Rosaclear system

Overdose

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.

There is no human experience with overdosage of metronidazole vaginal gel. Vaginally applied Rosaclear System could be absorbed in sufficient amounts to produce systemic effects.

Contraindications

The use of VANDAZOLE (metronidazole vaginal gel) is contraindicated in patients with a history of hypersensitivity to metronidazole, other nitroimidazole derivatives, or parabens. Reported reactions include urticaria; erythematous rash; Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing; nasal congestion; dryness of the mouth, vagina, or vulva; fever; pruritus; fleeting joint pains.

Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer VANDAZOLE (metronidazole vaginal gel) to patients who have taken disulfiram within the last two weeks.

Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue alcohol consumption during and for at least three days after therapy with VANDAZOLE (metronidazole vaginal gel).

Rosaclear System is contraindicated in persons who have shown hypersensitivity to metronidazole, parabens, other ingredients of the formulation, or other nitroimidazole derivatives.

Psychotic reactions have been reported with co-administration disulfiram and oral metronidazole. Do not administer concurrently with or within 2 weeks of disulfiram.

Disulfiram-like reactions to alcohol have been reported with co-administration of oral metronidazole; do not consume ethanol or propylene glycol, during and for at least 24 hours following treatment.

Pharmaceutical form

Undesirable effects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to VANDAZOLE compared to another formulation of vaginal metronidazole in 220 women in a single trial. The population was non-pregnant females (age range 18 to 72 years, the mean was 33 years +/- 11 years) with bacterial vaginosis. The racial demographic of those enrolled was 71 (32%) of White, 143 (65%) of Black, 3 (1%) of Hispanic, 2 (1%) of Asian, and 1 (0%) of other. Patients administered an applicator full of VANDAZOLE (metronidazole vaginal gel) intravaginally once daily at bedtime for 5 days.

There were no deaths or serious adverse reactions related to drug therapy in the clinical trial. VANDAZOLE (metronidazole vaginal gel) was discontinued in 5 patients (2.3%) due to adverse reactions.

The incidence of all adverse reactions in VANDAZOLE (metronidazole vaginal gel) -treated patients was 42% (92/220). Adverse reactions occurring in ≥ 1% of patients were: fungal infection* (12%), headache (7%), pruritus (6%), abdominal pain (5%), nausea (3%), dysmenorrhea (3%), pharyngitis (2%), rash (1%), infection (1%), diarrhea (1%), breast pain (1%), and metrorrhagia (1%).

* Known or previously unrecognized vaginal candidiasis may present more prominent symptoms during therapy with VANDAZOLE (metronidazole vaginal gel). Approximately 10% of patients treated with VANDAZOLE (metronidazole vaginal gel) developed Candida vaginitis during or immediately after therapy.

Additional uncommon events, reported by < 1% of those women treated with VANDAZOLE (metronidazole vaginal gel) included:

General: allergic reaction, back pain, flu syndrome, mucous membrane disorder, pain

Gastrointestinal: anorexia, constipation, dyspepsia, flatulence, gingivitis, vomiting

Nervous System: depression, dizziness, insomnia

Respiratory System: asthma, rhinitis

Skin and Appendages: acne, sweating, urticaria

Urogenital System: breast enlargement, dysuria, female lactation, labial edema, leucorrhea, menorrhagia, pyleonephritis, salpingitis, urinary frequency, urinary tract infection, vaginitis, vulvovaginal disorder

Other reactions that have been reported in association with the use of other formulations of metronidazole vaginal gel include: unusual taste and decreased appetite.

Other reactions 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 reactions exceeded an incidence of 2% of patients.

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.

Nervous System: The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and 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; Stevens-Johnson Syndrome, toxic epidermal necrolysis, 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.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Rosaclear System was evaluated in a randomized, double-blind, vehicle-controlled study in subjects with bacterial vaginosis. A total of 321 non-pregnant females with a mean age of 33.4 years (range 18 to 67 years) received Rosaclear System. Subjects were primarily Black/African American (58.3%) or White (39.3%). Subjects administered a single dose of Rosaclear System at bedtime on the first day of the study.

