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*Potency expressed as oxiconazole
R x Only
FOR TOPICAL DERMATOLOGIC USE ONLY—
NOT FOR OPHTHALMIC OR INTRAVAGINAL USE
DESCRIPTION
OXISTAT® (oxiconazole nitrate cream) Cream, 1% and OXISTAT® (oxiconazole nitrate lotion) Lotion, 1% 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 molecular formula C18H13ON3CI4·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.
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CLINICAL PHARMACOLOGY
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
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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:
| OXISTAT® Lotion | |
| Patient Outcome | b.i.d. | q.d. | Vehicle |
| 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 2 clinical trials at the 2-week post-treatment follow-up visit are shown in the following table:
| OXISTAT® Cream | |
| Patient Outcome | b.i.d. | q.d. | Vehicle |
| 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.
| OXISTAT® Cream | |
| Patient Outcome | q.d. | Vehicle |
| 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.
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