Usage
- Ergotamine is prescribed for the treatment of acute migraine and cluster headaches. It is effective in aborting or preventing vascular headaches, including migraine variants and “histaminic cephalalgia.” It is not intended for the prophylaxis of migraine or for common tension headaches. It is most effective when taken at the first sign of a migraine attack.
- Pharmacological Classification: Ergotamine is classified as an ergot alkaloid and an antimigraine agent.
- Mechanism of Action: Ergotamine acts as a vasoconstrictor, primarily affecting the cranial blood vessels. It exerts partial agonist activity at serotonin (5-HT) receptors, leading to constriction of these vessels and reducing the throbbing pain associated with vascular headaches. It also has effects on dopamine and alpha-adrenergic receptors.
Alternate Names
- International/Regional Variations: Ergotamine tartrate (salt form).
- Brand Names: Ergomar, Cafergot (in combination with caffeine), Migergot (in combination with caffeine).
How It Works
- Pharmacodynamics: Ergotamine’s primary effect is vasoconstriction of cranial blood vessels. Its action on serotonin (5-HT) receptors, specifically 5-HT1B and 5-HT1D receptors, plays a crucial role in this vasoconstriction. It also interacts with dopamine and alpha-adrenergic receptors, though to a lesser extent. These combined effects help alleviate the symptoms of migraine and cluster headaches.
- Pharmacokinetics:
- Absorption: Ergotamine is poorly absorbed from the gastrointestinal tract, with bioavailability generally less than 5%. Sublingual administration offers slightly improved absorption.
- Metabolism: Ergotamine undergoes extensive first-pass metabolism in the liver, primarily by CYP3A4 enzymes.
- Elimination: Excreted primarily in the feces (approximately 90%, mostly as metabolites) and to a lesser extent in urine (around 4%). It has a biphasic elimination half-life, with an initial phase of about 2 hours and a terminal phase of roughly 21 hours.
- Mode of Action: Ergotamine binds to 5-HT1B and 5-HT1D receptors on cranial blood vessels, causing vasoconstriction. It also interacts with dopamine D2 receptors and alpha-adrenergic receptors. These actions reduce vasodilation and neurogenic inflammation, contributing to its antimigraine effects.
- Elimination Pathways: Primarily hepatic metabolism via CYP3A4, followed by fecal excretion; minor renal excretion.
Dosage
Standard Dosage
Adults:
- Sublingual: 2 mg at the onset of migraine symptoms, then 2 mg every 30 minutes as needed. Maximum dose: 6 mg per 24 hours and 10 mg per week.
- Oral (with caffeine): 2 tablets (containing 1 mg ergotamine and 100 mg caffeine each) at the onset, followed by 1 tablet every 30 minutes if needed. Maximum dose: 6 tablets per attack, 10 tablets per week.
- Rectal (with caffeine): 1 suppository (containing 2 mg ergotamine and 100 mg caffeine) at the onset. A second suppository can be used after 1 hour if needed. Maximum dose: 2 suppositories per attack, 5 suppositories per week.
Children:
- Ergotamine use in children is generally avoided due to the potential for serious side effects. If deemed necessary, dosage must be carefully determined by a physician, considering age and weight.
Special Cases:
- Elderly Patients: Close monitoring is advised due to potential age-related decline in hepatic and renal function. Dosage adjustments may be necessary.
- Patients with Renal Impairment: Contraindicated.
- Patients with Hepatic Dysfunction: Contraindicated.
- Patients with Comorbid Conditions: Use with caution in patients with coronary artery disease, peripheral vascular disease, hypertension, sepsis, or other cardiovascular conditions. Careful cardiovascular evaluation is needed before initiating therapy.
Clinical Use Cases
Ergotamine’s use is limited to the treatment of migraine and cluster headaches. It is not indicated for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments:
Dosage adjustments are necessary based on patient response and tolerability. Renal and hepatic impairment are contraindications to its use. Close monitoring is necessary for elderly patients and those with comorbid conditions.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Dizziness
- Weakness
- Itching
- Tingling
- Numbness
Rare but Serious Side Effects:
- Peripheral ischemia (numbness, tingling, pain, and cyanosis in the extremities)
- Vasospasm
- Myocardial ischemia or infarction
- Ergotism (prolonged vasospasm leading to gangrene)
- Fibrotic complications (retroperitoneal, pleuropulmonary, or valvular fibrosis)
- Seizures
Long-Term Effects:
- Ergotism
- Fibrotic complications
- Medication overuse headache
Adverse Drug Reactions (ADR):
- Peripheral ischemia
- Myocardial ischemia/infarction
- Stroke
- Anaphylaxis
Contraindications
- Peripheral vascular disease
- Coronary heart disease
- Uncontrolled hypertension
- Sepsis
- Shock
- Temporal arteritis
- Hemiplegic or basilar migraine
- Renal impairment
- Hepatic impairment
- Pregnancy
- Breastfeeding
- Concurrent use of potent CYP3A4 inhibitors (e.g., protease inhibitors, macrolide antibiotics, azole antifungals)
- Concurrent use of other vasoconstrictors
Drug Interactions
Ergotamine interacts with a large number of drugs, including:
- CYP3A4 Inhibitors: These can significantly increase ergotamine levels, leading to serious toxicity. Examples include macrolide antibiotics (e.g., erythromycin, clarithromycin), protease inhibitors (e.g., ritonavir), azole antifungals (e.g., ketoconazole), and grapefruit juice.
