HYDROGENATED ERGOT ALKALOIDS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDROGENATED ERGOT ALKALOIDS (HYDROGENATED ERGOT ALKALOIDS).
Hydrogenated ergot alkaloids act as partial agonists/antagonists at α-adrenergic receptors, serotonergic (5-HT1B/1D) receptors, and dopaminergic receptors. They cause vasoconstriction by activating α-adrenoceptors and 5-HT receptors on vascular smooth muscle, and inhibit prolactin secretion via D2 receptor agonism.
| Metabolism | Metabolized primarily by CYP3A4 to active metabolites (e.g., 8'-hydroxy-dihydroergotamine). |
| Excretion | Primarily hepatic metabolism (70-80%) with biliary excretion; renal excretion accounts for less than 10% of unchanged drug. |
| Half-life | 2-3 hours for dihydroergotamine; 12-15 hours for ergoloid mesylates, requiring cautious dosing in hepatic impairment. |
| Protein binding | 65-70% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.5-2.0 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: <1% due to extensive first-pass metabolism; Sublingual: 5-10%; Intramuscular: 40-60%; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Sublingual: 15-30 minutes; Intramuscular: 5-15 minutes; Intravenous: 1-5 minutes. |
| Duration of Action | Oral/Sublingual: 4-6 hours; Intramuscular: 3-4 hours; Intravenous: 2-4 hours. |
| Molecular Weight | 167.21 (average of dihydroergocornine, dihydroergocristine, and dihydroergocryptine mixture) |
1 mg orally three times daily, or 0.3 mg intramuscularly or subcutaneously once daily.
| Dosage form | TABLET |
| Renal impairment | GFR <30 mL/min: avoid use; GFR 30-50 mL/min: caution, dose not well established. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use with caution; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for use in children; safety and efficacy not established. |
| Geriatric use | Lower initial dose recommended due to increased sensitivity; monitor for cognitive and cardiovascular effects. |
| 1st trimester | Contraindicated due to oxytocic and vasoconstrictive effects; risk of fetal hypoxia and miscarriage. |
| 2nd trimester | Contraindicated due to risk of uteroplacental insufficiency and fetal harm. |
| 3rd trimester | Contraindicated due to induction of premature labor and uterine tetany. |
Clinical note
Comprehensive clinical and safety monograph for HYDROGENATED ERGOT ALKALOIDS (HYDROGENATED ERGOT ALKALOIDS).
| Placental transfer | Crosses the placenta; detected in fetal circulation with potential for uterine blood flow reduction. |
| Breastfeeding | Excreted into breast milk in low amounts; however, due to potential for vasoconstriction and gastrointestinal disturbances in infants, use is not recommended. Alternative agents are preferred. |
■ FDA Black Box Warning
Boxed warning: Serious and/or life-threatening peripheral ischemia has been associated with coadministration of ergot alkaloids with potent CYP3A4 inhibitors (e.g., protease inhibitors, macrolide antibiotics) or ergotism due to acute overdose.
| Common Effects | Skin peeling Itching Stinging sensation Erythema skin redness Edema swelling |
| Serious Effects |
PregnancyHypersensitivity to ergot alkaloidsCoronary artery diseasePeripheral vascular diseaseHypertensionSevere hepatic or renal impairmentSepsisConcomitant use with potent CYP3A4 inhibitors (e.g., macrolides, protease inhibitors)
| Precautions | Risk of ergotism (vasospasm, ischemia, gangrene) with overdose or CYP3A4 inhibition; coronary vasospasm in patients with CAD; caution in sepsis, hypertension, hepatic/renal impairment; avoid prolonged use. |
| Food/Dietary |
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| Lactation Rating |
| L4 (Possibly Hazardous) |
| Teratogenic Risk | Hydrogenated ergot alkaloids are contraindicated in pregnancy due to their oxytocic and vasoconstrictive properties. First trimester: potential for uteroplacental insufficiency and miscarriage. Second and third trimesters: risk of uterine hyperstimulation, fetal distress, prematurity, and neonatal ergotism. Category X. |
| Fetal Monitoring | Monitor maternal blood pressure, uterine tone (palpation), fetal heart rate, and signs of ergotism (nausea, muscle pain, paresthesia). Assess for symptoms of vasospasm (cyanosis, pulselessness). Serial fetal ultrasound for growth restriction if inadvertent exposure. |
| Fertility Effects | Ergot alkaloids are dopaminergic agonists; they may suppress prolactin secretion, leading to inhibition of lactation and potential disruption of menstrual cycle and ovulation. Use may cause amenorrhea, galactorrhea, or infertility, usually reversible upon discontinuation. |
| Grapefruit juice increases systemic exposure to hydrogenated ergot alkaloids via CYP3A4 inhibition, raising risk of ergotism. Avoid grapefruit and pomelo products. Alcohol may exacerbate vasodilatory side effects or increase CNS depression. No other significant food interactions. |
| Clinical Pearls | Hydrogenated ergot alkaloids (dihydroergotamine, ergoloid mesylates) are contraindicated with potent CYP3A4 inhibitors (e.g., protease inhibitors, macrolides, azole antifungals) due to risk of ergotism (vasospasm, ischemia). For acute migraine, injectable dihydroergotamine can be used after failure of triptans. Monitor for signs of ergotism: peripheral cyanosis, severe headache, muscle pain. Avoid concurrent use with other vasoconstrictors (triptans, sympathomimetics). |
| Patient Advice | Take this medication exactly as prescribed; do not exceed the recommended dose. · Contact your doctor immediately if you experience symptoms of ergotism: coldness, numbness, pain in fingers or toes, severe headache, or unusual muscle cramps. · Avoid grapefruit juice and alcohol during treatment. · Do not take this drug with other migraine medications (triptans) or certain antibiotics (macrolides) without your doctor's approval. · Store at room temperature away from heat and moisture. |