Methergine

Mechanism of Action

Produces vasoconstriction to increase strength, duration, & frequency of uterine contraction which in turn impedes uterine blood flow

Pharmacokinetics

Bioavailability: 60% (PO); 78% (IM)

Peak Plasma Time: 30 min

Peak Plasma Concentration: 3 ng/mL

Onset: uterine contractions are usually initiated within 5-15 min following oral administration, within 2-5 min after IM injection, & immediately following IV injection

Duration: 3 hr (PO); 3hr (IM); 45 min (IV)

Vd: 39-73L

Metabolism: Liver

Excretion: Urine and feces

Half-Life

• Initial phase: 1-5 min
• Terminal phase: 0.5-2 hr

IV Administration

Give IV only in emergency because of potential for HTN & CVA

Give over >1 min & monitor BP & uterine contractions

Methergine is part of the drug class:

• Ergot Oxytocics

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of methylergonovine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of methylergonovine have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving methylergonovine.

Pregnancy

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Almotriptan
• Amprenavir
• Atazanavir
• Azithromycin
• Boceprevir
• Clarithromycin
• Cobicistat
• Darunavir
• Delavirdine
• Dirithromycin
• Eletriptan
• Erythromycin
• Fosamprenavir
• Frovatriptan
• Indinavir
• Itraconazole
• Josamycin
• Ketoconazole
• Lopinavir
• Mepartricin
• Miokamycin
• Naratriptan
• Nefazodone
• Nelfinavir
• Posaconazole
• Ritonavir
• Rizatriptan
• Rokitamycin
• Roxithromycin
• Saquinavir
• Spiramycin
• Sumatriptan
• Telaprevir
• Tipranavir
• Troleandomycin
• Voriconazole
• Zolmitriptan

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ephedrine
• Fluconazole
• Fluvoxamine
• Propatyl Nitrate
• Telithromycin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Coronary artery disease or
• Diabetes or
• Hypercholesterolemia (high cholesterol in the blood)—May increase risk for more serious side effects.

• Hypertension (high blood pressure) or
• Toxemia (high blood pressure during pregnancy)—Should not be used in patients with these conditions.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Obliterative vascular disease (blood vessel disease) or
• Sepsis (severe infection in the blood)—Use with caution. May make these conditions worse.

Methergine®(methylergonovine maleate) is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage.

Methergine is available in tablets for oral ingestion containing 0.2 mg methylergonovine maleate.

Tablets

Active ingredient: Methylergonovine maleate, USP, 0.2 mg.

Inactive ingredients: acacia, corn starch, gelatin, lactose monohydrate, methylparaben, microcrystalline cellulose, povidone, propylparaben, stearic acid, and tartaric acid.

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:

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.

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.1

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

Postmarketing Experience

The following adverse drug reactions have been derived from post-marketing experience with Methergine via spontaneous case reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known.

Nervous system disorders

Cerebrovascular accident, paraesthesia

Cardiac disorders

Ventricular fibrillation, ventricular tachycardia, angina pectoris, atrioventricular block

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

1 mL, 0.2 mg, administered slowly over a period of no less than 60 seconds (See WARNINGS.)

Orally

One tablet, 0.2 mg, 3 or 4 times daily in the puerperium for a maximum of 1 week.

White, round, biconvex compressed tablets debossed with "n" on one side and "01" on the other side.  Available in bottles of 7, 12, 28 and 100 tablets.

Bottles of 7………………………………NDC   27437-050-19

Bottles of 12…………………………….NDC   27437-050-57

Bottles of 28…………………………….NDC   27437-050-56

Bottles of 100………………………...…NDC   27437-050-01

STORE AND DISPENSE

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

Methergine is a registered trademark of Novartis AG

Manufactured by:

Novel Laboratories, Inc.

Somerset, NJ 08873

Manufactured for:

Lupin Pharma

Baltimore, MD 21202

PI1400003901

Iss. 01/2016