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 ERGOMAR
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 acts as a partial agonist at serotonin 5-HT1B and 5-HT1D receptors, causing vasoconstriction of cranial blood vessels. It also inhibits norepinephrine reuptake and has alpha-adrenergic blocking activity.
Acute treatment of migraine headaches with or without aura,Acute treatment of cluster headaches
Abortive treatment of acute migraine headaches with or without aura,Cluster headache
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.
Ergotamine tartrate 1-2 mg sublingually or orally at onset of migraine, then 1-2 mg every 30 minutes as needed, maximum 6 mg per attack and 10 mg 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.
Terminal elimination half-life is approximately 2-3 hours for ergotamine, but clinical effects may persist longer due to active metabolites (e.g., ergotamine's half-life is 2.4 hours; metabolites have half-lives up to 10 hours).
Ergotamine is extensively metabolized by CYP3A4. Caffeine is metabolized primarily by CYP1A2.
Primarily hepatic via CYP3A4; minor contributions from CYP2D6. Undergoes extensive first-pass metabolism.
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 with extensive biliary excretion; less than 5% excreted unchanged in urine. Fecal elimination accounts for approximately 30-40% of the dose as metabolites.
Ergotamine is approximately 90% bound to plasma proteins, primarily to albumin and alpha-1 acid glycoprotein. Caffeine is about 35% bound, mainly to albumin.
90-95% 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.
Approximately 0.4 L/kg (16-18 L in adults), indicating moderate tissue distribution.
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%.
Sublingual: ~40-50%; Oral: <10% due to extensive first-pass metabolism; Rectal: ~25-30%.
No specific dose adjustments available; contraindicated in severe renal impairment (Cr Cl < 20 m L/min) due to risk of accumulation.
GFR > 30 m L/min: No adjustment. GFR 10-30 m L/min: Caution; reduce dose by 50%. GFR < 10 m L/min: Contraindicated.
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.
Child-Pugh A: Caution; reduce dose by 50%. Child-Pugh B: Contraindicated. Child-Pugh C: Contraindicated.
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 children under 12 years. Pediatric use not established; avoid use.
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.
Elderly patients are more sensitive to vasoconstriction; use lower initial dose (e.g., 1 mg) and monitor for adverse effects.
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 and vasospasm have been associated with the concomitant use 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 ischemic events (peripheral, cardiac, cerebral), fibrosis (retroperitoneal, pulmonary, cardiac), elderly patients (more sensitive to adverse effects), ergotism, drug interactions with CYP3A4 inhibitors, and prolonged use leading to medication-overuse headache.
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
Hypersensitivity to ergot alkaloids, peripheral vascular disease, coronary artery disease, uncontrolled hypertension, sepsis, hepatic or renal impairment, pregnancy, breastfeeding, concomitant use with potent CYP3A4 inhibitors, hemiplegic or basilar migraine.
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 grapefruit and grapefruit juice as they inhibit CYP3A4, increasing ergotamine levels and risk of toxicity. No other significant food interactions.
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.
Ergotamine (ERGOMAR) is contraindicated in pregnancy due to its oxytocic properties and potential for uterine hyperstimulation, fetal hypoxia, and congenital anomalies. First trimester: Increased risk of spontaneous abortion and major malformations (e.g., limb defects, CNS abnormalities) based on case reports. Second and third trimesters: Uterine hypertonicity and decreased placental perfusion leading to fetal distress, preterm labor, and low birth weight. Use only if benefit outweighs risk and no alternative; avoid in all trimesters.
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.
Ergotamine is excreted into breast milk with a milk-to-plasma ratio of approximately 0.5-0.9. Potential for ergotism symptoms in infants (vomiting, diarrhea, seizures). It may also reduce milk production due to prolactin inhibition. Contraindicated during breastfeeding per manufacturer guidelines. If exposure occurs, monitor infant for symptoms and consider abrupt cessation.
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.
Pregnancy may alter ergotamine pharmacokinetics (increased plasma volume, renal clearance, hepatic metabolism), but no established dose adjustment guidelines. Standard doses may be ineffective or toxic due to variable absorption. Avoid use if possible; if necessary, lowest effective dose for shortest duration, with close monitoring for toxicity.
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.
Ergomar (ergotamine tartrate sublingual tablets) is a first-line abortive therapy for acute migraine attacks, but its use is limited by vasoconstrictive risks. Avoid in patients with coronary artery disease, hypertension, peripheral vascular disease, or pregnancy. Administer at the first sign of migraine; sublingual route offers rapid absorption. Concomitant use with potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors) is contraindicated due to risk of ergotism. Limit total dose to 6 mg per attack and 10 mg per week.
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 one sublingual tablet at the first sign of migraine, placing it under the tongue to dissolve, and do not swallow.,Do not exceed 3 tablets per attack or 5 tablets per week; overuse can lead to serious side effects.,Seek immediate medical attention if you experience symptoms of ergotism like severe coldness, numbness, or pain in hands/feet, muscle cramps, chest pain, or rapid heartbeat.,Avoid grapefruit and grapefruit juice during treatment as it may increase the risk of side effects.,Inform your doctor if you are pregnant, breastfeeding, or have any history of heart disease, high blood pressure, or peripheral artery disease.
"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 ERGOMAR, 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.. ERGOMAR is a Ergot Alkaloid Antimigraine that works by Ergotamine acts as a partial agonist at serotonin 5-HT1B and 5-HT1D receptors, causing vasoconstriction of cranial blood vessels. It also inhibits norepinephrine reuptake and has alpha-adrenergic blocking activity.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ERGOTAMINE TARTRATE AND CAFFEINE and ERGOMAR 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 ERGOMAR is: Ergotamine tartrate 1-2 mg sublingually or orally at onset of migraine, then 1-2 mg every 30 minutes as needed, maximum 6 mg per attack and 10 mg 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 ERGOMAR 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 . ERGOMAR is classified as Category C. Ergotamine (ERGOMAR) is contraindicated in pregnancy due to its oxytocic properties and potential for uterine hyperstimulation, fetal hypoxia, and congenital anomalies. First trime. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.