Generic Name: ergotamine

Brand Names: Ergomar

Uses

Vascular Headaches

Prevention or abortion of vascular headaches (e.g., migraine, cluster headaches), when used alone or in fixed combination with caffeine. Should not be used for prophylactic or chronic daily management of migraine headache.

Ineffective in the treatment of muscle contraction headaches.

Vasomotor Symptoms Associated with Menopause

Amelioration of vasomotor symptoms (e.g., hot flushes, sweating, restlessness, insomnia) in menopausal women, when used in fixed combination with belladonna alkaloids and phenobarbital.

Other Uses

Used for its autonomic effects in the treatment of various cardiovascular and GI disorders (when given in fixed combination with belladonna alkaloids and phenobarbital); generally has been replaced by more specific agents for these uses.

Dosage and Administration

General

Vascular Headaches
• Administer as soon as possible after onset of first symptoms of vascular headache.
• After administering the initial dose, patient should lie down and relax in a quiet, darkened room.
• Dosage adjustments may be required when administered concomitantly with other drugs used in the treatment of vascular headaches. (See Specific Drugs under Interactions.)

Administration

Administer orally or rectally (as fixed-combination preparation containing ergotamine and caffeine) for the treatment of vascular headaches.

Administer orally (as fixed-combination preparation containing ergotamine, levorotatory alkaloids of belladonna, and phenobarbital) for the treatment of vasomotor symptoms of menopause.

Administer sublingually (as single-entity preparation) for the treatment of vascular headaches.

Oral Administration

Administer fixed-combination preparation containing ergotamine, levorotatory alkaloids of belladonna, and phenobarbital twice daily (morning and evening).

Sublingual Administration

Place tablets under the tongue and allow to dissolve.

Rectal Administration

If suppositories become softened, chill them in ice-cold water to solidify before removing the foil wrapper.

Dosage

Available as ergotamine tartrate; dosage expressed in terms of the salt.

Adults

Vascular Headaches

Oral

Fixed-combination ergotamine and caffeine (e.g., Cafergot^®) tablets: 2 mg (2 tablets) initially, followed by 1 mg at 30-minute intervals until attack has abated (maximum 6 mg per attack).

Sublingual

Ergotamine tartrate (Ergomar^®) tablets: 2 mg (1 tablet) initially, followed by 2 mg at 30-minute intervals until attack has abated (maximum 6 mg per 24-hour period).

Rectal

Fixed-combination ergotamine and caffeine (e.g., Cafergot^®) suppositories: 2 mg (1 suppository) initially. If necessary, may give a second 2-mg dose in 1 hour.

In some patients with cluster headaches in the morning, 2–4 mg (1–2 suppositories) may be given at bedtime on a short-term basis.

Vasomotor Symptoms Associated with Menopause

Oral

Fixed-combination ergotamine, levorotatory alkaloids of belladonna, and phenobarbital (e.g., Bellamine^® S) tablets: 0.6 mg (1 tablet) twice daily (morning and evening).

Prescribing Limits

Adults

Vascular Headaches

Oral

Maximum 6 mg (6 Cafergot^® tablets) per attack or 10 mg (10 Cafergot^® tablets) per week.

Sublingual

Maximum 6 mg (3 Ergomar^® tablets) per 24-hour period or 10 mg (5 Ergomar^® tablets) per week.

Rectal

Maximum 4 mg (2 Cafergot^® suppositories) per attack or 10 mg (5 Cafergot^® suppositories) per week.

Vasomotor Symptoms Associated with Menopause

Oral

Maximum 10 mg (16 Bellamine^® S tablets) per week.

Cautions

Contraindications

• Known or suspected pregnancy.
• Concomitant therapy with potent CYP3A4 inhibitors. (See Interactions.)
• Peripheral vascular disease, CHD, or hypertension.
• Impaired hepatic or renal function.
• Sepsis.
• Known hypersensitivity to ergot alkaloids or any ingredient in the formulation.

Warnings/Precautions

Warnings

Fibrosis

Possible retroperitoneal and pleuropulmonary fibrosis.

Possible fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with continuous, long-term administration; do not administer on a chronic daily basis.

Examine patients regularly for development of fibrotic complications; perform appropriate tests (e.g., ECG, laboratory tests, radiographic examination) if signs or symptoms of these conditions occur.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; fetal growth retardation observed in animals.

