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Ergotamine and caffeine: Drug information

Ergotamine and caffeine: Drug information
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For additional information see "Ergotamine and caffeine: Patient drug information" and "Ergotamine and caffeine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Concurrent drug therapy:

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.

Brand Names: US
  • Cafergot [DSC];
  • Migergot
Pharmacologic Category
  • Antimigraine Agent;
  • Central Nervous System Stimulant;
  • Ergot Derivative
Dosing: Adult
Migraine, moderate to severe, acute treatment

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 (Ref).

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 (Ref). 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.

Dosing: Kidney Impairment: Adult

Use is contraindicated.

Dosing: Liver Impairment: Adult

Use is contraindicated.

Dosing: Older Adult

Refer to adult dosing; use caution due to vasoconstrictive properties (Ref).

Dosing: Pediatric

(For additional information see "Ergotamine and caffeine: Pediatric drug information")

Migraine

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 (Ref).

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 (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Use is contraindicated in patients with impaired renal function.

Dosing: Liver Impairment: Pediatric

Use is contraindicated in patients with impaired hepatic function.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified. Also see individual agents.

Frequency not defined:

Cardiovascular: Bradycardia, cold extremity, ECG changes, hypertension, ischemia, tachycardia

Dermatologic: Gangrene of skin and/or subcutaneous tissues, pruritus

Gastrointestinal: Anal fissure (with overuse of suppository), nausea, rectal ulcer (with overuse of suppository), vomiting

Local: Localized edema

Nervous system: Asthenia, numbness, paresthesia, precordial pain, vertigo

Neuromuscular & skeletal: Myalgia

Respiratory: Cyanosis

Postmarketing:

Cardiovascular: Valvular sclerosis

Genitourinary: Retroperitoneal fibrosis

Nervous system: Drug abuse, drug dependence

Respiratory: Pleuropulmonary fibrosis

Contraindications

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.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

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).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suppository, Rectal:

Migergot: Ergotamine tartrate 2 mg and caffeine 100 mg (12 ea)

Tablet, Oral:

Cafergot: Ergotamine tartrate 1 mg and caffeine 100 mg [DSC]

Generic: Ergotamine tartrate 1 mg and caffeine 100 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Suppository (Migergot Rectal)

2-100 mg (per each): $246.48

Tablets (Ergotamine-Caffeine Oral)

1-100 mg (per each): $29.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: Administer with or without food.

Rectal: Suppository: Administer rectally.

Administration: Pediatric

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.

Use: Labeled Indications

Migraine, moderate to severe, acute treatment: Treatment of migraine.

Medication Safety Issues
Sound-alike/look-alike issues:

Cafergot may be confused with Carafate

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

Acebrophylline: May increase stimulatory effects of CNS Stimulants. Risk X: Avoid

Adenosine: Caffeine and Caffeine Containing Products may decrease therapeutic effects 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 increase vasoconstricting effects of Alpha-/Beta-Agonists. Risk X: Avoid

Alpha1-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may increase vasoconstricting effects of Alpha1-Agonists. Risk X: Avoid

Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor

Aprepitant: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor

Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Beta-Blockers: May increase vasoconstricting effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor

Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Broccoli: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor

Bromocriptine: Ergot Derivatives may increase adverse/toxic effects of Bromocriptine. Risk X: Avoid

Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Bromperidol: Caffeine and Caffeine Containing Products may decrease absorption of Bromperidol. Risk C: Monitor

BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor

Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor

Cannabis: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor

Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Chloroprocaine (Systemic): May increase hypertensive effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. Risk C: Monitor

Cocaine (Topical): May increase hypertensive effects 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 serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor

CYP1A2 Inhibitors (Moderate): May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor

CYP1A2 Inhibitors (Strong): May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor

CYP3A4 Inhibitors (Moderate): May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

CYP3A4 Inhibitors (Strong): May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Diazoxide Choline: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid

Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor

Dihydroergotamine: Ergot Derivatives may increase vasoconstricting effects of Dihydroergotamine. Risk X: Avoid

Doxofylline: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Doxofylline. Risk X: Avoid

DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Erythromycin (Systemic): May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor

