Indication: For the prevention and control of excessive bleeding following vaginal childbirth
Pharmacology: Methylergonovine is a semisynthetic ergot alkaloid and a derivative of ergonovine and is used for the prevention and control of postpartum and post-abortion hemorrhage. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result.
Mechanism Of Action: Methylergonovine acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions through binding and the resultant antagonism of the dopamine D1 receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss.
Dosage Forms: INJECTION (intramuscular or intravenous), TABLETS
Absorption: Absorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.
Interactions:
DrugBank: Interactions for Methylergonovine
Interactions for Methylergonovine:
CYP 3A4 Inhibitors (e.g. Macrolide Antibiotics and Protease Inhibitors)
There have been rare reports of serious adverse events in connection with the coadministration of certain ergot
alkaloid drugs (e.g. dihydroergotamine and ergotamine) and potent CYP 3A4 inhibitors, resulting in vasospasm leading
to cerebral ischemia and/or ischemia of the extremities. Although there have been no reports of such interactions
with methylergonovine alone, potent CYP 3A4 inhibitors should not be coadministered with methylergonovine. Examples
of some of the more potent CYP 3A4 inhibitors include macrolide antibiotics (e.g., erythromycin, troleandomycin,
clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g., ritonavir, indinavir, nelfinavir,
delavirdine) or azole antifungals (e.g., ketoconazole, itraconazole, voriconazole). Less potent CYP 3A4 inhibitors
should be administered with caution. Less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit
juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole. These lists are not exhaustive, and the prescriber should
consider the effects on CYP 3A4 of other agents being considered for concomitant use with methylergonovine.
No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
Caution should be exercised when Methergine® (methylergonovine maleate) is used concurrently with other
vasoconstrictors or ergot alkaloids.