There were no deaths or serious adverse reactions in this trial. Adverse reactions were reported by 19.0% of subjects treated with Rosaclear System versus 16.1% of subjects treated with Vehicle Gel.

Adverse reactions occurring in ≥1% of subjects receiving Rosaclear System were: vulvovaginal candidiasis (5.6%), headache (2.2%), vulvovaginal pruritus (1.6%), nausea (1.6%), diarrhea (1.2%), and dysmenorrhea (1.2%). No subjects discontinued treatment due to adverse reactions.

The safety of Rosaclear System was evaluated in a multicenter, open-label study evaluating the safety and tolerability of Rosaclear System in 60 pediatric subjects between the ages of 12 and less than 18 years old all of whom were treated with a single dose of Rosaclear System administered once at bedtime intravaginally. Most subjects in this study were either Black/African-American, non-Hispanic (47%) or Hispanic (35%)

Safety in pediatric female subjects aged 12 to less than 18 years old was comparable to adult women. No deaths occurred and no subjects discontinued treatment due to adverse reactions. Adverse reactions occurring in ≥ 1% of pediatric subjects included: vulvovaginal discomfort (2%).

Other reactions that have been reported in association with the use of other formulations of metronidazole vaginal gel include: unusual taste and decreased appetite.

Other reactions 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 reactions exceeded an incidence of 2% of patients.

The following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of metronidazole:

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

The most serious adverse reactions reported in patients treated with oral metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia.

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.

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

Reversible neutropenia, reversible thrombocytopenia.

Urticaria; erythematous rash; Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing; nasal congestion; dryness of the mouth, vagina, or vulva; fever; pruritus; fleeting joint pains.

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

Rosaclear System price

Therapeutic indications

VANDAZOLE (metronidazole vaginal gel) is indicated in the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in non-pregnant women.

Rosaclear System is indicated for the treatment of bacterial vaginosis in females 12 years of age and older.

Pharmacokinetic properties

Following a single, intravaginal 5 g dose of Rosaclear System (equivalent to 65 mg of metronidazole) to 20 healthy female subjects, a mean maximum serum metronidazole concentration (Cmax) of 239 ng/mL was observed (range: 114 to 428 ng/mL). The average time to achieve this Cmax was 7.3 hours (range: 4 to 18 hours). This Cmax is approximately 2% of the mean maximum serum concentration reported in healthy subjects administered a single, oral 500 mg dose of metronidazole tablets (mean Cmax = 12,785 ng/mL).

The extent of exposure [area under the curve (AUC)] of metronidazole, when administered as a single intravaginal 5 g dose of Rosaclear System (equivalent to 65 mg of metronidazole), was 5,434 ng•hr/mL (range: 1382 to 12744 ng•hr/mL). This AUC0-∞ is approximately 4% of the reported AUC of metronidazole following a single oral 500 mg dose of metronidazole (approximately 125,000 ng•hr/mL).

Name of the medicinal product

Qualitative and quantitative composition

Special warnings and precautions for use

Included as part of the PRECAUTIONS section.

Use of oral or intravenous metronidazole is associated with convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or parethesia of an extremity. VANDAZOLE (metronidazole vaginal gel) should be administered with caution to patients with central nervous system diseases. Discontinue VANDAZOLE (metronidazole vaginal gel) promptly if a patient develops abnormal neurologic signs.

Metronidazole has been shown to be carcinogenic in mice and rats. Unnecessary use of metronidazole should be avoided. Use of VANDAZOLE (metronidazole vaginal gel) should be reserved for the treatment of bacterial vaginosis

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminostransferase (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. Consider postponing chemistry laboratory tests to after treatment with VANDAZOLE (metronidazole vaginal gel).

Instruct the patient not to consume alcoholic beverages and preparations containing ethanol or propylene glycol during and for at least 3 days after treatment with VANDAZOLE.

