OXISTAT Cream and Lotion formulations contain the antifungal active compound oxiconazole nitrate. Both formulations are for topical dermatologic use only.

Chemically, oxiconazole nitrate is 2',4'-dichloro-2-imidazol-1-ylacetophenone (Z)-[0-(2,4-dichlorobenzyl)oxime], mononitrate. The compound has the empirical formula C₁₈H₁₃ON₃Cl₄•HNO₃, a molecular weight of 492.15, and the following structural formula:

Oxiconazole nitrate is a nearly white crystalline powder, soluble in methanol; sparingly soluble in ethanol, chloroform, and acetone; and very slightly soluble in water.

OXISTAT Cream contains 10 mg of oxiconazole per gram of cream in a white to off-white, opaque cream base of purified water USP, white petrolatum USP, stearyl alcohol NF, propylene glycol USP, polysorbate 60 NF, cetyl alcohol NF, and benzoic acid USP 0.2% as a preservative.

OXISTAT Lotion contains 10 mg of oxiconazole per gram of lotion in a white to off-white, opaque lotion base of purified water USP, white petrolatum USP, stearyl alcohol NF, propylene glycol USP, polysorbate 60 NF, cetyl alcohol NF, and benzoic acid USP 0.2% as a preservative.

Last updated on RxList: 5/5/2008

OXISTAT Cream and Lotion are indicated for the topical treatment of the following dermal infections: tinea pedis, tinea cruris, and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum. OXISTAT Cream is indicated for the topical treatment of tinea (pityriasis) versicolor due to Malassezia furfur (see DOSAGE AND ADMINISTRATION and Clinical Studies).

OXISTAT Cream may be used in pediatric patients for tinea corporis, tinea cruris, tinea pedis, and tinea (pityriasis) versicolor; however, these indications for which OXISTAT Cream has been shown to be effective rarely occur in children below the age of 12.

OXISTAT Cream or Lotion should be applied to affected and immediately surrounding areas once to twice daily in patients with tinea pedis, tinea corporis, or tinea cruris. OXISTAT Cream should be applied once daily in the treatment of tinea (pityriasis) versicolor. Tinea corporis, tinea cruris, and tinea (pityriasis) versicolor should be treated for 2 weeks and tinea pedis for 1 month to reduce the possibility of recurrence. If a patient shows no clinical improvement after the treatment period, the diagnosis should be reviewed.

Note: Tinea (pityriasis) versicolor may give rise to hyperpigmented or hypopigmented patches on the trunk that may extend to the neck, arms, and upper thighs. Treatment of the infection may not immediately result in restoration of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental sun exposure. Although tinea (pityriasis) versicolor is not contagious, it may recur because the organism that causes the disease is part of the normal skin flora.

OXISTAT Cream, 1% is supplied in 15-g tubes (NDC 0173-0423-00), 30-g tubes (NDC 0173-0423-01), and 60-g tubes (NDC 0173-0423-04). Store between 15° and 30°C (59° and 86°F).

OXISTAT Lotion, 1% is supplied in a 30-mL bottle (NDC 0173-0448-01). Store between 15° and 30°C (59° and 86°F). Shake well before using.

GlaxoSmithKline Consumer Healthcare LP Pittsburgh, PA 15230. January 23, 2004. FDA revision date: 1/23/2004

Last updated on RxList: 5/5/2008

During clinical trials, of 955 patients treated with oxiconazole nitrate cream, 1%, 41 (4.3%) reported adverse reactions thought to be related to drug therapy. These reactions included pruritus (1.6%); burning (1.4%); irritation and allergic contact dermatitis (0.4% each); folliculitis (0.3%); erythema (0.2%); and papules, fissure, maceration, rash, stinging, and nodules (0.1% each).

In a controlled, multicenter clinical trial of 269 patients treated with oxiconazole nitrate lotion, 1%, 7 (2.6%) reported adverse reactions thought to be related to drug therapy. These reactions included burning and stinging (0.7% each) and pruritus, scaling, tingling, pain, and dyshidrotic eczema (0.4% each).

Potential drug interactions between OXISTAT and other drugs have not been systematically evaluated.

Last updated on RxList: 5/5/2008

OXISTAT Cream and Lotion are not for ophthalmic or intravaginal use.

General: OXISTAT Cream and Lotion are for external dermal use only. Avoid introduction of OXISTAT Cream or Lotion into the eyes or vagina. If a reaction suggesting sensitivity or chemical irritation should occur with the use of OXISTAT Cream or Lotion, treatment should be discontinued and appropriate therapy instituted. If signs of epidermal irritation should occur, the drug should be discontinued.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Although no long-term studies in animals have been performed to evaluate carcinogenic potential, no evidence of mutagenic effect was found in 2 mutation assays (Ames test and Chinese hamster V79 in vitro cell mutation assay) or in 2 cytogenetic assays (human peripheral blood lymphocyte in vitro chromosome aberration assay and in vivo micronucleus assay in mice).

