What are ergotamine medications?

Ergotamine Medications: Mechanism and Clinical Use

Ergotamine medications are 5-hydroxytryptamine (5-HT) nonselective agonists that act as alpha-adrenergic blockers with direct stimulating effects on smooth muscle of peripheral and cranial blood vessels, producing vasoconstriction and depression of central vasomotor centers. 1, 2

Mechanism of Action

• Ergotamine compounds function as serotonin antagonists with vasoconstrictive properties that are greater than their adrenergic blocking actions 2, 3
• They produce direct stimulation of smooth muscle in peripheral and cranial blood vessels while depressing central vasomotor centers 2
• Ergotamine enters the cerebrospinal fluid and acts through selective arterial vasoconstriction on certain cranial vessel beds or by depression of central serotonergic neurons that mediate pain transmission 4

Types of Ergotamine Medications

• Ergotamine tartrate (ET): The original ergot alkaloid used for migraine treatment 5

  • Available in oral form and rectal suppositories (combined with caffeine as Cafergot) 1
  • Oral bioavailability is approximately 5% or less 4

• Dihydroergotamine (DHE): A semisynthetic ergot alkaloid and nonselective 5-HT1 receptor agonist 1

  • Available in parenteral preparations (IV/IM) and as a nasal spray 1
  • Considered more appropriate for treatment of severe migraines than ergotamine 1
  • Offers benefits including lower incidence of nausea/vomiting, less headache recurrence, and lack of rebound headache compared to ergotamine 5

Clinical Use and Dosing

• Ergotamine tartrate:

  • Dosage: 1-2 mg orally every hour, maximum of three doses in 24 hours 1
  • Rectal suppository: 1 mg, maximum two to three per day and 12 per month 1
  • Caffeine plus ergotamine (Cafergot): Two tablets (100 mg caffeine/1 mg ergotamine) at onset, then one tablet every 30 minutes, up to six tablets per attack, 10 per week 1

• Dihydroergotamine (DHE):

  • Parenteral: Initial dose 0.5-1.0 mg, can be repeated hourly to maximum 3 mg IM or 2 mg IV per day, and 6 mg per week 1
  • Intranasal: One 0.5-mg spray in each nostril, followed by one spray in each nostril 15 minutes later; maximum four sprays (2 mg) per day 1, 6

Efficacy and Administration Timing

• Effectiveness of ergotamine depends on administration at the onset of migraine pain 1
• DHE can be administered at any time during a migraine attack, including during the aura 5
• Rectal ergotamine is most effective for patients with severe, rapid-onset migraine accompanied by nausea/vomiting 5
• IV administration of DHE provides rapid peak plasma levels and is most effective when a rapid effect is desired or for intractable severe headache 5

Contraindications

• Use of triptans (concurrent use contraindicated) 1
• Pregnancy and lactation 1
• Coronary artery disease or significant cardiovascular conditions 1
• Uncontrolled hypertension 1
• Use of MAOIs within 14-15 days 1
• Renal impairment, sepsis, ergot alkaloid sensitivity 1
• Concomitant use of macrolide antibiotics (e.g., clarithromycin, erythromycin) or protease inhibitors due to inhibition of cytochrome P450 3A metabolism of ergotamine 2, 3, 7

Adverse Effects

• Common adverse effects: Nausea, vomiting, dizziness, weakness, muscle pains, paresthesias, coldness of extremities 1, 4
• Serious adverse effects: Increased incidence of migraines, daily headaches, ergot poisoning, tachycardia, bradycardia, arterial spasm 1
• Severe reactions: Myocardial infarction, myocardial or pleuropulmonary fibrosis, vasospastic ischemia 1, 8

Important Clinical Considerations

• Ergotamine has limited use now due to its potential for causing medication-overuse headaches, increasing headache frequency, ergot poisoning, and negative effects on migraine prophylactic medications 1
• Chronic use should be avoided due to potential for peripheral vasoconstriction and ergotamine dependence 1, 4
• Dosage must be limited to no more than 10 mg per week to minimize toxicity 4
• Triptans have largely replaced ergotamine as first-line therapy for migraine attacks due to better safety profile and efficacy 9
• Ergotamine may still be useful in patients with status migrainosus and patients with frequent headache recurrence 9

Drug Interactions

• Significant interactions can occur with drugs that have vasoconstrictive properties or inhibit ergotamine metabolism 7
• Concomitant use with macrolide antibiotics can lead to ergotism, sometimes resulting in gangrene 7
• Similar interactions may occur with HIV protease inhibitors, heparin, cyclosporin, or tacrolimus 7
• Serotonin syndrome has been reported when ergots are used in persons taking serotonin reuptake inhibitors 7