Methergine

INDICATIONS AND USAGE Following delivery of placenta, for routine management of uterine atony, hemorrhage and subinvolution of the uterus. For control of uterine hemorrhage in the second stage of labor following delivery of the anterior shoulder.

DOSAGE AND ADMINISTRATION Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Intramuscularly 1 mL, 0.2 mg, after delivery of the anterior shoulder, after delivery of the placenta, or during the puerperium. May be repeated as required, at intervals of 2-4 hours. Intravenously 1 mL, 0.2 mg, administered slowly over a period of no less than 60 seconds (See WARNINGS .) Orally One tablet, 0.2 mg, 3 or 4 times daily in the puerperium for a maximum of 1 week.

CONTRAINDICATIONS Hypertension; toxemia; pregnancy; and hypersensitivity.

WARNINGS General This drug should not be administered I.V. routinely because of the possibility of inducing sudden hypertensive and cerebrovascular accidents. If I.V administration is considered essential as a lifesaving measure, Methergine (methylergonovine maleate) should be given slowly over a period of no less than 60 seconds with careful monitoring of blood pressure. Intra-arterial or periarterial injection should be strictly avoided. Caution should be exercised in presence of impaired hepatic or renal function. Breast-feeding Mothers should not breast-feed during treatment with Methergine. Milk secreted during this period should be discarded. Methergine may produce adverse effects in the breast-feeding infant. Methergine may also reduce the yield of breast milk. Mothers should wait at least 12 hours after administration of the last dose of Methergine before initiating or resuming breast feeding. Coronary artery disease Patients with coronary artery disease or risk factors for coronary artery disease (e.g., smoking, obesity, diabetes, high cholesterol) may be more susceptible to developing myocardial ischemia and infarction associated with methylergonovine-induced vasospasm. Medication errors Inadvertent administration of Methergine to newborn infants has been reported. In these cases of inadvertent neonatal exposure, symptoms such as respiratory depression, convulsions, cyanosis and oliguria have been reported. Usual treatment is symptomatic. However, in severe cases, respiratory and cardiovascular support is required. Methergine has been administered instead of vitamin K and Hepatitis B vaccine, medications which are routinely administered to the newborn. Due to the potential for accidental neonatal exposure, Methergine injection should be stored separately from medications intended for neonatal administration.

Drug Interactions 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. CYP3A4 inducers Drugs (e.g. nevirapine, rifampicin) that are strong inducers of CYP3A4 are likely to decrease the pharmacological action of Methergine. Beta-blockers Caution should be exercised when Methergine is used concurrently with beta-blockers. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids. Anesthetics Anesthetics like halothan and methoxyfluran may reduce the oxytocic potency of Methergine. Glyceryl trinitrate and other antianginal drugs Methylergonovine maleate produces vasoconstriction and can be expected to reduce the effect of glyceryl trinitrate and other antianginal drugs. No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known. Caution should be exercised when Methergine (methylergonovine maleate) is used concurrently with other vasoconstrictors, ergot alkaloids, or prostaglandins.

ADVERSE REACTIONS The most common adverse reaction is hypertension associated in several cases with seizure and/or headache. Hypotension has also been reported. Abdominal pain (caused by uterine contractions), nausea and vomiting have occurred occasionally. Rarely observed reactions have included: acute myocardial infarction, transient chest pains, vasoconstriction, vasospasm, coronary arterial spasm, bradycardia, tachycardia, dyspnea, hematuria, thrombophlebitis, water intoxication, hallucinations, leg cramps, dizziness, tinnitus, nasal congestion, diarrhea, diaphoresis, palpitation, rash, and foul taste. 1 There have been rare isolated reports of anaphylaxis, without a proven causal relationship to the drug product. Postmarketing Experience The following adverse drug reactions have been derived from post-marketing experience with Methergine via spontaneous case reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Nervous system disorders Cerebrovascular accident, paraesthesia Cardiac disorders Ventricular fibrillation, ventricular tachycardia, angina pectoris, atrioventricular block

Pregnancy Category C: Animal reproductive studies have not been conducted with Methergine. It is also not known whether methylergonovine maleate can cause fetal harm or can affect reproductive capacity. Use of Methergine is contraindicated during pregnancy because of its uterotonic effects. (See INDICATIONS AND USAGE ).