METROGEL Gel Ref.[10873] Active ingredients: Methronidazole

5.1 Neurologic Disease

Peripheral neuropathy, characterized by numbness or paresthesia of an extremity, has been reported in patients treated with systemic metronidazole. Peripheral neuropathy has been reported with the post approval use of topical metronidazole. Immediately reevaluate METROGEL therapy if abnormal neurologic signs appear. Administer metronidazole with caution to patients with central nervous system diseases.

5.2 Blood Dyscrasias

METROGEL is a nitroimidazole; use with care in patients with evidence of, or history of, blood dyscrasia.

5.3 Contact Dermatitis

Irritant and allergic contact dermatitis have been reported with METROGEL. If dermatitis occurs, patients may need to discontinue use.

5.4 Eye Irritation

Topical metronidazole has been reported to cause tearing of the eyes. Avoid contact with the eyes.

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Neurologic Disease [see Warnings and Precautions (5.1)]
• Contact Dermatitis [see Warnings and Precautions (5.3)]
• Eye Irritation [see Warnings and Precautions (5.4)]

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.

In a controlled clinical trial, 557 subjects used METROGEL and 189 subjects used the gel vehicle once daily for up to 10 weeks. The following table summarizes selected adverse reactions that occurred at a rate of ≥1% and at a higher rate than vehicle:

Table 1. Adverse Reactions That Occurred at a Rate of ≥1% and Higher Than Vehicle in Subjects Treated with METROGEL for Up to 10 Weeks:

Table 2. Local Cutaneous Signs and Symptoms of Irritation That Were Worse Than Baseline in Subjects Treated with METROGEL for Up to 10 Weeks:

The following additional adverse reactions have been reported with the topical use of metronidazole: transient redness, metallic taste, tingling or numbness of extremities, and nausea.

The following adverse reaction has been identified during post-approval use of topical metronidazole. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Nervous System Disorders: Peripheral neuropathy

Ophthalmic Adverse Reactions: Tearing of the eyes

Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin, resulting in a prolongation of prothrombin time. Use caution when prescribing for patients who are receiving anticoagulant treatment.

Risk Summary

Available data have not established an association between metronidazole use during pregnancy and major birth defects, miscarriage or other adverse maternal or fetal outcomes. No fetotoxicity was observed after oral administration of metronidazole in pregnant rats or mice. The available data do not allow the calculation of relevant comparisons between the systemic exposures of metronidazole observed in animal studies to the systemic exposures that would be expected in humans after topical use of METROGEL.

The 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 2-4% and 15-20%, respectively.

Risk Summary

It is not known whether metronidazole is present in human milk after topical administration. Published literature reports the presence of metronidazole in human milk after oral administration. There are no data on the effects of metronidazole on milk production. Because of the potential for serious adverse reactions, advise patients that breastfeeding is not recommended during treatment with METROGEL.

Safety and effectiveness of METROGEL have not been established in pediatric patients.

Sixty-six subjects aged 65 years and older were treated with METROGEL in the clinical study. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.