Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ERGOTAMINE TARTRATE AND CAFFEINE vs CAFERGOT
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Ergotamine is a partial agonist/antagonist at serotonin (5-HT), dopamine, and alpha-adrenergic receptors, causing vasoconstriction of cranial blood vessels. Caffeine enhances ergotamine absorption and has additive vasoconstrictive 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,Acute treatment of cluster headaches
Acute treatment of migraine headaches with or without aura,Acute treatment of cluster headache episodes
Oral: 2 mg ergotamine tartrate and 200 mg caffeine at onset of migraine, then 1 mg ergotamine tartrate and 100 mg caffeine every 30 minutes as needed; maximum 6 mg ergotamine tartrate and 600 mg caffeine per day or 10 mg ergotamine tartrate and 1000 mg caffeine per week. Rectal: 2 mg ergotamine tartrate and 200 mg caffeine as a single suppository at onset; repeat once after 1 hour if needed; maximum 4 mg ergotamine tartrate and 400 mg caffeine per day or 8 mg ergotamine tartrate and 800 mg caffeine per week.
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.
Ergotamine has a terminal elimination half-life of approximately 2 hours (range 1.5–2.5 hours) for the alpha phase, but a longer terminal half-life of 12–24 hours due to slow tissue release; this contributes to its prolonged duration of action and risk of accumulation with frequent dosing.
2.5-3.9 hours (ergotamine); clinical context: t1/2 may be prolonged in hepatic impairment.
Ergotamine is extensively metabolized by CYP3A4. Caffeine is metabolized primarily by CYP1A2.
Primarily hepatic via CYP3A4; ergotamine is extensively metabolized, and caffeine is metabolized via CYP1A2.
Ergotamine is primarily excreted in bile and feces as metabolites, with approximately 90% of a dose eliminated via the biliary-fecal route and less than 4% excreted unchanged in urine. Caffeine is extensively metabolized in the liver and its metabolites are excreted renally, with only about 1% excreted unchanged.
Primarily hepatic metabolism and biliary excretion; less than 5% excreted unchanged in urine. Fecal elimination accounts for most of the administered dose.
Ergotamine is approximately 90% bound to plasma proteins, primarily to albumin and alpha-1 acid glycoprotein. Caffeine is about 35% bound, mainly to albumin.
98-99% bound to plasma proteins, primarily albumin.
Ergotamine has a large volume of distribution, approximately 2–3 L/kg (range 1.5–4 L/kg), indicating extensive tissue distribution and binding to tissues, including the brain. Caffeine has a Vd of about 0.5–0.7 L/kg.
1.1-2.0 L/kg; clinical meaning: extensive tissue distribution, particularly into liver and spleen.
Oral: bioavailability of ergotamine is low and erratic due to extensive first-pass metabolism, typically <5% (range 0–5%). Sublingual: bioavailability is slightly higher but still low, around 1–3%. Rectal: bioavailability is approximately 2–5%, somewhat more consistent than oral. Caffeine is well absorbed orally with bioavailability near 100%.
Oral: <5% due to extensive first-pass metabolism; Sublingual: approximately 15-20%; Rectal: approximately 20-30%.
No specific dose adjustments available; contraindicated in severe renal impairment (Cr Cl < 20 m L/min) due to risk of accumulation.
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.
Contraindicated in hepatic impairment (Child-Pugh class B or C). Use with caution in mild impairment (Child-Pugh class A); reduce initial dose by 50% and closely monitor for adverse effects.
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 younger than 12 years due to lack of safety and efficacy data. For adolescents aged 12-17 years: 1 mg ergotamine tartrate and 100 mg caffeine orally at onset, repeat every 30 minutes if needed; maximum 3 mg ergotamine tartrate and 300 mg caffeine per day; or rectal suppository (1 mg ergotamine tartrate/100 mg caffeine) at onset, repeat once after 1 hour; maximum 2 mg ergotamine tartrate and 200 mg caffeine per day.
Not recommended for use in pediatric patients due to risk of ergotism and lack of safety data. No established weight-based dosing.
Use with caution due to increased risk of peripheral vascular disease, coronary artery disease, and reduced hepatic/renal function. Initiate at lowest effective dose (e.g., 1 mg ergotamine tartrate and 100 mg caffeine orally) and monitor for signs of ischemia. Avoid in patients over 65 with uncontrolled hypertension or vascular risk.
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 or life-threatening peripheral ischemia and cerebral ischemia have been associated with ergotamine use, especially with prolonged use or overdose. Concomitant use with potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors) increases risk.
