Oxistat

Oxiconazole comes in a cream or lotion to be applied to your skin. Oxiconazole usually is applied once a day (in the evening) or twice a day (in the morning and evening). Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use oxiconazole exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.

Thoroughly clean the infected area, allow it to dry, and then gently rub the medication in until most of it disappears. Use just enough medication to cover the affected area. You should wash your hands after applying the medication.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

OXISTAT (oxiconazole) 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.

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 (oxiconazole) Lotion and OXISTAT (oxiconazole) 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 (oxiconazole) 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:

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:

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 (oxiconazole) Cream in tinea (pityriasis) versicolor involved 219 evaluable patients in the q day OXISTAT (oxiconazole) and vehicle arms of the trial with clinical and mycological evidence of tinea (pityriasis) versicolor. Patients were treated for 2 weeks with OXISTAT (oxiconazole) 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 (oxiconazole) group and 97 in the vehicle group) with efficacy evaluations at this visit.

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.

Oxistat is a prescription medication used to treat fungal skin infections such as ringworm, jock itch, and athlete's foot.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

An overdose of oxiconazole topical is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medication.

Administration

Topical Administration

Apply topically to the skin as a 1% cream or lotion.1

Do not apply to the eye1 or administer intravaginally.1 32 33

Avoid contact with the nose, mouth, and other mucous membranes.1

Do not use with occlusive dressings or wrappings, unless otherwise directed by clinician.1

Shake lotion well before using.1

Apply a sufficient amount of cream or lotion; rub gently into affected area and immediately surrounding healthy skin.1

Dosage

Available as oxiconazole nitrate; dosage expressed in terms of oxiconazole.1

Pediatric Patients

Apply 1% cream once or twice daily for 2 weeks.1

If clinical improvement does not occur after treatment, reevaluate diagnosis.1

Apply 1% cream once or twice daily for 1 month.1

If clinical improvement does not occur after treatment, reevaluate diagnosis.1

Apply 1% cream once daily for 2 weeks.1

If clinical improvement does not occur after treatment, reevaluate diagnosis.1

Normalization of hyper- or hypopigmented patches on trunk, neck, arms, and upper thighs is variable and may take months.1

Adults

Apply 1% cream or lotion once or twice daily for 2 weeks.1

If clinical improvement does not occur after treatment, reevaluate diagnosis.1

Apply 1% cream or lotion once or twice daily for 1 month.1

If clinical improvement does not occur after treatment, reevaluate diagnosis.1

Apply 1% cream once daily for 2 weeks.1

If clinical improvement does not occur after treatment, reevaluate diagnosis.1

Normalization of hyper- or hypopigmented patches on trunk, neck, arms, and upper thighs is variable and may take months.1

Special Populations

No special population dosage recommendations at this time.1

Contraindications

Known hypersensitivity to oxiconazole or any ingredient in the formulation.1

Warnings/Precautions

Warnings

For external use only.1 Use only for topical application to the skin; not for ophthalmic1 or intravaginal use.1 32 33

Sensitivity Reactions

Contact dermatitis reported following topical application of oxiconazole or other imidazole-derivative azole antifungals.1 21 22 47

If irritation or sensitivity occurs, discontinue the drug and initiate appropriate therapy.1

Possible cross-sensitization among the imidazoles.21 22 44 45 46 47 48

Specific Populations

Category B.1

Distributed into milk; caution if used in nursing women.1 32

Cream may be used in pediatric patients; has been used in children ≤10 years of age without unusual adverse effect.1

Safety and efficacy of lotion not established in children.1

Insufficient experience in patients ≥65 years of age to determine whether safety and efficacy differ from that in younger adults.1

Available data to date indicate no difference in safety compared with younger adults; dosage adjustment not recommended.1

Common Adverse Effects

Pruritus, burning, irritation, stinging.1

No formal drug interaction studies to date.1

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).