Each tablet for oral administration contains 1 mg ergotamine tartrate, USP, and 100 mg caffeine, USP.

ERGOTAMINE TARTRATE:

Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(phenyl-methyl)-,(5' α)-, [R-(R*,R*)]-2,3- dihydroxy-butanedioate (2:1) (salt).

CAFFEINE:

1H-Purine-2,6-dione, 3,7-dihydro-1,3,7-trimethyl-.

Inactive ingredients include acacia, calcium carbonate, compressible sugar, confectioner's sugar (sucrose and corn starch), magnesium stearate, methylparaben, microcrystalline cellulose, povidone, propylparaben, sodium benzoate, sodium starch glycolate, starch (potato), sucrose, synthetic iron oxide, titanium dioxide and other ingredients.

CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) 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 1/2 hour, if needed for full relief (maximum 6 tablets per attack, 10 per week).

Maximum Adult Dosage: Total 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.

CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) for oral administration are available as:

1 mg/100 mg: round tablets, sugar coated beige and imprinted CAFERGOT in black ink.

Bottles of 100...................................................NDC 0078-0349-05

Store at controlled room temperature 15° -30° C (59° -86° F).

Dispense in a tight, light-resistant container.

Manufactured By: Geneva Pharmaceuticals, Inc. Broomfield, CO 80020. Distributed By: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936. Rev 03-2003. FDA Rev date: 7/26/1999

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

(see WARNINGS).

Drug Abuse And Dependence: There have been reports of drug abuse and psychological dependence in patients on CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) therapy. Due to the 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).

CYP 3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors): See CONTRAINDICATIONS and WARNINGS.

CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) 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 CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) 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.

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 (see CONTRAINDICATIONS). While these reactions have not been reported with less potent CYP 3A4 inhibitors, there is a potential risk for serious toxicity including vasospasm when these drugs are used with ergotamine. Examples of less potent CYP 3A4 inhibitors include: saquinavir, nefazodone, fluconazole, fluoxetine, grapefruit juice, fluvoxamine, zileuton, metronidazole, and clotrimazole. These lists are not exhaustive, and the prescriber should consider the effects on CYP 3A4 of other agents being considered for concomitant use with ergotamine.

Fibrotic Complications: There have been a few reports of patients on ergotamine tartrate and caffeine therapy developing retroperitoneal and/or pleuropulmonary fibrosis. There have also been rare reports of fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with long-term continuous use of ergotamine tartrate and caffeine. Ergotamine tartrate and caffeine tablets should not be used for chronic daily administration (see DOSAGE AND ADMINISTRATION).

General: 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.

Ergotism is manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia. Ergotamine induces vasoconstriction by a direct action on vascular smooth muscle. In chronic intoxication with ergot derivatives, headache, intermittent claudication, muscle pains, numbness, coldness and pallor of the digits may occur. If the condition is allowed to progress untreated, gangrene can result.

While most cases of ergotism associated with ergotamine treatment result from frank overdosage, some cases have involved apparent hypersensitivity. There are few reports of ergotism among patients taking doses within the recommended limits or for brief periods of time. In rare instances, patients, particularly those who have used the medication indiscriminately over long periods of time, may display withdrawal symptoms consisting of rebound headache upon discontinuation of the drug.

Pregnancy

Teratogenic Effects

Pregnancy Category X: There are no studies on the placental transfer or teratogenicity of the combined products of CAFERGOT® (ergotamine tartrate and caffeine tablets, USP). 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 the 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 (see CONTRAINDICATIONS).

Nonteratogenic Effects: CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) is contraindicated in pregnancy due to the oxytocic effects of ergotamine (see CONTRAINDICATIONS).

Labor and Delivery: CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) is contraindicated in labor and delivery due to its oxytocic effect which is maximal in the third trimester (see CONTRAINDICATIONS).

Nursing Mothers: Ergot drugs are known to inhibit prolactin but there are no reports of decreased lactation with CAFERGOT® (ergotamine tartrate and caffeine tablets, USP). Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhea, weak pulse and unstable blood pressure in nursing infants. Because of the potential for serious adverse reactions in nursing infants from CAFERGOT® (ergotamine tartrate and caffeine tablets, USP), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

The toxic effects of an acute overdosage of CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) 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. 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, gastric lavage, and catharsis. 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.

Coadministration of ergotamine with potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erthromycin, 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 CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) 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 drugs and other potent inhibitors of CYP 3A4 (e.g., ketoconazole, itraconazole) (see WARNINGS: CYP 3A4 Inhibitors).

CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) may cause fetal harm when administered to pregnant women. CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) 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.

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.

Patients should be advised that two tablets of CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) should be taken at the first sign of a migraine headache. No more than 6 tablets should be taken for any single migraine attack. No more than 10 tablets should be taken during any 7-day period. Administration of ergotamine tartrate and caffeine tablets should not exceed the dosing guidelines and should not be used for chronic daily administration (see DOSAGE AND ADMINISTRATION). CAFERGOT® (ergotamine tartrate and caffeine tablets, USP) should be used only for migraine headaches. It is not effective for other types of headaches and it lacks analgesic properties. Patients should be advised to report to the physician immediately any of the following: numbness or tingling in the fingers and toes, muscle pain in the arms and legs, weakness in the legs, pain in the chest or temporary speeding or slowing of the heart rate, swelling or itching.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ERGOTAMINE/CAFFEINE - ORAL

(er-GOT-uh-meen/KAF-een)

COMMON BRAND NAME(S): Ercaf, Wigraine

WARNING: This medication has infrequently caused a lack of blood flow to the hands and feet (peripheral ischemia). It has also rarely caused a lack of blood flow to the brain (cerebral ischemia). The chances of these effects are increased when this medication is taken with certain drugs. Do not take this medication with macrolide antibiotics (e.g., erythromycin, clarithromycin, troleandomycin, telithromycin), protease inhibitors (e.g., amprenavir, indinavir, nelfinavir, ritonavir, saquinavir), or azole antifungals (e.g., ketoconazole, itraconazole, voriconazole). Consult your doctor or pharmacist for more details.

