Methylergometrine

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/

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/