metroNIDAZOLE 0.75 % Vaginal Gel

Details

Generic Name: METRONIDAZOLE

Brand Name: Metronidazole

Substance Name(s):
METRONIDAZOLE

WARNINGS

Convulsive Seizures and Peripheral Neuropathy: Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with oral or intravenous metronidazole.

The appearance of abnormal neurologic signs demands the prompt discontinuation of metronidazole vaginal gel therapy.

Metronidazole vaginal gel should be administered with caution to patients with central nervous system diseases.

Psychotic Reactions: Psychotic reactions have been reported in alcoholic patients who were using oral metronidazole and disulfiram concurrently.

Metronidazole vaginal gel should not be administered to patients who have taken disulfiram within the last two weeks.

DRUG INTERACTIONS

Oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time.

This possible drug interaction should be considered when metronidazole vaginal gel is prescribed for patients on this type of anticoagulant therapy.

In patients stabilized on relatively high doses of lithium, short-term oral metronidazole therapy has been associated with elevation of serum lithium levels and, in a few cases, signs of lithium toxicity.

Use of cimetidine with oral metronidazole may prolong the half-life and decrease plasma clearance of metronidazole.

OVERDOSAGE

There is no human experience with overdosage of metronidazole vaginal gel.

Vaginally applied metronidazole gel, 0.75% could be absorbed in sufficient amounts to produce systemic effects.

(See WARNINGS .)

DESCRIPTION

Metronidazole vaginal gel USP, 0.75% is the intravaginal dosage form of the synthetic antibacterial agent, metronidazole, USP at a concentration of 0.75%.

Metronidazole is a member of the imidazole class of antibacterial agents and is classified therapeutically as an antiprotozoal and antibacterial agent.

Chemically, metronidazole is a 2-methyl-5-nitroimidazole-1-ethanol.

It has a chemical formula of C 6 H 9 N 3 O 3 , a molecular weight of 171.16, and has the following structure: Metronidazole vaginal gel USP, 0.75% is a gelled, purified water solution, containing metronidazole at a concentration of 7.5 mg/g (0.75%).

The gel is formulated at pH 5.5.

The gel also contains carbopol 974P, edetate disodium, methylparaben, propylene glycol, propylparaben and sodium hydroxide.

Each applicator full of 5 grams of vaginal gel contains approximately 37.5 mg of metronidazole.

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CLINICAL STUDIES

In a randomized, single-blind clinical trial of non-pregnant women with bacterial vaginosis who received metronidazole vaginal gel USP, 0.75% daily for 5 days, the clinical cure rates for evaluable patients determined at 4 weeks after completion of therapy for the QD and BID regimens were 98/185 (53%) and 109/190 (57%), respectively.

Manufactured by TOLMAR Inc.

Fort Collins, CO 80526 for Sandoz Inc.

Princeton, NJ 08540 04486 Rev.

6 11/16

HOW SUPPLIED

Metronidazole vaginal gel USP, 0.75% is supplied in a 70 gram tube and packaged with 5 vaginal applicators.

The NDC number for the 70 gram tube is 0781-7077-87.

Store at 20° – 25°C (68° – 77°F) [see USP Controlled Room Temperature].

Protect from freezing.

INDICATIONS AND USAGE

INDICATIONS & USAGE Metronidazole vaginal gel USP, 0.75% is indicated in the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis).

NOTE: For purposes of this indication, a clinical diagnosis of bacterial vaginosis is usually defined by the presence of a homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a “fishy” amine odor when mixed with a 10% KOH solution, and (c) contains clue cells on microscopic examination.

Gram’s stain results consistent with a diagnosis of bacterial vaginosis include (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells.

Other pathogens commonly associated with vulvovaginitis, e.g., Trichomonas vaginalis , Chlamydia trachomatis , N .

gonorrhoeae , Candida albicans , and Herpes simplex virus should be ruled out.

PEDIATRIC USE

Safety and effectiveness in children have not been established.

PREGNANCY

Teratogenic Effects: Pregnancy Category B There has been no experience to date with the use of metronidazole vaginal gel USP, 0.75% in pregnant patients.

Metronidazole crosses the placental barrier and enters the fetal circulation rapidly.

No fetotoxicity or teratogenicity was observed when metronidazole was administered orally to pregnant mice at six times the recommended human dose (based on mg/m 2 ); however, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed.

The relationship of these findings to the drug is unknown.

There are, however, no adequate and well-controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, and because metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed.

NUSRING MOTHERS

NURSING MOTHERS Specific studies of metronidazole levels in human milk following intravaginally administered metronidazole have not been performed.

However, metronidazole is secreted in human milk in concentrations similar to those found in plasma following oral administration of metronidazole.

Because of the potential for tumorigenicity shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

INFORMATION FOR PATIENTS

The patient should be cautioned about drinking alcohol while being treated with metronidazole vaginal gel.

While blood levels are significantly lower with metronidazole vaginal gel USP, 0.75% than with usual doses of oral metronidazole, a possible interaction with alcohol cannot be excluded.

The patient should be instructed not to engage in vaginal intercourse during treatment with this product.

DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION The recommended dose is one applicator full of metronidazole vaginal gel USP, 0.75% (approximately 5 grams containing approximately 37.5 mg of metronidazole) intravaginally once or twice a day for 5 days.

For once a day dosing, metronidazole vaginal gel USP, 0.75% should be administered at bedtime.