DailyMed Label: Methergine

DailyMed Label: METHERGINE

2010

DailyMed Prescription

METHERGINE

METHYLERGONOVINE MALEATE

Apotheca, Inc.

NDC: 12634-179

NDC: 12634-179

Methergine® (methylergonovine malate) is a semi-synthetic ergot alkaloid used for the prevention and control of postpartum hemorrhage. Methergine Tablets are for oral ingestion containing 0.2mg of methylergonovine maleate. Active ingredient methylergonovine maleate, USP, 0.2mg. Inactive Ingredients Acacia, carnauba wax, gelatin special, D and C Red #7, FD and C Blue #1, lactose, maleic acid, mixed parabens, povidone, sodium benzoate, sodium hydroxide, starch, stearic acid, sucrose, talc, and titanium dioxide. Its structural formula is image of structural formula

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

Hypertension; toxemia; pregnancy; and hypersensitivity.

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. 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 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. 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.) The uterotonic effect of Methergine is utilized after delivery to assist involution and decrease hemorrhage, shortening the third stage of labor. 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. Safety and effectiveness in pediatric patients have not been established. 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.

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.

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

Tablets 0.2 mg round, coated, orchid, branded “78-54” one side, “SANDOZ” other side. Bottles of 6............ NDC 12634-179-96 Bottles of 8............ NDC 12634-179-98 Bottles of 10 ..........NDC 12634-179-00 Bottles of 12 ..........NDC 12634-179-82 Bottles of 15.......... NDC 12634-179-85 Bottles of 20...........NDC 12634-179-80 Blister Pack of 1.... NDC 12634-179-91 Tablets : Store below 25°C (77°F); in tight, light-resistant container.

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

6 Tablets NDC 12634-179-96 Methergine® (methylergononovine maleate) Tablets, USP Rx Only 0.2MG Each Tablet Contains methytergonovine maleate 0.2MG Usual Adult Dosage See package insert for full prescribing information. Keep This and all Medications Out of the Reach of Children Dispense in a tight, light-resistant container as defined in the USP, using a child-resistant closure Manufactured by Novartis Pharmaceuticals Suffern, N.Y. 10901 NDC 0078-0054-05 Repackaged and Distributed by Apotheca, Inc. Phoenix, AZ. 85006 image of label