Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DIHYDROERGOTAMINE MESYLATE vs CAFERGOT
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Ergotamine is a serotonin (5-HT1B/1D) receptor agonist that causes vasoconstriction of cranial blood vessels and inhibits neurogenic inflammation. Caffeine is a methylxanthine that enhances ergotamine absorption and may contribute to vasoconstriction.
Acute treatment of migraine headaches with or without aura (FDA-approved),Acute treatment of cluster headache episodes (off-label)
Acute treatment of migraine headaches with or without aura,Acute treatment of cluster headache episodes
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.
1 to 2 tablets (each containing ergotamine tartrate 1 mg and caffeine 100 mg) orally at onset of migraine, then 1 tablet every 30 minutes as needed, maximum 6 tablets per attack or 10 tablets per week. Alternatively, 1 rectal suppository (ergotamine tartrate 2 mg and caffeine 100 mg) at onset, repeat once after 1 hour if needed, maximum 2 suppositories per attack or 5 per week.
Terminal half-life is approximately 9 hours (range 7-13 hours) after IM administration; clinical effect duration corresponds to this elimination phase.
2.5-3.9 hours (ergotamine); clinical context: t1/2 may be prolonged in hepatic impairment.
Primarily hepatic via CYP3A4; undergoes first-pass metabolism. The main metabolite is 8'-hydroxy-dihydroergotamine, which is also active.
Primarily hepatic via CYP3A4; ergotamine is extensively metabolized, and caffeine is metabolized via CYP1A2.
Primarily hepatic metabolism; <10% excreted unchanged in urine; biliary/fecal excretion accounts for ~90% of metabolites.
Primarily hepatic metabolism and biliary excretion; less than 5% excreted unchanged in urine. Fecal elimination accounts for most of the administered dose.
Approximately 93% bound, primarily to serum albumin and alpha-1-acid glycoprotein.
98-99% bound to plasma proteins, primarily albumin.
Approximately 0.25-0.3 L/kg; indicates moderate tissue distribution with high affinity for vascular receptors.
1.1-2.0 L/kg; clinical meaning: extensive tissue distribution, particularly into liver and spleen.
Intramuscular: ~30-40% (due to first-pass metabolism); intranasal: ~38-50% (relative to IM); oral: <1% (not clinically used orally).
Oral: <5% due to extensive first-pass metabolism; Sublingual: approximately 15-20%; Rectal: approximately 20-30%.
Cr Cl <30 m L/min: contraindicated; Cr Cl 30-60 m L/min: use with caution, reduce dose by 50%; Cr Cl >60 m L/min: no adjustment needed.
Contraindicated in severe renal impairment. In moderate renal impairment (e GFR 30-59 m L/min/1.73 m²): use with caution; dose reduction not specifically defined but monitor for adverse effects. Mild impairment (e GFR ≥60 m L/min/1.73 m²): no adjustment needed.
Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: contraindicated; Child-Pugh Class C: contraindicated.
Contraindicated in Child-Pugh Class C. Child-Pugh Class A: no adjustment; Class B: use with caution, reduce dose by 50% and monitor. No specific dose recommendations from manufacturer; clinical judgment advised.
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.
Not recommended for use in pediatric patients due to risk of ergotism and lack of safety data. No established weight-based dosing.
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).
Use with caution due to increased risk of ergotism, renal/hepatic impairment, and drug interactions. Lower initial dose (e.g., 1 tablet) and careful monitoring. Avoid in patients over 65 with significant vascular disease.
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).
Serious and/or life-threatening peripheral ischemia has been associated with coadministration of ergotamine with potent CYP3A4 inhibitors (including protease inhibitors, macrolide antibiotics, and azole antifungals).
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
Risk of ergotism (ischemia, gangrene) with prolonged use or overdosage,May cause vasospastic reactions, including coronary artery vasospasm and myocardial infarction,Rebound headache (medication overuse headache) with frequent use,Caffeine withdrawal may exacerbate headaches,Avoid concurrent use with potent CYP3A4 inhibitors
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)
Peripheral vascular disease,Coronary artery disease,Hypertension (uncontrolled),Sepsis,Severe hepatic or renal impairment,Pregnancy (Category X),Breastfeeding,Concurrent use of potent CYP3A4 inhibitors
Grapefruit juice may increase systemic exposure; avoid concurrent consumption. Alcohol may exacerbate headache or adverse effects.
Avoid excessive caffeine intake (e.g., coffee, tea, cola, energy drinks) as Cafergot contains caffeine and may cause additive stimulation or toxicity. Limit caffeine to no more than 200 mg per day during treatment.
