DIHYDROERGOTAMINE MESYLATE
Clinical safety rating: avoid
Contraindicated (not allowed)
Dihydroergotamine mesylate is an ergot alkaloid with potent agonist activity at serotonin 5-HT1B/1D receptors, leading to vasoconstriction of cranial blood vessels. It also has partial agonist/antagonist activity at alpha-adrenergic and dopamine receptors, contributing to its antimigraine effects.
| Metabolism | Primarily hepatic via CYP3A4; undergoes first-pass metabolism. The main metabolite is 8'-hydroxy-dihydroergotamine, which is also active. |
| Excretion | Primarily hepatic metabolism; <10% excreted unchanged in urine; biliary/fecal excretion accounts for ~90% of metabolites. |
| Half-life | Terminal half-life is approximately 9 hours (range 7-13 hours) after IM administration; clinical effect duration corresponds to this elimination phase. |
| Protein binding | Approximately 93% bound, primarily to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 0.25-0.3 L/kg; indicates moderate tissue distribution with high affinity for vascular receptors. |
| Bioavailability | Intramuscular: ~30-40% (due to first-pass metabolism); intranasal: ~38-50% (relative to IM); oral: <1% (not clinically used orally). |
| Onset of Action | IM: 15-30 minutes; IV: immediate (within minutes); intranasal: 30-60 minutes. |
| Duration of Action | IM/IV: 3-4 hours for headache relief; may persist up to 24 hours due to prolonged vasoconstriction; clinical effect may outlast plasma levels. |
| Molecular Weight | 679.78 |
1 mg intramuscularly or subcutaneously, repeat at 1-hour intervals as needed, maximum 3 mg per 24 hours and 6 mg per week; intravenous use is reserved for severe cases: 0.5-1 mg IV, may repeat once after 1 hour, maximum 2 mg per 24 hours.
| Dosage form | SPRAY, METERED |
| Renal impairment | CrCl <30 mL/min: contraindicated; CrCl 30-60 mL/min: use with caution, reduce dose by 50%; CrCl >60 mL/min: no adjustment needed. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: contraindicated; Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for patients under 12 years of age due to lack of safety data; for adolescents (12-17 years): 0.5-1 mg subcutaneously or intramuscularly, repeat at 1-hour intervals as needed, maximum 2 mg per 24 hours and 4 mg per week. |
| Geriatric use | Elderly patients may have increased sensitivity; initiate at 0.5 mg intramuscularly or subcutaneously, maximum 2 mg per 24 hours; monitor for adverse effects (e.g., vasospasm, ischemia). |
| 1st trimester | Contraindicated: ergot alkaloids are oxytocic and can cause uterine contractions and fetal harm; also associated with teratogenic effects in animal studies. |
| 2nd trimester | Contraindicated: risk of uterine hyperstimulation and fetal distress; potential for ergotism with prolonged use. |
| 3rd trimester | Contraindicated: high risk of uterine hyperstimulation, fetal distress, and neonatal ergotism; use for postpartum hemorrhage only under specific protocols. |
Clinical note
Strong CYP3A4 inhibitors (eg clarithromycin) are contraindicated due to risk of ergotism Contraindicated in coronary artery disease and uncontrolled hypertension.
| Placental transfer | Crosses placenta; ergot alkaloids are known to transfer and can cause uteroplacental insufficiency and fetal toxicity. |
| Breastfeeding | Excreted into breast milk; may cause ergotism in infants (vomiting, diarrhea, convulsions); may inhibit lactation via prolactin suppression. Use only if benefit outweighs risk and with close infant monitoring. |
■ FDA Black Box Warning
Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors (including protease inhibitors, azole antifungals, and macrolide antibiotics).
| Common Effects | Nausea |
| Serious Effects |
Hypersensitivity to ergot alkaloidsUncontrolled hypertensionCoronary artery diseasePeripheral vascular diseaseSepsisSevere hepatic or renal impairmentPregnancy (for migraine use)Concurrent use of potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors, azole antifungals) or triptans
| Precautions | Risk of cerebral and peripheral vasospasm, especially with prolonged use or overdose, May cause ergotism (symptoms include numbness, tingling, cyanosis, and gangrene), Caution in patients with hypertension, coronary artery disease, or impaired hepatic/renal function, Avoid repeated administration within 24 hours due to risk of accumulation and toxicity |
Loading safety data…
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | FDA Pregnancy Category X. Dihydroergotamine is contraindicated in all trimesters due to oxytocic effects and uterine hypertonicity risk. Case reports of fetal hypoxia, growth restriction, and malformations (including limb defects and neural tube defects) from ergot alkaloids. First trimester: increased risk of spontaneous abortion and congenital anomalies. Second and third trimesters: risk of preterm labor, fetal distress, and low birth weight due to uteroplacental insufficiency. |
| Fetal Monitoring | Monitor fetal growth, amniotic fluid index, and umbilical artery Doppler every 4-6 weeks due to potential uteroplacental insufficiency. Assess for signs of fetal distress (non-stress test, biophysical profile). Monitor maternal blood pressure and signs of ergotism (nausea, vomiting, paresthesia, chest pain). Avoid concomitant use with potent CYP3A4 inhibitors. |
| Fertility Effects | May impair fertility due to prolactin inhibition and potential hormonal disruption. Ergot alkaloids can interfere with ovulation and implantation. Limited data on male fertility; theoretical risk of reduced sperm quality. |
| Food/Dietary |
| Grapefruit juice may increase systemic exposure; avoid concurrent consumption. Alcohol may exacerbate headache or adverse effects. |
| Clinical Pearls | Avoid use within 24 hours of other ergot alkaloids or triptans due to additive vasospasm risk. Administer at first sign of migraine aura or headache; may repeat after 1 hour (max 3 mg/day, 6 mg/week). Contraindicated in coronary artery disease, uncontrolled hypertension, and pregnancy. Intranasal route may cause rhinorrhea or nasal congestion. |
| Patient Advice | Use exactly as prescribed at the first sign of a migraine headache. · Do not exceed 3 mg in 24 hours or 6 mg in one week. · Seek emergency help if you experience signs of ergotism: severe muscle pain, cold or numb fingers/toes, or chest tightness. · Avoid grapefruit juice as it may increase drug levels. · Do not take with other migraine medications (triptans, other ergots) within 24 hours. · Report any chest pain, shortness of breath, or irregular heartbeat immediately. |