Instruct the patient not to use VANDAZOLE (metronidazole vaginal gel) if disulfiram had been used within the last two weeks , and to inform their healthcare provider if they are taking oral anticoagulants, or lithium.

Instruct the patient not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with VANDAZOLE (metronidazole vaginal gel).

Inform the patient that vaginal fungal infections can occur following use of VANDAZOLE (metronidazole vaginal gel) and may require treatment with an antifungal drug.

Advise women that they may consider discontinuing milk feeding or pump and discard their milk during treatment and for 24 hours after the last dose of VANDAZOLE (metronidazole vaginal gel).

Inform the patient that VANDAZOLE (metronidazole vaginal gel) 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 and consult a healthcare provider.

Inform the patient to discontinue use and consult a healthcare provider if vaginal irritation occurs with use of VANDAZOLE (metronidazole vaginal gel).

Instruct the patient that VANDAZOLE (metronidazole vaginal gel, 0.75%) is supplied with 5 vaginal applicators. For once daily dosing, one applicator should be used per dose. See DIRECTIONS FOR USE for complete instructions on how to use the product and the vaginal applicator.

Metronidazole has shown evidence of carcinogenic activity after chronic oral administration in mice and rats. Pulmonary tumors and lymphomas were reported in several oral mouse studies in which mice were dosed at 75 mg/kg and above (about 5 times the clinical human dose based on body surface area comparison). Malignant liver tumors were reported in male mice dosed at doses equivalent to a human dose of 41 mg/kg/day (33 times the recommended clinical dose based on body surface area comparisons). Chronic oral dosing of metronidazole in rats at doses above 150 mg/kg (about 20 times the clinical human dose based on body surface area comparison) has resulted in mammary and hepatic tumors. Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative. Although no life-time studies were performed to evaluate the carcinogenic potential of VANDAZOLE (metronidazole vaginal gel, 0.75%), published data have shown that intravaginal administration of metronidazole to Wistar rats for 5 days, at doses 26 times the recommended human dose based on body surface area comparisons, has resulted in an increased frequency of micronuclei in rat vaginal mucosal cells.

Metronidazole has shown mutagenic activity in a number of in vitro assay systems. In addition, a dose dependent increase in the frequency of micronuclei was observed in mice after intraperitoneal injections. An increase in chromosome aberrations has been reported in one study of patients with Crohn's disease who were treated with 200 to 1200 mg/day of metronidazole for 1 to 24 months. However, in a second study, no increase in chromosome aberrations was reported in patients with Crohn's disease who were treated with metronidazole for 8 months.

Fertility studies have been performed in mice up to six times the recommended human oral dose (based on mg/m²) and have revealed no evidence of impaired fertility.

VANDAZOLE (metronidazole vaginal gel) should be used during pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women.

There are published data from case-control studies, cohort studies, and two meta-analyses that include more than 5000 pregnant women who used metronidazole systemically during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in-utero; however, these findings were not confirmed. In addition, more than ten randomized, placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of systemic antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Three studies conducted to assess the risk of infant cancer following systemic metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited.

Oral reproductive toxicity studies have been performed in mice at doses up to six times the recommended human dose based on body surface area comparisons and have revealed no evidence of impaired fertility or harm to the fetus. However, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed.

Animal studies have shown that metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Because animal reproduction studies are not always predictive of human response, and because metronidazole crosses the placental barrier and is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed.

Caution should be exercised when VANDAZOLE is administered to a nursing woman. Following oral metronidazole administration, concentrations of metronidazole in human milk are similar to concentrations in plasma. Since some metronidazole is systemically absorbed following vaginal administration of metronidazole, excretion in human milk is possible.

Because of the potential for tumorigenicity shown for metronidazole in animal studies, a decision should be made whether to discontinue nursing or to discontinue VANDAZOLE (metronidazole vaginal gel) , taking into account the importance of the therapy to the mother. A nursing mother may choose to pump and discard her milk for the duration of VANDAZOLE (metronidazole vaginal gel) therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula.