Esketamine (Nasal): May increase hypertensive effects of CNS Stimulants. Risk C: Monitor

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid

Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Formoterol: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Formoterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Formoterol. Risk C: Monitor

Fosamprenavir: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Grapefruit Juice: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor

Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Indacaterol: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Indacaterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Indacaterol. Risk C: Monitor

Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 increase adverse/toxic effects 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 increase adverse/toxic effects 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

Itraconazole: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid

Landiolol: Sympathomimetics may decrease therapeutic effects of Landiolol. Risk C: Monitor

Lenacapavir: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Letermovir: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor

Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification

Lisuride: May increase adverse/toxic effects of Ergot Derivatives. Risk X: Avoid

Lithium: Caffeine and Caffeine Containing Products may decrease serum concentration of Lithium. Risk C: Monitor

Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Metergoline: Ergot Derivatives may increase adverse/toxic effects of Metergoline. Management: Combined use of metergoline with other ergot alkaloids after birth and during the postpartum period is specifically not recommended. Risk D: Consider Therapy Modification

Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Methysergide: Ergot Derivatives may increase vasoconstricting effects of Methysergide. Risk X: Avoid

MigALAstat: Caffeine and Caffeine Containing Products may decrease serum concentration of MigALAstat. Risk X: Avoid

Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Nefazodone: May increase serotonergic effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). This could result in serotonin syndrome. Nefazodone may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Nicotine: May increase vasoconstricting effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

Nitroglycerin: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may decrease vasodilatory effects of Nitroglycerin. Nitroglycerin may increase 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 serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor

OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Olodaterol: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Olodaterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Olodaterol. Risk C: Monitor

Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pergolide: May increase adverse/toxic effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid

Pipemidic Acid: May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor

Primaquine: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor

Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Reboxetine: May increase hypertensive effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

Regadenoson: Caffeine and Caffeine Containing Products may decrease vasodilatory effects of Regadenoson. Management: Avoid use of caffeine and caffeine-containing products for at least 12 hours prior to regadenoson administration. Risk D: Consider Therapy Modification

RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Roxithromycin: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Serotonergic Agents (High Risk): Ergot Derivatives may increase serotonergic effects 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

Serotonin 5-HT1D Receptor Agonists (Triptans): May increase vasoconstricting effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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

Solriamfetol: CNS Stimulants may increase hypertensive effects of Solriamfetol. CNS Stimulants may increase tachycardic effects of Solriamfetol. Risk C: Monitor

Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor

Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sulprostone: May increase vasoconstricting effects of Ergot Derivatives. Risk C: Monitor

Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor

Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor

Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor

Tipranavir: May increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid

TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification

Tobacco (Smoked): May decrease serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor

Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Warfarin: Caffeine and Caffeine Containing Products may decrease anticoagulant effects of Warfarin. Risk C: Monitor

Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Food Interactions

See individual agents.

Pregnancy Considerations

Ergotamine and caffeine both cross the placenta.

Use of this combination is contraindicated during pregnancy. Refer to individual monographs for additional information.

Breastfeeding Considerations

Caffeine and ergotamine are present in breast milk.

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 this combination, considering the importance of treatment to the mother.

Refer to individual monographs for additional information.

Monitoring Parameters

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.

