Ergotamine Tartrate

Class: Non-selective alpha-Adrenergic Blocking Agents
VA Class: CN105
CAS Number: 379-79-3
Brands: Cafergot, Ergomar, Migergot

Warning(s)

  • Possible serious and/or life-threatening cerebral and/or peripheral ischemia when used concomitantly with potent CYP3A4 inhibitors (see Interactions); concomitant use contraindicated.138 139 140

Introduction

Naturally occurring ergot alkaloid.b 140

Uses for Ergotamine Tartrate

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

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

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 Tartrate 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 Tartrate

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

Interactions for Ergotamine Tartrate

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

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 extremities123 124 125 126 127 138 139 140

Concomitant use contraindicated124 125 126 127 138 139 140

Caffeine

Increased plasma ergotamine concentrations143 b

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

Inhibition of ergotamine metabolism; increased risk of potentially fatal cerebral ischemia and/or ischemia of the extremities123 124 125 126 127 138 139 140

Concomitant use contraindicated124 125 126 127 138 139 140

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

Inhibition of ergotamine metabolism; increased risk of potentially fatal cerebral ischemia and/or ischemia of the extremities123 124 125 126 127 138 139 140

Concomitant use contraindicated124 125 126 127 138 139 140

Methysergide (no longer commercially available in US)

Potential for excessive vasoconstriction143

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

Nicotine

Possible vasoconstriction and increased ischemic response138 139 140

Concomitant use not recommended138 139 140

Propranolol

Potentiation of ergotamine’s vasoconstrictive action138 139 140

Use with cautionb

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

Additive vasoconstrictor effects115 116 117 118 119 144 145

Use within 24 hours contraindicated115 116 144 145

Sympathomimetic agents

Potential for extreme BP elevations138 139 140

Concomitant use not recommended138 139 140

Ergotamine Tartrate 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.

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).130 131 132 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.131 132 There currently are approved ergotamine-containing preparations on the US market.130 131 132

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Cafergot 1-100MG Tablets (SANDOZ): 30/$105.99 or 90/$309.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions December 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

14. Medications: In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson textbook of pediatrics. 18th ed. Philadelphia: WB Saunders Company; 2007: 2974.

100. A Redfield MM, Nicholson WJ, Edwards WD. Valve disease associated with ergot alkaloid use: echocardiographic and pathologic correlations. Ann Intern Med. 1992; 117:50-52. [IDIS 298556] [PubMed 1596047]

101. Bana DS, MacNeal PS, LeCompte PM et al. Cardiac murmurs and endocardial fibrosis associated with methysergide therapy. Am Heart J. 1974; 88:640-55. [IDIS 46354] [PubMed 4420941]

102. Misch KA. Development of heart valve lesions during methysergide therapy. Br Med J. 1974; 2:365-6. [IDIS 4307] [PubMed 4835843]

103. Hauck AJ, Edwards WD, Danielson K et al. Mitral and aortic valve disease associated with ergotamine therapy for migraine. Arch Pathol Lab Med. 1990; 114:62-4. [PubMed 2403780]

104. Munroe DS, Allen P, Cox AR. Mitral regurgitation occurring during methysergide (Sansert) therapy. Can Med Assoc J. 1969; 101:62-5. [IDIS 10120] [PubMed 5348490]

105. Mason JW, Billingham ME, Friedman JP. Methysergide-induced heart disease: a case of multivalvular and myocardial fibrosis. Circulation. 1977; 56:889-90. [IDIS 98306] [PubMed 912852]

106. Spierings ELH. Cardiac murmurs indicative of aortic valve disease with chronic and excessive intake of ergotamine. Headache. 1988; 28:278-9. [PubMed 3170186]

107. Graham JR. Cardiac and pulmonary fibrosis during methysergide therapy for headache. Am J Med Sci. 1967; 254:1-12. [IDIS 86] [PubMed 6027684]

108. Khan MA, Herzog CA, St Peter JV et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med. 1998; 339:713-8. [IDIS 411507] [PubMed 9731086]

109. Graham JR, Suby HI, LeCompte PR et al. Fibrotic disorders associated with methysergide therapy for headache. N Engl J Med. 1966; 274:359-68. [IDIS 1053] [PubMed 5903120]

110. Slugg PH, Kunkel RS. Complications of methysergide therapy: retroperitoneal fibrosis, mitral regurgitation, edema, and hemolytic anemia. JAMA. 1970; 213:297-8. [IDIS 13760] [PubMed 5467905]

111. Orlando RC, Moyer P, Barnett TB. Methysergide therapy and constrictive pericarditis. Ann Intern Med. 1978; 88:213-4. [IDIS 77377] [PubMed 626452]

112. Ergomar (ergotamine tartrate sublingual tablets) prescribing information (dated 1997 Jun). In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998:1518-9.

113. Sansert (methysergide maleate tablets) prescribing information (dated 1995 Jun). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2424-5.

