Methylergonovine Maleate Injection

Name: Methylergonovine Maleate Injection

Indications and Usage for Methylergonovine Maleate Injection

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.

Precautions

General

Caution should be exercised in the presence of sepsis or 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.

Drug Interactions

CYP3A4 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 CYP3A4 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 CYP3A4 inhibitors should not be coadministered with methylergonovine. Examples of some of the more potent CYP3A4 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 CYP3A4 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 CYP3A4 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 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

Pregnancy

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

Labor and Delivery

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

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of methylergonovine maleate did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported 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.

Drug Abuse and Dependence

Methylergonovine maleate has not been associated with drug abuse or dependence of either a physical or psychological nature.

Overdosage

Symptoms of acute overdose may include: nausea, vomiting, oliguria, abdominal pain, numbness, tingling of the extremities, rise in blood pressure, in severe cases followed by hypotension, respiratory depression, hypothermia, convulsions, and coma.

Because reports of overdosage with methylergonovine maleate are infrequent, the lethal dose in humans has not been established. The oral LD50(in mg/kg) for the mouse is 187, the rat 93, and the rabbit 4.5. Several cases of accidental Methylergonovine Maleate Injection in newborn infants have been reported, and in such cases 0.2 mg represents an overdose of great magnitude. However, recovery occurred in all but one case following a period of respiratory depression, hypothermia, hypertonicity with jerking movements, and convulsions.

Also, several children 1 to 3 years of age have accidentally ingested up to 10 tablets (2 mg) with no apparent ill effects. A postpartum patient took 4 tablets at one time in error and reported paresthesias and clamminess as her only symptoms.

Treatment of acute overdosage is symptomatic and includes the usual procedures of:

  1. removal of offending drug by inducing emesis, gastric lavage, catharsis, and supportive diuresis.
  2. maintenance of adequate pulmonary ventilation, especially if convulsions or coma develop.
  3. correction of hypotension with pressor drugs as needed.
  4. control of convulsions with standard anticonvulsant agents.
  5. control of peripheral vasospasm with warmth to the extremities if needed.

Methylergonovine Maleate Injection 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 to 4 hours.

Intravenously

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

Orally

One tablet, 0.2 mg, 3 or 4 times daily in the puerperium for a maximum of 1 week.

Package label.principal display panel

PRINCIPAL DISPLAY PANEL - 1 mL Label

NDC 0517-0740-01

METHYLERGONOVINE
MALEATE
INJECTION, USP

0.2 mg/mL

1 mL

SINGLE DOSE VIAL

FOR IM OR IV USE

Rx Only

 

Methylergonovine RN1090-00 Label

 

PRINCIPAL DISPLAY PANEL - 1 mL Carton

NDC 0517-0740-20

METHYLERGONOVINE
MALEATE
INJECTION, USP

0.2 mg/mL

20 x 1 mL
SINGLE DOSE VIALS

FOR INTRAMUSCULAR OR
INTRAVENOUS USE

Rx Only

AMERICAN
REGENT, INC.
SHIRLEY, NY 11967

METHYLERGONOVINE MALEATE 
Methylergonovine Maleate Injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0517-0740
Route of Administration INTRAMUSCULAR, INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
METHYLERGONOVINE MALEATE (METHYLERGONOVINE) METHYLERGONOVINE MALEATE 0.2 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
MALEIC ACID 0.10 mg  in 1 mL
SODIUM CHLORIDE 7.0 mg  in 1 mL
WATER  
Packaging
# Item Code Package Description
1 NDC:0517-0740-20 20 VIAL, SINGLE-DOSE in 1 CARTON
1 NDC:0517-0740-01 1 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090193 06/21/2010
Labeler - American Regent, Inc. (622781813)
Revised: 01/2017   American Regent, Inc.
(web3)