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.
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):
The following in vitro data are available; however, their
clinical s ignificance 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:
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.
- 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
THERE ARE NO HEAD-TO-HEAD COMPARISON TRIALS OF THE
OXISTAT CREAM AND LOTION FORMULATIONS IN THE TREATMENT OF TINEA PEDIS.
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.
Seventyseven 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
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.
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:
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
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 eczemalike 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 q.d.
Only once a day was shown in both studies to be
statistically superior to vehicle for all efficacy parameters at 2 weeks and