ERTACZO(sertaconazole nitrate) Cream, 2%

Pharmacokinetics: In a multiple dose pharmacokinetic study that included 5 male patients with interdigital tinea pedis (range of diseased area, 42 - 140 cm²; mean, 93 cm²), ERTACZO^® Cream, 2%, was topically applied every 12 hours for a total of 13 doses to the diseased skin (0.5 grams sertaconazole nitrate per 100 cm² ). Sertaconazole concentrations in plasma measured by serial blood sampling for 72 hours after the thirteenth dose were below the limit of quantitation (2.5 ng/mL) of the analytical method used.

Microbiology: Sertaconazole is an antifungal that belongs to the imidazole class of antifungals. While the exact mechanism of action of this class of antifungals is not known, it is believed that they act primarily by inhibiting the cytochrome P450-dependent synthesis of ergosterol. Ergosterol is a key component of the cell membrane of fungi, and lack of this component leads to fungal cell injury primarily by leakage of key constituents in the cytoplasm from the cell.

ActivityIn Vivo: Sertaconazole nitrate has been shown to be active against isolates of the following microorganisms in clinical infections as described in the INDICATIONS AND USAGE section:

   Trichophyton rubrum

   Trichophyton mentagrophytes

   Epidermophyton floccosum

General: ERTACZO^® Cream, 2%, is for use on the skin only. If irritation or sensitivity develops with the use of ERTACZO^® Cream, 2%, treatment should be discontinued and appropriate therapy instituted.

Diagnosis of the disease should be confirmed either by direct microscopic examination of infected superficial epidermal tissue in a solution of potassium hydroxide or by culture on an appropriate medium.

Physicians should exercise caution when prescribing ERTACZO^® Cream, 2%, to patients known to be sensitive to imidazole antifungals, since cross-reactivity may occur.

Information for Patients: The patient should be instructed to:

1. Use ERTACZO^® Cream, 2%, 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. ERTACZO^® Cream, 2%, is for external use only.
2. Dry the affected area(s) thoroughly before application, if you wish to use ERTACZO^® Cream, 2%, after bathing.
3. 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 the end of the prescribed treatment period, or sooner, if the condition worsens.
4. Inform the physician if the area of application shows signs of increased irritation, redness, itching, burning, blistering, swelling or oozing.
5. Avoid the use of occlusive dressings unless otherwise directed by the physician.
6. Do not use this medication for any disorder other than that for which it was prescribed.

Drug/Laboratory Test Interactions: Potential interactions between ERTACZO^® Cream, 2%, and other drugs or laboratory tests have not been systematically evaluated.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies to evaluate the carcinogenic potential of sertaconazole nitrate have not been conducted. No clastogenic potential was observed in a mouse micronucleus test. Sertaconazole nitrate was considered negative for sister chromatid exchange (SCE) in the in vivo mouse bone marrow SCE assay. There was no evidence that sertaconazole nitrate induced unscheduled DNA synthesis in rat primary hepatocyte cultures. Sertaconazole nitrate exhibited no toxicity or adverse effects on reproductive performance or fertility of male or female rats given up to 60 mg/kg/day orally by gastric intubation (16 times the maximum recommended human dose based on a body surface area comparison).

Pregnancy: Teratogenic Effects. Pregnancy Category C: Oral reproduction studies in rats and rabbits did not produce any evidence of maternal toxicity, embryotoxicity or teratogenicity of sertaconazole nitrate at an oral dose of 160 mg/kg/day (40 times (rats) and 80 times (rabbits) the maximum recommended human dose on a body surface area comparison). In an oral peri-postnatal study in rats, a reduction in live birth indices and an increase in the number of still-born pups was seen at 80 and 160 mg/kg/day.

There are no adequate and well-controlled studies that have been conducted on topically applied ERTACZO^® Cream, 2%, in pregnant women. Because animal reproduction studies are not always predictive of human response, ERTACZO^® Cream, 2%, should be used during pregnancy only if clearly needed.

Nursing Mothers: It is not known if sertaconazole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when prescribing ERTACZO^® Cream, 2%, to a nursing woman.

Pediatric Use: The efficacy and safety of ERTACZO^® Cream, 2%, have not been established in pediatric patients below the age of 12 years.

Geriatric Use: Clinical studies of ERTACZO^® Cream, 2%, did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.