Ergotamine Tartrate – Caffeine
Action And Clinical Pharmacology: Ergotamine is an alpha adrenergic blocking agent with a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels; it produces depression of the central vasomotor centers. Its properties also include serotonin antagonism. In comparison to dihydrogenated ergotamine, the adrenergic blocking actions of ergotamine tartrate are less pronounced and vasoconstrictive actions are greater. The addition of caffeine to ergotamine tartrate facilitates the absorption of ergotamine when administered orally or rectally, resulting in a more rapid onset of the vasoconstrictive effect and an increase in effectiveness. The migraine attack will be aborted in over 80% of the patients as long as the medication is taken early enough in the course of the attack.
Ergotamine is rapidly and incompletely (approximately 62% of the oral dose) absorbed by the gastrointestinal tract. Peak plasma levels are reached about 2 hours after ingestion. Ergotamine is extensively metabolized in the liver. The bioavailability of unchanged drug is about 2% when the drug is administered orally and 5% when it is administered by the rectal route. It has been suggested that the therapeutic effects of the drug are partially due to active metabolites. Protein binding amounts to 98%. Parent drug and metabolites are mainly excreted with the bile. Their elimination from plasma is biphasic with a half-life of 2.7 hours and 21 hours, respectively.
Caffeine is rapidly and almost completely absorbed; it is to a large extent metabolized. The metabolites are mainly excreted in the urine. Plasma elimination half-life is about 3.5 hours, protein binding 35%.
Indications And Clinical Uses: In acute attacks of migraine with or without aura.
The suppositories are available for the treatment of patients who have nausea and vomiting early in the attack and cannot retain or absorb anything taken orally. They have a faster onset of action due to by-pass of portal circulation.
Contra-Indications: Peripheral vascular disorders; obliterative vascular disease; coronary heart disease; severe hypertension and pregnancy, because of the vasoconstrictor action of ergotamine; hepatic insufficiency and septic conditions due to impaired inactivation of ergotamine; renal insufficiency; known hypersensitivity to ergot alkaloids or any other components of the formulation.
Lactation: Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhea, weak pulse and unstable blood pressure in infants. Thus, Cafergot is contraindicated in nursing mothers.
Precautions: Although signs and symptoms of ergotism rarely develop even after long-term intermittent use of the orally or rectally administered drugs, care should be exercised to remain within the limits of recommended dosage. Excessive or prolonged dosage is not recommended. Such symptoms as tingling in the fingers or toes should be reported to the physician immediately and the drug should be discontinued at once.
Cafergot is not recommended for the prophylaxis of migraine.
Like all drugs, Cafergot should be kept out of the reach of children.
The occurrence of drug-induced headaches has been reported during prolonged and uninterrupted treatment with Cafergot.
Rare cases of a solitary rectal or anal ulcer have occurred from abuse of ergotamine-containing suppositories, usually at higher than recommended doses or with continual use at the recommended dose for many years.
Drug Interactions: There is some evidence that the concomitant use of macrolide antibiotics such as troleandomycin, erythromycin or josamycin, and Cafergot can result in an elevated concentration of ergotamine in the plasma, thereby causing untoward peripheral vasoconstriction.
Among patients treated concomitantly with ergotamine-containing preparations and propranolol a few cases of vasospastic reactions have been reported. Concurrent use of vasoconstrictor agents including ergotamine, sumatriptan and nicotine may enhance the risk of vasoconstriction.
Adverse Reactions: Non-migraine-related nausea and vomiting are the most commonly observed adverse events.
Paresthesia, pain and weakness in the extremities or peripheral vasoconstriction may occur in susceptible patients or following prolonged treatment, which is unadvisable. If ergotamine containing drugs are used excessively over years, they may induce fibrotic changes, in particular of the pleura and the retroperitoneum. There have also been rare reports of fibrotic changes of the cardiac valves.
Owing to its vasoconstrictor properties ergotamine may cause precordial pain, myocardial ischemia or, in rare cases, infarction, even in patients with no known history of coronary heart disease.
