英文药名：Methergine(methylergonovine maleate Tablets)

中文药名：马来酸甲麦角片

生产厂家：诺华制药
药品介绍
马来酸甲麦角新碱是一种麦角生物碱，常用于妇产科预防和治疗产后出血。新生儿意外服用该药会引起严重后果，应严密预防该药被误用。由诺华制药公司生产的Methergin®是一种广泛使用的含马来酸甲麦角新碱的妇产科药物
适应症
产后或流产后子宫收缩无力或恢复不佳引起的子宫出血。
用法用量
口服，0.2mg～0.4mg/次，2次～4次/日，直到纠正宫缩无力和流血停止，48h为一疗程。
注意事项
哺乳期妇女应用时应权衡利弊，胎儿及胎盘未娩出前禁用。有冠心病、妊娠中毒症及高血压病患者禁用。用药期间不得吸烟，因烟碱（尼古丁）可使本品的血管收缩加剧。遇有低钙血症，本品的效应减弱，应谨慎静注钙盐。

SPL UNCLASSIFIED SECTION
T2006-91
Methergine®
(methylergonovine maleate)
Tablets, USP
(methylergonovine maleate)
Injection, USP
Rx only
DESCRIPTION
Methergine® (methylergonovine maleate) is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage.
Methergine is available in sterile ampuls of 1 mL, containing 0.2 mg methylergonovine maleate for intramuscular or intravenous injection and in tablets for oral ingestion containing 0.2 mg methylergonovine maleate.
Tablets
Active Ingredient: methylergonovine maleate, USP, 0.2 mg.
Inactive Ingredients: acacia, carnauba wax, D&C Red #7, FD&C Blue #1, gelatin special, lactose, maleic acid, mixed parabens, povidone, sodium benzoate, sodium hydroxide, starch, stearic acid, sucrose, talc, and titanium dioxide.
Ampuls, 1 mL, clear, colorless solution.
Active Ingredient: 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-[1-(hydroxymethyl)propyl]-6-methyl-, [8β(S)]-, (Z)-2-butenedioate (1:1) (salt).
Its structural formula is

CLINICAL PHARMACOLOGY
Methergine® (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 Methergine 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 Methergine tablet might be observed in postpartum women during continuous treatment with this oxytocic agent.
INDICATIONS AND USAGE
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.
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, Methergine® (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.
PRECAUTIONS
General Caution should be exercised in the presence of sepsis, obliterative vascular disease, hepatic or renal involvement. 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
CYP 3A4 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 CYP 3A4 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 CYP 3A4 inhibitors should not be coadministered with methylergonovine. Examples of some of the more potent CYP 3A4 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 CYP 3A4 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 CYP 3A4 of other agents being considered for concomitant use with methylergonovine.
No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
Caution should be exercised when Methergine® (methylergonovine maleate) is used concurrently with other vasoconstrictors or ergot alkaloids.
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 Methergine. It is also not known whether methylergonovine maleate can cause fetal harm or can affect reproductive capacity. Use of Methergine  is contraindicated during pregnancy because of its uterotonic effects. (See INDICATIONS AND USAGE.)
Labor and Delivery The uterotonic effect of Methergine is utilized after delivery to assist involution and decrease hemorrhage, shortening the third stage of labor.
Nursing Mothers Methergine® (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 Methergine is administered to a nursing woman.
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Geriatric Use Clinical studies of Methergine 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.
ADVERSE REACTIONS
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, rash, and foul taste.1
There have been rare isolated reports of anaphylaxis, without a proven causal relationship to the drug product.
DRUG ABUSE AND DEPENDENCE
Methergine® (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, 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 Methergine® (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 4.5.2 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.
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.3
DOSAGE AND ADMINISTRATION
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Intramuscularly
1mL, 0.2mg, 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.
Intravenously
Dosage same as intramuscular. (See WARNINGS.)
Orally
One tablet, 0.2 mg, 3 or 4 times daily in the puerperium for a maximum of 1 week.
HOW SUPPLIED
HOW SUPPLIED Tablets
0.2mg round, coated, orchid, branded “78-54” one side, “SANDOZ” other side.
Bottles of 100…………………………………………………………..NDC 0078-0054-05
Ampuls
1 mL size
Boxes of 20…………………………………………………………….NDC 0078-0053-03
Store and Dispense Tablets: Store below 25°C (77°F); in tight, light-resistant container.
Ampuls: Store in refrigerator, 2ºC-8°C (36°F-46°F). Protect from light. Administer only if solution is clear and colorless.
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产地国家：美国
原产地英文商品名:
METHERGINE 0.2mg/tab 100tabs/bottle 
原产地英文药品名:
Methylergometrine MALEATE
中文参考商品译名:
甲基麦角新碱片 0.2毫克/片 100片/瓶
中文参考药品译名:
马来酸甲麦角新碱
生产厂家中文参考译名:
诺华制药
生产厂家英文名:
NOVARTIS