Adult: Ergotamine 1 mg and caffeine 100 mg tab
Initially, 2 tabs as a single dose at the 1st sign of an attack. If symptoms persist or recur, may give 1 tab every 30 minutes as necessary. Max: 6 tabs/attack or 6 tabs daily. Max weekly dose: 10 tabs. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Rectal Migraine
Adult: Ergotamine 2 mg and caffeine 100 mg supp
Initially, 1 supp at the 1st sign of an attack. If symptoms persist or recur, may give 1 supp after 1 hour as necessary. Max: 2 supp/attack. Max weekly dose: 5 supp. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal Impairment
Contraindicated.
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food.
Contraindications
Peripheral vascular disease, CHD, hypertension, sepsis, shock, temporal arteritis, hemiplegic or basilar migraine. Renal and hepatic impairment. Pregnancy (including women of childbearing potential) and lactation. Concomitant use with potent CYP3A4 inhibitors and other vasoconstrictor agents.
Special Precautions
Not indicated for prolonged daily use. Elderly.
Adverse Reactions
Significant: Cardiovascular effects (e.g. vasospasm, vasoconstriction, myocardial toxicity). Prolonged use: Ergotism (resulting in peripheral vascular ischaemia and gangrene), pleural and/or retroperitoneal fibrosis (rare), fibrotic valve thickening (e.g. aortic, mitral, tricuspid), headache; solitary rectal or anal ulcers (rectal). Gastrointestinal disorders: Nausea, vomiting (not migraine-related), abdominal pain, diarrhoea. Musculoskeletal and connective tissue disorders: Pain or weakness in extremity. Nervous system disorders: Dizziness, paraesthesia, hypoaesthesia. Vascular disorders: Cyanosis.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Obtain BUN, serum creatinine, LFTs (at baseline). Asses CV status prior to initiating treatment and periodically thereafter. Monitor for signs of peripheral ischaemia.
Overdosage
Symptoms: Nausea, vomiting, abdominal pain, lightheadedness, headache, drowsiness, confusion, tachycardia or bradycardia associated with hypotension, dizziness, respiratory depression, gangrene, shock, coma, convulsions; numbness, tingling, pain and cyanosis of the extremities associated with diminished or absent peripheral pulses. Rarely, MI. Management: Symptomatic treatment. Administer activated charcoal for orally ingested drug. May perform gastric lavage for recent oral ingestion. May administer IV peripheral vasodilators (e.g. nitroprusside, phentolamine or dihydralazine), apply warmth and nursing care to the affected area for severe vasospastic reactions. May give nitroglycerin for coronary constriction.
Drug Interactions
Ergotamine: Enhanced vasoconstriction effect with other vasoconstrictor agents such as drugs containing ergot alkaloids, sumatriptan, other 5-HT1 receptor agonists and nicotine. Increased risk for vasospastic reaction with less potent CYP3A4 inhibitors (e.g. saquinavir, nefazodone, fluconazole, fluoxetine, fluvoxamine, zileuton, metronidazole, clotrimazole), β-blockers (e.g. propranolol). May cause serotonin syndrome with serotonin reuptake inhibitors (e.g. amitriptyline). Decreased pharmacological activity with CYP3A4 inducers (e.g. rifampicin, nevirapine).
Caffeine: Concurrent use with fluoroquinolones, mexiletine and oral contraceptives may increase plasma exposure to caffeine. May cause a rise in blood pressure with sympathomimetics. May lead to excitation and hallucinations with enoxacin. Potentially Fatal: Ergotamine: Increased risk for vasospasm leading to cerebral and/or peripheral ischaemia with potent CYP3A4 inhibitors such as azole antifungals (e.g. ketoconazole, itraconazole, voriconazole), HIV protease or reverse transcriptase inhibitors (e.g. ritonavir, nelfinavir, indinavir, delavirdine), macrolide antibiotics (e.g. erythromycin, clarithromycin, troleandomycin).
Food Interaction
Ergotamine: Increased risk for vasospasm with grapefruit juice.
Action
Description: Mechanism of Action: Ergotamine is an ergot alkaloid derivative which has vasoconstrictor effects by stimulating the α-adrenergic and serotonin (5-HT) receptors. Its useful effect in migraine is mainly due to its agonist properties at 5-HT1B and 5-HT1D receptors. Additionally, it has a specific vasotonic action on the distended extracranial arteries which results in the abortion of migraine attacks.
Caffeine is a methylxanthine which inhibits the phosphodiesterase enzyme, therefore increasing the levels of 3',5'-cyclic adenosine monophosphate (cAMP). It increases and accelerates the enteral absorption of ergotamine thus, enhancing the vasoconstrictive effect without the need of increasing the dosage of ergotamine. Pharmacokinetics: Absorption: Ergotamine: Bioavailability: Approx ≤5% (oral and rectal). Time to peak plasma concentration: 2 hours (oral).
Caffeine: Rapidly and almost completely absorbed from the gastrointestinal tract. Distribution: Ergotamine: Crosses the placenta and enters breast milk. Volume of distribution: 1.85 L/kg. Plasma protein binding: Approx 93-98%.
Caffeine: Widely distributed throughout the body. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.6 L/kg. Plasma protein binding: 36%. Metabolism: Ergotamine: Extensively metabolised in the liver by CYP3A4 isoenzyme. Undergoes high first-pass metabolism.
Caffeine: Almost completely metabolised in the liver via oxidation, demethylation and acetylation by CYP1A2 isoenzyme. Excretion: Ergotamine: Via faeces (90%, mainly as metabolites); urine (approx 4%). Elimination half-life: 2-2.5 hours.
Caffeine: Via urine (1%, as unchanged drug). Elimination half-life: Approx 3-7 hours.
Chemical Structure
Ergotamine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 8223, Ergotamine. https://pubchem.ncbi.nlm.nih.gov/compound/Ergotamine. Accessed Mar. 29, 2023.
Caffeine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2519, Caffeine. https://pubchem.ncbi.nlm.nih.gov/compound/Caffeine. Accessed Mar. 29, 2023.
Storage
Tab: Store between 20-25°C. Protect from light. Rectal supp: Store between 2-8°C.
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