MetroLotion® (metronidazole lotion) Topical Lotion contains metronidazole, USP, at a concentration of 7.5 mg per gram (0.75% w/w) in a lotion consisting of benzyl alcohol, carbomer 941, cyclomethicone, glycerin, glyceryl stearate, light mineral oil, PEG-100 stearate, polyethylene glycol 400, potassium sorbate, purified water, steareth-21, stearyl alcohol, and sodium hydroxide and/or lactic acid to adjust pH.

Metronidazole is an imidazole and is classified therapeutically as an antipro-tozoal and antibacterial agent. Chemically, metronidazole is 2-methyl-5-nitro- 1H-imidazole-1-ethanol. The molecular formula is C₆H₉N₃O₃ and molecular weight is 171.16. Metronidazole is represented by the following structural formula:

Last updated on RxList: 9/3/2008

MetroLotion® Topical Lotion is indicated for topical application in the treatment of inflammatory papules and pustules of rosacea.

Apply a thin layer to entire affected areas after washing. Use morning and evening or as directed by physician. Avoid application close to the eyes. Patients may use cosmetics after waiting for the MetroLotion® Topical Lotion to dry (not less than 5 minutes).

MetroLotion® (metronidazole lotion) Topical Lotion, 0.75% is supplied in the following size:

2 fl. oz. (59 mL) plastic bottle - NDC 0299-3838-02

Storage

Store at controlled room temperature 68° to 77°F (20° - 25°C). Protect from freezing.

Marketed by: GALDERMA LABORATORIES, L.P. Fort Worth, Texas 76177, USA. Manufactured by: Galderma Production Canada, Inc. Montreal, QC H9X 3N7 Canada. Revised: August 2003. FDA Rev date: 5/11/2004

Last updated on RxList: 9/3/2008

In a controlled clinical trial, safety data from 141 patients who used MetroLotion® Topical Lotion (n=71), or the lotion vehicle (n=70), twice daily and experienced a local cutaneous adverse event which may or may not have been related to the treatments include: local allergic reaction, MetroLotion® Topical Lotion 2 (3%), lotion vehicle 0; contact dermatitis, MetroLotion® Topical Lotion 2 (3%), lotion vehicle 1 (1%); pruritus, MetroLotion® Topical Lotion 1 (1%), lotion vehicle 0; skin discomfort (burning and stinging), MetroLotion® Topical Lotion 1 (1%), lotion vehicle 2 (3%); erythema, MetroLotion® Topical Lotion 4 (6%), lotion vehicle 0; dry skin, MetroLotion® Topical Lotion 0, lotion vehicle 1 (1%); and worsening of rosacea, MetroLotion® Topical Lotion 1 (1%), lotion vehicle 7 (10%). The following additional adverse experiences have been reported with the topical use of metronidazole: skin irritation, transient redness, metallic taste, tingling or numbness of extremities, and nausea.

Oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and coumarin anticoagulants, resulting in a prolongation of prothrombin time. The effect of topical metronidazole on prothrombin time is not known.

Last updated on RxList: 9/3/2008

No information provided.

General: Topical metronidazole formulations have been reported to cause tearing of the eyes. Therefore, contact with the eyes should be avoided. If a reaction suggesting local irritation occurs, patients should be directed to use the medication less frequently or discontinue use. Metronidazole is a nitroim-idazole and should be used with care in patients with evidence or history of blood dyscrasia.

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 but not in studies involving hamsters. Neither carcinogenicity nor photocarcinogenicity studies have been performed by the topical route with MetroLotion® Topical Lotion or any marketed metronidazole formulations.

In several long-term studies in mice, oral doses of approximately 198 mg/m²/day or greater (approximately 29 to 71 times the human topical dose on a mg/m² basis) were associated with an increase in lung tumors in male mice and lymphomas in female mice.

Several long-term studies by the oral route in rats have shown statistically significant increases in mammary and hepatic tumors in female rats and testicular tumors and pituitary adenomas in male rats at doses (in feed) of 1593 mg/m²/day or greater (approximately 230 to 573 times the human topical dose on a mg/m² basis). In another oral study (by gavage), mammary tumors in female rats were observed with a dose of 177 mg/m²/day (approximately 26 to 64 times the human topical dose on a mg/m² basis).

In a published study, the ultraviolet radiation-induced carcinogenesis was enhanced in albino hairless mice by intraperitoneal administration of 45 mg/m² metronidazole, as shown by a decreased latency period to the development of skin neoplasms. The concentration of metronidazole in the skin following the intraperitoneal administration was not determined. This study did not distinguish whether metronidazole must be present during the exposure to ultraviolet radiation in order to enhance tumor formation or whether metronidazole could promote tumor formation from preexisting ultraviolet radiation-initiated cells. The significance of these results in the topical use of metronidazole for the treatment of rosacea is unclear.

Metronidazole has shown evidence of mutagenic activity in several in vitro bacterial assay systems. In addition, a dose-response increase in the frequency of micronuclei was observed in mice after intraperitoneal injections. An increase in chromosome aberrations in peripheral blood lymphocytes was reported in patients with Crohn's disease who were treated with 200-1200 mg/day of metronidazole for 1 to 24 months. However, in another study, no excess chromosomal aberrations in circulating human lymphocytes were observed in patients treated for 8 months.

