Metrocream 0.750 %

METROGEL 1%: Apply and rub in a thin film once daily to entire affected area(s).

METROGEL 0.75%, METROCREAM 0.75%, AND METROLOTION 0.75%: Apply and rub in a thin film twice daily, morning and evening, to entire affected areas.

Significant therapeutic results should be noticed within three weeks. Clinical studies have demonstrated continuing improvement through nine weeks of therapy. The dosage required for long-term administration is uncertain (see Warnings and Precautions).

Areas to be treated should be cleansed before application of METROGEL, METROCREAM, or METROLOTION. The face must be dry before applying medication.

Patients may use cosmetics after application of METROGEL, METROCREAM, or METROLOTION. The medication should have absorbed into the skin (“dry”) before the cosmetics are applied.

lacrimation increased.

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

paraesthesia.

dermatitis contact, dry skin, erythema, pruritus, rash pustular, dermatitis bullous, skin burning sensation, skin irritation.

leucopenia.

condition aggravated.

Adverse Reactions Attributed to METROLOTION (metronidazole topical lotion)

The safety profile of METROGEL (metronidazole topical gel 0.75% and 1%), METROCREAM (metronidazole topical cream 0.75%) and METROLOTION (metronidazole topical lotion 0.75%) has been established in clinical trials. The results of the safety analyses indicate topical application of metronidazole is well tolerated.

hypersensitivity.

dysgeusia, nausea.

Adverse Reactions Attributed to METROCREAM (metronidazole topical cream)

Adverse Reactions Attributed to METROGEL 0.75% (metronidazole topical gel)

Safety and effectiveness in pediatrics have not been established.

While specific clinical trials in the geriatric population have not been conducted, 66 patients aged 65 years and older treated with METROGEL 1% over 10 weeks showed comparable safety and efficacy as compared to the general study population.

The clear, colorless gel contains: metronidazole 0.75%. Nonmedicinal ingredients: carbomer 940, edetate disodium, methylparaben, propylene glycol, propylparaben, purified water and sodium hydroxide. Aluminum tubes of 60 g.

The fluid, emollient lotion, contains: metronidazole 0.75%. Nonmedicinal ingredients: benzyl alcohol, carbomer 941, cyclomethicone, glycerin, glyceryl stearate, light mineral oil, polyethylene glycol 100 stearate, polyethylene glycol 400, potassium sorbate, purified water, sodium hydroxide and/or lactic acid, stearyl alcohol and steareth-21. Oval plastic bottles of 120 mL.

The white, smooth, emollient cream contains: metronidazole 0.75%. Nonmedicinal ingredients: benzyl alcohol, emulsifying wax, glycerin, isopropyl palmitate, lactic acid and/or sodium hydroxide, purified water and sorbitol solution. Aluminum tubes of 60 g.

The aqueous gel contains: metronidazole 1%. Nonmedicinal ingredients: betadex, edetate disodium, hydroxyethyl cellulose 250 HHX, methylparaben, niacinamide, phenoxyethanol, propylene glycol, propylparaben and purified water. Aluminum tubes of 60 g.

If a reaction suggesting local irritation occurs, patients should be directed to use the medication less frequently, discontinue use temporarily, or discontinue use until further instructions.

There were no reports of contact dermatitis attributed to METROGEL and METROCREAM, during clinical trials. However, there have been reports of contact dermatitis/allergic reaction reported during METROLOTION clinical trials and as post marketing adverse reactions (see Adverse Reactions). Physicians should be aware of the possibility of skin sensitivity reactions and of cross-sensitization with other imidazole preparations, such as clotrimazole and tioconazole.

Exposure to excessive sunlight, including sunlamps and tanning beds, should be avoided when using METROGEL, METROCREAM, or METROLOTION (based on studies in hairless mice treated with intraperitoneal metronidazole).

Metronidazole is a nitroimidazole and should be used with care in patients with evidence of, or history of, blood dyscrasia.

Avoid contact with the eyes. Topical metronidazole has been reported to cause tearing of the eyes. It should not be used in or close to the eye. If contact does occur, flush with water.

Conjunctivitis associated with topical use of metronidazole on the face has been reported.

Information from preclinical studies indicates that metronidazole and its principal metabolite are mutagenic in bacteria and that tumours were observed in animal studies after oral administration of metronidazole. The relevance of these findings to the topical use of metronidazole in humans is unknown. The anaerobic or hypoxic conditions that might lead to the production of genotoxic compounds are unlikely to occur in topical use. There is no conclusive evidence after 30 years of clinical use of systemic metronidazole for either a genotoxic or carcinogenic potential.

Because of the minimal absorption of metronidazole, and consequently its insignificant plasma concentration after topical administration, the systemic adverse reactions reported with the oral form of the drug should not be expected with METROGEL, METROCREAM, or METROLOTION (metronidazole topical gel, cream, or lotion).

Physicians should consider the most appropriate formulation (gel, cream, or lotion) for their patients.

Although rosacea is a chronic disease, data on the long-term use of METROGEL, METROCREAM, or METROLOTION in rosacea is not available. In controlled clinical trials, patients were treated for up to12 weeks (see Dosage and Administration).

There has been no experience to date with the use of METROGEL, METROCREAM, or METROLOTION (metronidazole) in pregnant patients. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. No fetotoxicity was observed after oral metronidazole in rats or mice. However, because animal reproduction studies are not always predictive of human response, this drug should only be used during pregnancy after careful assessment of the risk/benefit ratio.

Even though metronidazole blood levels are significantly lower after topical application than after oral administration 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. After oral administration, metronidazole is secreted in breast milk in concentrations similar to those found in the plasma.

Serum metronidazole levels have been shown to be below detection limits (<25 ng/mL) at the majority of time points after administration of topical metronidazole. At the time points that it could be detected, topical metronidazole produced blood levels (C_max 40.6 ng/mL) that were approximately 80% less than a similar dose administered orally (C_max 212 ng/mL). Therefore, with normal usage, topical metronidazole results in minimal blood levels of metronidazole.

METROGEL, METROCREAM, and METROLOTION (metronidazole topical gel, cream, and lotion) preparations are particularly effective against the inflammatory, papulopustular component of rosacea. The mechanisms by which topical metronidazole acts in reducing inflammatory lesions of rosacea are unknown, but may include an anti-bacterial and/or an anti-inflammatory effect.