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Metrogel Vaginal (Metronidazole Vaginal) - Description and Clinical Pharmacology

 
 



FOR INTRAVAGINAL USE ONLY

NOT FOR OPHTHALMIC, DERMAL, OR ORAL USE

DESCRIPTION

METROGEL-VAGINAL 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 anti‑bacterial agent. Chemically, metronidazole is a 2-methyl-5-nitroimidazole-1-ethanol. It has a chemical formula of C6H9N3O3, a molecular weight of 171.16, and has the following structure:

METROGEL-VAGINAL is a gelled, purified water solution, containing metronidazole at a concentration of 7.5 mg/g (0.75%). The gel is formulated at pH 4.0. The gel also contains carbomer 934P, edetate disodium, methyl paraben, propyl paraben, propylene glycol, and sodium hydroxide.

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

CLINICAL PHARMACOLOGY

Normal Subjects:

Following a single, intravaginal 5 gram dose of metronidazole vaginal gel (equivalent to 37.5 mg of metronidazole) to 12 normal subjects, a mean maximum serum metronidazole concentration of 237 ng/mL was reported (range: 152 to 368 ng/mL). This is approximately 2% of the mean maximum serum metronidazole concentration reported in the same subjects administered a single, oral 500 mg dose of metronidazole (mean Cmax  = 12,785 ng/mL, range: 10,013 to 17,400 ng/mL). These peak concentrations were obtained in 6 to 12 hours after dosing with metronidazole vaginal gel and 1 to 3 hours after dosing with oral metronidazole.

The extent of exposure [area under the curve (AUC)] of metronidazole, when administered as a single intravaginal 5 gram dose of metronidazole vaginal gel (equivalent to 37.5 mg of metronidazole), was approximately 4% of the AUC of a single oral 500 mg dose of metronidazole (4977 ng-hr/mL and approximately 125,000 ng-hr/mL, respectively).

Dose-adjusted comparisons of AUCs demonstrated that, on a mg to mg comparison basis, the absorption of metronidazole, when administered vaginally, was approximately half that of an equivalent oral dosage.

Patients with Bacterial Vaginosis:

Following single and multiple 5 gram doses of metronidazole vaginal gel to 4 patients with bacterial vaginosis, a mean maximum serum metronidazole concentration of 214 ng/mL on day 1 and 294 ng/mL (range: 228 to 349 ng/mL) on day five were reported. Steady state metro‑nidazole serum concentrations following oral dosages of 400 to 500 mg BID have been reported to range from 6,000 to 20,000 ng/mL.

Microbiology:

The intracellular targets of action of metronidazole on anaerobes are largely unknown. The 5-nitro group of metronidazole is reduced by metabolically active anaerobes, and studies have demonstrated that the reduced form of the drug interacts with ‑bacterial DNA. However, it is not clear whether interaction with DNA alone is an important component in the bactericidal action of metronidazole on anaerobic organisms.

Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis. (See INDICATIONS AND USAGE.)

Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens, Gardnerella vaginalis, Mobiluncus spp., and Mycoplasma hominis, has not been defined. Nonetheless, metronidazole is an antimicrobial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:

     Bacteroides spp.
     Gardnerella vaginalis
     Mobiluncus spp.
     Peptostreptococcus spp.

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