METHERGINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METHERGINE (METHERGINE).
Methylergonovine is an ergot alkaloid that acts as a partial agonist at α-adrenergic receptors in the uterine smooth muscle, causing sustained contractions. It also exhibits serotonergic (5-HT2) and dopaminergic activity.
| Metabolism | Primarily hepatic via CYP3A4 with significant first-pass metabolism; active metabolite is methylergonovine itself; excreted mainly in bile and urine. |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine. Biliary/fecal excretion accounts for ~80% of metabolites. |
| Half-life | Terminal elimination half-life is approximately 2–3 hours in healthy adults; prolonged in hepatic impairment. |
| Protein binding | Approximately 93% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6 L/kg (range 0.3–0.8 L/kg), indicating moderate distribution into tissues. |
| Bioavailability | Oral bioavailability is approximately 10–20% due to extensive first-pass metabolism. Intramuscular administration provides 100% bioavailability. |
| Onset of Action | Intravenous: within 30–60 seconds. Intramuscular: within 2–5 minutes. Oral: within 5–10 minutes. |
| Duration of Action | Intravenous: ~45 minutes. Intramuscular: 2–4 hours. Oral: 3–6 hours. Note: prolonged effect may occur in patients with hepatic dysfunction. |
| Molecular Weight | 339.43 |
0.2 mg intramuscularly or intravenously after delivery of placenta and every 2-4 hours as needed, up to a maximum of 5 doses.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in renal impairment due to risk of hypertension. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For Child-Pugh class A or B, use with caution and monitor for signs of toxicity. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy in children have not been established. |
| Geriatric use | Use with caution in elderly patients due to increased sensitivity to vasoconstrictive effects and higher risk of hypertension and myocardial ischemia. |
| 1st trimester | Contraindicated. Methergine (methylergonovine) is an ergot alkaloid that can cause uterine tetany and may lead to fetal hypoxia or miscarriage. Avoid use during first trimester. |
| 2nd trimester | Contraindicated. Similar risks as first trimester; may induce premature labor or placental abruption. Not recommended. |
| 3rd trimester | Contraindicated. Can cause prolonged uterine contraction, placental insufficiency, and fetal distress. Use only for postpartum hemorrhage after delivery. |
Clinical note
Comprehensive clinical and safety monograph for METHERGINE (METHERGINE).
| Placental transfer | Crosses placenta. Ergot alkaloids are known to cross the placental barrier and can cause fetal distress and uterine tetany. |
| Breastfeeding | Excreted into breast milk in small amounts. May cause ergotism in infants (vomiting, diarrhea, weak pulse, hypotension). Avoid use during breastfeeding. If necessary, discontinue nursing for at least 12 hours after dose. |
■ FDA Black Box Warning
Not for use during pregnancy (except during delivery) due to risk of uterine tetany and fetal hypoxia. Contraindicated in patients with hypertension, preeclampsia, or eclampsia due to risk of severe hypertension and stroke.
| Common Effects | High blood pressure Headache Seizure |
| Serious Effects |
HypertensionPreeclampsiaEclampsiaIschemic heart diseasePeripheral vascular diseaseHyperthyroidismPregnancy (except during third stage of labor)Ergot alkaloid hypersensitivitySepsisHepatic or renal impairment (severe)
| Precautions | Risk of severe hypertension, especially in patients with preeclampsia, eclampsia, or hypertension., Use with caution in patients with sepsis, hepatic or renal impairment, or coronary artery disease., May cause ergotism with prolonged use or high doses (symptoms: vasospasm, ischemia)., Monitor blood pressure and uterine response during administration. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Methergine (methylergonovine) is contraindicated in pregnancy due to its oxytocic properties and risk of uterine hyperstimulation, fetal distress, and abortion. First trimester: potential teratogenic effects not well studied; avoid use. Second and third trimesters: can cause abruptio placentae, premature labor, and fetal anoxia. It is FDA Pregnancy Category X. |
| Fetal Monitoring | Monitor maternal blood pressure, uterine tone, and bleeding. Observe for signs of uterine hyperstimulation or tetany. In neonates, monitor for jitteriness, vomiting, or diarrhea if exposed via breast milk. |
| Fertility Effects | No specific data on fertility effects. As an ergot alkaloid, it may interfere with implantation if used in early pregnancy, but it is not indicated for use in conception cycles. |
| Avoid grapefruit juice as it may increase serum levels of methylergonovine via CYP3A4 inhibition. No specific food restrictions other than avoiding excessive caffeine intake, which may potentiate vasoconstrictive effects. |
| Clinical Pearls | METHERGINE (methylergonovine) is an ergot alkaloid used primarily for postpartum hemorrhage due to uterine atony. Do not use for routine induction of labor or for threatened abortion. Avoid in patients with hypertension, preeclampsia, coronary artery disease, or severe hepatic/renal disease. Monitor blood pressure closely during administration. Administer intramuscularly for rapid effect; onset is 2-5 minutes. Intravenous administration should be reserved for emergencies due to risk of hypertensive crisis. Contraindicated in pregnancy except immediately after delivery. Drug interactions: avoid concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, macrolides, protease inhibitors) due to risk of ergotism and vasospasm. As of April 2025, there is no generic form; brand METHERGINE only. |
| Patient Advice | This medication is used to prevent or treat excessive bleeding after childbirth by causing contractions of the uterus. · Report immediately if you experience severe headache, chest pain, vision changes, muscle cramps, or numbness/tingling in the arms or legs. · Avoid breastfeeding within 8 hours after the last dose if possible; if breastfeeding is necessary, pump and discard for 8 hours to reduce infant exposure. · Do not use this medication if you have uncontrolled high blood pressure, heart disease, or liver/kidney disease. · Avoid alcohol and grapefruit juice while on this medication as they may affect blood levels. · Take this medication exactly as prescribed; do not take double doses if a dose is missed. |