Boxed Warning
Concurrent drug therapy:
Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine with potent CYP 3A4 inhibitors, including protease inhibitors and macrolide antibiotics. Because CYP3A4 inhibition elevates the serum levels of ergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Therefore, concomitant use of these medications is contraindicated.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Sublingual, Sublingual, as tartrate:
Ergomar: 2 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, saccharin sodium]
Pharmacology
Mechanism of Action
Has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha-adrenergic receptors depending upon their site; is a highly active uterine stimulant; it causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers
Pharmacokinetics/Pharmacodynamics
Absorption
Oral, rectal: Erratic (Perrin 1985)
Distribution
Vd: Adults: 1.85 L/kg
Metabolism
Extensively hepatic, including high first-pass metabolism (Perrin 1985)
Excretion
Feces (90%, primarily as metabolites) (Perrin 1985)
Time to Peak
Serum: Oral: 2 hours (Perrin 1985)
Half-Life Elimination
2-2.5 hours (Perrin 1985)
Use: Labeled Indications
Vascular headache: Abort or prevent vascular headaches, such as migraine, migraine variants, or so-called “histaminic cephalalgia”
Contraindications
Hypersensitivity to ergotamine or any component of the formulation; peripheral vascular disease; hepatic or renal impairment; coronary artery disease; hypertension; sepsis; ergot alkaloids are contraindicated with strong inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); pregnancy
Dosage and Administration
Dosing: Adult
Vascular headache: Sublingual: 2 mg (1 tablet) under tongue at first sign of migraine, then 2 mg every 30 minutes if needed; maximum dose: 6 mg per 24 hours, 10 mg per week
Dosing: Geriatric
Not recommended for use in the elderly.
Dosing: Pediatric
Vascular headache: Very limited data available; efficacy results variable; not routinely used: Adolescents: Sublingual: 2 mg (1 tablet) under tongue at first sign of migraine, then 2 mg (1 tablet) every 30 minutes as tolerated; maximum dose: 6 mg/24 hours, or 10 mg/week has been reported in clinical experience (Geraoud 2004; Wellborn 1997) Note: Not a preferred agent, use of ergotamine has largely been replaced by newer agents with improved efficacy and adverse effect profile.
Administration
Do not crush sublingual tablets..
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from heat and light.
Ergotamine Images
Drug Interactions
Alpha-/Beta-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Avoid combination
Alpha1-Agonists: Ergot Derivatives may enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Avoid combination
Antihepaciviral Combination Products: May increase the serum concentration of Ergot Derivatives. Avoid combination
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives. Consider therapy modification
Chloroprocaine: May enhance the hypertensive effect of Ergot Derivatives. Monitor therapy
Clarithromycin: May increase the serum concentration of Ergotamine. Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Cobicistat: May increase the serum concentration of Ergotamine. Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Crizotinib: May increase the serum concentration of Ergotamine. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Enzalutamide: May decrease the serum concentration of Ergotamine. Avoid combination
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Itraconazole: May increase the serum concentration of Ergotamine. Avoid combination
Ketoconazole (Systemic): May increase the serum concentration of Ergotamine. Avoid combination
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Letermovir: May increase the serum concentration of Ergot Derivatives. Avoid combination
Lorcaserin: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Avoid combination
Macrolide Antibiotics: May increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of Ergotamine. Management: Avoid ergotamine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. Avoid combination
Nefazodone: Ergot Derivatives may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Nitroglycerin: Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Avoid combination
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Posaconazole: May increase the serum concentration of Ergotamine. Avoid combination
Protease Inhibitors: May increase the serum concentration of Ergot Derivatives. Avoid combination
Reboxetine: May enhance the hypertensive effect of Ergot Derivatives. Monitor therapy
Roxithromycin: May increase the serum concentration of Ergot Derivatives. Avoid combination
Serotonergic Agents (High Risk): Ergot Derivatives may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Nefazodone. Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the vasoconstricting effect of Ergot Derivatives. Avoid combination
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Voriconazole: May increase the serum concentration of Ergotamine. Avoid combination
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, cold extremities, ECG changes, edema, hypertension, ischemia, tachycardia, valvular sclerosis, vasospasm
Central nervous system: Numbness, paresthesia, precordial pain, vertigo
Dermatologic: Gangrene of skin or other tissue, pruritus
Gastrointestinal: Nausea, vomiting
Genitourinary: Retroperitoneal fibrosis
Neuromuscular & skeletal: Myalgia, weakness
Respiratory: Cyanosis, pleuropulmonary fibrosis
Warnings/Precautions
Concerns related to adverse effects:
- Cardiac valvular fibrosis: Ergot alkaloids have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.
- Cardiovascular effects: Vasospasm or vasoconstriction can occur, possibly resulting in decreased cerebral blood flow, ECG changes, and hypertension; sustained vasoconstriction may also lead to ischemic colitis, intermittent claudication, aggravation of angina, or precipitation of MI. Do not use is any patient at risk or predisposed to vascular effects of ergot alkaloids. In a scientific statement from the American Heart Association, ergotamine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).
- Ergotism: Ergot alkaloid use may result in ergotism (intense vasoconstriction) resulting in peripheral vascular ischemia and possible gangrene. Ergotism is usually associated with overdosage or prolonged chronic use; do not exceed dosing guidelines and avoid prolonged administration.
- Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use.
Concurrent drug therapy issues:
- CYP3A4 inhibitors: [US Boxed Warning]: Ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); concomitant use associated with acute ergot toxicity (ergotism).
Special populations:
- Elderly: Avoid use in the elderly due to the vasoconstrictive properties and cardiovascular adverse effects associated with ergot alkaloids.
Other warnings/precautions:
- Appropriate use: Acute migraine agents (eg, 5-HT1 agonists, opioids, ergotamine, or a combination of the agents) used for 10 or more days per month may lead to worsening of headaches (medication overuse headache); withdrawal treatment may be necessary in the setting of overuse (Thorlund 2016)
- Withdrawal: Discontinuation even after limited use may result in withdrawal symptoms (ie, rebound headache, nausea, vomiting).
Pregnancy
Pregnancy Risk Factor
X
Pregnancy Considerations
Ergotamine crosses the placenta. Use is contraindicated in pregnancy. Ergotamine may cause prolonged constriction of the uterine vessels and/or increased myometrial tone leading to reduced placental blood flow. This has contributed to fetal growth retardation in animals.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea or vomiting. Have patient report immediately to prescriber chest pain, slow heartbeat, fast heartbeat, abnormal heartbeat, edema, severe dizziness, passing out, severe headache, vision changes, muscle pain, muscle weakness, change in color of hands or feet from pale to blue or red, burning or numbness of hands or feet, or wounds on fingers or toes (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