In rats, oral metronidazole at doses of 1770 mg/m²/day (approximately 255 to 637 times the human topical dose on a mg/m² basis) induced inhibition of spermatogenesis and severe testicular degeneration. In two strains of mice (ICR and CF1), conflicting results have been reported indicating either no effect or a similar effect to that reported in rats.

Pregnancy

Teratogenic Effects: Pregnancy Category B

There are no adequate and well-controlled studies with the use of MetroLotion® Topical Lotion in pregnant women. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. No fetotoxicity was observed after oral administration of metronidazole in rats or mice. However, because animal reproduction studies are not always predictive of human response and since oral metronidazole has been shown to be a carcinogen in some rodents, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

After oral administration, metronidazole is secreted in breast milk in concentrations similar to those found in the plasma. Even though blood levels are significantly lower with topically applied metronida-zole than those achieved after oral administration of metronidazole, 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 pediatric patients have not been established.

Last updated on RxList: 9/3/2008

No information provided.

MetroLotion® Topical Lotion is contraindicated in individuals with a history of hypersensitivity to metronidazole or to other ingredients of the formulation.

Last updated on RxList: 9/3/2008

The mechanisms by which metronidazole acts in the treatment of rosacea are unknown, but appear to include an anti-inflammatory effect.

Pharmacokinetics

Absorption of metronidazole after topical application of MetroLotion® Topical Lotion is less complete and more prolonged than after oral administration. Detectable plasma levels were found in all subjects following the administration of a 1 gram dose of MetroLotion® Topical Lotion (containing 7.5 mg of metronidazole) applied every morning and evening for 4 days to the faces of 8 patients. The highest concentration (96 ng/mL) seen following the morning dose on Day 5 was approximately 80 times lower than the peak concentrations produced by a single 250 mg tablet of metronidazole. The mean (±SD) AUC_0-24 after twice daily administration was 962±373 ng.hr/mL.

Clinical Studies

A controlled clinical study was conducted in 144 patients with moderate to severe rosacea, in which MetroLotion® Topical Lotion was compared with its vehicle. Applications were made twice daily for 12 weeks during which patients were instructed to avoid spicy foods, thermally hot foods and drinks, alcoholic beverages, and caffeine. Patients were also provided samples of a soapless cleansing lotion and, if requested, a moisturizer. MetroLotion® Topical Lotion was significantly more effective than its vehicle in mean percent reduction of inflammatory lesions associated with rosacea and in the investigators' global assessment of improvement. The results of the mean percent reduction in inflammatory lesion counts from baseline after 12 weeks of treatment and the investigators' global assessment of improvement at week 12 are presented in the following table:

Efficacy Outcomes at Week 12
Mean Percent Reduction in Inflammatory Lesion Counts from Baseline

The scale is based on the following definitions:

Worse: Exacerbation of either erythema or quantitative assessment of papules and/or pustules.

No Change: Condition remains the same.

Minimal Improvement: Slight improvement in the quantitative assessment of papules and/or pustules, and/or slight improvement in erythema.

Definite Improvement: More pronounced improvement in the quantitative assessment of papules and/or pustules, and/or more pronounced improvement in erythema.

Marked Improvement: Obvious improvement in the quantitative assessment of papules and/or pustules, and/or obvious improvement in erythema.

Clear: No papules or pustules and minimal residual or no erythema.

Last updated on RxList: 9/3/2008

Patients using MetroLotion® Topical Lotion should receive the following information and instructions:

1. This medication is to be used only as directed by the physician.
2. It is for external use only.
3. Avoid contact with the eyes.
4. Cleanse affected area(s) before applying this medication.
5. Patients should report any adverse reaction to their physician.

Last updated on RxList: 9/3/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METRONIDAZOLE - TOPICAL

(meh-troh-NID-uh-zole)

COMMON BRAND NAME(S): Metrocream, Metrogel, Metrolotion, Noritate

USES: This medication is used on the skin to treat a certain skin disorder known as rosacea, a type of adult acne. It may help to decrease redness, swelling and the number of pimples caused by rosacea.

This medication is an antibiotic. For the treatment of rosacea, metronidazole is believed to work by decreasing swelling (inflammation).

HOW TO USE: Use this medication on the skin only. Wash and dry your hands before and after applying this medication. Wash and dry the area to be treated. Wait 15 minutes, then apply a thin layer of medication usually once or twice daily, or as directed by your doctor. Wait 5 minutes before applying cosmetics.

Avoid using this medication around the eye area, unless directed by your doctor. Watery eyes or tearing of the eyes may occur if this medication is applied too close to the eyes. Avoid getting this medication in your eyes. If this occurs, rinse your eyes with large amounts of cool water.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day.

It may take about three weeks before any improvement is seen, and up to nine weeks for full benefit. If no improvement is seen after three weeks, consult your doctor.

SIDE EFFECTS: Stinging, burning, skin irritation, dryness, redness, metallic taste, nausea, or headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if you have this unlikely but serious side effect: tingling or numbness of the hands and feet.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using metronidazole, tell your doctor or pharmacist if you are allergic to it; or to other nitroimidazole antibiotics (e.g., tinidazole); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood disorders (blood dyscrasias).

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Breast-feeding while using this medication is not recommended. Consult with your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another condition unless told to do so by your doctor. A different medication may be necessary in those cases.

Avoid certain triggers that may worsen rosacea such as excessive sunlight, wind, hot beverages, spicy foods, alcohol, and extreme cold. Discuss with your doctor.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. If using the lotion, do not freeze. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.