Usage
- Caffeine + Ergotamine is prescribed for the treatment of acute migraine and other vascular headaches, such as migraine variants and cluster headaches. It is effective in aborting or preventing these types of headaches but not intended for chronic daily use or other types of pain.
- Pharmacological classification: Antimigraine, vasoconstrictor. It combines ergotamine, an ergot alkaloid and vasoconstrictor, with caffeine, a central nervous system stimulant that enhances ergotamine absorption.
- Mechanism of action: Caffeine + Ergotamine primarily works by constricting cranial blood vessels, which are often dilated during migraine attacks. Caffeine also enhances the absorption of ergotamine, increasing its bioavailability.
Alternate Names
- International/Regional variations: Ergotamine-Caffeine
- Brand names: Cafergot, Migergot, Ercaf
How It Works
- Pharmacodynamics: Ergotamine acts as a 5-HT1B/1D receptor agonist, causing vasoconstriction of cranial blood vessels. This vasoconstriction is thought to reverse the vasodilation associated with migraine attacks. Caffeine acts as an adenosine receptor antagonist with vasoconstricting properties, further contributing to the therapeutic effect. It also increases the bioavailability of ergotamine.
- Pharmacokinetics: Ergotamine is poorly absorbed orally, but caffeine enhances its absorption. Both drugs are metabolized in the liver, mainly by CYP3A4 enzymes. Excretion occurs primarily through the biliary route into the feces. Some renal excretion also occurs.
- Mode of Action: Ergotamine acts as a partial agonist at serotonin (5-HT) receptors, particularly 5-HT1B and 5-HT1D receptors, found on cranial blood vessels. Stimulation of these receptors leads to vasoconstriction, relieving migraine symptoms. Caffeine also contributes to vasoconstriction and improves ergotamine absorption. Ergotamine inhibits the release of vasoactive neuropeptides involved in the inflammatory response during migraine attacks.
- Elimination pathways: Primarily hepatic metabolism and biliary excretion, with some renal excretion.
Dosage
Standard Dosage
Adults:
- Oral: 2 tablets (ergotamine 1 mg/caffeine 100 mg per tablet) at the onset of a migraine attack. If needed, 1 additional tablet may be taken every 30 minutes, up to a maximum of 6 tablets per attack and 10 tablets per week.
- Rectal: 1 suppository (ergotamine 2 mg/caffeine 100 mg) at the onset of a migraine attack. If needed, a second suppository may be administered after 1 hour. Do not exceed 2 suppositories per attack or 5 suppositories per week.
Children:
- Use is generally not recommended for children under 12 years of age due to lack of established safety and efficacy data. In certain cases, physicians might prescribe a lower dose for adolescents, but it should be under strict supervision.
Special Cases:
- Elderly Patients (over 65 years): Use with caution and careful monitoring due to potential age-related decrease in hepatic and renal function. Lower doses might be necessary.
- Patients with Renal Impairment: Contraindicated in severe renal impairment. Caution and dose adjustment needed in mild to moderate impairment.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution and dose adjustment needed in mild to moderate impairment.
- Patients with Comorbid Conditions: Use with caution in patients with coronary artery disease, peripheral vascular disease, uncontrolled hypertension, sepsis, or other cardiovascular conditions.
Clinical Use Cases
- The primary clinical use of Caffeine + Ergotamine is for the acute treatment and prevention of migraine headaches. It is not indicated for regular or preventative use in other clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
- Dosage adjustments are necessary for patients with renal or hepatic impairment, elderly patients, and those with comorbid conditions like cardiovascular disease. Dose reductions should be considered, and patient monitoring is essential.
Side Effects
Common Side Effects
- Nausea, vomiting, muscle pain, numbness and tingling in extremities, dizziness, and weakness.
Rare but Serious Side Effects
- Chest pain, peripheral ischemia (cold, numb, or painful fingers and toes), myocardial infarction, stroke, ergotism (severe vasoconstriction leading to gangrene), and allergic reactions.
Long-Term Effects
- Prolonged or excessive use can lead to ergotism, dependence, and medication overuse headache.
Adverse Drug Reactions (ADR)
- Severe allergic reactions, myocardial ischemia, peripheral ischemia, and ergotism require immediate medical intervention.
Contraindications
- Peripheral vascular disease, coronary heart disease, uncontrolled hypertension, sepsis, pregnancy, breastfeeding, severe renal or hepatic impairment, hypersensitivity to ergot alkaloids or caffeine. Concomitant use with potent CYP3A4 inhibitors, macrolide antibiotics, HIV protease inhibitors, azole antifungals, other vasoconstrictors (including triptans, other ergot alkaloids, and dihydroergotamine).