Symptoms And Treatment Of Overdose: Symptoms: In humans, the minimum lethal dose of ergotamine ranges from 15 to 20 mg. The following cases of ergotamine overdosage are cited to provide broad guidelines only:
An overdosage of 44 mg ergotamine taken by an adult female, presumably all absorbed, was followed by recovery on supportive therapy only.
A 14-month-old child died following the ingestion of 12 mg ergotamine. Although vomiting was induced shortly after ingestion, the child was not exposed to expert treatment for some 13 hours after ingestion.
Ergotamine poisoning results in nausea, vomiting, diarrhea, thirst, tingling and paresthesias of the extremities, muscle pain, cold and pale skin, itching, a rapid and weak pulse, bradycardia or tachycardia, pain suggestive of angina, rise and/or fall of blood pressure (usually in that order), mental confusion, dizziness, headache, depression, drowsiness and possible unconsciousness. The most prominent effects of ergotism are circulatory changes. CNS changes can rarely include convulsions and hemiplegia. Respiratory depression can occur.
Treatment: In the case of orally ingested drug, administration of activated charcoal is recommended. In the case of very recent oral intake gastric lavage may be considered.
Treatment should be symptomatic. In the event of severe vasospastic reactions, i.v. administration of a peripheral vasodilator such as nitroprusside, phentolamine or dihydralazine, local application of warmth to the affected area and nursing care to prevent tissue damage are recommended. In the event of coronary constriction, appropriate treatment such as nitroglycerine should be initiated.
Dosage And Administration: Should be given at the first symptoms of an attack. Should not be administered prophylactically.
Tablets: Adults: The first time Cafergot is taken, an initial dose of 2 tablets is recommended. If relief is not obtained within half an hour, a further tablet should be taken; this may be repeated at half-hourly intervals (see maximum daily dosage).
For subsequent attacks the initial dose may be increased up to 3 tablets, depending on the dose required in previous attacks. If necessary, additional doses may be taken at half-hourly intervals up to the maximum dosage indicated below.
Children (6 to 12 years): The initial dose is 1 tablet; additional doses of 1 tablet may be given twice only, if required, in the course of an attack.
Suppositories: Adults: Average dose: 1 suppository rectally at start of attack, followed by 1 after one hour, if required.
Children (6 to 12 years): The initial dose is half of a suppository; additional doses of half of a suppository may be given twice only, if required, in the course of an attack.
If supplemental antimigraine medication is required, a minimum of 6 to 8 hours should elapse before the use of any ergotamine or dihydroergotamine-containing preparations; and at least 24 hours should elapse before the use of sumatriptan. Conversely, Cafergot should not be taken until at least 6 hours have elapsed following the use of sumatriptan or ergotamine or dihydroergotamine-containing preparations.
Maximum dose per attack per day: Adults: 6 mg=6 tablets or 3 suppositories.
Children: 3 mg=3 tablets or 1 1/2 suppositories.
Maximum weekly dose: Adults: 10 mg=10 tablets or 5 suppositories.
Children: 5 mg=5 tablets or 2 1/2 suppositories.
Availability And Storage: Suppositories: Each white, torpedo shaped suppository contains: ergotamine tartrate USP 2 mg and caffeine USP 100 mg. Nonmedicinal ingredients: cocoa butter. Boxes of 12. Store below 25°C in tight container (sealed foil). If soft, chill in refrigerator before opening foil wrapper.
Tablets: Each circular, flat-faced, yellowish-white mottled, compressed tablet, beveled-edged, 9 mm in diameter, with Cafergot imprint on one side, and single scored on the other, contains: ergotamine tartrate USP 1 mg and caffeine USP 100 mg. Nonmedicinal ingredients: cornstarch, iron oxide pigment yellow, magnesium stearate, microcrystalline cellulose, talc and tartaric acid. Bottles of 100.
CAFERGOT® Novartis Pharmaceuticals Ergotamine Tartrate – Caffeine Migraine Therapy