The safety and efficacy of VANDAZOLE (metronidazole vaginal gel) in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. The safety and efficacy of VANDAZOLE (metronidazole vaginal gel) in premenarchal females have not been established.

Clinical studies with VANDAZOLE (metronidazole vaginal gel) did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other reported clinical experience in using metronidazole gel, 1% has not identified differences in responses between elderly and younger patients.

Included as part of the PRECAUTIONS section.

Convulsive seizures, encephalopathy, aseptic meningitis, optic 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. Rosaclear System should be administered with caution to patients with central nervous system diseases. Discontinue promptly if abnormal neurologic signs develop.

Metronidazole has been shown to be carcinogenic at high doses administered orally in mice and rats. Unnecessary use of metronidazole should be avoided. Use of Rosaclear System should be reserved for the treatment of bacterial vaginosis.

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.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Instruct the patient not to consume alcoholic beverages and preparations containing ethanol or propylene glycol during and for at least 24 hours after treatment with Rosaclear System.

Instruct the patient not to use Rosaclear System if disulfiram had been used within the last two weeks , and to inform their healthcare provider if they are taking oral anticoagulants, or lithium.

Instruct the patient not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) following the single administration of Rosaclear System.

Advise women not to breastfeed during treatment with Rosaclear System and to discontinue breastfeeding for 2 days after treatment with Rosaclear System. Also advise a nursing mother that she may choose to pump and discard her milk during treatment with Rosaclear System and for 2 days after the therapy with Rosaclear System and, feed her infant stored human milk or formula.

Inform the patient to discontinue use and consult a healthcare provider if vaginal irritation occurs with use of Rosaclear System.

Instruct the patient that Rosaclear System is supplied as a single dose in a pre-filled applicator. See Instructions for Use for complete instructions on how to use the product and the vaginal applicator.

Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic oral administration in mice and rats. Pulmonary tumors were reported in several mouse studies in which mice were dosed orally at 75 mg/kg and above (about 6 or more times the maximum recommended human dose based on mg/m²). Malignant lymphoma was reported at 66 mg/kg and above (about 5 or more times the maximum recommended human dose based on mg/m²). These tumors have been observed in all six reported studies in the mouse, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only). All these effects were statistically significant.

There were statistically significant increases in the incidence of mammary tumors, among female rats administered metronidazole at 270 mg/kg and above (about 40 times the maximum human dose based on mg/m²). Hepatic adenomas and carcinomas were observed in rats administered 300 mg/kg (about 45 times the maximum human dose based on mg/m²).

Two lifetime oral tumorigenicity studies in hamsters have been performed and reported to be negative at doses up to 80 mg/kg (about 10 times the maximum human dose based on mg/m²).

Carcinogenesis studies have not been conducted with Rosaclear System.

Although metronidazole has shown in vitro mutagenic activity in bacterial reverse mutation tests, it was negative in in vitro mammalian mutation systems including CHO/HGPRT and CH V79 lung cell assays. Metronidazole was not clastogenic in vitro chromosome aberration tests in CHO cells up to 5000 μg/mL but was positive in human and monkey peripheral blood lymphocytes at 0.1 μg/mL.

In general, numerous micronucleus studies in rats and mice have failed to demonstrate a potential for genetic damage up to single oral doses 3000 mg/kg in mice (about 225 times the maximum human dose based on mg/m²). However, a dose dependent increase in the frequency of micronuclei was observed in CFW mice after intraperitoneal injections of up to 160 mg/kg (about 12 times the maximum human dose based on mg/m²). Â Fertility studies have been performed in mice orally dosed up to 500 mg/kg (about 37 times the maximum human dose based on mg/m²) revealed no evidence of impaired fertility.

While no effects on fertility were observed in female rats dosed intraperitoneally at doses up to 1000 mg/kg (about 300 times the maximum human dose based on mg/m²), studies in male rats resulted in effects on testes and sperm production at oral doses of 100 mg/kg and above (about 30 times the maximum human dose based on mg/m²).

