Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine/caffeine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of ergotamine/caffeine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.
Migraine, moderate to severe, acute treatment (alternative agent):
Note: Contraindicated in patients with coronary artery disease, hypertension, peripheral vascular disease, renal or hepatic disease, or patients who are pregnant or of childbearing potential. May be associated with significant side effects and may worsen nausea and vomiting associated with migraine. Other migraine-specific agents are preferred; ergotamine may be considered in patients with migraine attacks >48 hours or those with frequent headache recurrence (EHF/WHO [Steiner 2019]; Tfelt-Hansen 2000; manufacturer's labeling).
Oral: Ergotamine 2 mg/caffeine 200 mg (2 tablets) as a single dose at onset of attack. If symptoms persist or return, may administer ergotamine 1 mg/caffeine 100 mg (1 tablet) every 30 minutes as needed; some experts recommend separating by 1 hour and limiting to 3 repeat doses (CHS [Worthington 2013]; manufacturer’s labeling). Maximum dose: Ergotamine 6 mg/caffeine 600 mg (6 tablets) per attack; do not exceed ergotamine 10 mg/caffeine 1,000 mg (10 tablets) per week.
Rectal: Ergotamine 2 mg/caffeine 100 mg (1 suppository) as a single dose at onset of attack; if symptoms persist or return, may administer an additional suppository after 1 hour. Maximum dose: Ergotamine 4 mg/caffeine 200 mg (2 suppositories) per attack; do not exceed ergotamine 10 mg/caffeine 500 mg (5 suppositories) per week.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Use is contraindicated.
Use is contraindicated.
(For additional information see "Ergotamine and caffeine: Pediatric drug information")
Migraine: Limited data available; efficacy results variable: Note: Not for chronic daily administration. Not a preferred agent; use of ergotamine has largely been replaced by newer agents with improved efficacy and adverse effect profile.
Adolescents:
Oral: Tablets (ergotamine 1 mg/caffeine 100 mg per tablet): Initial dose: 1 or 2 tablets at onset of attack; then 1 tablet every 30 minutes as needed up to 4 additional doses; maximum dose per attack: 6 tablets (ergotamine 6 mg/caffeine 600 mg); maximum weekly dose: 10 tablets/week (ergotamine 10 mg/caffeine 1,000 mg). Note: Some experts have recommended lower maximum doses (maximum dose per attack: ergotamine 3 mg/attack; maximum weekly dose: ergotamine 5 mg/week) in patients <14 years (Géraud 2004; Krupp 1953; Nelson 1996; Singer 1994; Welborn 1997).
Rectal: Suppository (ergotamine 2 mg/caffeine 100 mg per suppository): Initial: 1/2 suppository (ergotamine 1 mg/caffeine 50 mg) at first sign of an attack; may repeat in 45 minutes if necessary. Maximum dose per attack: 1 suppository (ergotamine 2 mg/caffeine 100 mg)/attack; maximum dose per day: 2 suppositories (ergotamine 4 mg/caffeine 200 mg)/attack; maximum weekly dose: 4 suppositories (ergotamine 8 mg/caffeine 400 mg)/week (Singer 1994).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Use is contraindicated in patients with impaired renal function.
Use is contraindicated in patients with impaired hepatic function.
Refer to adult dosing; use caution due to vasoconstrictive properties (CHS [Worthington 2013]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suppository, Rectal:
Migergot: Ergotamine tartrate 2 mg and caffeine 100 mg (12 ea)
Tablet, Oral:
Cafergot: Ergotamine tartrate 1 mg and caffeine 100 mg
Generic: Ergotamine tartrate 1 mg and caffeine 100 mg
May be product dependent
Oral: Administer with or without food.
Rectal: Suppository: Administer rectally.
Oral: Tablets may be taken without regard to meals.
Rectal: Suppository: Remove foil from rectal suppository and insert pointed end first. Avoid handling unwrapped suppository for too long. If necessary to cut suppository, cut lengthwise.
Migraine, moderate to severe, acute treatment: Treatment of migraine.
Cafergot may be confused with Carafate
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Bradycardia, cold extremities, ECG changes, edema, hypertension, ischemia, tachycardia, valvular sclerosis, vasospasm
Central nervous system: Numbness, paresthesia, precordial pain, vertigo
Dermatologic: Gangrene of skin or other tissue, pruritus
Gastrointestinal: Anal fissure (with overuse of suppository), nausea, rectal ulcer (with overuse of suppository), vomiting
Genitourinary: Retroperitoneal fibrosis
Neuromuscular & skeletal: Myalgia, weakness
Respiratory: Cyanosis, pleuropulmonary fibrosis
Hypersensitivity to ergotamine, caffeine, or any component of the formulation; peripheral vascular disease; hepatic or renal impairment; coronary artery disease; hypertension; sepsis; concomitant use with strong inhibitors of CYP3A4 (includes protease inhibitors, cobicistat, azole antifungals, and some macrolide antibiotics); pregnancy or childbearing potential.
Concerns related to adverse effects:
• Cardiac valvular fibrosis: Ergot alkaloids have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.
• Cardiovascular effects: Vasospasm or vasoconstriction can occur, possibly resulting in decreased cerebral blood flow, ECG changes, and hypertension; sustained vasoconstriction may also lead to ischemic colitis, intermittent claudication, aggravation of angina, or precipitation of myocardial infarction. Do not use in any patient at risk or predisposed to vascular effects of ergot alkaloids. In a scientific statement from the American Heart Association, ergotamine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).
