METRONIDAZOLE- metronidazole gel

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
METRONIDAZOLE (UNII: 140QMO216E) (METRONIDAZOLE - UNII:140QMO216E)
Available from:
NuCare Pharmaceuticals,Inc.
Administration route:
VAGINAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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. 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
Product summary:
Metronidazole vaginal gel USP, 0.75% is supplied in a 70 gram tube and packaged with 5 vaginal applicators. The NDC 68071-5009-7 box of 70g Store at 20° – 25°C (68° – 77°F) [see USP Controlled Room Temperature]. Protect from freezing.
Authorization status:
Abbreviated New Drug Application
Authorization number:
68071-5009-7

METRONIDAZOLE- metronidazole gel

NuCare Pharmaceuticals,Inc.

----------

Metronidazole Vaginal Gel USP, 0.75%

Rx only

FOR INTRAVAGINAL USE ONLY

NOT FOR OPHTHALMIC, DERMAL, OR ORAL USE

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

, 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.

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 C

= 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

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 one and 294 ng/mL

(range: 228 to 349 ng/mL) on day five were reported. Steady state metronidazole 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.

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.

CONTRAINDICATIONS

Metronidazole vaginal gel USP, 0.75% is contraindicated in patients with a prior history of

hypersensitivity to metronidazole, parabens, other ingredients of the formulation, or other

nitroimidazole derivatives.

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.

PRECAUTIONS

Metronidazole vaginal gel USP, 0.75% affords minimal peak serum levels and systemic exposure

(AUCs) of metronidazole compared to 500 mg oral metronidazole dosing. Although these lower levels

of exposure are less likely to produce the common reactions seen with oral metronidazole, the

possibility of these and other reactions cannot be excluded presently. Data from well-controlled trials

directly comparing metronidazole administered orally to metronidazole administered vaginally are not

available.

General:

Patients with severe hepatic disease metabolize metronidazole slowly. This results in the accumulation

of metronidazole and its metabolites in the plasma. Accordingly, for such patients, metronidazole

vaginal gel should be administered cautiously.

Known or previously unrecognized vaginal candidiasis may present more prominent symptoms during

therapy with metronidazole vaginal gel. Approximately 6-10% of patients treated with metronidazole

vaginal gel USP, 0.75% developed symptomatic Candida vaginitis during or immediately after therapy.

Disulfiram-like reaction to alcohol has been reported with oral metronidazole, thus the possibility of

such a reaction occurring while on metronidazole vaginal gel therapy cannot be excluded.

Metronidazole vaginal gel USP, 0.75% contains ingredients that may cause burning and irritation of the

eye. In the event of accidental contact with the eye, rinse the eye with copious amounts of cool tap

water.

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.

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.

DRUG & OR LABORATORY TEST INTERACTIONS

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as

aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate

dehydrogenase (LDH), triglycerides, and glucose hexokinase. Values of zero may be observed. All of

the assays in which interference has been reported involve enzymatic coupling of the assay to

oxidation-reduction of nicotinamide-adenine dinucleotides (NAD + NADH). Interference is due to the

similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic

oral administration in mice and rats. Prominent among the effects in the mouse was the promotion of

pulmonary tumorigenesis. This has been observed in all six reported studies in that species, including

one study in which the animals were dosed on an intermittent schedule (administration during every

fourth week only). At very high dose levels (approximately 500 mg/kg/day), there was a statistically

significant increase in the incidence of malignant liver tumors in males. Also, the published results of

one of the mouse studies indicate an increase in the incidence of malignant lymphomas as well as

pulmonary neoplasms associated with lifetime feeding of the drug. All these effects are statistically

significant. Several long-term oral dosing studies in the rat have been completed. There were

statistically significant increases in the incidence of various neoplasms, particularly in mammary and

hepatic tumors, among female rats administered metronidazole over those noted in the concurrent female

control groups. Two lifetime tumorigenicity studies in hamsters have been performed and reported to

be negative.

These studies have not been conducted with 0.75% metronidazole vaginal gel, which would result in

significantly lower systemic blood levels than those obtained with oral formulations.

Although metronidazole has shown mutagenic activity in a number of in vitro assay systems, studies in

mammals ( in vivo) have failed to demonstrate a potential for genetic damage.

Fertility studies have been performed in mice up to six times the recommended human oral dose (based

on mg/m

) and have revealed no evidence of impaired fertility.

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

); 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.

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.

PEDIATRIC USE

Safety and effectiveness in children have not been established.

ADVERSE REACTIONS

Clinical Trials

There were no deaths or serious adverse events related to drug therapy in clinical trials involving 800

non-pregnant women who received metronidazole vaginal gel USP, 0.75%.