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 Category X. First trimester: ergotamine is a potent vasoconstrictor and uterine stimulant, associated with increased risk of spontaneous abortion, congenital anomalies (including micrognathia, microphthalmia, cleft palate, and limb defects). Second and third trimesters: continued risk of uteroplacental insufficiency, intrauterine growth restriction, preterm labor, and fetal distress due to vasoconstriction and increased uterine tone.
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.
Contraindicated during breastfeeding. Ergotamine reduces prolactin secretion and may suppress lactation. It is excreted into breast milk; M/P ratio not established. Reported infant adverse effects include vomiting, diarrhea, and seizures. Risk of vasospasm and ergotism in the infant.
Not applicable; contraindicated in pregnancy. No pharmacokinetic studies exist due to safety concerns. No dose adjustments are recommended as the drug should not be used.
Contraindicated in pregnancy; no dosing adjustments recommended. Use is not safe; alternative therapy should be sought.
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.
Cafergot is ergotamine-caffeine combination for acute migraine. Avoid in pregnancy, uncontrolled hypertension, CAD, and peripheral vascular disease. Maximum dose: 6 tablets per attack or 10 tablets per week. Use at first sign of migraine. Not for prophylaxis. Can cause ergotism with prolonged use. Monitor for signs of ischemia.
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.
Take at the first sign of migraine headache for best effect.,Do not take more than 6 tablets per attack or 10 tablets per week.,Avoid use if you are pregnant, breastfeeding, or have high blood pressure, heart disease, or circulation problems.,Seek emergency care if you experience severe stomach pain, chest pain, numbness, tingling, or muscle cramps.,Do not take with other ergotamine drugs or strong CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics).,Store at room temperature, away from heat and moisture.
"Dihydroergotamine is a potent inhibitor of CYP3A4, the primary enzyme responsible for the metabolism of bortezomib. Co-administration can significantly decrease bortezomib clearance, leading to elevated plasma concentrations and increased risk of bortezomib-related toxicities, particularly peripheral neuropathy, thrombocytopenia, and hypotension. Clinicians should monitor for enhanced adverse effects and consider dose adjustments or alternative therapies."
"Seratrodast, a thromboxane A2 receptor antagonist, inhibits CYP3A4-mediated metabolism of dihydroergotamine, a vasoconstrictor ergot alkaloid. This results in elevated plasma dihydroergotamine concentrations, increasing the risk of ergotism (severe vasospasm, ischemia, and potential gangrene). Clinical outcomes may include hypertension, myocardial ischemia, and peripheral vascular compromise, particularly in patients with risk factors such as coronary artery disease or smoking."
"Dexchlorpheniramine maleate, a first-generation antihistamine with significant anticholinergic properties, may inhibit the metabolism of dihydroergotamine via competitive antagonism of cytochrome P450 (CYP) 3A4 isoenzymes. This interaction can lead to elevated plasma concentrations of dihydroergotamine, increasing the risk of ergotism (e.g., vasospasm, ischemia, gangrene) and hypertensive crisis. Clinically, patients may present with peripheral coldness, muscle pain, cyanosis, or severe hypertension, particularly with concurrent use or overdose."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about DIHYDROERGOTAMINE MESYLATE vs CAFERGOT, answered by our medical review team.
DIHYDROERGOTAMINE MESYLATE is a Ergot Alkaloid that works by 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.. CAFERGOT is a Antimigraine Agent (Ergot Alkaloid) that works by Ergotamine is a serotonin (5-HT1B/1D) receptor agonist that causes vasoconstriction of cranial blood vessels and inhibits neurogenic inflammation. Caffeine is a methylxanthine that enhances ergotamine absorption and may contribute to vasoconstriction.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DIHYDROERGOTAMINE MESYLATE and CAFERGOT depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of DIHYDROERGOTAMINE MESYLATE is: 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.. The standard adult dose of CAFERGOT is: 1 to 2 tablets (each containing ergotamine tartrate 1 mg and caffeine 100 mg) orally at onset of migraine, then 1 tablet every 30 minutes as needed, maximum 6 tablets per attack or 10 tablets per week. Alternatively, 1 rectal suppository (ergotamine tartrate 2 mg and caffeine 100 mg) at onset, repeat once after 1 hour if needed, maximum 2 suppositories per attack or 5 per week.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between DIHYDROERGOTAMINE MESYLATE and CAFERGOT in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. DIHYDROERGOTAMINE MESYLATE is classified as Category D/X. FDA Pregnancy Category X. Dihydroergotamine is contraindicated in all trimesters due to oxytocic effects and uterine hypertonicity risk. Case reports of fetal hypoxia, growth restr. CAFERGOT is classified as Category C. FDA Category X. First trimester: ergotamine is a potent vasoconstrictor and uterine stimulant, associated with increased risk of spontaneous abortion, congenital anomalies (includi. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.