114. Elkind AH, Friedman AP, Bachman A et al. Silent retroperitoneal fibrosis associated with methysergide therapy. JAMA. 1968; 206:1041-44. [IDIS 7031] [PubMed 5695652]

115. GlaxoSmithKline. Imitrex (sumatriptan succinate) injection prescribing information. Research Triangle Park, NC; 2008 Feb.

116. GlaxoSmithKline. Imitrex (sumatriptan succinate) tablets prescribing information. Research Triangle Park, NC; 2007 Oct.

117. Anon. New medicines: sumatriptan. Intl Pharm J. 1992; 6:55-7.

118. Myerburg RJ, Kessler KM, Mallon SM et al. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary artery spasm. N Engl J Med. 1992; 326:1451-5. [IDIS 296579] [PubMed 1574091]

119. Tfelt-Hansen P, Sperling B, Winter PDO’B. Transient additional effect of sumatriptan on ergotamine-induced constriction of peripheral arteries in man. Clin Pharmacol Ther. 1992; 51:149.

120. Henry P, d’Allens H, French Migraine Network Bordeaux-Lyon-Grenoble. Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. Headache. 1993; 33:432-5. [PubMed 8262783]

121. US Headache Consortium. Evidence-based guidelines for migraine headache in the primary care setting. St. Paul, MN; 2001. From the American Academy of Neurology web site. [pharmacologic management of acute attacks]).

123. Clarithromycin (Biaxin) interactions: ergotamine (Ergomar). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. St. Louis, MO: Facts and Comparisons; 2002:350.

124. Horowitz RS, Dart RC, Gomez HF. Clinical ergotism with lingual ischemia induced by clarithromycin-ergotamine interaction. Arch Intern Med. 1996; 156:456-8. [IDIS 363451] [PubMed 8607732]

125. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000; 38:41-57. [PubMed 10668858]

126. Ergotamine (Ergostat) interactions: indinavir (Crixivan). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. St. Louis, MO: Facts and Comparisons; 2002:356.

127. Ergotamine (Ergostat) interactions: ritonavir (Norvir). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. St. Louis, MO: Facts and Comparisons; 2002:357a.

128. Ergotamine. In: Briggs GG, Freeman RK, Yaffe SJ eds. Drugs in pregnancy and lactation. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:497-501/e.

129. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Policy statement. Pediatrics. 2001; 108:776-89. [IDIS 468574] [PubMed 11533352]

130. Food and Drug Administration. Ergotamine tartrate. Rockville, MD; 2007 Mar 2. From FDA website.

131. Food and Drug Administration. FDA takes action to halt marketing of unapproved ergotamine–Companies ordered to cease manufacturing and distribution of illegal drugs to treat migraine headaches. FDA News March 1, 2007. From FDA web site.

132. Food and Drug Administration. Warning letters for ergotamine-containing drug products (issued February 26, 2007). From FDA web site.

133. Custer JW, Rau RE, eds. The Harriet Lane Handbook: a manual for pediatric house officers. 18th ed. Philadelphia, PA: Elsevier Mosby: 2009:821.

134. Schreiber CP, Young WB. Cluster headache. In Freitag F, Cady R, eds. Standards of care for headache diagnosis and treatment. Chicago: National Headache Foundation; 2008: 66-74.

135. Agency for Healthcare Research and Quality. Treatment of primary headache: cluster headache. Standards of care for headache diagnosis and treatment. From the National Guideline Clearinghouse website. Accessed 7/31/09.

136. Capobianco DJ, Dodick DW. Diagnosis and treatment of cluster headache. Semin Neurol. 2006; 26:242-59. [PubMed 16628535]

137. May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet. 2005 Sep 3-9; 366:843-55.

138. Rosedale Therapeutics. Ergomar (ergotamine tartrate) sublingual tablets prescribing information. Bristol, TN. 2007 Aug.

139. G and W Laboratories, Inc. Ergotamine tartrate and caffeine suppositories prescribing information. South Plainfield, NJ. 2003 Apr.

140. Novartis. Cafergot (ergotamine tartrate and caffeine) tablets prescribing information. East Hanover, NJ. 2003 Mar.

141. Balasubramaniam R, Klasser GD. Trigeminal autonomic cephalalgias. Part 1: cluster headache. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104:345-58. [PubMed 17618143]

142. Ekbom K, Hardebo JE. Cluster headache: aetiology, diagnosis and management. Drugs. 2002; 62:61-9. [PubMed 11790156]

143. Eadie MJ. Clinically significant drug interactions with agents specific for migraine attacks. CNS Drugs. 2001; 15:105-18. [PubMed 11460889]

144. AstraZeneca. Zomig (zolmitriptan) nasal spray prescribing information. Wilmington, DE; 2008 Oct.

145. Merck & Co., Inc. Maxalt (rizatriptan benzoate) tablets and Maxalt-MLT (rizatriptan benzoate) orally distinegrating tablets prescribing information. Whitehouse Station, NJ; 2008 Feb.

b. AHFS drug information 2009. McEvoy GK, ed. Ergotamine tartrate. Bethesda, MD: American Society of Health-System Pharmacists; 2009:1406-9.

Hide
(web2)