Methylergonovine Maleate Tablets, USP

Rx Only

Methylergonovine maleate is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage.

Methylergonovine maleate tablets, USP are available in tablets for oral ingestion containing 0.2 mg methylergonovine maleate.

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.

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 (Vd_ss/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 (T_max about 3 hours) of methylergonovine maleate tablets might be observed in postpartum women during continuous treatment with this oxytocic agent.

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.

Hypertension; toxemia; pregnancy; and hypersensitivity.

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.

There have been rare isolated reports of anaphylaxis, without a proven causal relationship to the drug product.

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

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 1-3 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.

White, round, biconvex compressed tablets debossed with "T" on one side and "01" on the other side. Available in bottles of 12 and 28 tablets.

Manufactured by:
Tulex Pharmaceuticals, Inc.
Cranbury, NJ 08512

Manufactured for:
Volley Pharmaceuticals, LLC
Chester, NJ 07930

PI10001

Rev. 03/2024

NDC 83400-100-12

Methylergonovine
Maleate
Tablets, USP
0.2mg

Volley
Pharmaceuticals

Rx Only

12 Tablets