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.

toxicity

Signs and symptoms of overexposure: hypertension, seizures, headache, hypotension, nausea, and vomiting.

biotransformation

Hepatic, with extensive first-pass metabolism.

absorption

Absorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.

half life

3.39 hours

route of elimination

Ergot alkaloids are mostly eliminated by hepatic metabolism and excretion, and the decrease in bioavailability following oral administration is probably a result of first-pass metabolism in the liver.

drug interactions

Almotriptan: Possible severe and prolonged vasoconstriction

Atazanavir: Increases the effect and toxicity of ergot derivative

Delavirdine: The antiretroviral agent may increase the ergot derivative toxicity

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Efavirenz: The antiretroviral agent may increase the ergot derivative toxicity

Eletriptan: Possible severe and prolonged vasoconstriction

Epinephrine: Possible marked increase of arterial pressure

Erythromycin: Possible ergotism and severe ischemia with this combination

Frovatriptan: Possible severe and prolonged vasoconstriction

Isosorbide Dinitrate: Possible antagonism of action

Isosorbide Mononitrate: Possible antagonism of action

Naratriptan: Possible severe and prolonged vasocontriction

Nitroglycerin: Possible antagonism of action

Phenylephrine: Possible marked increase of arterial pressure

Telithromycin: Telithromycin may reduce clearance of Methylergonovine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Methylergonovine if Telithromycin is initiated, discontinued or dose changed.

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Methylergonovine. Concomitant therapy is contraindicated.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of methylergonovine by decreasing its metabolism. Concomitant therapy is contraindicated.

Zolmitriptan: Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, methylergonovine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.