Drug Interactions
- CYP3A4 inhibitors: Macrolide antibiotics (e.g., erythromycin, clarithromycin), azole antifungals (e.g., ketoconazole, itraconazole), HIV protease inhibitors (e.g., ritonavir) can significantly increase ergotamine levels, leading to toxicity.
- Vasoconstrictors: Triptans (e.g., sumatriptan), other ergot alkaloids, and dihydroergotamine can potentiate vasoconstriction, increasing the risk of adverse effects.
- Beta-blockers: Can increase the risk of peripheral vasoconstriction.
- Nicotine can increase the vasoconstricting effects of ergotamine.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X. Contraindicated in pregnancy due to the risk of uterine contractions and fetal harm.
- Breastfeeding: Ergotamine is excreted in breast milk and can cause serious adverse effects in infants. Breastfeeding is contraindicated while taking this medication.
Drug Profile Summary
- Mechanism of Action: Cranial vasoconstriction via 5-HT1B/1D receptor agonism (ergotamine) and adenosine receptor antagonism (caffeine). Caffeine also enhances ergotamine absorption.
- Side Effects: Nausea, vomiting, muscle pain, numbness/tingling, dizziness, weakness. Serious: Chest pain, peripheral ischemia, myocardial infarction, stroke, ergotism.
- Contraindications: Peripheral vascular disease, coronary artery disease, uncontrolled hypertension, sepsis, pregnancy, breastfeeding, severe renal/hepatic impairment, hypersensitivity.
- Drug Interactions: CYP3A4 inhibitors, vasoconstrictors, beta-blockers, nicotine.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: Oral: 2 tablets initially, then 1 tablet every 30 minutes, max 6/attack, 10/week. Rectal: 1 suppository initially, then 1 more after 1 hour, max 2/attack, 5/week.
- Monitoring Parameters: Blood pressure, heart rate, peripheral circulation (check for coldness, numbness, or pain in extremities).
Popular Combinations
Caffeine + Ergotamine is usually not combined with other medications for migraine due to the risk of increased adverse effects. If a combination is necessary, it must be done under close medical supervision.
Precautions
- General Precautions: Thorough patient history, including cardiovascular and renal/hepatic function assessment, is essential before prescribing.
- Specific Populations: Contraindicated in pregnancy and breastfeeding. Use with caution in elderly patients and those with renal/hepatic impairment.
- Lifestyle Considerations: Smoking and alcohol consumption can exacerbate vasoconstriction. Caution patients against operating machinery or driving while experiencing side effects like dizziness or weakness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Caffeine + Ergotamine?
A: Adults: Oral: 2 tablets initially, then 1 tablet every 30 minutes as needed, max 6/attack, 10/week. Rectal: 1 suppository initially, then 1 more after 1 hour if needed, max 2/attack, 5/week. Not recommended for children under 12.
Q2: Can Caffeine + Ergotamine be used to treat tension headaches?
A: No, Caffeine + Ergotamine is specifically indicated for vascular headaches like migraine and cluster headaches. It is not effective for tension-type headaches.
Q3: What are the most serious side effects of Caffeine + Ergotamine?
A: Serious side effects include chest pain, peripheral ischemia (coldness, numbness, or pain in fingers and toes), myocardial infarction, stroke, and ergotism (severe vasoconstriction potentially leading to gangrene).
Q4: Can a patient take Caffeine + Ergotamine with triptans?
A: No, concurrent use with triptans or other vasoconstrictors is contraindicated due to the increased risk of severe vasoconstriction and serious adverse events.
Q5: Can Caffeine + Ergotamine be used during pregnancy or breastfeeding?
A: No, Caffeine + Ergotamine is contraindicated in pregnancy and breastfeeding due to the risk of fetal harm and potential adverse effects on the infant.
Q6: What should be done if a patient experiences chest pain after taking Caffeine + Ergotamine?
A: Chest pain could indicate a serious cardiovascular event. Patients should immediately discontinue the medication and seek emergency medical attention.
Q7: How does caffeine interact with ergotamine in this combination?
A: Caffeine enhances the absorption of ergotamine, increasing its bioavailability and therefore its effectiveness. It also contributes to the vasoconstrictive effects.
Q8: Can patients with liver or kidney problems take Caffeine + Ergotamine?
A: Caffeine + Ergotamine is contraindicated in patients with severe hepatic or renal impairment. Caution and dose adjustments are needed in patients with mild to moderate impairment. Careful monitoring is essential.
Q9: Can Caffeine + Ergotamine be used for long-term migraine prevention?
A: No, it is not intended for long-term or chronic daily use. Prolonged use can lead to medication overuse headache, dependence, and ergotism. It is primarily used for acute treatment of migraine attacks.
