Ergotamine + Caffeine

Pharmacologic Category

Antimigraine Agent; Central Nervous System Stimulant; Ergot Derivative

Dosing: Adult

Vascular headache:

Oral: Note: Each tablet contains ergotamine 1 mg and caffeine 100 mg: Ergotamine 2 mg and caffeine 200 mg (2 tablets) at onset of attack; then ergotamine 1 mg and caffeine 100 mg (1 tablet) every 30 minutes as needed

Maximum dose: Ergotamine 6 mg and caffeine 600 mg (6 tablets) per attack; do not exceed ergotamine 10 mg and caffeine 1,000 mg (10 tablets) per week

Rectal: Ergotamine 2 mg and caffeine 100 mg (1 suppository) at first sign of an attack; follow with second dose after 1 hour, if needed

Maximum dose: Ergotamine 4 mg and caffeine 200 mg (2 suppositories) per attack; do not exceed ergotamine 10 mg and 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: Renal Impairment: Adult

Use is contraindicated.

Dosing: Hepatic Impairment: Adult

Use is contraindicated.

Dosing: Pediatric

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 Not a preferred agent; use of ergotamine has largely been replaced by newer agents with improved efficacy and adverse effect profile.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.

Dosing: Renal Impairment: Pediatric

Use is contraindicated in patients with impaired renal function.

Dosing: Hepatic Impairment: Pediatric

Use is contraindicated in patients with impaired hepatic function.

Use: Labeled Indications

Vascular headache: Prevention or treatment of vascular headaches, such as migraine, migraine variants, or so-called “histaminic cephalalgia”

Administration: Oral

Administer with or without food.

Administration: Rectal

Suppository: Remove foil from rectal suppository and insert pointed end first. Avoid handling unwrapped suppository for too long.

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.

Storage/Stability

Suppositories: Store refrigerated at 2°C to 8°C (36°F to 46°F) in sealed foil.

Tablet: Store at 20°C to 25°C (68°F to 77°F). Protect from light.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat migraine headaches.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Chest pain

• Slow heartbeat

• Fast heartbeat

• Abnormal heartbeat

• Shortness of breath

• Swelling of arms or legs

• Excessive weight gain

• Swelling

• Severe dizziness

• Passing out

• Severe headache

• Vision changes

• Muscle weakness

• Muscle pain

• Change in color of hands or feet from pale to blue or red

• Sensation of cold in extremities

• Numbness, pain, or tingling in extremities

• Rectal sores

• Rectal pain

• Wounds on fingers or toes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to ergotamine, caffeine, or any component of the formulation; peripheral vascular disease; hepatic or renal impairment; coronary heart disease; hypertension; sepsis; concomitant use of ergot alkaloids with strong inhibitors of CYP3A4 (includes HIV and HCV protease inhibitors, cobicistat, azole antifungals, and some macrolide antibiotics); pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac valvular fibrosis: Ergot alkaloids have been associated (rarely) 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 cyanosis, decreased cerebral blood flow, bradycardia or tachycardia, asystole, and hypertension; sustained vasoconstriction may also lead to intermittent claudication, precordial distress, and pain. Do not use in any patient at risk or predisposed to vascular effects of ergot alkaloids.

• 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.

Concurrent drug therapy issues:

• CYP3A4 inhibitors: [U.S. Boxed Warning]: Ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors and some macrolide antibiotics). Serum levels of ergotamines may be elevated, leading to increased risk of vasospasm leading to cerebral ischemia and/or ischemia of extremities. Serious and/or life-threatening peripheral ischemia has been associated with concomitant use.

Special populations:

• Elderly: Avoid use in the elderly 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).

Geriatric Considerations

Not recommended for use in the elderly. May be harmful due to reduction in cerebral blood flow. May precipitate angina, myocardial infarction, or aggravate intermittent claudication.

Pregnancy Considerations

Ergotamine and caffeine both cross the placenta. Use is contraindicated in pregnant women. Refer to individual monographs for additional information.

