メチルエルゴメトリン

Prisms from methanol, acetone

Shiny crystals from benzene

Soluble in ethanol, acetone

Freely soluble in alcohol, acetone

Sparingly soluble in water

Insoluble in water

2.04e-01 g/L

Breast Feeding; Lactation; Milk, Human; Ergot Alkaloids; Oxytocics

Pharmaceuticals

Uterotonics

172 °C with some decomposition

172 °C

SPECIFIC ROTATION: +44 TO +55; PH (1 IN 5000 SOLN) BETWEEN 4.4 & 5.2 /MALEATE/

Odorless; bitter taste; white to pinkish-tan microcrystalline powder; slightly soluble in water, alcohol; very slightly soluble in ether, chloroform /Methylergonovine maleate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including methylergonovine maleate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Methylergonovine maleate/

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Tablets: Store below 25 °C (77 °F); in tight, light-resistant container.

Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. Store in a refrigerator.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

/Wear/ chemically compatible /gloves/ and safety goggles and glasses /for eye protection/. Protect exposed skin.

Engineering controls such as exhaust ventilation are recommended.

Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Treatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (L1921)

Caffeine enhances action of ergot alkaloids in treatment of migraine... /Ergot alkaloids/

Peripheral and coronary vasoconstriction may be antagonized by nitrites or papaverine. /Ergot alkaloids/

Concomitant use of methylergonovine and inhibitors of cytochrome (CYP) 3A4 may result in vasospasm, cerebral ischemia, and/or ischemia of the extremities. Concomitant use of ergot alkaloids and human immunodeficiency virus (HIV) protease inhibitors, delavirdine, or nevirapine is contraindicated.

Intravenous atropine sulphate following methylergonovine maleate administration may lead to severe hypertension and tachycardia.

/EXPERIMENTAL:/ Methylergometrine concentrations in the maternal plasma and breast milk were determined by a radioimmunoassay during continuous treatment with 0.125 mg of methylergometrine 3 times daily. On the fifth postpartum day at 8:00 a.m. the patients (n=8) took 2 tablets of Myomergin (0.250 mg of methylergometrine) orally, and the levels in the plasma and milk were determined at 1 and 8 hr after the drug administration. Measurable amounts of the drug were found only in 5 out of 16 milk samples. It was concluded that this oxytocic drug does not appear in the breast milk in quantities sufficient to affect the infant. No accumulation in the plasma or in the breast milk was found.

Reports on the effect of methylergometrine hydrogenmaleate (MEM) on prolactin (PRL) secretion and lactation are still controversial. Therefore a prospective study was designed to follow the influence of MEM on post-partum PRL levels and milk production. MEM was given orally to 30 post-partum women from day 1 to day 7 in a daily dose of 0.6 mg. Thirty untreated women served as control. PRL plasma levels and milk yield were compared at day 1, 3 and 7. PRL levels were significantly lower in the treated group at day 7 (P less than 0.01), while the difference at day 3 was statistically not significant. Milk yield was significantly reduced at day 3 (P less than 0.05) and day 7 (P less than 0.01). These results indicate PRL inhibiting properties of MEM resulting consequently in reduced lactation.

Methylergonovine has been detected in the milk of lactating women, but apparently not in quantities sufficient to affect nursing infants.

Ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. (A2914, A2915, A2916)

Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (L1920)

/HUMAN EXPOSURE STUDIES/ Reports on the effect of methylergometrine hydrogenmaleate (MEM) on prolactin (PRL) secretion and lactation are still controversial. Therefore a prospective study was designed to follow the influence of MEM on post-partum PRL levels and milk production. MEM was given orally to 30 post-partum women from day 1 to day 7 in a daily dose of 0.6 mg. Thirty untreated women served as control. PRL plasma levels and milk yield were compared at day 1, 3 and 7. PRL levels were significantly lower in the treated group at day 7 (P less than 0.01), while the difference at day 3 was statistically not significant. Milk yield was significantly reduced at day 3 (P less than 0.05) and day 7 (P less than 0.01). These results indicate PRL inhibiting properties of MEM resulting consequently in reduced lactation.

/SIGNS AND SYMPTOMS/ 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.

/SIGNS AND SYMPTOMS/ Several cases of accidental Methergine 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.

/SIGNS AND SYMPTOMS/ Most common...symptoms are headache, nausea, vomiting, diarrhea, and dizziness. Also there may be noticeable weakness, formication, itching, and coldness of skin. Symptom ... referable to CNS are confusion, depression, drowsiness, and rarely, convulsions, hemiplegia, tabetic manifestations, and fixed miosis. /Ergot alkaloids/

For more Human Toxicity Excerpts (Complete) data for METHYLERGONOVINE (13 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

methylergonovine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Overdosage ... may ... /cause/ vomiting, diarrhea, dyspnea ... incoordination, epileptiform convulsions, and agalactia. /Ergonovine maleate/

/OTHER TOXICITY INFORMATION/ Ergot alkaloids specifically injure capillary endothelium, resulting in blocking of capillary flow and vascular stasis. This effect is followed by thrombosis in small arterioles and by dry gangrene. /Ergot alkaloids/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including methylergonovine maleate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Methylergonovine maleate/

G02AB01

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

Methylergometrine is a semisynthetic ergot alkaloid and a derivative of ergonovine and is used for the prevention and control of postpartum and post-abortion hemorrhage. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result.

