METHYLERGONOVINE MALEATE

Methylergonovine maleate, USP is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage. Methylergonovine maleate, USP is available in tablets for oral ingestion containing 0.2 mg methylergonovine maleate, USP. Tablets Active Ingredient: methylergonovine maleate, USP, 0.2 mg. Inactive Ingredients: corn starch, lactose monohydrate, microcrystalline cellulose, povidone, stearic acid, and tartaric acid. Chemically, methylergonovine maleate, USP is designated as ergoline-8-carboxamide, 9,10-didehydro- N -[1- (hydroxymethyl)propyl]-6-methyl-, [8β( S )]-, ( Z )-2-butenedioate (1:1) (salt). Its structural formula is: 1

Following delivery of the 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.

Orally The recommended dosage of methylergonovine maleate is One tablet, 0.2 mg, orally 3 or 4 times daily in the puerperium for a maximum of 1 week.

Hypertension; toxemia; pregnancy; and hypersensitivity.

Clinical trials experience Common 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. Rare Adverse Reactions 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. 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 methylergonovine maleate 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 To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CYP 3A4 Inhibitors (e.g., Macrolide Antibiotics and Protease Inhibitors) There have been rare reports of serious adverse events in connection with the co-administration 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, strong and moderate CYP 3A4 inhibitors should not be co-administered with methylergonovine. Examples of some of the strong CYP 3A4 inhibitors include saquinavir grapefruit juice, nefazodone, macrolide antibiotics (e.g., troleandomycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g., ritonavir, indinavir, nelfinavir) or azole antifungals (e.g., ketoconazole, itraconazole, voriconazole). Moderate inhibitors include fluconazole, fluvoxamine and clotrimazole. Weak CYP 3A4 inhibitors should be administered with caution. Weak inhibitors include chlorzoxazone, cilostazol, and ranitidine. 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, rifampin) that are strong inducers of CYP3A4 are likely to decrease the pharmacological action of methylergonovine maleate. Beta-blockers Caution should be exercised when methylergonovine maleate is used concurrently with beta-blockers. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids. Anesthetics Anesthetics like halothane and methoxyflurane may reduce the oxytocic potency of methylergonovine maleate. 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 methylergonovine maleate is used concurrently with other vasoconstrictors, ergot alkaloids, or prostaglandins.