Reproductive studies revealed no impairment of fertility in rats at oral doses of 3 mg/kg/day in females (1 times the human dose based on mg/m²) and 15 mg/kg/day in males (4 times the human dose based on mg/m²). However, at doses above this level, the following effects were observed: a reduction in the fertility parameters of males and females, a reduction in the number of sperm in vaginal smears, extended estrous cycle, and a decrease in mating frequency.

Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rabbits, rats, and mice at oral doses up to 100, 150, and 200 mg/kg/day (57, 40, and 27 times the human dose based on mg/m²), respectively, and revealed no evidence of harm to the fetus due to oxiconazole nitrate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers: Because oxiconazole is excreted in human milk, caution should be exercised when the drug is administered to a nursing woman.

Pediatric Use: OXISTAT Cream may be used in pediatric patients for tinea corporis, tinea cruris, tinea pedis, and tinea (pityriasis) versicolor; however, these indications for which OXISTAT Cream has been shown to be effective rarely occur in children below the age of 12.

Geriatric Use: A limited number of patients at or above 60 years of age (n ˜ 396) have been treated with OXISTAT Cream in US and non-US clinical trials, and a limited number (n = 43) have been treated with OXISTAT Lotion in US clinical trials. The number of patients is too small to permit separate analyses of efficacy and safety. No adverse events were reported with OXISTAT Lotion in geriatric patients, and the adverse reactions reported with OXISTAT Cream in this population were similar to those reported by younger patients. Based on available data, no adjustment of dosage of OXISTAT Cream and Lotion in geriatric patients is warranted.

Last updated on RxList: 5/5/2008

When 5% oxiconazole cream (5 times the concentration of the marketed product) was applied at a rate of 1 g/kg to approximately 10% of body surface area of a group of 40 male and female rats for 35 days, 3 deaths and severe dermal inflammation were reported. No overdoses in humans have been reported with use of oxiconazole nitrate cream or lotion.

OXISTAT Cream and Lotion are contraindicated in individuals who have shown hypersensitivity to any of their components.

Last updated on RxList: 5/5/2008

Pharmacokinetics: The penetration of oxiconazole nitrate into different layers of the skin was assessed using an in vitro permeation technique with human skin. Five hours after application of 2.5 mg/cm² of oxiconazole nitrate cream onto human skin, the concentration of oxiconazole nitrate was demonstrated to be 16.2 μmol in the epidermis, 3.64 μmol in the upper corium, and 1.29 μmol in the deeper corium. Systemic absorption of oxiconazole nitrate is low. Using radiolabeled drug, less than 0.3% of the applied dose of oxiconazole nitrate was recovered in the urine of volunteer subjects up to 5 days after application of the cream formulation.

Neither in vitro nor in vivo studies have been conducted to establish relative activity between the lotion and cream formulations.

Microbiology: Oxiconazole nitrate is an imidazole derivative whose antifungal activity is derived primarily from the inhibition of ergosterol biosynthesis, which is critical for cellular membrane integrity. It has in vitro activity against a wide range of pathogenic fungi.

Oxiconazole has been shown to be active against most strains of the following organisms both in vitro and in clinical infections at indicated body sites (see INDICATIONS AND USAGE):

Epidermophyton floccosum
Trichophyton mentagrophytes
Trichophyton rubrum
Malassezia furfur

The following in vitro data are available; however, their clinical significance is unknown. Oxiconazole exhibits satisfactory in vitro minimum inhibitory concentrations (MICs) against most strains of the following organisms; however, the safety and efficacy of oxiconazole in treating clinical infections due to these organisms have not been established in adequate and well-controlled clinical trials:

Candida albicans
Microsporum audouini
Microsporum canis
Microsporum gypseum
Trichophyton tonsurans
Trichophyton violaceum

Clinical Studies

The following definitions were applied to the clinical and microbiological outcomes in patients enrolled in the clinical trials that form the basis for the approvals of OXISTAT Lotion and OXISTAT Cream.

Definitions

Mycological Cure: No evidence (culture and KOH preparation) of the baseline (original) pathogen in a specimen from the affected area taken at the 2-week post-treatment visit (for tinea [pityriasis] versicolor, mycological cure was limited to KOH only).

Treatment Success: Both a global evaluation of ≥ 90% clinical improvement and a microbiologic eradication (see above) at the 2-week post-treatment visit.

Tinea Pedis: THERE ARE NO HEAD-TO-HEAD COMPARISON TRIALS OF THE OXISTAT CREAM AND LOTION FORMULATIONS IN THE TREATMENT OF TINEA PEDIS.

Lotion Formulation: The clinical trial for the lotion formulation line extension involved 332 evaluable patients with clinically and microbiologically established tinea pedis. Of these evaluable patients, 64% were diagnosed with hyperkeratotic plantar tinea pedis and 28% with interdigital tinea pedis. Seventy-seven percent (77%) had disease secondary to infection with Trichophyton rubrum, 18% had disease secondary to infection with Trichophyton mentagrophytes, and 4% had disease secondary to infection with Epidermophyton floccosum.

