NORITATE™ (metronidazole cream) Cream, 1%, contains metronidazole, USP. Chemically, metronidazole is 2-methyl-5-nitro-1H-imidazole-1-ethanol.

The molecular formula for metronidazole is C₆H₉N₃O₃.

Metronidazole has a molecular weight of 171.16. It is a white to pale yellow crystalline powder. It is slightly soluble in alcohol and has a solubility in water of 10 mg/mL at 20°C. Metronidazole is a member of the imidazole class of anti-bacterial agents and is classified as an antiprotozoal and anti-bacterial agent.

NORITATE is an emollient cream; each gram contains 10 mg micronized metronidazole USP, in a base of purified water USP, stearic acid NF, glyceryl monostearate NF, glycerin USP, methylparaben NF, trolamine NF and propylparaben NF.

Last updated on RxList: 12/8/2004

NORITATE is indicated for the topical treatment of inflammatory lesions and erythema of rosacea.

Areas to be treated should be cleansed before application of NORITATE. Apply and rub in a thin film of NORITATE once daily to entire affected area(s). Patients may use cosmetics after application of NORITATE.

Cream - 30 gram aluminum tube NDC 0066-9850-30. Keep out of the reach of children.

Storage Conditions: Store at controlled room temperature: 20 to 25°C (68 to 77°F).

Manufactured by: PanGeo Quebec Pharma Inc. Montreal, Quebec, Canada Marketed by: Dermik Laboratories, Inc. Berwyn, PA 19312 USA Made in Canada

Last updated on RxList: 12/8/2004

Safety data from 302 patients who used NORITATE (n=200) or vehicle control (n=102) once daily in clinical trials and experienced an adverse event considered to be treatment-related include: application site reaction (NORITATE 1, vehicle 1), condition aggravated (NORITATE 1, vehicle 0), paresthesia (NORITATE 0, vehicle 1), acne (NORITATE 1, vehicle 0), dry skin (NORITATE 0, vehicle 2). The majority of adverse reactions were mild to moderate in severity.

Two patients treated with NORITATE once daily discontinued treatment because of adverse events: one for a severe flare of comedonal acne and one for rosacea aggravated.

Oral metronidazole has been reported to potentiate the anticoagulant effect of coumarin and warfarin resulting in a prolongation of prothrombin time. Drug interactions should be kept in mind when NORITATE is prescribed for patients who are receiving anticoagulant treatment, although they are less likely to occur with topical metronidazole administration because of low absorption. (See CLINICAL PHARMACOLOGY, Pharmacokinetics section)

Carcinogenesis, Mutagenesis and 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. In several long term studies in mice, oral doses of approximately 225 mg/m2/day or greater (approximately 37 times the human topical dose on a mg/m2 basis) were associated with an increase in pulmonary tumors and lymphomas. Several long term oral studies in the rat have shown statistically significant increases in mammary and hepatic tumors at doses >885 mg/m2/day (144 times the topical human dose).

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

In one published study, using albino hairless mice, intraperitoneal administration of metronidazole at a dose of 45 mg/m2/day (approximately 7 times the human topical dose on a mg/m2 basis) was associated with an increase in ultraviolet radiation-induced skin carcinogenesis. Neither dermal carcinogenicity nor photocarcinogenicity studies have been performed with NORITATE or any marketed metronidazole formulations.

Pregnancy: Teratogenic Effects: Pregnancy Category B. There are no adequate and well controlled studies with the use of NORITATE in pregnant women. Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. No fetotoxicity was observed after oral administration of metronidazole to rats or mice at 200 and 20 times, respectively, the expected clinical dose. However, oral metronidazole has shown carcinogenic activity in rodents. Because animal reproduction studies are not always predictive of human response, NORITATE 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 taken after topical metronidazole application are significantly lower than those achieved after oral 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 and the risk to the infant.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Last updated on RxList: 12/8/2004

No information available at present.

General: If a reaction suggesting local skin irritation occurs, patients should be directed to discontinue use of the medication. Conjunctivitis associated with topical use of metronidazole on the face has been reported. Contact with the eyes should be avoided. Metronidazole is a nitroimidazole and should be used with care in patients with evidence of, or history of, blood dyscrasia.

Information for Patients: Patients using NORITATE should receive the following information and instructions:

1. This medication is to be used as directed. 2. It is for external use only.

3. Avoid contact with the eyes.

4. Cleanse affected area(s) before applying NORITATE.

5. This medication should not be used for any disorder other than that for which it is prescribed.

6. Patients should report any adverse reaction to their physician.

Last updated on RxList: 12/8/2004

No specific information available.

NORITATE is contraindicated in those patients with a history of hypersensitivity to metronidazole or to any other ingredient in this formulation.

Last updated on RxList: 12/8/2004

Pharmacokinetics: When one gram dose of NORITATE cream, 1%, was applied in a single application to the face of 16 healthy volunteers, low concentrations of metronidazole were detected in the plasma of 7 of the volunteers. The mean ± SD Cmax of metronidazole was 27.6 ± 7.3 ng/mL, which is about 1% of the value reported for a single 250 mg oral dose of metronidazole. The time to maximum plasma concentration (T_max) in the volunteers with detectable metronidazole was 8-12 hours after topical application.

Pharmacodynamics: The mechanisms by which metronidazole acts in reducing inflammatory lesions of rosacea are unknown. Clinical Studies: Safety and efficacy of NORITATE were evaluated in two randomized vehicle-controlled clinical studies for the treatment of rosacea, which excluded patients who had nodules, moderate or severe rhinophyma, dense telangiectases, plaque-like facial edema or ocular involvement and those who had a history of not responding to metronidazole therapy for rosacea. Of the patients included in the efficacy database (n=416), there were 142 men and 274 women. Endpoint efficacy data comparisons for patients treated with daily NORITATE or vehicle applications are listed below.

*Statistically significant differences between NORITATE and vehicle groups with p≤0.05. Erythema scores: 0=none, 1=mild, 2=moderate and 3=severe.

Safety Studies: Studies of contact sensitization (n=258), phototoxicity (n=21), and photocontact sensitization (n=29) of NORITATE were conducted. No evidence of sensitization or phototoxicity was seen in these studies.

Last updated on RxList: 12/8/2004

No separate information available at present.

However, please refer to WARNINGS and PRECAUTIONS.

Last updated on RxList: 12/8/2004

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.