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 Ergometrine / Methylergonovine
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.
Ergometrine and methylergonovine are ergot alkaloids that act as partial agonists at alpha-adrenergic, dopaminergic, and serotonergic (5-HT2) receptors. Their primary uterotonic effect is mediated by stimulation of 5-HT2 receptors in uterine smooth muscle, leading to sustained contractions and vasoconstriction.
Acute treatment of migraine headaches with or without aura,Acute treatment of cluster headaches
Prevention and treatment of postpartum hemorrhage (FDA approved),Uterine atony (FDA approved),Ovarian hyperstimulation syndrome (off-label),Variceal bleeding (off-label),Migraine headache (off-label)
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.
0.2 mg intramuscularly or intravenously, repeated every 2-4 hours as needed, up to 5 doses total. Maximum single dose: 0.5 mg. Maximum total dose: 1 mg.
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.
30-120 min (biphasic: initial 10 min, terminal 30-120 min); clinical context: short half-life allows repeated dosing for postpartum hemorrhage but requires monitoring for accumulation
Ergotamine is extensively metabolized by CYP3A4. Caffeine is metabolized primarily by CYP1A2.
Primarily hepatic via CYP3A4; also undergoes first-pass metabolism. Metabolites are excreted in urine and bile.
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.
Renal (20% unchanged), biliary/fecal (35% as metabolites and parent compound)
Ergotamine is approximately 90% bound to plasma proteins, primarily to albumin and alpha-1 acid glycoprotein. Caffeine is about 35% bound, mainly to albumin.
85-90% (primarily to albumin and α1-acid glycoprotein)
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.
0.4-0.6 L/kg; clinical meaning: moderate tissue distribution, consistent with limited extravascular binding
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: 20-40% (due to extensive first-pass metabolism); IM: ~80%
No specific dose adjustments available; contraindicated in severe renal impairment (Cr Cl < 20 m L/min) due to risk of accumulation.
No specific guidelines; use with caution in severe renal impairment (GFR <30 m L/min) due to risk of accumulation and hypertensive effects.
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 Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% or extend interval. Child-Pugh Class C: avoid use.
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.
0.1-0.2 mg intramuscularly or intravenously every 2-4 hours as needed; maximum single dose 0.2 mg. For postpartum hemorrhage, 0.2 mg IM/IV repeated every 2-4 hours, max 5 doses.
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 lowest effective dose due to increased sensitivity and higher risk of hypertension and coronary vasospasm; consider 0.1 mg initially and titrate cautiously.
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.
Concurrent use with potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors, azole antifungals) may result in acute ergot toxicity (vasospasm, cerebral and peripheral ischemia). Contraindicated in pregnancy for induction of labor due to risk of uterine rupture and fetal harm.
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
May cause hypertension, especially in patients with preeclampsia or hypertension. Use with caution in patients with sepsis, hepatic or renal impairment, coronary artery disease, or peripheral vascular disease. Avoid prolonged use. Monitor uterine tone and bleeding.
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
Pregnancy (except for postpartum hemorrhage), hypertension, preeclampsia, eclampsia, coronary artery disease, peripheral vascular disease, Raynaud's phenomenon, sepsis, hypersensitivity to ergot alkaloids, 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.
No known 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.
First trimester: Limited human data; animal studies show embryotoxicity and fetotoxicity at high doses due to uterotonic effects, but no structural malformations. Increased risk of spontaneous abortion from uterine hyperstimulation. Second trimester: Uterotonic effects may cause placental abruption, preterm labor, or fetal hypoxia. Third trimester: Contraindicated due to potent uterotonic activity; can cause uterine tetany, fetal distress, and stillbirth. Avoid during pregnancy unless for postpartum hemorrhage.
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.
Ergometrine and methylergonovine are excreted into breast milk in small amounts; M/P ratio estimated at 0.2-0.3. Milk concentrations are low (approximately 1-2% of maternal weight-adjusted dose). The American Academy of Pediatrics considers use compatible with breastfeeding, but may cause ergotism in infants (vomiting, diarrhea, seizures) with prolonged use. Short-term use for postpartum hemorrhage is generally acceptable.
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.
No dose adjustment required for pregnancy because drug is contraindicated during pregnancy due to uterotonic effects. In postpartum use (which is the approved indication), no pharmacokinetic changes necessitate dose adjustment; normal adult dosing applies (0.2 mg IM/IV for ergometrine, 0.2 mg IM for methylergonovine).
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.
Administer intramuscularly or intravenously (slow push over 1 minute) for uterine atony; avoid in hypertension, preeclampsia, and sepsis. Store ampules protected from light; discard if discolored. Contraindicated in impaired hepatic or renal function.
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.
This medication may cause nausea, vomiting, or headache.,Report severe abdominal pain, chest pain, or difficulty breathing immediately.,Avoid driving or operating machinery if dizziness occurs.,Do not use during pregnancy except for postpartum hemorrhage.,Inform your doctor if you have high blood pressure, heart disease, or are breastfeeding.
"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."
"Coadministration of bromocriptine, a dopamine D2 receptor agonist with vasoconstrictive properties, and ergometrine, an ergot alkaloid that acts as a partial agonist at alpha-adrenergic and serotonin receptors, synergistically increases peripheral vasoconstriction. This additive effect can lead to severe hypertension, myocardial ischemia, cerebral vasospasm, and potentially life-threatening ergotism. Patients may present with headache, chest pain, altered mental status, or peripheral ischemia."
"Nylidrin, a beta-adrenergic agonist, and ergometrine, an ergot alkaloid with vasoconstrictive properties, exhibit a synergistic hypertensive effect. By stimulating beta-2 receptors, nylidrin may cause peripheral vasodilation and reflex tachycardia, while ergometrine induces vasoconstriction via alpha-adrenergic and serotonin receptor activation. This opposing mechanism can lead to unopposed vasoconstriction, potentially resulting in severe hypertension, myocardial ischemia, or stroke."
"Simvastatin, a HMG-CoA reductase inhibitor, may increase the serum concentration of ergometrine, an ergot alkaloid used for postpartum hemorrhage, by inhibiting its metabolism via CYP3A4. This can lead to enhanced vasoconstrictive effects of ergometrine, potentially causing severe hypertension, myocardial ischemia, or peripheral vasospasm. Concomitant use poses a risk of ergotism, manifesting as ischemic complications, and should be approached with caution."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ERGOTAMINE TARTRATE AND CAFFEINE vs Ergometrine / Methylergonovine, 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.. Ergometrine / Methylergonovine is a Ergot Alkaloid Uterotonic that works by Ergometrine and methylergonovine are ergot alkaloids that act as partial agonists at alpha-adrenergic, dopaminergic, and serotonergic (5-HT2) receptors. Their primary uterotonic effect is mediated by stimulation of 5-HT2 receptors in uterine smooth muscle, leading to sustained contractions and vasoconstriction.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ERGOTAMINE TARTRATE AND CAFFEINE and Ergometrine / Methylergonovine 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 Ergometrine / Methylergonovine is: 0.2 mg intramuscularly or intravenously, repeated every 2-4 hours as needed, up to 5 doses total. Maximum single dose: 0.5 mg. Maximum total dose: 1 mg.. 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 Ergometrine / Methylergonovine 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 . Ergometrine / Methylergonovine is classified as Category C. First trimester: Limited human data; animal studies show embryotoxicity and fetotoxicity at high doses due to uterotonic effects, but no structural malformations. Increased risk of. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.