There are no data available on the use of Rosaclear System in pregnant women. Metronidazole usage in pregnancy has been associated with certain congenital anomalies (see Data). In animal reproduction studies, no fetotoxicity or teratogenicity was observed when metronidazole was administered orally, during organogenesis to pregnant rats and rabbits at up to 60 times and 30 times the recommended human dose based on body surface area comparison, respectfully(see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Human Data

Blood levels following Rosaclear System vaginal administration are lower than those achieved with oral metronidazole. Following a single intravaginal 5 g dose of Rosaclear System, mean maximum concentration (Cmax) and total exposure (AUC0-∞) are approximately 2% and 4%, respectively, of those following a single oral 500 mg dose of metronidazole tablets. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly.

There are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero; however, these findings were not confirmed.

In addition, more than ten randomized placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy.

Three studies conducted to assess the risk of infant cancer following metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited.

Animal Data

No fetotoxicity or teratogenicity was observed when metronidazole was administered orally to pregnant rabbits at up to 200 mg/kg (about 60 times the maximum human dose based on body surface area comparison). Similarly, no fetotoxic or teratogenic effects were observed in five studies in rats where dosing was administered orally in the diet or by gastric intubation at doses up to 200 mg/kg (about 30 times the maximum human dose based on body surface area comparison).

As well, no fetotoxicity or teratogenicity was observed when metronidazole was administered orally to pregnant mice at doses up to 100 mg/kg (about 7 times the maximum human dose based on body surface area comparison). However, some intrauterine deaths were observed in Swiss Webster mice administered metronidazole intraperitoneally at doses up to 15 mg/kg (about 1 times the maximum human dose based on body surface area comparison). The relationship of these intraperitoneal findings in mice to the vaginal use of Rosaclear System is unknown.

There is no information on the presence of metronidazole in human milk, or the effects on the breast-fed child, or the effects on milk production following intravaginal administration of Rosaclear System. Metronidazole is present in human milk following oral metronidazole administration, at concentrations similar to plasma concentrations (see Data). Since some metronidazole is systemically absorbed following vaginal administration of Rosaclear System, excretion in human milk following topical use is possible.

Because of the potential risk for tumorigenicity shown in animal studies with metronidazole, breastfeeding is not recommended during treatment with Rosaclear System and for 2 days (based on half-life) after Rosaclear System therapy ends (see Clinical Considerations).

A nursing mother may choose to pump and discard her milk during Rosaclear System therapy and for 2 days after Rosaclear System therapy ends, and feed her infant stored human milk or formula.

In a study of nursing mothers receiving oral metronidazole 600 (n=11) or 1200 (n=4) mg daily, mean maternal plasma concentrations were 5.0 and 12.5 mcg/mL, respectively, within 2 hours following administration; the milk: maternal plasma ratio was approximately 1.

The safety and effectiveness of Rosaclear System have been established in pediatric subjects between the ages of 12 and less than 18 years old. Use of Rosaclear System in this age group is supported by evidence from a multicenter, open-label safety and tolerability study in 60 pediatric subjects with bacterial vaginosis and, evidence from adequate and well-controlled studies in adult women,

The safety and effectiveness of Rosaclear System in pediatric subjects below the age of 12 years have not been established.

Clinical studies with Rosaclear System did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects.

Dosage (Posology) and method of administration

The recommended dose is one applicator full of VANDAZOLE (metronidazole vaginal gel) , (approximately 5 grams of gel containing approximately 37.5 mg of metronidazole) administered intravaginally once a day for 5 days. For once a day dosing, VANDAZOLE should be administered at bedtime.

Not for ophthalmic, dermal, or oral use.

A single-dose, pre-filled disposable applicator (which delivers approximately 5 g of gel containing 65 mg of metronidazole) administered once intravaginally. Rosaclear System should be administered at bedtime.

Rosaclear System is not for ophthalmic, dermal or oral use.