Ergotamine (Monograph)

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 21, 2024. Written by ASHP.

Introduction

Naturally occurring ergot alkaloid.^{b 140}

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.^{138 139 140} Should not be used for chronic daily management of vascular headaches.^{138 139 140}

Generally not preferred for terminating acute cluster headaches; onset of action is slower than that of other therapies (e.g., sumatriptan, oxygen).^{134 136 141 142}

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.^{134 136 137 141 142} Prophylactic administration at bedtime may be particularly useful in selected patients with nocturnal cluster attacks.^{134 135 136 139 140 141}

Ineffective in the treatment of muscle contraction headaches.^b

Ergotamine Dosage and Administration

General

Vascular Headaches

• Administer as soon as possible after onset of first symptoms of vascular headache.^{138 139 140}

• After administering the initial dose, patient should lie down and relax in a quiet, darkened room.^b

• Do not administer within 24 hours of a selective serotonin agonist (e.g., sumatriptan).^{115 116 144 145} (See Specific Drugs under Interactions.)

Administration

Administer orally or rectally (as fixed-combination preparation containing ergotamine and caffeine).^{139 140}

Administer sublingually (as single-entity preparation).¹³⁸

Sublingual Administration

Place tablets under the tongue and allow to dissolve.¹³⁸

Rectal Administration

If suppositories become softened, chill them in ice-cold water to solidify before removing the foil wrapper.¹³⁹

Dosage

Available as ergotamine tartrate; dosage expressed in terms of the salt.^{138 139 140}

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).¹⁴⁰

For short-term prophylaxis of cluster headaches, 3–4 mg daily (in divided doses) has been administered for up to 3 weeks.^{135 142} May be administered 30–60 minutes prior to an expected attack in patients with consistent attack patterns.^{135 142} In selected patients with nocturnal attacks, 1–2 mg may be given at bedtime on a short-term basis.^{134 137 140 142} Monitor carefully to avoid excessive weekly dosages;¹⁴² give due consideration to recommended maximum weekly dosage (see Prescribing Limits under Dosage and Administration).¹⁴⁰

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).¹³⁸

For short-term prophylaxis of cluster headaches, 3–4 mg daily (in divided doses) has been administered for up to 3 weeks.^{135 142} May be administered 30–60 minutes prior to an expected attack in patients with consistent attack patterns.^{135 142} Monitor carefully to avoid excessive weekly dosages;¹⁴² give due consideration to recommended maximum weekly dosage (see Prescribing Limits under Dosage and Administration).¹⁴⁰

Rectal

Fixed-combination ergotamine and caffeine (e.g., Migergot) suppositories: 2 mg of ergotamine tartrate (1 suppository) initially.¹³⁹ If necessary, may give a second 2-mg dose after 1 hour.¹³⁹

In selected patients with cluster headaches at night, 1–2 mg may be given at bedtime on a short-term basis.^{137 139 142} Give due consideration to recommended maximum weekly dosage (see Prescribing Limits under Dosage and Administration).^{139 142}

Prescribing Limits

Adults

Vascular Headaches

Oral

Maximum 6 mg (6 Cafergot tablets) per attack or 10 mg (10 Cafergot tablets) per week.¹⁴⁰

Sublingual

Maximum 6 mg (3 Ergomar tablets) per 24-hour period or 10 mg (5 Ergomar tablets) per week.¹³⁸

Rectal

Maximum 4 mg (2 Migergot suppositories) per attack or 10 mg (5 Migergot suppositories) per week.¹³⁹

Cautions for Ergotamine

Contraindications

• Known or suspected pregnancy.^{138 139 140}

• Concomitant therapy with potent CYP3A4 inhibitors.^{124 125 126 127 138 139 140} (See Interactions.)

