About Cafergot
What Cafergot is used for
CAFERGOT tablets are intended to relieve your migraine headache and other associated symptoms of a migraine attack.
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Use CAFERGOT tablets only to treat an actual migraine attack.
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CAFERGOT tablets should not be used continuously to prevent or reduce the number of attacks you experience.
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CAFERGOT should not be used to relieve pain other than that associated with migraine headache.
What Cafergot does
Migraine headache is believed to be caused by a widening of the blood vessels in the head. CAFERGOT narrows the vessels and relieves the pain and other symptoms of migraine attacks.
Caffeine may increase the absorption of ergotamine from the gastrointestinal tract and may help to relieve migraine.
When Cafergot should not be used
Do not take CAFERGOT if you:
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Are allergic to the active ingredients ergotamine, caffeine, to other ergot alkaloids, or to any other ingredient in the CAFERGOT tablets (see What the nonmedicinal ingredients are:).
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Are being treated for an infection with so-called macrolide antibiotics for example: erythromycin, troleandomycin, clarithromycin.
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Are being treated for HIV/AIDS with medicines like ritonavir, nelfinavir, indinavir or delavirdine.
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Are being treated for fungal infection with medicines like ketoconazole, itraconazole or voriconazole.
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Are being treated with other agents which constrict blood vessels and are used to treat migraine such as 5-HT1 receptor-agonists including triptans or as preparation containing ergot alkaloids such as dihydroergotamine.
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Have conditions which predispose you to an excessive contraction of blood vessels (vasospastic reactions) such as: heart disease (particularly angina pectoris), vascular disease, inadequately controlled hypertension (high blood pressure), septic conditions (a serious complication of an infection) and shock.
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Have a severe liver disease.
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Have a severe kidney disease.
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Are pregnant, think you may be, are trying to become pregnant, or are using inadequate contraception (see Pregnant women:).
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If you are breast-feeding (see Breast-feeding mothers:).
CAFERGOT should not be used for the treatment of other types of headaches that are different from migraine attacks.
What the medicinal ingredients for Cafergot are
Ergotamine tartrate and caffeine.
What the nonmedicinal ingredients for Cafergot are
Each tablet also contains the following inactive ingredients: cellulose microcrystalline, iron oxide pigment yellow, magnesium stearate, maize starch, talc and tartaric acid.
What dosage forms Cafergot comes in
CAFERGOT is available in tablets containing 1 mg ergotamine tartrate USP and 100 mg caffeine USP.
Warnings and Precautions
Serious Warnings and Precautions
Some medicines used to treat infection and HIV/AIDS may cause an increase in the amount of CAFERGOT in the blood, increasing the risk of serious side effects. You should not take CAFERGOT if you are treated with any of these medicines (see When it should not be used:).
Take special care with CAFERGOT if you:
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Have pleural fibrosis (thickening of the serous membranes that covers the lungs and lines the chest cavity).
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Have retroperitoneal fibrosis (thickening of the serous membranes that covers the gut system and lines the abdominal wall).
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Have mild to moderate impairment of liver function.
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Are taking selective serotonin reuptake inhibitors (SSRIs) such as Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline), or serotonin norepinephrine reuptake inhibitors (SNRIs) such as Effexor XR (venlafaxine), two types of drugs for depression or other disorders.
If any of these apply to you, tell your doctor before you take CAFERGOT.
CAFERGOT and children
There is no experience with the use of CAFERGOT in children below 6 years of age.
Pregnant women
If you are pregnant or think you may be, tell your doctor. CAFERGOT must not be given to pregnant women.
Women who might get pregnant are advised to use effective contraception during treatment with CAFERGOT.
Breast-feeding mothers
If you are breast-feeding, tell your doctor. Do not breast-feed during the treatment with CAFERGOT. The active ingredient of CAFERGOT may pass into breast milk and may affect your baby.
Driving and using machines
Do not drive or use machines if you experience side effects such as dizziness or vertigo.
Interactions with Cafergot
Tell you doctor or pharmacist if you are taking or have recently taken any other medicines. Remember also those not prescribed by a doctor.
Some medicines may increase the risk of serious side effects if taken concurrently with CAFERGOT.
Do not take CAFERGOT if you:
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Are being treated with any of the following medicines: erythromycin, troleandomycin, clarithromycin, ritonavir, nelfinavir, indinavir, delavirdine, ketoconazole, itraconazole or voriconazole.
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If you are being treated with other agents which constrict blood vessels and are used to treat migraine such as 5-HT1 receptor-agonists for example triptans or as preparation containing ergot alkaloids such as dihydroergotamine.
In addition, nicotine (e.g., smoking), β-blockers (such as propranolol, a medicine used to prevent migraine and also to treat high blood pressure), estrogen-based contraceptives and grapefruit juice may cause interactions.
