Ergotamine + Caffeine


Concise Prescribing Info
Indications/Uses
Acute migraine attacks.
Dosage/Direction for Use
Adult : PO Each tab contains ergotamine 1 mg and caffeine 100 mg: Initial: 2 tab at onset of attack, then 1 tab every 30 min, if necessary. Max: 6 tab/day; 10 tab/wk. Rectal Each supp contains ergotamine 2 mg and caffeine 100 mg: Initial: 1 supp at onset of attack, then 1 supp after 1 hr, if necessary. Max: 2 supp/day; 5 supp/wk.
Dosage Details
Oral
Acute migraine attacks
Adult: Available preparation:
Ergotamine 1 mg and caffeine 100 mg
Initially, 2 tab at onset of attack, then 1 tab every 30 min, if necessary. Max: 6 tab/day; 10 tab/wk.

Rectal
Acute migraine attacks
Adult: Available preparation:
Ergotamine 2 mg and caffeine 100 mg
Initially, 1 supp at onset of attack, then 1 supp after 1 hr, if necessary. Max: 2 supp/day; 5 supp/wk.
Renal Impairment
Severe: Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food.
Contraindications
Peripheral vascular disease, obliterative vascular disease, CHD, HTN, septic condition e.g. shock, temporal arteritis, hemiplegic or basilar migraine. Concomitant use w/ potent CYP3A4 inhibitors (e.g. azole antifungals, protease inhibitors, macrolide antibiotics. Severe renal and hepatic impairment. Pregnancy and lactation.
Special Precautions
Patient w/ risk or predisposed vascular effects.
Adverse Reactions
Significant: Vasospasm, myocardial ischaemia, ergotism; pleural, retroperitoneal, and pulmonary fibrosis; drug-induced headaches, dependence, headache, transient loss of vision. Rarely, infarction.
Nervous: Dizziness, numbness, paraesthesia, drowsiness, precordial pain, vertigo.
CV: Peripheral vasoconstriction, cold extremities, ECG changes, oedema, transient bradycardia, tachycardia, and HTN.
GI: Anal fissure, nausea, rectal ulcers, vomiting, abdominal pain, diarrhoea.
Resp: Cyanosis.
Musculoskeletal: Myalgia, weakness.
Dermatologic: Gangrene, pruritus, rash, urticaria.
Patient Counseling Information
This drug may cause visual disturbances, dizziness, or other CNS disturbances, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor BUN, serum creatinine, LFT.
Overdosage
Symptoms: Nausea, vomiting, drowsiness, confusion, tachycardia, dizziness, resp depression, hypotension, convulsion, shock, coma, symptoms and complications of ergotism. Management: Symptomatic and supportive treatment. Employ activated charcoal. Gastric lavage may be considered for recent ingestion. Maintain adequate pulmonary ventilation, correction of hypotension and control or BP and convulsions. Keep the extremities warm to treat peripheral vasospasm. Vasodilators may be beneficial.
Drug Interactions
Ergotamine: Enhanced vasospastic reaction w/ β-blockers (e.g. propranolol).
Caffeine: Reduced metabolic clearance w/ mexiletine, fluvoxamine, OC and sympathomimetics.
Potentially Fatal: Increased serum concentration and ergot toxicity (e.g. vasospasm and cerebral/peripheral ischaemia) w/ potent CYP3A4 inhibitors (e.g. azole antifungals, protease inhibitors, macrolide antibiotics). Increased vasoconstrictor effect w/ sympathomimetics (e.g. epinephrine), ergot alkaloids, 5HT1 receptor agonists, and nicotine.
Food Interaction
Increased serum concentration w/ grapefruit and grapefruit juice.
Action
Description: Ergotamine is an ergot alkaloid that has marked vasoconstrictor effects and partial agonistic action at serotonin (5-HT) receptors. It causes central vasomotor depression, stimulates vasoconstriction of peripheral smooth muscles and cranial blood vessels thus alleviating migraine. It also has significant oxytocic action on the uterus.
Caffeine is a methylxanthine that inhibits phosphodiesterase enzyme causing increased levels of intracellular cyclic 3’,5’-adenosine monophosphate(cAMP). It enhances vasoconstrictive effect and increases ergotamine enteral absorption. It also exerts analgesic activity by blocking peripheral pronociceptive action of adenosine and activating central noradrenergic pathway that constitute endogenous pain suppressing system. Additionally, it antagonises central adenosine receptors thus stimulating the CNS and resp center, producing wakefulness, increased mental activity, increased rate and depth of respiration.
Pharmacokinetics:
Absorption: Ergotamine: Poorly absorbed from the GI tract. Bioavailability: Approx ≤5%. Time to peak plasma concentration: W/in 0.5-3 hr.
Caffeine: Well absorbed from the GI tract (oral); slow and erratic (rectal). Time to peak plasma concentration: 30-120 min.
Distribution: Crosses blood-brain barrier and enters breast milk.
Ergotamine: Plasma protein binding: Approx 93-98%.
Caffeine: Rapidly distributed throughout the body tissues. Crosses placenta. Volume of distribution: 0.6 L/kg. Plasma protein binding: Approx 17-36%.
Metabolism: Ergotamine: Undergoes extensive metabolism in the liver by CYP3A4 isoenzyme including first-pass effect.
Caffeine: Rapidly metabolised in the liver into 1-methyluric acid, 1-methylxanthine and 7-methylxanthine metabolites.
Excretion: Ergotamine: Via faeces (90%, mainly as metabolites); urine (approx 4%). Elimination half-life: Biphasic: Approx 2 hr (initial phase); 21 hr (terminal phase).
Caffeine: Via urine (1% as unchanged drug). Elimination half-life: 3-5 hr.
Chemical Structure

Chemical Structure Image
Ergotamine

Source: National Center for Biotechnology Information. PubChem Database. Ergotamine, CID=8223, https://pubchem.ncbi.nlm.nih.gov/compound/Ergotamine (accessed on Jan. 22, 2020)


Chemical Structure Image
Caffeine

Source: National Center for Biotechnology Information. PubChem Database. Caffeine, CID=2519, https://pubchem.ncbi.nlm.nih.gov/compound/Caffeine (accessed on Jan. 22, 2020)

Storage
Tab: Store below 25°C. Protect from light. Supp: Store between 2-8°C.
ATC Classification
N02CA52 - ergotamine, combinations excl. psycholeptics ; Belongs to the class of ergot alkaloids preparations. Used to relieve migraine.
References
AFT Pharmaceuticals Ltd. Cafergot Tablets data sheet 24 Nov 2016. Medsafe. http://www.medsafe.govt.nz/. Accessed 31/07/2017.

Anon. Ergotamine and Caffeine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 31/07/2017.

Buckingham R (ed). Caffeine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/07/2017.

Buckingham R (ed). Ergotamine Tartrate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/07/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine, Citrated. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 31/07/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Ergotamine Tartrate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 31/07/2017.

Migergot Suppository (Crealta Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 31/07/2017.

Disclaimer: This information is independently developed by MIMS based on Ergotamine + Caffeine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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