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. |
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 | 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.
| Breastfeeding | Contraindicated in breastfeeding. Dihydroergotamine is excreted in breast milk; M/P ratio unknown. Ergot alkaloids can cause vomiting, diarrhea, weak pulse, unstable blood pressure, and convulsions in infants. May also suppress lactation via prolactin inhibition. |
| 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. |
■ 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 |
["Concurrent use with potent CYP3A4 inhibitors (e.g., protease inhibitors, azole antifungals, macrolides)","Uncontrolled hypertension","Coronary artery disease, including angina or history of myocardial infarction","Peripheral vascular disease","Sepsis","Pregnancy (category X)","Severe hepatic or renal impairment","History of hemiplegic or basilar migraine (due to risk of vasospasm)"]
| 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"] |
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| 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. |