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

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)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BD) Bangladesh: Cafergot | Migrin;
  • (BG) Bulgaria: Coffergamin;
  • (CH) Switzerland: Cafergot | Migrexa;
  • (CL) Chile: Ergopast;
  • (CN) China: Ergotamine and caffeine | Ergotamine+caffein;
  • (CO) Colombia: Ergotamina/cafeina | Fencafen | Migradol;
  • (DE) Germany: Cafergot n;
  • (EC) Ecuador: Cafergot;
  • (FI) Finland: Cafergot;
  • (FR) France: Gynergene cafeine;
  • (GR) Greece: Cafergot;
  • (HK) Hong Kong: Cafergot;
  • (ID) Indonesia: Cafergot | Ericaf;
  • (IE) Ireland: Cafergot;
  • (IL) Israel: Cafergot;
  • (IN) India: Migranil | Migranil ec;
  • (IR) Iran, Islamic Republic of: Ergotamine C;
  • (IT) Italy: Cafergot;
  • (KE) Kenya: Cafergot;
  • (KR) Korea, Republic of: Caffel q | Caffer q | Craming;
  • (LT) Lithuania: Cafergot;
  • (LV) Latvia: Cafergot;
  • (MA) Morocco: Gynergene cafeine;
  • (MX) Mexico: Ergocaf;
  • (MY) Malaysia: Cafergot | Caffox;
  • (NG) Nigeria: Cafetal | Cefergot;
  • (NL) Netherlands: Cafergot;
  • (NO) Norway: Cafergot;
  • (NZ) New Zealand: Cafergot;
  • (PE) Peru: Ergocaf | Ergonex | Ergotamina + cafeina;
  • (PK) Pakistan: Cafergot;
  • (PL) Poland: Cafergot n;
  • (PR) Puerto Rico: Cafergot | Ercaf | Ergotamine tartrate and caffeine | Ergotamine/cafeine;
  • (PT) Portugal: Cafergot;
  • (QA) Qatar: Cafergot;
  • (SE) Sweden: Cafergot;
  • (SG) Singapore: Cafergot | Caffox;
  • (TH) Thailand: Avamigran | Berraga f | Cafargo | Cafergot | Degran | Hofergot | Migana | Migrano | Neogot | Polygot | Tofago;
  • (TN) Tunisia: Gynergene cafeine;
  • (TW) Taiwan: Antimigraine | Cafergot | Cafeton | Coffegot | Ergocafe | Ergocaine | Ergodan | Ergoffeine | Ergolar caffeine | Ergoton | Iruton | Tonpen;
  • (VE) Venezuela, Bolivarian Republic of: Cafergot;
  • (ZA) South Africa: Cafergot
  1. Cafergot (ergotamine tartrate and caffeine tablets, USP) [prescribing information]. Princeton, NJ: Sandoz Inc; May 2018.
  2. Géraud G, Lantéri-Minet M, Lucas C, Valade D, French Society for the Study of Migraine Headache (SFEMC). French guidelines for the diagnosis and management of migraine in adults and children. Clin Ther. 2004;26(8):1305-1318. [PubMed 15476911]
  3. Krupp GR, Friedman AP. Migraine in children; a report of fifty children. AMA Am J Dis Child. 1953;85(2):146-150. [PubMed 13007165]
  4. Migergot (ergotamine tartrate and caffeine) suppositories, USP [prescribing information]. South Plainfield, NJ: Cosette Pharmaceuticals Inc; June 2020.
  5. Nelson WE, Behrman RE, Kliegman RM, et al, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: WB Saunders Company; 1996: 2058-2078.
  6. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):e32-e69. doi:10.1161/CIR.0000000000000426 [PubMed 27400984]
  7. Perrin VL, “Clinical Pharmacokinetics of Ergotamine in Migraine and Cluster Headache,” Clin Pharmacokinetics, 1985, 10(4):334-52. [PubMed 3899452]
  8. Refer to the manufacturer's labeling.
  9. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-1345. doi:10.1212/WNL.0b013e3182535d20 [PubMed 22529202]
  10. Singer HS. Migraine headaches in children. Pediatr Rev. 1994;15(3):94-101. [PubMed 8041676]
  11. Steiner TJ, Jensen R, Katsarava Z, et al. Aids to management of headache disorders in primary care (2nd edition): on behalf of the European Headache Federation and Lifting the Burden: the Global Campaign Against Headache. J Headache Pain. 2019;20(1):57. doi:10.1186/s10194-018-0899-2 [PubMed 31113373]
  12. Tfelt-Hansen P, Saxena PR, Dahlöf C, et al. Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000;123(pt 1):9-18. doi:10.1093/brain/123.1.9 [PubMed 10611116]
  13. Welborn CA. Pediatric migraine. Emerg Med Clin North Am. 1997;15(3):625-636. [PubMed 9255136]
  14. Worthington I, Pringsheim T, Gawel MJ, et al; Canadian Headache Society Acute Migraine Treatment Guideline Development Group. Canadian Headache Society guideline: acute drug therapy for migraine headache. Can J Neurol Sci. 2013;40(5)(suppl 3):S1-S80. [PubMed 23968886]
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