Ertaczo (Sertaconazole Nitrate Topical) - Description and Clinical Pharmacology

For Topical Dermatologic Use Only - Not for Oral, Ophthalmic or Intravaginal Use

DESCRIPTION

ERTACZO^® (sertaconazole nitrate) Cream, 2%, contains the imidazole antifungal, sertaconazole nitrate. Sertaconazole nitrate contains one asymmetric carbon atom and exists as a racemic mixture of equal amounts of R and S enantiomers.

Sertaconazole nitrate is designated chemically as (±)-1-[2,4-dichloro-β-[(7-chlorobenzo-[ b ]thien-3-yl)methoxy]phenethyl]imidazole nitrate. It has a molecular weight of 500.8. The molecular formula is C₂₀H₁₅Cl₃N₂OS • HNO₃, and the structural formula is as follows:

Sertaconazole nitrate is a white or almost white powder. It is practically insoluble in water, soluble in methanol, sparingly soluble in alcohol and in methylene chloride. Each gram of ERTACZO^® Cream, 2%, contains 17.5 mg of sertaconazole (as sertaconazole nitrate, 20 mg) in a white cream base of ethylene glycol and polyethylene glycol palmitostearate, glyceryl isostearate, light mineral oil, methylparaben, polyoxyethylened saturated glycerides and glycolized saturated glycerides, sorbic acid and purified water.

CLINICAL PHARMACOLOGY

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.

Activity In 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

CLINICAL STUDIES

In two randomized, double-blind, clinical trials, patients 12 years and older with interdigital tinea pedis applied either ERTACZO^® Cream, 2%, or vehicle, twice daily for four weeks. Patients with moccasin-type (plantar) tinea pedis and/or onychomycosis were excluded from the study. Two weeks after completion of therapy (six weeks after beginning therapy), patients were evaluated for signs and symptoms related to interdigital tinea pedis.

Treatment outcomes are summarized in the table below.

Treatment Outcomes as Percent (%) of Total Subjects

* Complete Cure - Patients who had complete clearing of signs and symptoms and Mycological Cure.
** Effective Treatment - Patients who had minimal residual signs and symptoms of interdigital tinea pedis and Mycological Cure.
*** Mycological Cure - Patients who had both negative microscopic KOH preparation and a negative fungal culture.
	Study 1		Study 2
	Sertaconazole	Vehicle	Sertaconazole	Vehicle
Complete Cure* (Primary Efficacy Variable)	13/99 (13.1%)	3/92 (3.3%)	28/103 (27.2%)	5/103 (4.9%)
Effective Treatment**	32/99 (32.3%)	11/92 (12.0%)	52/103 (50.5%)	16/103 (15.5%)
Mycological Cure***	49/99 (49.5%)	18/92 (19.6%)	71/103 (68.9%)	20/103 (19.4%)

In clinical trials, complete cure in sertaconazole treated patients was achieved in 32 of 160 (20%) patients with Trichophyton rubrum, in 7 of 28 (25%) patients with Trichophyton mentagrophytes and in 2 of 13 (15%) patients with Epidermophyton floccosum.