Methylergometrine acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions through binding and the resultant antagonism of the dopamine D1 receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss.

Methylergonovine 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.

Ergonovine maleate and methylergonovine maleate are pharmacologically similar. Both drugs directly stimulate contractions of uterine and vascular smooth muscle. Following administration of usual therapeutic doses of ergonovine or methylergonovine, intense contractions of the uterus are produced and are usually followed by periods of relaxation. Larger doses of the drugs, however, produce sustained, forceful contractions followed by only short or no periods of relaxation. The drugs increase the amplitude and frequency of uterine contractions and uterine tone which in turn impede uterine blood flow. Ergonovine and methylergonovine also increase contractions of the cervix.

Ergonovine and methylergonovine produce vasoconstriction, mainly of capacitance vessels; increased central venous pressure, elevated blood pressure, and, rarely, peripheral ischemia and gangrene may result. Methylergonovine reportedly may interfere with prolactin secretion, but this effect has not been definitely established.

Ergot alkaloids are antagonists of actions of 5-hydroxytryptamine and of certain metabolic actions of catecholamines. /Ergot alkaloids/

3.39 hours

The plasma level decline was biphasic with a mean elimination half-life of 3.39 hours (range 1.5 to 12.7 hours).

Plasma concentrations of methylergonovine appear to decline in a biphasic manner. Following IV administration of methylergonovine to adults with normal renal function, the half-life of the drug in the initial phase (t1/2 alpha?) reportedly ranges from about 1-5 minutes and the half-life in the terminal phase (t1/2 beta) ranges from about 0.5-2 hours.

Hepatic, with extensive first-pass metabolism.

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.

Hepatic, with extensive first-pass metabolism. Route of Elimination: 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. Half Life: 3.39 hours

W53L6FE61V

METHYLERGONOVINE

Chemical Structure [CS] - Ergolines

Established Pharmacologic Class [EPC] - Ergot Derivative

Methylergonovine is an Ergot Derivative.

METHYLERGONOVINE

Drugs that stimulate contraction of the myometrium. They are used to induce LABOR, OBSTETRIC at term, to prevent or control postpartum or postabortion hemorrhage, and to assess fetal status in high risk pregnancies. They may also be used alone or with other drugs to induce abortions (ABORTIFACIENTS). Oxytocics used clinically include the neurohypophyseal hormone OXYTOCIN and certain prostaglandins and ergot alkaloids. (From AMA Drug Evaluations, 1994, p1157)

Absorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.

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.

56.1 ± 0 L

A delayed gastrointestinal absorption (Tmax about 3 hours) of methylergonovine tablets might be observed in postpartum women during continuous treatment with this oxytocic agent.

Pharmacokinetic studies following an iv 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.

MEDICATION

Methylergometrine is a synthetic analogue of ergonovine, an alkaloid of the ergoline family that occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi like other ergoline alkaloids. Methylergometrine is a blood vessel constrictor and smooth muscle agonist most commonly used to prevent or control excessive bleeding following childbirth and spontaneous or elective abortion. It also causes uterine contractions to aid in expulsion of retained products of conception after a missed abortion (miscarriage in which all or part of the fetus remains in the uterus) and to help deliver the placenta after childbirth. The drug is currently prepared via reaction of (+)-lysergic acid with L-(+)-aminobutanol, using different coupling reagents, and is available under the name Methergine as tablets or injection (IM or IV) or in liquid form to be taken orally. (L1918, L1923)

METHYLERGONOVINE IS NOT /A/ NATURAL ERGOT ALKALOID. IT IS SYNTHESIZED FROM LYSERGIC ACID BY /THE/ SAME PROCEDURE AS THAT EMPLOYED FOR ERGONOVINE...EXCEPT THAT (+)-2-AMINO-1-BUTANOL IS USED TO FURNISH PEPTIDE MOIETY.

THE BASE, DISSOLVED IN SUITABLE SOLVENT, READILY YIELDS OFFICIAL MALEATE BY REACTION WITH EQUIMOLAR QUANTITY OF MALEIC ACID. /MALEATE/

Preparation: A. Stoll, A. Hofmann, US 2265207 (1941 to Sandoz).

Methylergonovine Maleate preparations: (AHFS, 2011)

Basofortina; Methylergobrevin; Methergin; Ryegonovin; Spametrin-M. /Methylergonovine maleate/