Methylergonovine (injection)

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# Overview
Methylergonovine (injection) is an ergot alkaloid that is FDA approved for the treatment of for routine management after delivery of the placenta, postpartum atony, hemorrhage and subinvolution. Under full obstetric supervision, it may be given in the second stage of labor following delivery of the anterior shoulder.   Common adverse reactions include hypertension, headache.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- For routine management after delivery of the placenta; postpartum atony and hemorrhage; subinvolution. Under full obstetric supervision, it may be given in the second stage of labor following delivery of the anterior shoulder.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
- 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.
- Dosage same as 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.
- Dosage same as intramuscular.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Methylergonovine (injection) in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Methylergonovine (injection) in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Methylergonovine (injection) in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Methylergonovine (injection) in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Methylergonovine (injection) in pediatric patients.

# Contraindications
- Hypertension; toxemia; pregnancy; and hypersensitivity.

# Warnings
- 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.

# Adverse Reactions

## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Methylergonovine (injection) in the drug label.

## Postmarketing Experience
- The most common adverse reaction is hypertension associated in several cases with seizure and/or headache. Hypotension has also been reported.
- Nausea and vomiting have occurred occasionally. Rarely observed reactions have included: acute myocardial infarction, transient chest pains, arterial spasm (coronary and peripheral), bradycardia, tachycardia, dyspnea, hematuria, thrombophlebitis, water intoxication, hallucinations, leg cramps, dizziness, tinnitus, nasal congestion, diarrhea, diaphoresis, palpitation, and foul taste.
- There have been rare isolated reports of anaphylaxis, without a proven casual relationship to the drug product.

# Drug Interactions
There is limited information regarding Methylergonovine (injection) Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 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.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methylergonovine (injection) in women who are pregnant.

### 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
- Methylergonovine maleate may be administered orally for a maximum of 1 week postpartum to control uterine bleeding. Recommended dosage is 1 tablet (0.2 mg) 3 or 4 times daily.
- At this dosage level a small quantity of drug appears in mothers' milk. Caution should be exercised when methylergonovine maleate is administered to a nursing woman.

### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.

### Geriatic Use
- 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 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.

### Gender
There is no FDA guidance on the use of Methylergonovine (injection) with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Methylergonovine (injection) with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Methylergonovine (injection) in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Methylergonovine (injection) in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Methylergonovine (injection) in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Methylergonovine (injection) in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Intravenous

### Monitoring
- 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.

# IV Compatibility
There is limited information regarding IV Compatibility of Methylergonovine (injection) in the drug label.

# Overdosage
- Symptoms of acute overdose may include: nausea, vomiting, 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 4.52. 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, in one case, a single convulsion.
- Also several children 1-3 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 listed below.
- Removal of offending drug by inducing emesis, gastric lavage, catharsis, and supportive diuresis.
- Maintenance of adequate pulmonary ventilation, especially if convulsions or coma develop.
- Correction of hypotension with pressor drugs as needed.
- Control of convulsions with standard anticonvulsant agents.
- Control of peripheral vasospasm with warmth to the extremities if needed.

# Pharmacology

## Mechanism of Action
- Methylergonovine maleate acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss.
- The onset of action after I.V. administration is immediate; after I.M. administration, 2-5 minutes, and after oral administration, 5-10 minutes.

## Structure
- Methylergonovine Maleate Injection, USP is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage.
- Methylergonovine Maleate Injection, USP is available in sterile ampuls of 1 mL, containing 0.2 mg methylergonovine maleate for intramuscular or intravenous injection.
- Ampuls, 1 mL, clear, colorless solution.
- Active Ingredients
- Methylergonovine maleate, USP, 0.2 mg.
- Inactive Ingredients
- Maleic acid, 0.10 mg; sodium chloride, 7.0 mg; water for injection, qs to 1 mL.
- Chemically, methylergonovine maleate is designated as ergoline-8-carboxamide, 9,10-didehydro-N--6-methy1-, -, (Z)-2-butenedioate (1:1) (salt).
Its structural formula is:

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Methylergonovine (injection) in the drug label.

## Pharmacokinetics
- Pharmacokinetic studies following an I.V. injection have shown that methylergonovine is rapidly distributed from plasma to peripheral tissues within 2-3 minutes or less.
- The bioavailability after oral administration was reported to be about 60% with no accumulation after repeated doses. During delivery with intramuscular injection, bioavailability increased to 78%. 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.
- Bioavailability studies conducted in fasting healthy female volunteers have shown that oral absorption of a 0.2 mg methylergonovine tablet was fairly rapid with a mean peak plasma concentration of 3243  1308 pg/mL observed at 1.12  0.82 hours. For a 0.2 mg intramuscular injection, a mean peak plasma concentration of 5918  1952 pg/mL was observed at 0.41  0.21 hours.
- The extent of absorption of the tablet, based upon methylergonovine plasma concentrations, was found to be equivalent to that of the I.M. solution given orally, and the extent of oral absorption of the I.M. solution was proportional to the dose following administration of 0.1, 0.2, and 0.4 mg. When given intramuscularly, the extent of absorption of methylergonovine maleate solution was about 25% greater than the tablet.
- The volume of distribution (Vdss/F) of methylergonovine was calculated to be 56.1  17.0 liters, and the plasma clearance (CLp/F) was calculated to be 14.4  4.5 liters per hour. The plasma level decline was biphasic with a mean elimination half-life of 3.39 hours (range 1.5 to 12.7 hours). A delayed gastrointestinal absorption (Tmax about 3 hours) of methylergonovine maleate tablet might be observed in postpartum women during continuous treatment with this oxytocic agent.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Methylergonovine (injection) in the drug label.

# Clinical Studies
There is limited information regarding Clinical Studies of Methylergonovine (injection) in the drug label.

# How Supplied
- 1 mL ampules in box of 10............................NDC 17478-501-01

## Storage
- 1 mL ampules in box of 10............................NDC 17478-501-01

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Methylergonovine (injection) in the drug label.

# Precautions with Alcohol
- Alcohol-Methylergonovine (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- METHYLERGONOVINE MALEATE 

# Look-Alike Drug Names
There is limited information regarding Methylergonovine (injection) Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price