The results of this clinical trial at the 2-week post-treatment follow-up visit are shown in the following table:

Patient Outcome	OXISTAT Lotion		Vehicle
	b.i.d.	q.d.
Mycological cure	67%	64%	28%
Treatment success	41%	34%	10%

In this study, the improvement and cure rates of the b.i.d.- and q.d.-treated groups did not differ significantly (95% confidence interval) from each other but were statistically (95% confidence interval) superior to the vehicle-treated group.

Cream Formulation: The two pivotal trials for the cream formulation involved 281 evaluable patients (total from both trials) with clinically and microbiologically established tinea pedis.

The combined results of these two clinical trials at the 2-week post-treatment follow-up visit are shown in the following table:

Patient Outcome	OXISTAT Cream		Vehicle
	b.i.d.	q.d.
Mycological cure	77%	79%	33%
Treatment success	52%	43%	14%

All the improvement and cure rates of the b.i.d.- and q.d.-treated groups did not differ significantly (95% confidence interval) from each other but were statistically (95% confidence interval) superior to the vehicle-treated group.

In addition, pediatric data (95 children ages 10 and under) available with the cream formulation indicate that it is safe and effective for use in children when used as directed. Adverse events were reported in 2 children; 1 child was reported to have reddening of the skin and 1 child was reported to have eczema-like skin alterations.

Tinea (pityriasis) Versicolor: Two pivotal clinical trials of OXISTAT Cream in tinea (pityriasis) versicolor involved 219 evaluable patients in the q day OXISTAT and vehicle arms of the trial with clinical and mycological evidence of tinea (pityriasis) versicolor. Patients were treated for 2 weeks with OXISTAT Cream once daily, or with cream vehicle. The combined results of these clinical trials at the 2-week post-treatment follow-up visit are shown in the following table. These results are based on 207 patients (110 in the OXISTAT group and 97 in the vehicle group) with efficacy evaluations at this visit.

Patient Outcome	OXISTAT Cream	Vehicle
	q.d.
Mycological cure	88%	67%
Treatment success	83%	62%

Only once a day was shown in both studies to be statistically superior to vehicle for all efficacy parameters at 2 weeks and follow-up.

Last updated on RxList: 5/5/2008

The patient should be instructed to:

1. Use OXISTAT as directed by the physician. The hands should be washed after applying the medication to the affected area(s). Avoid contact with the eyes, nose, mouth, and other mucous membranes. OXISTAT is for external use only.
2. Use the medication for the full treatment time recommended by the physician, even though symptoms may have improved. Notify the physician if there is no improvement after 2 to 4 weeks, or sooner if the condition worsens (see below).
3. Inform the physician if the area of application shows signs of increased irritation, itching, burning, blistering, swelling, or oozing.
4. Avoid the use of occlusive dressings unless otherwise directed by the physician.
5. Do not use this medication for any disorder other than that for which it was prescribed.

Last updated on RxList: 5/5/2008

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.

OXICONAZOLE NITRATE - TOPICAL

(ox-ee-CON-uh-zole NYE-trate)

COMMON BRAND NAME(S): Oxistat

USES: Oxiconazole is used to treat skin infections such as athlete's foot, jock itch and ringworm. This medication is also used to treat a skin condition known as pityriasis (tinea versicolor), a fungal infection that causes a lightening or darkening of the skin of the neck, chest, arms, or legs. Oxiconazole is an azole antifungal that works by preventing the growth of fungus.

HOW TO USE: Use this medication on the skin only. Clean and thoroughly dry the area to be treated. Apply this medication to the affected skin, usually once or twice a day or as directed by your doctor. Dosage and length of treatment depends on the type of infection being treated. Do not apply this more often than prescribed. Your condition will not clear faster, but side effects may be increased.

Apply enough cream or lotion to cover the affected area and some of the surrounding skin. If using the lotion, shake the bottle well just before applying. Use cotton balls or a soft cloth to apply the lotion. After applying this medication, wash your hands. Do not wrap, cover or bandage the area unless directed to do so by your doctor.

Do not apply this medication in the eyes, nose, mouth, or vagina.

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

Continue to use this medication until the full prescribed amount is finished, even if symptoms disappear after starting oxiconazole. Stopping the medication too early may allow the fungus to continue to grow, which may result in a relapse of the infection.

Inform your doctor if your condition persists after 2-4 weeks of treatment or worsens at any time.

SIDE EFFECTS: Burning, stinging, swelling, irritation, redness, pimple-like bumps, tenderness, or flaking of the treated skin 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 any of these unlikely but serious side effects occur: blistering, oozing, open sores.

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 oxiconazole, tell your doctor or pharmacist if you are allergic to it; or to other azole antifungals such as clotrimazole, ketoconazole, or miconazole; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history.

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

This medication passes into breast milk. Therefore, breast-feeding is not recommended while using this drug. Consult 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.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If swallowing 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.

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 infection unless told to do so by your doctor. A different medication may be necessary in those cases.

When treating pityriasis, this medication may not cause an immediate return to normal skin color. It may take several months after treatment is completed for your natural skin color to return.

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 59-86 degrees F (15-30 degrees C) away from heat and light. 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.