Ergometrine Maleate

Approved Indications:

• Prevention and treatment of postpartum hemorrhage (PPH): Used after delivery of the placenta to reduce uterine bleeding caused by uterine atony.
• Management of uterine atony: Increases uterine tone and reduces postpartum bleeding.
• Active management of the third stage of labor (AMTSL): Often used in combination with oxytocin (e.g., Syntometrine).
• Subinvolution of uterus: Sometimes used in cases where the uterus does not return to its normal size after delivery.

Clinically Accepted Off-label Uses:

• Medical management of miscarriage: Occasionally used for uterine evacuation in incomplete miscarriage (not routine).
• Control of bleeding after abortion procedures: As adjunct therapy.
• Diagnostic use in coronary spasm testing: Low-dose IV ergometrine is used during coronary angiography to provoke coronary spasm in suspected vasospastic angina (under specialist supervision only).

Route: Intramuscular (IM) or Intravenous (IV); oral forms exist but are rarely used.

Adults (Postpartum Hemorrhage):

• IM or slow IV injection: 200 micrograms (0.2 mg), may be repeated every 2–4 hours if necessary, up to a maximum of 1 mg per 24 hours.
• For prophylaxis: 0.2 mg IM given immediately after placental delivery.

Combination therapy (with Oxytocin):

• Syntometrine (Ergometrine 0.5 mg + Oxytocin 5 IU): Single IM injection during the third stage of labor.

Elderly:

• Not indicated in the elderly.

Pediatric:

• Not applicable.

Renal/Hepatic Impairment:

• Use with caution; no specific dosing, but increased risk of adverse effects due to reduced metabolism and clearance.

Administration notes:

• IV injection must be given slowly over at least 1 minute to reduce the risk of hypertensive crises.
• IM is the preferred route for routine use.
• Oral formulations (when used) are less effective and slower acting.

Ergometrine is a semi-synthetic ergot alkaloid that acts primarily on uterine smooth muscle by stimulating alpha-adrenergic, dopaminergic, and serotonin receptors. It causes rapid and sustained uterine contractions by increasing intracellular calcium levels and enhancing the sensitivity of the uterus to calcium. The drug acts mainly on the upper segment of the uterus to produce strong, tetanic contractions, thereby promoting hemostasis at the placental site. This uterotonic effect is central to its use in controlling postpartum bleeding.

• Absorption: Rapid absorption following IM administration; peak plasma levels in 30 minutes. Oral bioavailability is lower and variable.
• Distribution: Widely distributed throughout body tissues; crosses the placenta and is excreted in breast milk.
• Metabolism: Extensively metabolized in the liver.
• Active metabolites: No significant active metabolites.
• Elimination: Mainly via urine and feces.
• Half-life: Approximately 30–120 minutes (route-dependent).
• Onset of action:
• IM: 6–10 minutes
• IV: 1–2 minutes
• Oral: Up to 30 minutes

• Pregnancy: Category X (FDA) – Contraindicated during pregnancy due to potent uterotonic action which may cause miscarriage or premature labor.
• Lactation: Excreted into breast milk in small amounts. Generally considered safe during breastfeeding in standard postpartum doses. However, caution is advised in prolonged use due to potential suppression of prolactin and milk production.

• Primary Class: Uterotonic agent
• Subclass: Ergot alkaloid derivative
• Category: Obstetric medication

• Known hypersensitivity to ergometrine or other ergot alkaloids
• Pregnancy (prior to delivery)
• Hypertension or preeclampsia/eclampsia
• Ischemic heart disease or history of coronary artery disease
• Peripheral vascular disease
• Severe hepatic or renal impairment
• Sepsis
• Use with potent CYP3A4 inhibitors (e.g., macrolide antibiotics, protease inhibitors)

• Use only after delivery of the anterior shoulder or placenta to avoid uterine rupture.
• Monitor blood pressure closely; may cause hypertensive crises.
• Avoid use in women with cardiovascular risk factors.
• Risk of vasospasm and ischemia (e.g., coronary, cerebral, peripheral).
• Avoid prolonged use due to risk of ergotism (vascular ischemia and gangrene).
• Caution in hepatic or renal impairment.
• Avoid concurrent use with other vasoconstrictors.
• Clinical monitoring: Blood pressure, uterine tone, signs of ischemia or vasospasm.

Common (≥1%):

• Gastrointestinal: Nausea, vomiting, abdominal pain
• Neurological: Headache, dizziness
• Cardiovascular: Transient increase in blood pressure, palpitations

Uncommon to Rare:

• Serious Cardiovascular: Hypertension crisis, myocardial infarction, coronary vasospasm
• Neurological: Seizures, confusion (with overdose or prolonged use)
• Peripheral ischemia: Cold extremities, gangrene (in ergotism)
• Hepatic: Elevated liver enzymes (rare)

Note: Many side effects are dose-dependent or related to rapid IV administration.

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): Increased ergometrine levels → risk of ergot toxicity.
• Other vasoconstrictors (e.g., triptans, nicotine): Additive risk of vasospasm, ischemia.
• Beta-blockers: May potentiate peripheral vasoconstriction.
• Nitrates: Antagonize ergometrine-induced vasoconstriction.
• Oxytocin: May enhance uterine response; used together cautiously.

Metabolic Pathway: Primarily metabolized by CYP3A4; interaction risk with inhibitors and inducers of this enzyme.

• WHO recommendation (updated): Ergometrine (alone or in combination with oxytocin) is included as a second-line agent for prevention and treatment of PPH when oxytocin is unavailable or contraindicated.
• EMA/FDA alerts: Emphasis on avoiding use during pregnancy and in combination with strong CYP3A4 inhibitors due to risk of serious vasospasm or ischemia.
• Recent guideline preference: Oxytocin remains first-line; ergometrine reserved for specific cases or in combination therapy.

• Temperature: Store below 25°C (77°F)
• Light protection: Protect from light; store in original amber ampoules or packaging.
• Handling: Do not freeze. Discard if solution becomes discolored or contains particulate matter.
• Stability: Stable for limited time once opened or drawn into syringe; use immediately.