ERGOTAMINE

ERGOTAMINE TARTRATE AND CAFFEINE
TABLETS, USP
1MG/100 MG

Rev. 11/04Rx Only

WARNING

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine tartrate and caffeine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of ergotamine tartrate and caffeine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated. (See also CONTRAINDICATIONS and WARNINGS sections)

Ergotamine Tartrate and Caffeine Tablets USP

ergotamine tartrate USP . . . . . . . . . . . . . . . . . .1 mg

caffeine USP . . . . . . . . . . . . . . . . . . . . . . . . . . .100 mg

In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, compressible sugar, corn starch, magnesium stearate, mannitol, microcrystalline cellulose, sodium starch glycolate, sugar, and tartaric acid. Polishing and Film Coating Solutions may contain the following: FD&C Blue Lake #2, FD&C Yellow Lake #6, hydroxypropyl methylcellulose, polyethylene glycol, and titanium dioxide. The printing ink contains: amide resin, black pigment, natural resin, and wax.

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.

Many migraine patients experience excessive nausea and vomiting during attacks, making it impossible for them to retain any oral medication. In such cases, therefore, the only practical means of medication is through the rectal route where medication may reach the cranial vessels directly, evading the splanchnic vasculature and the liver.

Pharmacokinetics: Interactions

Pharmacokinetic interactions (increased blood levels of ergotamine) have been reported in patients treated orally with ergotamine and macrolide antibiotics (e.g., troleandomycin, clarithromycin, erythromycin), and in patients treated orally with ergotamine and protease inhibitors (e.g. ritonavir) presumably due to inhibition of cytochrome P450 3A metabolism of ergotamine (see CONTRAINDICATIONS). Ergotamine has also been shown to be an inhibitor of cytochrome P450 3A catalyzed reactions. No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.

Coadministration of ergotamine with potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, and troleandomycin) has been associated with acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities (see PRECAUTIONS: Drug Interactions), with some cases resulting in amputation. There have been rare reports of cerebral ischemia in patients on protease inhibitor therapy when ergotamine tartrate and caffeine was coadministered, at least one resulting in death. Because of the increased risk for ergotism and other serious vasospastic adverse events, ergotamine use is contraindicated with these drug and other potent inhibitors of CYP 3A4 (e.g., ketoconazole, itraconazole) (see WARNINGS: CYP 3A4 Inhibitors).

Ergotamine tartrate and caffeine may cause fetal harm when administered to pregnant women. Ergotamine tartrate and caffeine is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this product, the patient should be apprised of the potential hazard to the fetus.

Peripheral vascular disease, coronary heart disease, hypertension, impaired hepatic or renal function and sepsis.

Hypersensitivity to any of the components.

Cardiovascular: Vasoconstrictive complications of a serious nature may occur at times. These include ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes and muscle pains. Although these effects occur most commonly with long-term therapy at relatively high doses, they have also been reported with short-term or normal doses. Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension.

Gastrointestinal: Nausea and vomiting; rectal or anal ulcer (from overuse of suppositories).

Neurological: paresthesias, numbness, weakness, and vertigo.

Allergic: Localized edema and itching.

Fibrotic Complications: (see WARNINGS).

There have been reports of drug abuse and psychological dependence in patients on ergotamine tartrate and caffeine therapy. Due to chronicity of vascular headaches, it is imperative that patients be advised not to exceed recommended dosages with long-term use to avoid ergotism (see PRECAUTIONS).

The toxic effects of an acute overdosage of ergotamine tartrate 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, convulsion and shock. A case has been reported of reversible bilateral papillitis with ring scotomata in a patient who received five times the recommended daily adult dose over a period of 14 days.

Treatment consists of removal of the offending drug by induction of emesis. Maintenance of adequate pulmonary ventilation, correction of hypotension, and control of convulsions and blood pressure are important considerations. Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. Vasodilators may be beneficial but caution must be exercised to avoid aggravating an already existent hypotension.

Procedure: For the best results, dosage should start at the first sign of an attack.

Adults: Take 2 tablets at the start of attack; 1 additional tablet every ½ hour, if needed for full relief (maximum 6 tablets per attack, 10 per week).

Early Administration Gives Maximum Effectiveness.

Maximum Adult Dosage: Six tablets is the maximum dose for an individual attack.

Total weekly dosage should not exceed 10 tablets. Ergotamine tartrate and caffeine-tablets should not be used for chronic daily administration.

In carefully selected patients, with due consideration of maximum dosage recommendations, administration of the drug at bedtime may be an appropriate short-term preventive measure.

Ergotamine Tartrate and Caffeine Tablets USP, 1 mg/100 mg are round, film coated buff colored tablet; printed "WW 120" in black ink and are available in:

Bottles of 30 tablets.

Bottles of 100 tablets.

Bottles of 500 tablets.

Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Manufactured By:
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised November 2004

PRINCIPAL DISPLAY PANEL

NDC 0143-2120-01
Ergotamine Tartrate and Caffeine
Tablets, USP
1 mg/100 mg
Rx Only
100 Tablets
West-ward Pharmaceuticals Corp.

NDC 0143-2120-01 Ergotamine Tartrate and Caffeine Tablets, USP 1 mg/100 mg Rx Only 100 Tablets West-ward Pharmaceuticals Corp.