• Peripheral vascular disease, CHD, or hypertension.^{138 139 140}

• Impaired hepatic or renal function.^{138 139 140}

• Sepsis.^{138 139 140}

• Known hypersensitivity to ergot alkaloids or any ingredient in the formulation.^{138 139 140}

Warnings/Precautions

Warnings

Fibrosis

Possible retroperitoneal and pleuropulmonary fibrosis.^{106 138 139 140}

Possible fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with continuous, long-term administration;^{100 101 102 103 104 105 106 107 138 139 140} do not administer on a chronic daily basis.^{138 139 140}

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.^{100 109 113 114}

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; fetal growth retardation observed in animals.^{138 139 140}

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.^{138 139 140} Do not exceed recommended dosages.^{138 139 140}

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

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.¹³⁹

Possible withdrawal symptoms (e.g., rebound headache) upon discontinuance of the drug following indiscriminate use over long periods of time.^{138 139 140}

Use of Fixed Combinations

When used in fixed combination with caffeine, consider the cautions, precautions, and contraindications associated with caffeine.^{139 140}

Specific Populations

Pregnancy

Category X.^{138 139 140} (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)

Oxytocic effects are maximal in 3rd trimester; contraindicated in labor and delivery.^{138 139 140}

Lactation

Distributed into milk; may cause vomiting, diarrhea, weak pulse, seizures, and unstable BP in nursing infants.^{128 129 138 139 140} Discontinue nursing or the drug.^{138 139 140}

Inhibits prolactin, but no reports of decreased lactation.^{138 139 140}

Pediatric Use

Safety and efficacy not established in children.^{138 139 140}

Hepatic Impairment

Use contraindicated.^{138 139 140}

Renal Impairment

Use contraindicated.^{138 139 140}

Common Adverse Effects

Nausea, vomiting, abdominal pain, numbness and tingling of the fingers and toes, muscle pain in the extremities, weakness in the legs.^{138 139 140 b}

Drug Interactions

Extensively metabolized, principally by CYP3A4.^{138 139 140} Inhibits CYP3A.^{138 139 140}

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.^{123 124 125 126 127 138 139 140} Concomitant use with potent CYP3A4 inhibitors contraindicated.^{123 124 125 126 127 138 139 140}

Less-potent CYP3A4 inhibitors: Similar effects not reported to date; however, consider possibility of serious toxicity during concomitant use.^{138 139 140}

Specific Drugs

Ergotamine Pharmacokinetics

Absorption

Bioavailability

Absorption is variable following oral administration.^b

Undergoes first-pass metabolism following oral administration.^b

Distribution

Extent

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

Elimination

Metabolism

Extensively metabolized in the liver, mainly by CYP3A4.^b

Elimination Route

Metabolites are excreted mainly (90%) in bile;^b only traces of unchanged drug are excreted in urine and feces.¹¹²

Eliminated by dialysis.^b

Half-life

Biphasic; terminal half-life is approximately 21 hours.^b

Stability

Storage

Oral

Tablets

Tight, light-resistant container at 15–30°C.¹⁴⁰

Sublingual

Tablets

20–25°C (may be exposed to 15–30°C).¹³⁸ Protect from light and heat.¹³⁸

Rectal

Suppositories

2–8°C.¹³⁹

Actions

• Complex pharmacologic effects, including α-adrenergic blocking activity, direct stimulation of peripheral and cranial vascular smooth muscle, and serotonin antagonist activity.^{138 139 140}

• Mechanism by which ergotamine aborts vascular headaches is probably direct vasoconstriction of dilated carotid artery bed.^b

• Has greater vasoconstrictor activity than other ergot alkaloids but less α-adrenergic blocking activity than dihydroergotamine;^{b 138 139 140} weaker antagonist of serotonin than is methysergide.^b

Advice to Patients

• Risk of ergotism; importance of informing clinicians if intermittent claudication; muscle pain; or numbness, coldness, and pallor of the digits occur.^{138 139 140}

• Importance of informing clinicians if persistent paresthesia, chest/muscle/abdominal pain, speeding or slowing of heart rate, swelling, or itching occurs.^{b 138 139 140}

• Importance of taking ergotamine exactly as prescribed.^{138 139 140}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{138 139 140}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{138 139 140}

• Importance of informing patients of other important precautionary information.^{138 139 140} (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.

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

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