptor agonist and ergot alkaloid used for acute migraine treatment. Intranasal administration bypasses first-pass metabolism. Avoid use within 24 hours of triptans due to additive vasospasm risk. Contraindicated in coronary artery disease, uncontrolled hypertension, and hemiplegic/basilar migraine. |
| Patient Advice | Use one spray in each nostril at onset of migraine; do not exceed 3 sprays per day or 8 sprays per week. · Wait 15 minutes between sprays if needed; do not repeat dose within 24 hours. · Report chest tightness, palpitations, or numbness immediately. · Avoid driving if dizzy or drowsy after use. · Store at room temperature; do not freeze. |