Caffeine and Ergotamine

Ergotamine tartrate and caffeine tablets are indicated as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants or so-called “histaminic cephalalgia.”

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). Maximum Adult Dosage: Total daily dose for any one attack should not exceed 6 tablets. 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.

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, 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 tablets was coadministered, at least one resulting in death.

WARNING Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine tartrate and caffeine tablets with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of ergotamine tartrate and caffeine tablets, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. - CYP 3A4 Inhibitors (e.g. Macrolide Antibiotics and Protease Inhibitors) Coadministration of ergotamine with potent CYP 3A4 inhibitors such as protease inhibitors or macrolide antibiotics has been associated with serious adverse events, for this reason, these drugs should not be given concomitantly with ergotamine.

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 Neurological: Paresthesias, numbness, weakness, and vertigo Allergic: Localized edema and itching. Fibrotic Complications:

- CYP 3A4 Inhibitors (e.g. Macrolide Antibiotics and Protease Inhibitors) See CONTRAINDICATIONS and WARNINGS. Ergotamine tartrate and caffeine tablets should not be administered with other vasoconstrictors. Use with sympathomimetics (pressor agents) may cause extreme elevation of blood pressure. The beta-blocker Inderal (propranolol) has been reported to potentiate the vasoconstrictive action of ergotamine tartrate and caffeine tablets by blocking the vasodilating property of epinephrine. Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy. The blood levels of ergotamine-containing drugs are reported to be elevated by the concomitant administration of macrolide antibiotics and vasospastic reactions have been reported with therapeutic doses of the ergotamine-containing drugs when coadministered with these antibiotics.

Store at 20° to 25°C (68° to 77°F).