Ergotamine Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Ergotamine is an ergot alkaloid that is hypothesized to exert its antimigraine effects via its agonist activity at the serotonin 5-HT1D receptor, resulting in vasoconstriction of intracranial blood vessels and inhibition of inflammatory neuropeptide release. The drug also binds with high affinity to adrenergic receptors; however, the antimigraine effect of this binding is unknown. The mechanism in migraine is thought to be vasoconstriction of cranial blood vessels, with a concomitant decrease in the amplitude of pulsations as well as depression of serotonergic neurons that mediate pain.
Administration and Adult Dosage	For migraine treatment: - Oral (PO): 2 mg initially, then 1 mg every 30 min as needed, to a maximum of 6 mg/day or 10 mg/week - Rectal (PR): 2 mg initially, may repeat in 1 hr as needed, to a maximum of 4 mg/attack or 10 mg/week - Sublingual (SL): 2 mg initially, then 2 mg every 30 min as needed, to a maximum of 6 mg/day or 10 mg/week Note: Titrate the dosage during several attacks gradually, then administer the minimum effective dosage with subsequent attacks. Patients who routinely require over 2 mg/headache can be given the total effective dosage at the onset of the headache.
Special Populations - Pediatric Dosage	Safety and efficacy not established. - Children >12 years: 1 mg initially, then 1 mg every 30 min as needed, to a maximum of 3 mg/attack
Special Populations - Geriatric Dosage	No specific data available.
Other Conditions	Decrease dosage by 50% in patients receiving methysergide as prophylaxis.
Dosage Forms	- Sublingual Tablet: 2 mg - Tablet: 1 mg with caffeine 100 mg (Cafergot, Ercaf, various) - Suppository: 2 mg with caffeine 100 mg (Cafergot, Wigraine)
Patient Instructions	- Initiate therapy at the first signs of an attack - Take only as directed and do not exceed recommended dosages - Report tingling or pain in extremities immediately
Pharmacokinetics - Onset and Duration	- Oral: Onset ~5 hr - Rectal: Onset 1–3 hr
Pharmacokinetics - Serum Levels	- Therapeutic: ≥200 ng/L (176 pmol/L) - Adverse reactions frequent: >1.8 µg/L (1.5 nmol/L)
Pharmacokinetics - Fate	- Bioavailability: • Oral: 1–2% • Rectal: 5% • Order: PR > PO > SL - Peak Serum Levels: • Rectal (2 mg): 454 ± 407 ng/L (390 ± 350 pmol/L) at 50 ± 43 min • Oral (2 mg with caffeine 100 mg): 21 ± 12 ng/L (18 ± 11 pmol/L) at 69 ± 191 min - Distribution: Vd = 1.9 ± 0.8 L/kg - Clearance: Cl = 0.68 ± 0.24 L/hr/kg - Metabolism: Extensively metabolized in the liver; 90% of metabolites excreted in bile
Pharmacokinetics - t¹⁄₂	- Elimination half-life: 1.9 ± 0.3 hr - Apparent half-life (rectal): 3.4 ± 1.9 hr due to slow absorption
Adverse Reactions & Side Effects	Frequent: - Nausea and vomiting Rare (with recommended dosages): - Ergotamine intoxication symptoms: • Weakness in legs • Coldness and muscle pain in extremities • Numbness or tingling of fingers/toes • Precordial pain • Transient tachycardia or bradycardia • Localized edema Other: - Frequent or worsening headaches with frequent, long-term, or excessive dosages - Ergotamine dependence with withdrawal symptoms 24–48 hr post-discontinuation - Suppository use: Rectal or anal ulceration
Contraindications	- Pregnancy - Peripheral vascular disease - Coronary artery disease - Hypertension - Hepatic or renal impairment - Sepsis - Severe pruritus
Precautions & Warnings	- Use caution during lactation - Avoid excessive dosage or prolonged administration due to the potential for ergotism and gangrene
Drug Interactions	- Increased vasoconstriction/ischemia risk: Beta-blockers, dopamine, epinephrine - Inhibited ergot alkaloid metabolism: Macrolides (e.g., erythromycin, troleandomycin)
Class and Drug Brand Name	- Class: Analgesic and Anti-Inflammatory Drugs - Brand Names: Ergomar, Ergostat, Various
Notes	- Caffeine: Can improve dissolution of the oral formulation but may interfere with sleep - Efficacy: Provides relief in 50–90% of patients - Alternatives for mild cases: • Aspirin (650 mg) • Naproxen (750–1250 mg/day) • OTC products: Excedrin Migraine, Advil Migraine, Motrin Migraine • Prescription: Midrin, Fiorinal - Other options: • Butorphanol spray for infrequent, severe headaches in patients intolerant to ergot products or triptans (risk of dependency with frequent use) • Prophylaxis: Beta-blockers (propranolol, timolol, atenolol, nadolol), verapamil, tricyclic antidepressants (amitriptyline, nortriptyline), divalproex - Caution: Overuse of antimigraine products may cause rebound headaches

References

Hand of Clinical Drug Data