ALKERGOT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALKERGOT (ALKERGOT).
Ergotamine tartrate acts as a partial agonist at serotonin (5-HT) receptors, particularly 5-HT1B/1D, and also blocks alpha-adrenergic receptors. It causes vasoconstriction of intracranial blood vessels and reduces extravasation of plasma proteins, thereby alleviating migraine pain. Caffeine enhances ergotamine absorption and may provide additional vasoconstrictive effects.
| Metabolism | Ergotamine is primarily metabolized by CYP3A4 to hydroxylated metabolites. Caffeine is metabolized by CYP1A2 and xanthine oxidase. |
| Excretion | Primarily hepatic metabolism followed by biliary and fecal excretion (approx. 90%). Less than 2% is excreted unchanged in urine. Renal elimination of metabolites accounts for about 10%. |
| Half-life | Terminal elimination half-life is 2–4 hours. Clinical context: Short half-life supports use for acute migraine attacks; frequent dosing may be needed for prolonged symptoms. |
| Protein binding | Approximately 90% bound to serum albumin. |
| Volume of Distribution | 0.4–0.6 L/kg. Clinical meaning: Moderate distribution, primarily confined to extracellular fluid; does not extensively penetrate tissues. |
| Bioavailability | Oral: <5% due to extensive first-pass metabolism. Sublingual: approximately 5–10% due to partial bypass of hepatic metabolism. Rectal: approximately 5–10%. |
| Onset of Action | Oral: 30–60 minutes; Sublingual: 15–30 minutes; Rectal: 30–60 minutes. Onset correlates with time to peak plasma concentration. |
| Duration of Action | 3–4 hours. Clinical notes: Duration is sufficient for acute migraine; repeated doses may be required if symptoms recur. |
Oral: Ergotamine 1mg/caffeine 100mg combination: 2 tablets at onset of migraine, then 1 tablet every 30 minutes as needed, maximum 6 tablets per attack, maximum 10 tablets per week.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines available; contraindicated in severe renal impairment (CrCl <30 mL/min) due to risk of ergotism and toxicity. |
| Liver impairment | Child-Pugh A: Use with caution, reduce dose by 50%. Child-Pugh B or C: Contraindicated due to risk of hepatic metabolism impairment leading to ergotism. |
| Pediatric use | Safety and efficacy not established; contraindicated in children <12 years. For adolescents (12-18 years): Use same adult weight-based dosing (1 mg ergotamine) but limit to 2 tablets per attack, maximum 4 tablets per week. |
| Geriatric use | Elderly patients: Use with caution due to increased sensitivity, potential for peripheral vascular disease, and impaired renal/hepatic function. Start at lowest effective dose (1 tablet at onset); maximum 4 tablets per attack, 8 tablets per week. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALKERGOT (ALKERGOT).
| Breastfeeding | Contraindicated during breastfeeding. Ergot alkaloids suppress prolactin and may cause ergotism in infants. M/P ratio not established; avoid use or discontinue nursing. |
| Teratogenic Risk | Category X: Contraindicated in pregnancy due to risk of uterine contractions and fetal hypoxia. First trimester: potential for teratogenic effects based on ergot alkaloid vasoconstriction. Second and third trimesters: risk of preterm labor, placental insufficiency, and fetal distress. |
| Fetal Monitoring |
■ FDA Black Box Warning
Serious and/or life-threatening peripheral ischemia and ergotism have been associated with coadministration of ergotamine with potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors, azole antifungals). Concomitant use is contraindicated.
| Serious Effects |
["Concurrent use with potent CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir)","Peripheral vascular disease (e.g., obliterative vascular disease, Buerger's disease)","Coronary artery disease, uncontrolled hypertension, or history of myocardial infarction","Severe hepatic or renal impairment","Sepsis or severe infection","Pregnancy (Category X) and lactation","Hypersensitivity to ergot alkaloids or caffeine"]
| Precautions | ["Caution in patients with hypertension, coronary artery disease, or other vascular conditions due to risk of vasospasm","Risk of ergotism with prolonged use or overdose (symptoms: severe vasospasm, paresthesia, claudication)","May cause fibrotic complications (e.g., retroperitoneal, pulmonary, or cardiac valvular fibrosis) with chronic use","Not for prophylaxis of migraine; use only for acute attacks","Limit use to no more than 10 days per month to avoid medication-overuse headache"] |
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| Monitor for signs of ergotism (nausea, vomiting, muscle pain, paresthesias), uterine hypertonus, fetal heart rate abnormalities, and decreased placental perfusion. Assess uterine activity and fetal status if inadvertent exposure. |
| Fertility Effects | May inhibit ovulation due to prolactin suppression; used off-label for hyperprolactinemia. Reversible upon discontinuation. No evidence of permanent fertility impairment. |
| Food/Dietary |
| Avoid excessive caffeine from other sources (coffee, tea, soda) as it may increase side effects. No other significant food interactions. |
| Clinical Pearls | ALKERGOT (ergotamine tartrate and caffeine) is used for acute migraine attacks. Start at first sign of migraine; do not exceed 6 mg ergotamine per attack or 10 mg per week. Avoid in patients with peripheral vascular disease, coronary artery disease, hypertension, or pregnancy. Concomitant use with strong CYP3A4 inhibitors (e.g., macrolides, protease inhibitors) is contraindicated due to risk of ergotism. |
| Patient Advice | Take at the first sign of migraine headache. · Do not exceed 6 tablets per attack or 10 per week. · If vomiting occurs within 30 minutes, take another tablet. · Do not use if you are pregnant, breastfeeding, or have heart disease, high blood pressure, or circulation problems. · Seek immediate medical attention if you experience symptoms of ergotism: cold/blue fingers or toes, muscle pain, numbness or tingling. |