• Ergotism: Ergot alkaloid use may result in ergotism (intense vasoconstriction) resulting in peripheral vascular ischemia and possible gangrene. Ergotism is usually associated with overdosage or prolonged chronic use; do not exceed dosing guidelines and avoid prolonged administration.
• Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily administration.
Special populations:
• Older adults: Avoid use in older adults due to the vasoconstrictive properties and cardiovascular adverse effects associated with ergot alkaloids.
Dosage form specific issues:
• Rectal suppositories: Solitary rectal or anal ulcers have occurred rarely when suppositories are used in higher than recommended doses or with continual use of recommended doses for prolonged periods of time. After discontinuation, spontaneous healing occurs within 4 to 8 weeks.
Other warnings/precautions:
• Appropriate use: Do not use for prolonged daily administration; serious adverse effects are associated with long-term continuous use. Use caution and remain within recommended dosage limits.
• Medication-overuse headache/Withdrawal: Discontinuation even after limited use may result in withdrawal symptoms (ie, rebound headache, nausea, vomiting).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Risk X: Avoid combination
Adenosine: Caffeine and Caffeine Containing Products may diminish the therapeutic effect of Adenosine. Management: Monitor for decreased effect of adenosine if patient is receiving caffeine; significantly higher adenosine doses or alternative agents may be required. Discontinue caffeine 24 hours in advance of scheduled diagnostic use of adenosine if possible. Risk D: Consider therapy modification
Alpha-/Beta-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination
Alpha1-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Antipsychotic Agents: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Aprepitant: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy
Bromocriptine: Ergot Derivatives may enhance the adverse/toxic effect of Bromocriptine. Risk X: Avoid combination
Bromperidol: Caffeine and Caffeine Containing Products may decrease the absorption of Bromperidol. Risk C: Monitor therapy
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy
Chloroprocaine (Systemic): May enhance the hypertensive effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification
CYP1A2 Inducers (Moderate): May decrease the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Delavirdine: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Doxofylline: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Doxofylline. Risk X: Avoid combination
Erythromycin (Systemic): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Esketamine: May enhance the hypertensive effect of CNS Stimulants. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Formoterol: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Formoterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Formoterol. Risk C: Monitor therapy
Fosamprenavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Indacaterol: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Indacaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Indacaterol. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Lenacapavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Letermovir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Risk D: Consider therapy modification
Lisuride: May enhance the adverse/toxic effect of Ergot Derivatives. Risk X: Avoid combination
Lithium: Caffeine and Caffeine Containing Products may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin (Withdrawn From US Market) may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Risk X: Avoid combination
Methysergide: Ergot Derivatives may enhance the vasoconstricting effect of Methysergide. Risk X: Avoid combination
Nefazodone: May enhance the serotonergic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Nitroglycerin: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may diminish the vasodilatory effect of Nitroglycerin. Nitroglycerin may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Management: Avoid the use of ergot derivatives in patients receiving nitroglycerin for angina (or in any angina patient) if possible. If combined, monitor for decreased effects of nitroglycerin and increased adverse effects of the ergot derivative (eg, ergotism). Risk D: Consider therapy modification
Norfloxacin: May increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
Olodaterol: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Olodaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Olodaterol. Risk C: Monitor therapy
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Pergolide: May enhance the adverse/toxic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Pipemidic Acid: May increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
Reboxetine: May enhance the hypertensive effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Regadenoson: Caffeine and Caffeine Containing Products may diminish the vasodilatory effect of Regadenoson. Management: Avoiding using caffeine or other methylxanthine containing products (e.g., theophylline) for at least 12 hours prior to the administration of regadenoson. Risk D: Consider therapy modification
Roxithromycin: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Serotonergic Agents (High Risk): Ergot Derivatives may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. CNS Stimulants may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Tipranavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Tobacco (Smoked): May decrease the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
Warfarin: Caffeine and Caffeine Containing Products may diminish the anticoagulant effect of Warfarin. Risk C: Monitor therapy
See individual agents.
Ergotamine and caffeine both cross the placenta. Use is contraindicated in pregnancy. Refer to individual monographs for additional information.
Caffeine is excreted in breast milk and may cause adverse events in a breastfed infant (Atkinson 1988; Berlin 1984). Ergotamine is excreted in breast milk and may cause vomiting, diarrhea, weak pulse, and unstable BP in the breastfed infant. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
BUN, serum creatinine, LFTs (at baseline), signs of peripheral ischemia (eg, vasospasm, digit coldness, pallor), numbness, muscle pains, extremity weakness, chest pain, tachycardia or bradycardia, hypersensitivity reactions.
Has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha-adrenergic receptors depending upon their site; is a highly active uterine stimulant; it causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers
Absorption: Ergotamine: Oral, rectal: Erratic (Perrin, 1985)
Metabolism: Ergotamine: Extensively hepatic, including high first-pass metabolism (Perrin, 1985)
Bioavailability: Ergotamine: Oral, rectal: ≤5% (Perrin, 1985)
Half-life elimination: Ergotamine: 2 to 2.5 hours (Perrin, 1985)
Time to peak, serum: Ergotamine: 2 hours (Perrin, 1985)
Excretion: Ergotamine: Feces (90%, primarily as metabolites) (Perrin, 1985)
Suppository (Migergot Rectal)
2-100 mg (per each): $203.91
Tablets (Cafergot Oral)
1-100 mg (per each): $15.44
Tablets (Ergotamine-Caffeine Oral)
1-100 mg (per each): $13.88
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