Breast-Feeding Considerations

Caffeine is excreted in breast milk and may cause adverse events in a nursing infant (Atkinson, 1988; Berlin, 1984). Ergotamine is excreted in breast milk and may cause vomiting, diarrhea, weak pulse, and unstable blood pressure in the nursing infant. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Caffeine
• Ergotamine

Adverse Reactions

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

Allergy and Idiosyncratic Reactions

• Ergot Alkaloid Allergy

Toxicology

• Caffeine

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions Open Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Abametapir: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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 may enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination

Alpha1-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives 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

Antihepaciviral Combination Products: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Management: Avoid coadministration of beta-blockers and ergot derivatives whenever possible. If concomitant use cannot be avoided, monitor patients closely for evidence of excessive peripheral vasoconstriction. Risk D: Consider therapy modification

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

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. Exceptions: Cannabidiol. Risk C: Monitor therapy

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

Chloroprocaine: May enhance the hypertensive effect of Ergot Derivatives. Risk C: Monitor therapy

Clarithromycin: May increase the serum concentration of Ergotamine. Risk X: Avoid combination

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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Cobicistat: May increase the serum concentration of Ergotamine. Risk X: Avoid combination

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

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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 decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Risk D: Consider therapy modification

Doxofylline: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Doxofylline. Risk X: Avoid combination

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

Enzalutamide: May decrease the serum concentration of Ergotamine. Risk X: Avoid combination

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

Esketamine: May enhance the hypertensive effect of CNS Stimulants. Risk C: Monitor therapy

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

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

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

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

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Risk D: Consider therapy modification

Itraconazole: May increase the serum concentration of Ergotamine. Risk X: Avoid combination

Ketoconazole (Systemic): May increase the serum concentration of Ergotamine. Risk X: Avoid combination

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

Letermovir: May increase the serum concentration of Ergot Derivatives. 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

Macrolide Antibiotics: May increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk X: Avoid combination

MiFEPRIStone: May increase the serum concentration of Ergotamine. Management: Avoid ergotamine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Risk X: Avoid combination

Nefazodone: Ergot Derivatives may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

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

Nitroglycerin: Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

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. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Risk D: Consider therapy modification

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

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

Posaconazole: May increase the serum concentration of Ergotamine. Risk X: Avoid combination

Procarbazine: May enhance the adverse/toxic effect of Sympathomimetics. Management: Consider alternatives to this combination when possible. Procarbazine prescribing information states that this combination should be avoided. Risk D: Consider therapy modification

Protease Inhibitors: May increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination

Reboxetine: May enhance the hypertensive effect of Ergot Derivatives. 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. 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. Exceptions: Nefazodone. Risk C: Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the vasoconstricting effect of Ergot Derivatives. Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid combination

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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

Stiripentol: May increase the serum concentration of Caffeine and Caffeine Containing Products. Risk X: Avoid combination

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. Exceptions: Dyphylline. Risk C: Monitor therapy

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

Voriconazole: May increase the serum concentration of Ergotamine. Risk X: Avoid combination

Food Interactions

See individual agents.

Genes of Interest

• Cytochrome P450 1A2
• Cytochrome P450 3A4

Monitoring Parameters

BUN, serum creatinine, liver function tests at baseline, signs of peripheral ischemia (eg, vasospasm, digit coldness, and pallor), numbness, muscle pains, extremity weakness, chest pain, tachycardia or bradycardia, hypersensitivity reactions.

Advanced Practitioners Physical Assessment/Monitoring

Obtain baseline renal and liver function tests. Evaluate cardiovascular status prior to initiating medication and periodically thereafter. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Discontinuation even after limited use may result in withdrawal symptoms (eg, rebound headache).

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor for hypertension and cardiac events. Educate patient that discontinuation even after limited use may result in withdrawal symptoms (eg, rebound headache).

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); ergotamine tartrate 2 mg and caffeine 100 mg (12 ea [DSC])

Tablet, Oral:

Cafergot: ergotamine tartrate 1 mg and caffeine 100 mg

Generic: ergotamine tartrate 1 mg and caffeine 100 mg

Anatomic Therapeutic Chemical (ATC) Classification

• N02CA52

Generic Available (US)

May be product dependent

Pricing: US

Suppository (Migergot Rectal)

2-100 mg (per each): $168.55

Tablets (Cafergot Oral)

1-100 mg (per each): $15.44

Tablets (Ergotamine-Caffeine Oral)

1-100 mg (per each): $13.88

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.

