ergotamine/caffeine (Rx)

Brand and Other Names:Cafergot, Migergot
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Dosing & Uses


Dosage Forms & Strengths


oral tablet (Cafergot)

  • 1mg/100mg

rectal suppository (Migergot)

  • 2mg/100mg

Vascular Headache

Indicated as therapy to abort or prevent vascular headache (eg, migraine, migraine variants, “histaminic cephalalgia”)

Not for chronic daily use


  • 2 tablets (ergotamine 2 mg/caffeine 200 mg) PO at first sign of attack; may take 1 tablet (ergotamine 1 mg/caffeine 100 mg) q30min prn
  • Not to exceed 6 tablets/attack
  • Not to exceed 10 tablets/week


  • Insert 1 suppository rectally at first sign of attack; may repeat once after 1 hr
  • Not to exceed 2 suppositories/attack
  • Not to exceed 5 suppositories/week

Short-term prevention

  • In carefully selected patients, with due consideration of maximum dosage recommendations, administration of the drug at bedtime may be an appropriate short-term preventive measure

Dosage Modifications

Renal or hepatic impairment

  • Contraindicated

Dosing Considerations

Not effective for other types of headaches; lacks analgesic properties

Safety and efficacy not established



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            Adverse Effects

            Frequency Not Defined

            Gastrointestinal: Nausea and vomiting; rectal or anal ulcer (from overuse of suppositories)

            Neurological: Paresthesia, numbness, weakness, and vertigo

            Allergic: Localized edema and itching


            • Serious vasoconstrictive complications may occur including ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes, and muscle pains
            • Most commonly occurs with long-term therapy at relatively high doses; also reported with short-term or normal doses
            • Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension


            Black Box Warnings

            Serious and/or life-threatening peripheral ischemia associated with coadministration of ergotamine and caffeine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics

            Because CYP3A4 inhibition elevates ergotamine and caffeine serum levels, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased

            Concomitant use of these medications is contraindicated


            Potent CYP3A4 inhibitors owing to risk of acute ergot toxicity


            Peripheral vascular disease, coronary heart disease, hypertension, impaired hepatic or renal function, sepsis

            Hypersensitivity to any of the ingredients



            • Although ergotism rarely develop even after long-term intermittent use of orally administered ergotamine, do not exceed dosage recommendations
            • Ergotism manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia
            • Headache, intermittent claudication, muscle pains, numbness, or coldness and pallor of the digits may occur with chronic intoxication; if the condition is allowed to progress untreated, gangrene can result
            • While most cases result from frank overdosage, some cases involve hypersensitivity
            • There are few reports among patients taking doses within recommended limits or for brief periods
            • Withdrawal symptoms (eg, rebound headache) upon discontinuation are rare; typically reported with long, indiscriminate use

            Fibrotic complications

            • Retroperitoneal and/or pleuropulmonary fibrosis reported
            • Rare reports of fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with long-term, continuous use of ergotamine tartrate and caffeine
            • Do not use for chronic daily administration

            Drug interaction overview

            • Ergotamine is a CYP3A substrate and inhibitor
            • CYP3A inhibitors
              • Potent inhibitors: Contraindicated owing to risk for acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities
              • Less potent inhibitors: Although not contraindicated, avoid if possible owing to risk for vasospasm

            Pregnancy & Lactation


            Contraindicated; ergotamine elicits oxytocic effects

            There are no studies on placental transfer or teratogenicity of the combination of ergotamine and caffeine

            Labor and delivery

            • Contraindicated in labor and delivery owing to ergotamine’s oxytocic effect, which is maximal in the third trimester

            Animal studies

            • Caffeine is known to cross the placenta and has been shown to be teratogenic in animals
            • Ergotamine crosses the placenta in small amounts, although it does not appear to be embryotoxic in this quantity; however, prolonged vasoconstriction of uterine vessels and/or increased myometrial tone leading to reduced myometrial and placental blood flow may have contributed to fetal growth retardation observed in animals


            Ergot drugs are known to inhibit prolactin, but there are no reports of decreased lactation with ergotamine/caffeine

            Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhea, weak pulse, and unstable blood pressure in nursing infants

            Owing to the potential serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            Ergotamine: Alpha-adrenergic blocking agent with direct stimulating effect on smooth muscle of peripheral and cranial blood vessels; also elicits serotonin antagonism

            Caffeine: Cranial vasoconstrictor; added to further enhance vasoconstrictive effect without increasing ergotamine dosage


            Bioavailability: <5%

            Peak plasma time: 2 hr (PO)


            Vd: 1.85 L/kg


            Extensively metabolized in liver hepatic metabolism


            Half-life: 2-2.5 hr

            Excretion: Feces (90%, mostly as metabolites)



            Oral Administration

            May take with or without food

            Rectal Administration

            Remove suppository from foil wrap

            Lay on side and insert pointed end of suppository into rectum; remain on side to allow suppository to dissolve and absorb

            Avoid handling unwrapped suppository for too long

            If needed, may cut suppository lengthwise



            • Store at 20-25ºC (68-77ºF)
            • Dispense in tight, light-resistant container


            • Refrigerate at 2-8ºC (36-46ºF) in sealed foil


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            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.