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

Last updated on RxList: 8/14/2007

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.

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.

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.

Tablets

0.2 mg 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, 2°C-8°C (36°F-46°F). Protect from light. Administer only if solution is clear and colorless.

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. FDA Rev date: 4/26/2007

Last updated on RxList: 8/14/2007

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.

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.

1. Information on Adverse Reactions supplied by Medical Services Department, Novartis Pharmaceuticals, E. Hanover, N.J., based on computerized clinical reports.

Last updated on RxList: 8/14/2007

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.

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.

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.

Last updated on RxList: 8/14/2007

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

Hypertension; toxemia; pregnancy; and hypersensitivity.

2. Berde, B. and Schild, H.O.: Ergot Alkaloids and Related Compounds, Springer-Verlag, New York, 1978, p. 810.
3.   Treatment of Acute Overdosage. Novartis Consumer Health, Inc. Rx Products. Novartis, Medical Services Department.

Last updated on RxList: 8/14/2007

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 (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 (Tmax about 3 hours) of Methergine tablet might be observed in postpartum women during continuous treatment with this oxytocic agent.

Last updated on RxList: 8/14/2007

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 8/14/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METHYLERGONOVINE - ORAL

(METH-ill-er-go-NO-veen)

COMMON BRAND NAME(S): Methergine

USES: This medication is used to help stop bleeding after delivery of the placenta in childbirth. Methylergonovine maleate belongs to a class of drugs known as ergot alkaloids. It works by increasing the stiffness of the uterus muscles after the last stage of labor. This effect decreases bleeding.

HOW TO USE: Take this medication by mouth without food, usually 3-4 times daily for a maximum of 1 week or as directed by your doctor.

Dosage is based on your medical condition and response to therapy.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

Avoid eating grapefruit or drinking grapefruit juice while being treated with this medication unless your doctor instructs you otherwise. Grapefruit can increase the amount of certain medications in your bloodstream. Consult your doctor or pharmacist for more details.

Inform your doctor if your condition persists or worsens at any time.

SIDE EFFECTS: Headache, nausea, dizziness, or vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: leg cramps, ringing in the ears, stuffy nose, diarrhea, bad taste in the mouth.

Tell your doctor immediately if any of these rare but very serious side effects occur: sweating, fast/irregular heartbeat, breathing problems, hallucinations.

Seek immediate medical attention if this rare but very serious side effect occurs: chest pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking methylergonovine maleate, tell your doctor or pharmacist if you are allergic to it; or to similar ergot alkaloids (e.g., ergonovine); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: high blood pressure, a certain complication of pregnancy (toxemia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart disease (e.g., venoatrial shunt, mitral valve stenosis), other complications during pregnancy (e.g., pre-eclampsia, eclampsia), a serious blood infection (sepsis), blood vessel problems (e.g., Raynaud's phenomenon, obliterative vascular disease), kidney problems, liver problems.

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit or avoid alcoholic beverages.

This medication must not be used during pregnancy. It may harm an unborn baby. Consult your doctor for more details.

This drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also How to Use section.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: drugs that cause tightening (constriction) of the blood vessels (e.g., ergotamine, dihydroergotamine, eletriptan, sumatriptan, pseudoephedrine).

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting methylergonovine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: dopamine, drugs affecting liver enzymes that remove methylergonovine from your body (e.g., erythromycin, clarithromycin, ritonavir, indinavir, nelfinavir, delavirdine, ketoconazole, itraconazole, voriconazole, nefazodone, fluoxetine, fluvoxamine), nitrates (e.g., nitroglycerin).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. Symptoms of overdose may include: seizures, fainting, numbness/coldness of hands/feet, weak heartbeat, dark red/purple/black color of the fingers/toes.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood pressure measurements) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature below 77 degrees F (25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.