- CYP3A4 Inducers: These can decrease ergotamine levels, potentially reducing its effectiveness. Examples include rifampin, phenytoin, and St. John’s wort.
- Vasoconstrictors: Concurrent use can lead to dangerous elevations in blood pressure. Examples include sympathomimetics (e.g., epinephrine, pseudoephedrine), triptans (e.g., sumatriptan, rizatriptan), and other ergot alkaloids.
- Beta-blockers: May potentiate the vasoconstricting effects of ergotamine.
- Nicotine: Can increase the risk of vasoconstriction.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated). Ergotamine can cause serious harm to the fetus, including fetal death and miscarriage.
- Breastfeeding: Ergotamine is excreted in breast milk and can cause adverse effects in infants, such as vomiting, diarrhea, weak pulse, and convulsions. Breastfeeding is contraindicated while taking ergotamine.
Drug Profile Summary
- Mechanism of Action: Vasoconstriction of cranial blood vessels via 5-HT1B/1D receptor agonism.
- Side Effects: Nausea, vomiting, dizziness, peripheral ischemia, ergotism, fibrotic complications.
- Contraindications: Peripheral vascular disease, coronary heart disease, pregnancy, hepatic/renal impairment, potent CYP3A4 inhibitor use.
- Drug Interactions: CYP3A4 inhibitors, vasoconstrictors, triptans, beta-blockers.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Blood pressure, peripheral pulses, signs of ischemia, liver function tests.
Popular Combinations
- Caffeine is commonly combined with ergotamine (e.g., Cafergot, Migergot). Caffeine may enhance ergotamine’s absorption and provide additional analgesic effects.
Precautions
- General Precautions: Assess cardiovascular status prior to initiating therapy and periodically thereafter. Monitor for signs of peripheral ischemia. Avoid prolonged or excessive use.
- Specific Populations: See Special Cases under Dosage.
- Lifestyle Considerations: Smoking can exacerbate vasoconstriction, and patients should be advised to quit. Alcohol may worsen side effects. Caution is advised when driving or operating machinery due to potential dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ergotamine?
A: See detailed dosage guidelines above.
Q2: Can ergotamine be used to prevent migraines?
A: No, ergotamine is not indicated for migraine prophylaxis. It’s used to treat acute attacks.
Q3: What are the most serious side effects of ergotamine?
A: Peripheral ischemia, ergotism, myocardial infarction, and stroke are the most serious potential side effects.
Q4: What are the contraindications to using ergotamine?
A: Contraindications include peripheral vascular disease, coronary heart disease, pregnancy, hepatic/renal impairment, and concurrent use of potent CYP3A4 inhibitors.
Q5: Can ergotamine interact with other medications?
A: Yes, ergotamine interacts with many medications, particularly CYP3A4 inhibitors and other vasoconstrictors. See Drug Interactions section.
Q6: Is ergotamine safe during pregnancy or breastfeeding?
A: No, ergotamine is contraindicated during pregnancy and breastfeeding.
Q7: How does caffeine affect ergotamine?
A: Caffeine can enhance ergotamine absorption and may potentiate its analgesic effects.
Q8: What should patients be advised regarding lifestyle factors when taking ergotamine?
A: Patients should be advised to quit smoking and limit alcohol intake. Caution should be exercised when driving or operating machinery.
Q9: What should be monitored in patients taking ergotamine?
A: Monitor for signs of peripheral ischemia (e.g., changes in skin color, temperature, pain), changes in blood pressure, and hepatic function.
Q10: When should ergotamine be administered for optimal effect?
A: Ergotamine is most effective when taken at the very first sign of a migraine attack. Delayed administration may reduce its efficacy.
This information is current as of February 16, 2025, and is intended for use by qualified medical professionals in India. Prescribing information can vary between countries, and it’s essential to consult local guidelines and product-specific information before prescribing ergotamine.