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 ergotism (ischemia, gangrene) with prolonged use or high doses,May cause vasospastic reactions, including coronary vasospasm,Overuse can lead to medication-overuse headache,Avoid concomitant use with vasoconstrictors or ergot-like drugs,May cause nausea, vomiting, and paresthesias
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
Peripheral vascular disease (e.g., Raynaud's disease),Coronary artery disease, uncontrolled hypertension,Severe renal or hepatic impairment,Sepsis or severe infection,Concurrent use of potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors),Pregnancy (teratogenic, oxytocic effects),History of hypersensitivity to ergotamine or caffeine
Peripheral vascular disease,Coronary artery disease,Hypertension (uncontrolled),Sepsis,Severe hepatic or renal impairment,Pregnancy (Category X),Breastfeeding,Concurrent use of potent CYP3A4 inhibitors
Avoid grapefruit juice; it inhibits CYP3A4, increasing ergotamine absorption and risk of toxicity. Caffeine-containing foods (coffee, tea, cola) may be consumed in moderation but excessive caffeine intake may exacerbate 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.
Pregnancy Category X. Ergotamine is contraindicated in all trimesters due to potent uterotonic effects and vasoconstriction, which can cause fetal hypoxia, growth retardation, and spontaneous abortion. Caffeine may be associated with low birth weight and preterm delivery at high doses. There are no adequate studies in pregnant women.
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 during breastfeeding. Ergotamine is excreted into breast milk and can cause ergotism (vomiting, diarrhea, convulsions) in infants. Caffeine may cause irritability and poor sleep. M/P ratio unknown.
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.
No dose adjustment is recommended because use is contraindicated during pregnancy. Pharmacokinetic changes (increased plasma volume, reduced binding) do not warrant adjustment in this contraindicated setting.
Contraindicated in pregnancy; no dosing adjustments recommended. Use is not safe; alternative therapy should be sought.
Ergotamine tartrate is a serotonin 5-HT1B/1D receptor agonist and alpha-adrenergic blocker. Caffeine enhances ergotamine absorption and adds vasoconstriction. Contraindicated in coronary artery disease, uncontrolled hypertension, peripheral vascular disease, sepsis, and within 24 hours of triptans. Risk of ergotism with excessive use. Limit acute use to ≤6 mg/attack and ≤10 mg/week. Avoid prolonged daily use to prevent rebound headache.
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.
Take at the first sign of migraine headache; do not use for prevention.,Do not exceed one dose per 24 hours; maximum 2 tablets per attack and 5 tablets per week.,Seek emergency care if symptoms of ergotism (cold/blue extremities, muscle pain, numbness, tingling) occur.,Avoid concurrent use with triptans or other ergot alkaloids within 24 hours.,Not for use during pregnancy or breastfeeding; use reliable contraception.,Do not consume grapefruit juice as it may increase ergotamine levels.,Report chest pain, palpitations, or severe abdominal pain 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.
"Terbutaline, a beta-2 adrenergic agonist, can cause vasodilation and increased heart rate. Ergotamine, a vasoconstrictor used for migraine, may lead to excessive vasoconstriction when combined with terbutaline due to opposing vascular effects. This interaction can result in hypertensive crisis, ischemia, or peripheral vascular complications."
"Metronidazole inhibits CYP3A4, the primary enzyme responsible for the metabolism of ergotamine. Co-administration can lead to significantly elevated ergotamine plasma concentrations, increasing the risk of ergotism—a serious condition characterized by severe vasoconstriction, ischemia, and potential gangrene of the extremities. Patients may present with symptoms such as cold, painful extremities, muscle pain, and paresthesias, requiring immediate intervention."
"Concomitant use of ergotamine and cortisone acetate is contraindicated due to the potential for severe vasospasm and ischemic events. Corticosteroids like cortisone can inhibit the metabolism of ergotamine via CYP3A4, leading to increased ergotamine concentrations. This enhances ergotamine's vasoconstrictive effects, risking digital ischemia, cerebrovascular accidents, and myocardial infarction."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ERGOTAMINE TARTRATE AND CAFFEINE vs CAFERGOT, answered by our medical review team.
ERGOTAMINE TARTRATE AND CAFFEINE is a Ergot Alkaloid that works by Ergotamine is a partial agonist/antagonist at serotonin (5-HT), dopamine, and alpha-adrenergic receptors, causing vasoconstriction of cranial blood vessels. Caffeine enhances ergotamine absorption and has additive vasoconstrictive 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 ERGOTAMINE TARTRATE AND CAFFEINE 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 ERGOTAMINE TARTRATE AND CAFFEINE is: Oral: 2 mg ergotamine tartrate and 200 mg caffeine at onset of migraine, then 1 mg ergotamine tartrate and 100 mg caffeine every 30 minutes as needed; maximum 6 mg ergotamine tartrate and 600 mg caffeine per day or 10 mg ergotamine tartrate and 1000 mg caffeine per week. Rectal: 2 mg ergotamine tartrate and 200 mg caffeine as a single suppository at onset; repeat once after 1 hour if needed; maximum 4 mg ergotamine tartrate and 400 mg caffeine per day or 8 mg ergotamine tartrate and 800 mg caffeine per week.. 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 ERGOTAMINE TARTRATE AND CAFFEINE 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. ERGOTAMINE TARTRATE AND CAFFEINE is classified as Category D/X. Pregnancy Category X. Ergotamine is contraindicated in all trimesters due to potent uterotonic effects and vasoconstriction, which can cause fetal hypoxia, growth retardation, and . 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.