General Precautions

Ergotism

Potential for ergotism, manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia; if left untreated, can progress to gangrene. Do not exceed recommended dosages.

If signs and symptoms of impaired circulation occur, discontinue therapy and keep affected extremities warm.

Misuse and Abuse

Solitary rectal or anal ulcer associated with abuse of ergotamine suppositories (e.g., use of higher than recommended dosages or continual use at the recommended dose for many years); usually resolves 4–8 weeks following discontinuance of the drug.

Possible withdrawal symptoms (e.g., rebound headache) upon discontinuance of the drug following indiscriminate use over long periods of time.

Fixed-Combination Preparations

Consider the cautions, precautions, and contraindications associated with other drug(s) in fixed-combination preparations.

Specific Populations

Pregnancy

Category X. (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)

Oxytocic effects are maximal in 3rd trimester; contraindicated in labor and delivery.

Lactation

Distributed into milk; may cause vomiting, diarrhea, weak pulse, seizures, and unstable BP in nursing infants. Discontinue nursing or the drug.

Inhibits prolactin, but no reports of decreased lactation.

Pediatric Use

Safety and efficacy not established in children.

Hepatic Impairment

Use contraindicated.

Renal Impairment

Use contraindicated.

Common Adverse Effects

With oral tablets, numbness and tingling of the fingers and toes, muscle pains in the extremities, weakness in the legs, precordial distress and pain, transient tachycardia or bradycardia, nausea, vomiting, localized edema, itching.

With sublingual tablets, ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, ECG changes, muscle pains, transient tachycardia or bradycardia, hypertension, nausea, vomiting, paresthesias, numbness, weakness, vertigo, localized edema, itching.

With rectal suppositories, ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, ECG changes, muscle pains.

Interactions

Extensively metabolized, principally by CYP3A4. Inhibits CYP3A.

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased serum ergotamine concentrations); potentially fatal cerebral ischemia and/or ischemia of the extremities possible. Concomitant use with potent CYP3A4 inhibitors contraindicated.

Less-potent CYP3A4 inhibitors: Similar effects not reported to date; however, consider possibility of serious toxicity during concomitant use.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Absorption is variable following oral administration.

Undergoes first-pass metabolism following oral administration.

Distribution

Extent

Crosses the blood-brain barrier and is distributed into milk.

Elimination

Metabolism

Extensively metabolized in the liver, mainly by CYP3A4.

Elimination Route

Metabolites are excreted mainly (90%) in bile; only traces of unchanged drug are excreted in urine and feces.

Eliminated by dialysis.

Half-life

Biphasic; terminal half-life is approximately 21 hours.

Stability

Storage

Oral

Tablets

Tight, light-resistant container at 15–30°C.

Sublingual

Tablets

20–25°C (may be exposed to 15–30°C). Protect from light and heat.

Rectal

Suppositories

<25°C. Protect from moisture.

Actions

• Complex pharmacologic effects, including α-adrenergic blocking activity, direct stimulation of peripheral and cranial vascular smooth muscle, and serotonin antagonist activity.
• Mechanism by which ergotamine aborts vascular headaches is probably direct vasoconstriction of dilated carotid artery bed.
• Has greater vasoconstrictor activity than other ergot alkaloids but less α-adrenergic blocking activity than dihydroergotamine; weaker antagonist of serotonin than is methysergide.

Advice to Patients

• Risk of ergotism; importance of informing clinicians if intermittent claudication; muscle pain; or numbness, coldness, and pallor of the digits occur.
• Importance of informing clinicians if persistent paresthesia, chest/muscle/abdominal pain, speeding or slowing of heart rate, swelling, or itching occurs.
• Importance of taking ergotamine exactly as prescribed.
• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

On February 26, 2007, FDA warned 20 firms that manufacture or distribute unapproved drug preparations containing ergotamine tartrate of the agency’s intention to take enforcement action (e.g., seizure, injunction, other judicial proceeding) against all firms attempting to manufacture or distribute such preparations after April 25, 2007, or August 25, 2007, respectively, without an approved new drug application (NDA). Unapproved preparations manufactured or distributed before these dates may still be found on pharmacy shelves for a short period of time. Manufacturers' labelings for most of these unapproved preparations omit critical drug interaction warnings, and the preparations have not undergone FDA review of safety, efficacy, quality, and labeling. There currently are approved ergotamine-containing preparations on the US market.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions December 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.