Caffeine + Ergotamine Tartrate

Indications

Caffeine + Ergotamine Tartrate is used for: Acute Migraine, Vascular Headache

Adult Dose

Vascular Headache Indicated as therapy to abort or prevent vascular headache (eg, migraine, migraine variants, “histaminic cephalalgia”) Adult: Oral Each tablet contains ergotamine tartrate 2 mg and caffeine hydrate 100 mg. Initially, 1 tablet, additional doses of ½-1 tablet may be taken at half-hourly intervals, if needed. To be taken as soon as possible at the 1st warning of a migraine attack. Max: 3 tablets in 24 hr, 4 tablets per attack, 6 tablets per week and 2 courses of treatment per month. Ensure an interval of at least 4 days between successive treatment courses. Rectal Suppository: 1 suppository should be taken at the first sign of a migraine attack. If not relieved from the first dose, a 2nd dose may be taken no sooner than 1 hour after the first dose. The use of this suppository should not be used on a daily basis. Maximum 2 suppositories for any single migraine attack and maximum 5 suppositories during any 7-day period.

Child Dose

Renal Dose

Renal impairment Contraindicated

Administration

Contra Indications

Not to be used with potent inhibitors of CYP3A4 and protease inhibitors. Hyperthyroidism, renal or hepatic impairment. Pre-existing vascular disease including coronary disease, obliterative vascular disease, angina, claudication, peripheral ischaemia, Raynaud's syndrome and hypertension. Not to be used when there is sepsis. Pregnancy and lactation.

Precautions

Serious and/or life-threatening peripheral ischemia associated with coadministration of ergotamine and caffeine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics Because CYP3A4 inhibition elevates ergotamine and caffeine serum levels, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased Concomitant use of these medications is contraindicated Ergotism Although ergotism rarely develop even after long-term intermittent use of orally administered ergotamine, do not exceed dosage recommendations Ergotism manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia Headache, intermittent claudication, muscle pains, numbness, or coldness and pallor of the digits may occur with chronic intoxication; if the condition is allowed to progress untreated, gangrene can result While most cases result from frank overdosage, some cases involve hypersensitivity There are few reports among patients taking doses within recommended limits or for brief periods Withdrawal symptoms (eg, rebound headache) upon discontinuation are rare; typically reported with long, indiscriminate use Fibrotic complications Retroperitoneal and/or pleuropulmonary fibrosis reported Rare reports of fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with long-term, continuous use of ergotamine tartrate and caffeine Do not use for chronic daily administration

Pregnancy-Lactation

Pregnancy Contraindicated; ergotamine elicits oxytocic effects There are no studies on placental transfer or teratogenicity of the combination of ergotamine and caffeine Labor and delivery Contraindicated in labor and delivery owing to ergotamine’s oxytocic effect, which is maximal in the third trimester Animal studies Caffeine is known to cross the placenta and has been shown to be teratogenic in animals Ergotamine crosses the placenta in small amounts, although it does not appear to be embryotoxic in this quantity; however, prolonged vasoconstriction of uterine vessels and/or increased myometrial tone leading to reduced myometrial and placental blood flow may have contributed to fetal growth retardation observed in animals Lactation Ergot drugs are known to inhibit prolactin, but there are no reports of decreased lactation with ergotamine/caffeine Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhea, weak pulse, and unstable blood pressure in nursing infants Owing to the potential serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother

Interactions

Increased sedative effect when used with alcohol. Caffeine may increase clearance of lithium. Clearance of caffeine may be reduced when used with oestrogens, progesterones, mexiletine, fluvoxamine, disulfiram or quinoline antibacterial. Serum levels of ergotamine-containing drugs may be increased when used with macrolide antibacterial. Concurrent use with MAOIs or TCAs may increase the sedative and antimuscarinic effects of cyclizine. Increased clearance of caffeine by phenytoin. Increased risk of arterial occlusion with methysergide and vasospasm with 5-HT1 agonists. Avoid ergotamine for 6 hr after almotriptan, sumatriptan, rizatriptan and zolmitriptan, and for 24 hr after eletriptan. Avoid almotriptan, eletriptan, sumatriptan and rizatriptan for 24 hr, and zolmitriptan for 6 hr, after ergotamine. Increased sedative effects when used with anxiolytics and hypnotics. Increased risk of vasoconstriction when used with β-blockers or nicotine. May reduce anti-anginal effects of glyceryl trinitrate. May increase plasma levels of theophylline. Potentially Fatal: Concurrent use with HIV-proteases which are potent CYP3A4 inhibitors (e.g. amprenavir, indinavir, nelfinavir, ritonavir) is not recommended due to increased risk of ergotism. Contraindicated (32) almotriptan clarithromycin cobicistat eletriptan elvitegravir/cobicistat/emtricitabine/tenofovir DF fezolinetant frovatriptan glyceryl trinitrate pr isocarboxazid itraconazole ketoconazole letermovir levoketoconazole linezolid mifepristone naratriptan nirmatrelvir/ritonavir nitroglycerin IV nitroglycerin sublingual nitroglycerin topical nitroglycerin transdermal nitroglycerin translingual ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) phenelzine procarbazine pseudoephedrine rizatriptan selegiline transdermal sumatriptan sumatriptan intranasal tranylcypromine voriconazole

Adverse Effects

Side effects of Caffeine + Ergotamine Tartrate : Frequency Not Defined Gastrointestinal: Nausea and vomiting; rectal or anal ulcer (from overuse of suppositories) Neurological: Paresthesia, numbness, weakness, and vertigo Allergic: Localized edema and itching Cardiovascular Serious vasoconstrictive complications may occur including ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes, and muscle pains Most commonly occurs with long-term therapy at relatively high doses; also reported with short-term or normal doses Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension

Mechanism of Action

Ergotamine is an alpha-adrenergic blocker with a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels, it also depresses central vasomotor centers. Caffeine is also a cranial vasoconstrictor.