CAFERGOT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAFERGOT (CAFERGOT).
Ergotamine is a serotonin (5-HT1B/1D) receptor agonist that causes vasoconstriction of cranial blood vessels and inhibits neurogenic inflammation. Caffeine is a methylxanthine that enhances ergotamine absorption and may contribute to vasoconstriction.
| Metabolism | Primarily hepatic via CYP3A4; ergotamine is extensively metabolized, and caffeine is metabolized via CYP1A2. |
| Excretion | Primarily hepatic metabolism and biliary excretion; less than 5% excreted unchanged in urine. Fecal elimination accounts for most of the administered dose. |
| Half-life | 2.5-3.9 hours (ergotamine); clinical context: t1/2 may be prolonged in hepatic impairment. |
| Protein binding | 98-99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 1.1-2.0 L/kg; clinical meaning: extensive tissue distribution, particularly into liver and spleen. |
| Bioavailability | Oral: <5% due to extensive first-pass metabolism; Sublingual: approximately 15-20%; Rectal: approximately 20-30%. |
| Onset of Action | Oral: 30-60 minutes; Sublingual: 15-30 minutes; Rectal: 15-30 minutes. |
| Duration of Action | 4-6 hours; clinical notes: duration may be prolonged with repeated doses due to cumulative vasoconstrictor effects. |
| Molecular Weight | 581.66 |
1 to 2 tablets (each containing ergotamine tartrate 1 mg and caffeine 100 mg) orally at onset of migraine, then 1 tablet every 30 minutes as needed, maximum 6 tablets per attack or 10 tablets per week. Alternatively, 1 rectal suppository (ergotamine tartrate 2 mg and caffeine 100 mg) at onset, repeat once after 1 hour if needed, maximum 2 suppositories per attack or 5 per week.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment. In moderate renal impairment (eGFR 30-59 mL/min/1.73 m²): use with caution; dose reduction not specifically defined but monitor for adverse effects. Mild impairment (eGFR ≥60 mL/min/1.73 m²): no adjustment needed. |
| Liver impairment | Contraindicated in Child-Pugh Class C. Child-Pugh Class A: no adjustment; Class B: use with caution, reduce dose by 50% and monitor. No specific dose recommendations from manufacturer; clinical judgment advised. |
| Pediatric use | Not recommended for use in pediatric patients due to risk of ergotism and lack of safety data. No established weight-based dosing. |
| Geriatric use | Use with caution due to increased risk of ergotism, renal/hepatic impairment, and drug interactions. Lower initial dose (e.g., 1 tablet) and careful monitoring. Avoid in patients over 65 with significant vascular disease. |
| 1st trimester | Contraindicated due to ergotamine's oxytocic properties and risk of teratogenicity; may cause fetal harm. |
| 2nd trimester | Contraindicated; risk of uterine hypertonicity, reduced placental blood flow, and fetal hypoxia. |
| 3rd trimester | Contraindicated; can precipitate premature labor, uterine tetany, and fetal distress. |
Clinical note
Comprehensive clinical and safety monograph for CAFERGOT (CAFERGOT).
| Placental transfer | Ergotamine crosses the placenta; documented transfer in animal studies and human case reports, resulting in fetal vasoconstriction and hypoxia. |
| Breastfeeding | Ergotamine is excreted into breast milk and may cause ergotism in infants (vomiting, diarrhea, convulsions). The manufacturer recommends discontinuing breastfeeding during therapy. |
■ FDA Black Box Warning
Serious and/or life-threatening peripheral ischemia has been associated with coadministration of ergotamine with potent CYP3A4 inhibitors (including protease inhibitors, macrolide antibiotics, and azole antifungals).
| Serious Effects |
Hypersensitivity to ergot alkaloidsCoronary artery diseasePeripheral vascular diseaseHypertension (severe or uncontrolled)Hepatic or renal impairmentSepsisPregnancyLactation
| Precautions | Risk of ergotism (ischemia, gangrene) with prolonged use or overdosage, May cause vasospastic reactions, including coronary artery vasospasm and myocardial infarction, Rebound headache (medication overuse headache) with frequent use, Caffeine withdrawal may exacerbate headaches, Avoid concurrent use with potent CYP3A4 inhibitors |
| Food/Dietary | Avoid excessive caffeine intake (e.g., coffee, tea, cola, energy drinks) as Cafergot contains caffeine and may cause additive stimulation or toxicity. Limit caffeine to no more than 200 mg per day during treatment. |
Loading safety data…
| Lactation Rating |
| L5 - Contraindicated |
| Teratogenic Risk | FDA Category X. First trimester: ergotamine is a potent vasoconstrictor and uterine stimulant, associated with increased risk of spontaneous abortion, congenital anomalies (including micrognathia, microphthalmia, cleft palate, and limb defects). Second and third trimesters: continued risk of uteroplacental insufficiency, intrauterine growth restriction, preterm labor, and fetal distress due to vasoconstriction and increased uterine tone. |
| Fetal Monitoring | Monitor maternal blood pressure, signs of uterine hyperstimulation or fetal distress. During pregnancy, fetal heart rate monitoring and ultrasound for growth assessment. Assess for signs of ergotism (nausea, vomiting, paresthesias, chest pain, peripheral ischemia). |
| Fertility Effects | Ergotamine may decrease fertility due to its vasoconstrictive effects on uterine and ovarian blood flow. In males, may impair spermatogenesis and reduce sperm motility. Effects are generally reversible upon discontinuation. |
| Clinical Pearls | Cafergot is ergotamine-caffeine combination for acute migraine. Avoid in pregnancy, uncontrolled hypertension, CAD, and peripheral vascular disease. Maximum dose: 6 tablets per attack or 10 tablets per week. Use at first sign of migraine. Not for prophylaxis. Can cause ergotism with prolonged use. Monitor for signs of ischemia. |
| Patient Advice | Take at the first sign of migraine headache for best effect. · Do not take more than 6 tablets per attack or 10 tablets per week. · Avoid use if you are pregnant, breastfeeding, or have high blood pressure, heart disease, or circulation problems. · Seek emergency care if you experience severe stomach pain, chest pain, numbness, tingling, or muscle cramps. · Do not take with other ergotamine drugs or strong CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics). · Store at room temperature, away from heat and moisture. |