Proper Use of Cafergot
Follow your doctor’s instructions carefully. Do not exceed the recommended dosage.
Usual dose
Your doctor will tell you exactly how to take CAFERGOT.
Adults
CAFERGOT should only be used to treat acute migraine attacks and it must not be used to prevent them.
At the first sign of a migraine attack, swallow with some water 2 tablets of CAFERGOT. This dose is usually enough to stop an attack. If the migraine attack does not go away, you can take 1 additional tablet every half hour at to a maximum of 6 tablets in one day.
Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose for the next attack.
Do not take more than 6 tablets in one day.
Do not take more than 10 tablets in one week.
Do not use at the same time other ergot alkaloids or 5-HT1 receptor agonists for treating your migraine (see When it should not be used:).
If your migraine does not improve in spite of the recommended use of CAFERGOT, contact your doctor or the emergency department of your local hospital.
Children (from 6 to 12 years)
The initial dose is 1 CAFERGOT tablet; additional doses of 1 tablet may be given twice only, if required, in the course of an attack. Keep a record of how many tablets your child has taken each day and during the week.
The maximum dose in one day for children for 6 to 12 years is 3 tablets.
The maximum dose in one week for children for 6 to 12 years is 5 tablets.
How long to take CAFERGOT?
Do not use CAFERGOT more often than instructed since otherwise you may have increased risk of serious side effects such as ergotism (severe constriction of blood vessels), fibrotic changes (thickening of the chest and abdominal linings) (see Side Effects and What to Do About Them:).
Overdose
If you accidentally take too much CAFERGOT, talk immediately to a doctor or pharmacist or go to the nearest hospital emergency department and bring your prescription, remaining tablets, or container with you.
Technical InformationInformation for the Patient
Cafergot
Pharmacology
Ergotamine has been shown to be both an inhibitor and substrate of cytochrome P450 3A4 catalyzed reactions. Pharmacokinetic interactions (increased blood levels of ergotamine) have been reported in patients treated with ergotamine and macrolide antibiotics (e.g., troleandomycin, clarithromycin, erythromycin), and in patients treated with ergotamine and protease inhibitors (e.g., ritonavir) presumably due to inhibition of cytochrome P450 3A4 metabolism of ergotamine (see Contraindications). No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
Indications
CAFERGOT (ergotamine tartrate and caffeine) is indicated in acute attacks of migraine with or without aura.
CAFERGOT Tablets are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic, basilar, or ophthalmoplegic migraine (see Contraindications).
Precautions
Ergot alkaloids have been shown to be both inhibitors and substrates of CYP 3A4. The concomitant use of cytochrome P450 3A4 (CYP 3A4) inhibitors such as macrolide antibiotics (e.g., troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g., ritonavir, indinavir, nelfinavir, delavirdine) or azole antifungals (e.g., ketoconazole, itraconazole, voriconazole) and CAFERGOT must be avoided (see Contraindications), since this can result in an elevated exposure to ergotamine and ergot toxicity (vasospasm and ischemia of the extremities and other tissues). No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
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 preparations containing ergot alkaloids, and 5-HT1 receptor agonists (triptans), and nicotine (e.g., heavy smoking) must be avoided since this may result in enhanced vasoconstriction (see Contraindications).
There have been very few case reports of serotonin syndrome after i.v. administration of a related compound (dihydroergotamine) concomitantly with SSRI/SNRI. No such interactions have been reported to date with CAFERGOT (ergotamine and caffeine). However, cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. Therefore, if concomitant treatment with CAFERGOT and SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) or SNRIs (e.g., venlafaxine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
CAFERGOT should not be used in patients on estrogen-based contraceptives or those who are smoking. Estrogen-based contraceptives and cigarette are independent risk factors of thrombosis. The interactions of ergotamine, estrogen-based contraceptives, and smoking are complex; the combination of these conditions may significantly increase the risk of thrombosis.
Supplied
Each circular, flat, speckled yellowish-white with isolated dots of pigment, compressed tablet, flat-faced, bevelled edge, 9 mm in diameter, with “XL” and a score on one side, contains: ergotamine tartrate USP 1 mg and caffeine USP 100 mg. Nonmedicinal ingredients: cellulose microcrystalline, iron oxide pigment yellow, magnesium stearate, maize starch, talc and tartaric acid. Cartons of 10 blisters of 10 tablets each. Store tablets below 25°C, protect from light.
Contraindications
CAFERGOT is contraindicated in:
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Any known hypersensitivity to ergot alkaloids, caffeine, or any other components of the formulation.
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Concomitant treatment of any potent CYP 3A4 inhibitors, including macrolide antibiotics (e.g., clarithromycin, erythromycin, troleandomycin), HIV protease or reverse transcriptase inhibitors (e.g., delavirdine, indinavir, nelfinavir, and ritonavir), and azole antifungals (e.g., ketoconazole, itraconazole, voriconazole).
