Methylergonovine Maleate Injection, USP

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, 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 the presence of impaired hepatic or renal function.

Mothers should not breast-feed during treatment with Methylergonovine Maleate Injection. Milk secreted during this period should be discarded. Methylergonovine Maleate Injection may produce adverse effects in the breast-feeding infant. Methylergonovine Maleate Injection may also reduce the yield of breast milk. Mothers should wait at least 12 hours after administration of the last dose of Methylergonovine Maleate Injection before initiating or resuming breast-feeding.

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.

Inadvertent administration of Methylergonovine Maleate Injection 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.

Methylergonovine Maleate Injection 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, Methylergonovine Maleate Injection should be stored separately from medications intended for neonatal administration.

Caution should be exercised in the presence of sepsis, obliterative vascular disease. Also use with caution during the second stage of labor. The necessity for manual removal of a retained placenta should occur only rarely with proper technique and adequate allowance of time for its spontaneous separation.

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.

Drugs (e.g., nevirapine, rifampicin) that are strong inducers of CYP 3A4 are likely to decrease the pharmacological action of Methylergonovine Maleate Injection.

Caution should be exercised when Methylergonovine Maleate Injection is used concurrently with beta-blockers. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids.

Anesthetics like halothan and methoxyfluran may reduce the oxytocic potency of Methylergonovine Maleate Injection.

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 Methylergonovine Maleate Injection is used concurrently with other vasoconstrictors, ergot alkaloids, or prostaglandins.

No long-term studies have been performed in animals to evaluate carcinogenic potential. The effect of the drug on mutagenesis or fertility has not been determined.

The uterotonic effect of methylergonovine maleate is utilized after delivery to assist involution and decrease hemorrhage, shortening the third stage of labor.

Mothers should not breast-feed during treatment with Methylergonovine Maleate Injection and for at least 12 hours after administration of the last dose. Milk secreted during this period should be discarded.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of methylergonovine maleate did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other repeated clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

The following adverse drug reactions have been derived from post-marketing experience with Methylergonovine Maleate Injection 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.

Cerebrovascular accident, paraesthesia

Ventricular fibrillation, ventricular tachycardia, angina pectoris, atrioventricular block

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.

1 mL, 0.2 mg, administered slowly over a period of no less than 60 seconds. (See WARNINGS.)

Storage: Store in refrigerator, 2°C to 8°C (36°F to 46°F). Protect from light. Administer only if solution is clear and colorless.

AKORN
Manufactured for: Akorn, Inc.
Lake Forest, IL 60045
MM00N Rev. 02/13
206 417