USES: This combination medication is used to treat or prevent a certain type of headache (vascular headaches such as migraine headaches and cluster headaches). Ergotamine helps narrow widened blood vessels in the head, which reduces the throbbing effects of vascular headaches. Caffeine increases the effects of ergotamine by increasing the absorption of ergotamine and also by narrowing the widened blood vessels in the head.

HOW TO USE: Take this medication by mouth with or without food as directed by your doctor.

Dosage is based on your medical condition and response to therapy. This medication works best if it is taken as the first signs of the headache occur. If you wait until the headache has worsened, the medication may not work as well.

This medication usually should be taken only as needed. It is not meant for long-term daily use. The maximum dose is 6 tablets for a single headache attack and 10 tablets in any 7-day period.

This medication may cause dependence, especially if it has been used regularly for an extended time (more than a few weeks) or if it has been used in high doses. In such cases, if you suddenly stop this drug, "rebound headaches" may occur. This headache may be different from your original headache and may last a few days. Report any such headaches to your doctor immediately. Consult your doctor or pharmacist for more details.

Avoid eating grapefruit or drinking grapefruit juice while being treated with this medication unless your doctor instructs you otherwise. Grapefruit can increase the amount of certain medications in your bloodstream. Consult your doctor or pharmacist for more details.

Inform your doctor if you notice increased use of this medication, the medication not working as well, a worsening of headaches, an increase in the number of headaches, or use of this medication for more than 2 headache episodes a week. Your doctor may need to change your medication and/or add a separate medication to prevent the headaches.

SIDE EFFECTS: Nausea, vomiting, upset stomach, restlessness, trouble sleeping, and dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: slow/fast/irregular heartbeat, tingling/pain/coldness in the fingers/toes, whitish fingers/toes/nails, loss of feeling in the fingers/toes, bluish hands/feet, muscle pain/weakness, severe stomach/abdominal pain, lower back pain, little or no urine.

Seek immediate medical attention if any of these rare but very serious side effects occur: chest pain, vision changes, confusion, slurred speech.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to ergotamine or caffeine; or to other ergot alkaloids (e.g., dihydroergotamine) or to other xanthine drugs (e.g., theophylline); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: blood circulation disease (e.g., peripheral vascular disease such as arteriosclerosis, thrombophlebitis, Raynaud's disease), uncontrolled high blood pressure, nutrient deficiency (malnutrition), heart/blood vessel disease (e.g., coronary artery disease, stroke, recent heart attack), liver disease, kidney disease, severe infection, severe itching.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: abnormal heart rhythm, smoking, diabetes, high blood pressure (controlled), stomach problems (e.g., ulcers).

This drug may make you dizzy; use caution while engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages. Remember that alcohol may be a cause of headaches.

This medication may harm an unborn baby. Therefore, it must not be used during pregnancy. It is recommended that men and women use two effective forms of birth control (e.g., condoms, birth control pill) while taking this medication. If you become pregnant or think you may be pregnant, inform your doctor immediately. Consult your doctor for more details and to discuss reliable forms of birth control.

This drug may pass into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: (See also Warning section and How to Use section.)

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: delavirdine, efavirenz, sibutramine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting this medication.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: adenosine, certain beta blockers (e.g., propranolol), cimetidine, dopamine, drugs affecting liver enzymes that remove ergotamine from your body (such as fluoxetine, fluvoxamine, metronidazole, nefazodone, zileuton), lithium, nicotine (e.g., nicotine gum, nicotine patches), nitrates (e.g., isosorbide, nitroglycerin), other ergot alkaloids (e.g., methysergide), theophylline.

If you also take "triptan" migraine drugs (e.g., sumatriptan, rizatriptan), you will need to separate your "triptan" dose from your dose of this medication to reduce the risk of serious side effects. Ask your doctor how long you should wait between your doses of these drugs.

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, other migraine medications) because they may contain caffeine or other ingredients that could increase your heart rate or blood pressure. Also keep in mind that certain beverages (e.g., coffee, colas, tea) contain caffeine. Ask your pharmacist about the safe use of those products.

This medication may interfere with certain medical/laboratory tests (including dipyridamole-thallium imaging tests, urine catecholamine levels, urine 5-HIAA levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe dizziness/drowsiness, loss of feeling in the fingers/toes, rapid/weak heartbeat, bluish hands/feet, seizures.

NOTES: Do not share this medication with others.

Certain foods/beverages or food additives (e.g., red wine, cheese, chocolate, monosodium glutamate, alcohol) as well as some lifestyle patterns (e.g., irregular eating/sleeping habits, stress) may bring about a migraine headache. Avoiding these "triggers" may help decrease the frequency of migraine headaches. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.