Coadministration of ergotamine with potent CYP 3A4 inhibitors has been associated with acute ergot toxicity (ergotism) characterized by vasospasm and vascular ischemia of the extremities, with some cases resulting in amputation. Ergotism can also involve signs and symptoms of vascular ischemia of other tissues such as renal, cardiac, cerebral or gastrointestinal vasospasm. There have been rare reports of cerebral ischemia in patients on protease or reverse transcriptase inhibitor therapy when CAFERGOT (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 drugs and other potent inhibitors of CYP 3A4 (see Warnings, CYP 3A4 Inhibitors and also Precautions, Drug Interactions).
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Concomitant treatment with vasoconstrictive agents (including ergot alkaloids, triptans and other 5-HT1 receptor agonists) (see Precautions, Drug Interactions).
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Confirmed or suspected central or peripheral ischemic diseases, such as coronary vascular disease, stroke, transient ischemic attack, peripheral vascular disorders; obliterative vascular disease, because of the vasoconstrictor action of ergotamine.
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Complicated migraine, migraine with prolonged aura, temporal arteritis; hemiplegic or basilar migraine.
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Heart disease, inadequately controlled hypertension.
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Septic conditions, shock.
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Severe renal or hepatic impairment.
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Women who are or may be pregnant because ergotamine has oxytocic and vasoconstrictor effects on the placenta and umbilical cord.
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Nursing mothers. Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhea, weak pulse and unstable blood pressure in infants.
Warnings
Coadministration of ergotamine with potent CYP 3A4 inhibitors such as HIV protease or reverse transcriptase 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.
There have been reports of patients on CAFERGOT 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 CAFERGOT. CAFERGOT should not be used for chronic daily administration (see Dosage).
Adverse Effects
Rare: ergotism (intense arterial vasoconstriction, producing signs and symptoms of vascular ischemia of the extremities and other tissues [such as renal, cardiac, cerebral, or gastrointestinal vasospasm]).
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.
The occurrence of drug-induced headaches has been reported during prolonged and uninterrupted treatment with CAFERGOT (see Precautions).
Common: nausea and vomiting (not migraine related), abdominal pain. Uncommon: diarrhea.
Common: dizziness. Uncommon: paresthesia (e.g., tingling), hypoesthesia (e.g., numbness).
Rare: rash, face edema, urticaria.
Uncommon: weakness in extremities.
Uncommon: pain in extremities. Rare: myalgia.
Uncommon: peripheral vasoconstriction. Rare: increase in blood pressure. Very rare: gangrene.
Rare: hypersensitivity reactions (such as skin rash, face edema, urticaria and dyspnea).
Uncommon: cyanosis. Rare: bradycardia, tachycardia. Very rare: myocardial ischemia, myocardial infarction.
Overdose
In humans, the minimum lethal dose of ergotamine ranges from 15 to 20 mg. The following cases of ergotamine tartrate overdosage are cited to provide broad guidelines only:
1) An overdosage of 44 mg ergotamine tartrate taken by an adult female, presumably all absorbed, was followed by recovery on supportive therapy only.
2) A 14-month-old child died following the ingestion of 12 mg ergotamine tartrate. 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, 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, hypotension, convulsion, shock, possible unconsciousness, coma, symptoms and complications of ergotism. Ergotism may present with an intense arterial vasoconstriction, producing signs and symptoms of vascular ischemia of the extremities such as numbness, tingling and pain in the extremities, cyanosis, and absence of pulse. If the condition is allowed to progress untreated, gangrene may result. Ergotism can also involve signs and symptoms of vascular ischemia of other tissues such as renal, cardiac, cerebral, or gastrointestinal vasospasm. Most cases of ergotism are associated with chronic intoxication and/or overdose. Neurological changes can rarely include convulsions and hemiplegia. Respiratory depression can occur.
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 and supportive. 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
CAFERGOT (ergotamine tartrate and caffeine) should be given at the first symptoms of an attack. CAFERGOT should not be administered prophylactically.
Adults: CAFERGOT Tablets: The first time CAFERGOT is taken, an initial dose of 2 tablets of CAFERGOT 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 one tablet of CAFERGOT; additional doses of one tablet 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 a triptan. Conversely, CAFERGOT should not be taken until at least 6 hours have elapsed following the use of a triptan or ergotamine or dihydroergotamine-containing preparations.
Maximum Dose per Attack per Day: Adults: 6 mg ergotamine tartrate = 6 tablets.
Children: 3 mg ergotamine tartrate = 3 tablets.
Maximum Weekly Dose: Adults: 10 mg ergotamine tartrate = 10 tablets.
Children: 5 mg ergotamine tartrate = 5 tablets.
