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Ergotamine

Brand name: Ergomar
Drug class: Non-selective alpha-Adrenergic Blocking Agents
- Ergot Alkaloids
VA class: CN105
CAS number: 379-79-3

Medically reviewed by Drugs.com on Nov 22, 2021. Written by ASHP.

Warning

  • Possible serious and/or life-threatening cerebral and/or peripheral ischemia when used concomitantly with potent CYP3A4 inhibitors (see Interactions); concomitant use contraindicated.

Introduction

Naturally occurring ergot alkaloid.

Uses for Ergotamine

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 chronic daily management of vascular headaches.

Generally not preferred for terminating acute cluster headaches; onset of action is slower than that of other therapies (e.g., sumatriptan, oxygen).

Has been used for short-term (e.g., up to 3 weeks) prophylaxis of episodic cluster headaches to suppress a series of attacks and reduce duration of cluster period. Prophylactic administration at bedtime may be particularly useful in selected patients with nocturnal cluster attacks.

Ineffective in the treatment of muscle contraction headaches.

Ergotamine 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.

  • Do not administer within 24 hours of a selective serotonin agonist (e.g., sumatriptan). (See Specific Drugs under Interactions.)

Administration

Administer orally or rectally (as fixed-combination preparation containing ergotamine and caffeine).

Administer sublingually (as single-entity preparation).

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 of ergotamine tartrate (2 tablets) initially, followed by 1 mg at 30-minute intervals until attack has abated (maximum 6 mg per attack).

For short-term prophylaxis of cluster headaches, 3–4 mg daily (in divided doses) has been administered for up to 3 weeks. May be administered 30–60 minutes prior to an expected attack in patients with consistent attack patterns. In selected patients with nocturnal attacks, 1–2 mg may be given at bedtime on a short-term basis. Monitor carefully to avoid excessive weekly dosages; give due consideration to recommended maximum weekly dosage (see Prescribing Limits under Dosage and Administration).

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).

For short-term prophylaxis of cluster headaches, 3–4 mg daily (in divided doses) has been administered for up to 3 weeks. May be administered 30–60 minutes prior to an expected attack in patients with consistent attack patterns. Monitor carefully to avoid excessive weekly dosages; give due consideration to recommended maximum weekly dosage (see Prescribing Limits under Dosage and Administration).

Rectal

Fixed-combination ergotamine and caffeine (e.g., Migergot) suppositories: 2 mg of ergotamine tartrate (1 suppository) initially. If necessary, may give a second 2-mg dose after 1 hour.

In selected patients with cluster headaches at night, 1–2 mg may be given at bedtime on a short-term basis. Give due consideration to recommended maximum weekly dosage (see Prescribing Limits under Dosage and Administration).

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 Migergot suppositories) per attack or 10 mg (5 Migergot suppositories) per week.

Cautions for Ergotamine

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.

Use of Fixed Combinations

When used in fixed combination with caffeine, consider the cautions, precautions, and contraindications associated with caffeine.

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

Nausea, vomiting, abdominal pain, numbness and tingling of the fingers and toes, muscle pain in the extremities, weakness in the legs.

Interactions for Ergotamine

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

Drug

Interaction

Comment

Antifungals, azole (e.g., itraconazole, ketoconazole)

Inhibition of ergotamine metabolism; increased risk of potentially fatal cerebral ischemia and/or ischemia of the extremities

Concomitant use contraindicated

Caffeine

Increased plasma ergotamine concentrations

HIV protease inhibitors (e.g., ritonavir, nelfinavir, indinavir)

Inhibition of ergotamine metabolism; increased risk of potentially fatal cerebral ischemia and/or ischemia of the extremities

Concomitant use contraindicated

Macrolide antibiotics (e.g., erythromycin, clarithromycin, troleandomycin)

Inhibition of ergotamine metabolism; increased risk of potentially fatal cerebral ischemia and/or ischemia of the extremities

Concomitant use contraindicated

Methysergide (no longer commercially available in US)

Potential for excessive vasoconstriction

Decrease ergotamine dosage by about 50%; keep frequency of ergotamine administration at a minimum

Nicotine

Possible vasoconstriction and increased ischemic response

Concomitant use not recommended

Propranolol

Potentiation of ergotamine’s vasoconstrictive action

Use with caution

Serotonin (5-HT1) receptor agonists (e.g., sumatriptan)

Additive vasoconstrictor effects

Use within 24 hours contraindicated

Sympathomimetic agents

Potential for extreme BP elevations

Concomitant use not recommended

Ergotamine 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

2–8°C.

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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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). Manufacturers’ labelings for most of these unapproved preparations omitted critical drug interaction warnings, and the preparations did not undergo FDA review of safety, efficacy, quality, and labeling. There currently are approved ergotamine-containing preparations on the US market.

Ergotamine Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Sublingual

Tablets

2 mg

Ergomar

Rosedale

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ergotamine Tartrate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1 mg with Caffeine 100 mg*

Cafergot

Novartis

Rectal

Suppositories

2 mg with Caffeine 100 mg

Migergot

G&W

AHFS DI Essentials™. © Copyright 2022, Selected Revisions December 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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