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

Pharmacodynamics/Kinetics

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)

Local Anesthetic/Vasoconstrictor Precautions

Use vasoconstrictor with caution in patients taking ergotamine; this ergot alkaloid derivative causes constriction of peripheral blood vessels

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Ergotamine and caffeine cause tachycardia, increases in blood pressure, and palpitations. Consider monitoring blood pressure prior to using local anesthetic with a vasoconstrictor. Symptoms associated with bruxism have been observed in some patients.

Effects on Bleeding

No information available to require special precautions

Related Information

• Caffeine
• Ergotamine

Index Terms

Caffeine and Ergotamine; Ergotamine Tartrate and Caffeine; Ergotamine Tartrate/Caffeine

References

Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk. Clinical pharmacokinetic considerations. Clin Pharmacokinet. 1988;14(4):217-240. Review.[PubMed 3292101]

Berlin CM Jr, Denson HM, Daniel CH, Ward RM. Disposition of dietary caffeine in milk, saliva, and plasma of lactating women. Pediatrics. 1984;73(1):59-63.[PubMed 6691042]

Cafergot (ergotamine tartrate and caffeine tablets, USP) [prescribing information]. Princeton, NJ: Sandoz Inc; May 2018.

Edwards WM, “Accidental Poisoning of Newborn Infants With Ergonovine Maleate. A Lesson Application To All Delivery Rooms,” Clin Pediatr (Phila), 1971, 10(5):257-60.

Fratto G, Manzon L. Use of psychotropic drugs and associated dental diseases. Int J Psychiatry Med. 2014;48(3):185-197.[PubMed 25492713]

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]

Krupp GR, Friedman AP. Migraine in children; a report of fifty children. AMA Am J Dis Child. 1953;85(2):146-150.[PubMed 13007165]

McGuigan MA, “Ergot Alkaloids,” Clin Toxicol Rev, 1984, 6:1-2.

Migergot (ergotamine tartrate and caffeine suppositories) [prescribing information]. South Plainfield, NJ: Cosette Pharmaceuticals, Inc; July 2019.

Nelson WE, Behrman RE, Kliegman RM, et al, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: WB Saunders Company; 1996.

Orton DA and Richardson RJ, “Ergotamine Absorption and Toxicity,” Postgrad Med J, 1982, 58(675):6-11.[PubMed 7088766]

Perrin VL, “Clinical Pharmacokinetics of Ergotamine in Migraine and Cluster Headache,” Clin Pharmacokinetics, 1985, 10(4):334-52.[PubMed 3899452]

Singer HS. Migraine headaches in children. Pediatr Rev. 1994;15(3):94-101.[PubMed 8041676]

Welborn CA. Pediatric migraine. Emerg Med Clin North Am. 1997;15(3):625-636.[PubMed 9255136]

Brand Names: International

Avamigran (TH); Cafergot (AE, AT, BB, BE, BF, BJ, CH, CI, CY, EG, ES, ET, GH, GM, GN, GR, HK, IL, IQ, IR, IT, JO, JP, KE, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, NZ, OM, RU, SA, SC, SD, SE, SG, SL, SN, SY, TH, TN, TR, TW, TZ, UG, YE, ZA, ZM, ZW); Cafergot N (DE); Caffox (SG); Coffetamin (RU); Degran (TH); Enxak (BR); Ergam (HU); Ergofein (CZ); Ergokoffin (DK); Ergosanol (LU); Ergosanol Spezial N (LU); Ergoton (TW); Ericaf (ID); Fencafen (CO); Gynergene Cafeine (FR); Lingraine (IE); Migrano (TH); Migrexa (HR); Migrin (BD); Polygot (TH); Sydolil (MX); Tofago (TH); Trinergot (MX); Vascurin (BD)

Last Updated 10/8/20