In a randomized, single-blind clinical trial of 505 non-pregnant women who received metronidazole

vaginal gel USP, 0.75% once or twice a day, 2 patients (one from each regimen) discontinued therapy

early due to drug-related adverse events. One patient discontinued drug because of moderate abdominal

cramping and loose stools, while the other patient discontinued drug because of mild vaginal burning.

These symptoms resolved after discontinuation of drug.

Medical events judged to be related, probably related, or possibly related to administration of

metronidazole vaginal gel USP, 0.75% once or twice a day were reported for 195/505 (39%) patients.

The incidence of individual adverse reactions were not significantly different between the two

regimens. Unless percentages are otherwise stipulated, the incidence of individual adverse reactions

listed below was less than 1%:

Reproductive:

Vaginal discharge (12%),

Symptomatic Candida cervicitis/vaginitis (10%),

Vulva/vaginal irritative symptoms (9%),

Pelvic discomfort (3%).

Gastrointestinal:

Gastrointestinal discomfort (7%),

Nausea and/or vomiting (4%),

Unusual taste (2%),

Diarrhea/loose stools (1%),

Decreased appetite (1%),

Abdominal bloating/gas; thirsty, dry mouth.

Neurologic:

Headache (5%),

Dizziness (2%),

Depression.

Dermatologic:

Generalized itching or rash.

Other:

Unspecified cramping (1%),

Fatigue,

Darkened urine.

In previous clinical trials submitted for approved labeling of metronidazole vaginal gel USP, 0.75% the

following was also reported:

Laboratory:

Increased/decreased white blood cell counts (1.7%).

Other Metronidazole Formulations:

Other effects that have been reported in association with the use of topical (dermal) formulations of

metronidazole include skin irritation, transient skin erythema, and mild skin dryness and burning. None of

these adverse events exceeded an incidence of 2% of patients.

Metronidazole vaginal gel USP, 0.75% affords minimal peak serum levels and systemic exposure

(AUC) of metronidazole compared to 500 mg oral metronidazole dosing. Although these lower levels

of exposure are less likely to produce the common reactions seen with oral metronidazole, the

possibility of these and other reactions cannot be excluded presently.

The following adverse reactions and altered laboratory tests have been reported with the oral or

parenteral use of metronidazole:

Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.

Central Nervous System: (See WARNINGS.) Headache, dizziness, syncope, ataxia, confusion,

convulsive seizures, peripheral neuropathy, vertigo, incoordination, irritability, depression,

weakness, insomnia.

Gastrointestinal: Abdominal discomfort, nausea, vomiting, diarrhea, an unpleasant metallic taste,

anorexia, epigastric distress, abdominal cramping, constipation, “furry” tongue, glossitis, stomatitis,

pancreatitis, and modification of taste of alcoholic beverages.

Genitourinary: Overgrowth of Candida in the vagina, dyspareunia, decreased libido, proctitis.

Hematopoietic: Reversible neutropenia, reversible thrombocytopenia.

Hypersensitivity Reactions: Urticaria; erythematous rash; flushing; nasal congestion; dryness of the

mouth, vagina, or vulva; fever; pruritus; fleeting joint pains.

Renal: Dysuria, cystitis, polyuria, incontinence, a sense of pelvic pressure, darkened urine.

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.)

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.

HOW SUPPLIED

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

applicators.

The NDC 68071-5009-7 box of 70g

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

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

SPL PATIENT PACKAGE INSERT

Metronidazole Vaginal Gel USP, 0.75%

DIRECTIONS FOR USE

1. Filling the applicator

Remove cap and puncture metal seal on tube with the pointed tip of cap. (See Figure 1)

Screw end of applicator onto tube. (See Figure 2)

Gently squeeze the tube from the bottom to fill applicator. Plunger will stop when the applicator is

full. (See Figure 3)

Unscrew applicator and replace cap on tube.

Figure 1

Figure 2

Figure 3

2. Inserting the applicator

The applicator may be inserted while lying on your back with your knees bent or in any comfortable

position.

Hold filled applicator by barrel, and gently insert into vagina as far as it will comfortably go. (See

Figure 4)

Slowly press the plunger until it stops to deposit gel into vagina and then withdraw the applicator.

Figure 4

3. Care of the applicator

If physician prescribes twice-a-day dosing:

After use, pull the plunger out of the barrel. (See Figure 5)

Wash both plunger and barrel in warm soapy water and rinse thoroughly.

To reassemble applicator, gently push plunger back into barrel.

IMPORTANT:

For once-a-day dosing, apply one applicator full at bedtime. For twice-a-day dosing, apply one

applicator full each morning and evening for five days, or as directed by physician.

WARNINGS:

If significant irritation develops from the use of this medication, discontinue use and consult your

physician.

