Prescription Drugs

CLINICAL PHARMACOLOGY Ergotamine is an alpha adrenergic blocking agent with a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The compound also has the properties of serotonin antagonism. In comparison to hydrogenated ergotamine, the adrenergic blocking actions are less pronounced and vasoconstrictive actions are greater. Caffeine, also a cranial vasoconstrictor is added to further enhance the vasoconstrictive effect without the necessity of increasing ergotamine dosage.

DESCRIPTION Wigraine (ergotamine and caffeine) ® Tablets: Each tablet contains the following: Ergotamine Tartrate, USP 1 mg Caffeine, USP 100 mg Each tablet also contains: Lactose, Magnesium Stearate, Microcrystalline Cellulose, Corn Starch, Glycerin, Acacia Powder, Colloidal Silicon Dioxide, and Purified Water as inactive ingredients. Wigraine (ergotamine and caffeine) ® tablets are uncoated and prepared to insure rapid disintegration (by an exclusive manufacturing process) and facilitate quick absorption. Rapid onset of effect is important for the satisfactory treatment of acute attacks of vascular headaches.

INDICATIONS Wigraine (ergotamine and caffeine) ® (ergotamine tartrate and caffeine tablets, USP) is indicated as therapy to abort or prevent vascular headaches such as migraine, migraine variants, or so-called histamine cephalalgia. DOSAGE AND ADMINISTRATION Best results are obtained if the tablets are administered at the first sign of an attack. The average adult dose is 2 tablets at the start of a vascular headache (migraine) attack; followed by 1 additional tablet every 1 / 2 hour if needed, up to 6 tablets per attack. Total weekly dosage should not exceed 10 tablets. HOW SUPPLIED Wigraine (ergotamine and caffeine) ® tablets are white tablets embossed with "ORGANON 542" on one side. They are individually foil stripped and packaged in boxes of 20's NDC #0052-0542-20 and 100's NDC #0052-0542-91. STORAGE Wigraine (ergotamine and caffeine) ® tablets should be stored at a maximum of 30°C (86°F). CAUTION Rx only Organon Inc. West Orange, NJ 07052

PATIENT INFORMATION No Information Provided.

OVERDOSE The toxic effects of an acute overdosage of Wigraine (ergotamine and caffeine) ® are due primarily to the ergotamine component. The amount of caffeine is such that its toxic effects will be overshadowed by those of ergotamine. Symptoms include vomiting, numbness, tingling, pain and cyanosis of the extremities associated with diminished or absent peripheral pulses, hypertension or hypotension, drowsiness, stupor, coma, convulsions and shock. Treatment consists of removal of the offending drug by induction of emesis, gastric lavage and catharsis. Maintenance of adequate pulmonary ventilation, correction of hypotension, and control of convulsions are important considerations. Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. Vasodilators may be used with benefit but caution must be exercised to avoid aggravating an already existing hypotension. The LD50 limits of the various components as outlined in NIOSH 1978 Registry of Toxic Effects of Chemical Substances, published by U.S. Department of Health, Education and Welfare are as follows: Ergotamine Tartrate IV LD50 in rats = 80mg/Kg, Caffeine IV LD50 in rats = 105mg/Kg. CONTRAINDICATIONS Wigraine (ergotamine and caffeine) ® can cause fetal harm when administered to a pregnant women. It can produce prolonged uterine contractions which can result in abortion. Wigraine (ergotamine and caffeine) ® is contraindicated in women who are or may become pregnant. If this is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be advised of the potential hazard to the fetus. Peripheral vascular disease, coronary heart disease, hypertension, impaired hepatic or renal function, sepsis and hypersensitivity to any of the components.

SIDE EFFECTS In order of decreasing severity; precordial distress and pain, muscle pains in the extremities, numbness and tingling in fingers and toes, transient tachycardia or bradycardia, vomiting, nausea, weakness in the legs, diarrhea, localized edema and itching. DRUG INTERACTIONS No Information Provided.

WARNINGS No Information Provided. PRECAUTIONS Although signs and symptoms of ergotism rarely develop even after long term intermittent use of the orally administered drug, care should be exercised to remain within the limits of recommended dosage. Pregnancy Category X. See Contraindications section. Nursing Mothers. It is not known whether the ergotamine tartrate in Wigraine (ergotamine and caffeine) ® is excreted in human milk. Because some ergot alkaloids have been found in the milk of nursing mothers resulting in symptoms of ergotism in their children, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Usage. Safety and effectiveness in children have not been established.