D.H.E. 45
Clinical safety rating: caution
Comprehensive clinical and safety monograph for D.H.E. 45 (D.H.E. 45).
Dihydroergotamine (DHE) is a semi-synthetic ergot alkaloid that acts as an agonist at serotonin (5-HT1B/1D) receptors, causing vasoconstriction of intracranial blood vessels and inhibition of trigeminal nerve transmission, thereby aborting migraine attacks. It also has high affinity for alpha-adrenergic receptors and moderate affinity for dopamine D2 receptors.
| Metabolism | Primarily hepatic via CYP3A4. Undergoes extensive first-pass metabolism. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for approximately 90% of elimination, with 10% fecal. |
| Half-life | 2.5 hours (range 2-3.5 hours) for ergotamine; clinical context: short half-life supports its use in acute migraine, but frequent dosing risks ergotism. |
| Protein binding | 90% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 2 L/kg; indicates extensive tissue distribution, particularly into vascular smooth muscle. |
| Bioavailability | Subcutaneous: 47% (range 30-60%); intramuscular: 50% (range 40-60%); oral: <1% due to extensive first-pass metabolism. |
| Onset of Action | Subcutaneous/intramuscular: 15-30 minutes; intravenous: immediate but not recommended due to safety concerns. |
| Duration of Action | 3-4 hours; clinical note: may provide relief for up to 24 hours in some patients due to prolonged vasoconstriction, but standard dosing interval is 1-2 hours if needed. |
1 mg intramuscularly or subcutaneously at first sign of headache, repeat hourly up to 3 mg per day, maximum 6 mg per week.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose modifications established; use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation. |
| Liver impairment | Contraindicated in Child-Pugh Class B and C cirrhosis. In mild hepatic impairment (Child-Pugh A), use with caution and consider reduced dose. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Use with caution due to increased sensitivity to vasospastic effects and higher prevalence of cardiovascular disease; consider starting at lower dose (0.5 mg) and monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for D.H.E. 45 (D.H.E. 45).
| Breastfeeding | Not recommended during breastfeeding. Dihydroergotamine is excreted into breast milk; M/P ratio unknown. Potential for infant toxicity including vomiting, diarrhea, convulsions, and vasospasm. Theoretical risk of reduced milk production due to prolactin suppression. Alternative therapy preferred. |
| Teratogenic Risk | D.H.E. 45 (dihydroergotamine mesylate) is contraindicated in pregnancy (Category X). First trimester: associated with teratogenic effects including skeletal anomalies, microcephaly, and gastroschisis due to ergot alkaloid-induced vasoconstriction and uterine hypertonicity. Second and third trimesters: risk of placental insufficiency, intrauterine growth restriction, and preterm labor; can cause uterine contractions leading to miscarriage or premature delivery. |
■ FDA Black Box Warning
WARNING: SERIOUS AND/OR LIFE-THREATENING PERIPHERAL ISCHEMIA AND VASOSPASM. Dihydroergotamine has been associated with serious adverse events, including cerebral hemorrhage, myocardial infarction, and digital ischemia. Concomitant use with potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors) is contraindicated due to increased risk of vasospasm.
| Serious Effects |
Hypersensitivity to ergot alkaloids, ischemic heart disease (angina, history of MI, coronary vasospasm), uncontrolled hypertension, peripheral vascular disease (Raynaud's, thromboangiitis obliterans), severe hepatic or renal impairment, sepsis, pregnancy (Category X), concomitant use with potent CYP3A4 inhibitors, within 24 hours of triptan use.
| Precautions | Use with caution in patients at risk for coronary artery disease, uncontrolled hypertension, or previous history of cerebrovascular events. Avoid in patients with sepsis, severe hepatic or renal impairment, or peripheral vascular disease. Monitor for signs of ergotism (numbness, cyanosis, muscle pain). Concomitant use with triptans, other ergot alkaloids, or vasoconstrictors is not recommended within 24 hours. |
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| Fetal Monitoring | Inadvertent use during pregnancy requires fetal ultrasound to assess growth and anatomy. Monitor for signs of uterine hypertonicity or contractions. Serial growth scans if continued exposure. Maternal blood pressure and heart rate monitoring due to vasoconstrictive effects. |
| Fertility Effects | May impair fertility in females due to hyperprolactinemia and suppression of ovulation. Ergot alkaloids can inhibit prolactin secretion but paradoxically may cause galactorrhea and amenorrhea in some cases. Male fertility not specifically studied; theoretical risk of impaired spermatogenesis due to vasoconstriction. |