Do not use during pregnancy except under the supervision of a physician.

Keep this and all medications out of reach of children.

For vaginal use only. Not for use in the eyes, on the skin or in the mouth.

Store at room temperature. Avoid exposure to extreme heat or cold. See end of carton and crimp end of

tube for lot number and expiration date.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-

800-FDA-1088.

Manufactured by

TOLMAR Inc.

Fort Collins, CO 80526 for

Sandoz Inc.

Princeton, NJ 08540

04486 Rev. 6 11/16

Metronidazole Vaginal Gel USP, 0.75%

INSTRUCCIONES PARA EL USO

1. Como llenar el aplicador

Quite la tapa y con la punta de la misma perfore el sello metálico del tubo. (Véase Ilustración 1)

Enrosque el extremo del aplicador en el tubo. (Véase Ilustración 2)

Exprima el tubo suavemente desde abajo para llenar el aplicador. Cuando el aplicador esté lleno, el

émbolo dejará de moverse. (Véase Ilustración 3)

Desenrosque el aplicador y reponga la tapa en el tubo.

Ilustración 1

Ilustración 2

Ilustración 3

2. Como introducir el aplicador

El aplicador puede introducirse estando acostada boca arriba con las rodillas dobladas, o en

cualquier posición en que se sienta cómoda.

Sostenga el aplicador lleno por su cañón, e introduzcalo suave y profundamente en la vagina de

manera cómoda. (Véase Ilustración 4)

Para depositar la gelatina dentro de la vagina, suavemente empuje el émbolo hasta que deje de

moverse y entonces saque el aplicador.

Ilustración 4

3. Como limpiar el aplicador

Si la prescripción médica indica una dosis de dos veces al día:

Después de usar el aplicador, saque el émbolo del cañón. (Véase Ilustración 5)

Lave el émbolo y el cañón con agua tibia y jabón y luego enjuaguelos completamente.

Para volver a armar el aplicador, suavemente empuje el émbolo en su sitio dentro del cañón.

Ilustración 5

IMPORTANTE:

Para dosis de una vez al día, introduzca un aplicador lleno por la noche. Para dosis de dos veces al día,

introduzca un aplicador lleno cada mañana y cada noche durante cinco días, o según las indicaciones de

su médico.

ADVERTENCIAS:

Si una irritación significante se desarrolla debida al uso de este medicamento, deje de usarlo y

consulte a su médico.

No lo utilice cuando esté embarazada, excepto bajo la supervisión de un médico.

Mantenga éste y todo medicamento fuera del alcance de los niños.

Para uso vaginal únicamente. No debe aplicarse a los ojos, en la piel, ni en la boca.

Guarde a una temperatura ambiente. Evite que se exponga al calor o frío excesivo. Vea la feche de

vencimiento y el número del lote en la base del cartón y en el sello del tubo.

Llame a su doctor para opinión médica sobre efectos secundarios. Usted puede reportar los

efectos secundarios a la FDA al 1-800-FDA-1088.

Manufactured by

TOLMAR Inc.

Fort Collins, CO 80526 for

Sandoz Inc.

Princeton, NJ 08540

04486 Rev. 6 11/16

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

METRONIDAZOLE

metronidazole gel

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 8 0 71-50 0 9 (NDC:0 78 1-70 77)

Route of Administration

VAGINAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METRO NIDAZO LE (UNII: 140 QMO216 E) (METRONIDAZOLE - UNII:140 QMO216 E)

METRONIDAZOLE

7.5 mg in 1 g

Inactive Ingredients

Ingredient Name

Stre ng th

CARBO MER HO MO PO LYMER TYPE B ( ALLYL PENTAERYTHRITO L CRO SSLINKED) (UNII: HHT0 1ZNK31)

METHYLPARABEN (UNII: A2I8 C7HI9 T)

PRO PYLPARABEN (UNII: Z8 IX2SC1OH)

EDETATE DISO DIUM (UNII: 7FLD9 1C8 6 K)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

SO DIUM HYDRO XIDE (UNII: 55X0 4QC32I)

WATER (UNII: 0 59 QF0 KO0 R)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 8 0 71-50 0 9 -7

70 g in 1 BOX; Type 0 : No t a Co mbinatio n Pro duct

0 7/31/20 19

Marketing Information

NuCare Pharmaceuticals,Inc.

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 7726 4

10 /31/20 0 6

Labeler -

NuCare Pharmaceuticals,Inc. (010632300)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

NuCare Pharmaceuticals,Inc.

0 10 6 3230 0

re la be l(6 8 0 71-50 0 9 )

Revised: 7/2019

Similar products

Search alerts related to this product

View documents history

Share this information