DERMAZOLE

(sertaconazole nitrate) cream, 2%, is for topical application.

It contains the azole 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

C 20 H 15 Cl 3 N 2 OS ● HNO 3, 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, and 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, glyceryl isostearate, glycolized saturated glycerides, light mineral oil, methylparaben, polyethylene glycol palmitostearate, polyoxyethylened saturated glycerides, purified water, and sorbic acid.

Sertaconzole nitrate chemical structure.

® cream, 2%, is indicated for the topical treatment of interdigital tinea pedis in immunocompetent adult and pediatric patients 12 years of age and older caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

ERTACZO cream, 2% is an azole antifungal indicated for the topical treatment of interdigital tinea pedis in immunocompetent adult and pediatric patients 12 years of age and older caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

Sertaconazole nitrate is an azole antifungal. 12.2 Pharmacokinetics In a multiple-dose pharmacokinetic trial that included 5 male subjects with interdigital tinea pedis (range of diseased area, 42 - 140 cm 2; mean, 93 cm 2 ), ERTACZO cream, 2%, was topically applied every 12 hours for a total of 13 doses to the diseased skin (0.5 g sertaconazole nitrate per 100 cm 2 ).

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. 12.3 Microbiology Mechanism of Action Sertaconazole, an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme.

This enzyme functions to convert lanosterol to ergosterol.

Ergosterol is a key component of fungal cell membranes and lack of this component leads to fungal cell injury by leakage of key constituents in the cytoplasm from the cell.

Activity In Vitro and in

Infections Sertaconazole nitrate has been shown to be active against isolates of the following microorganisms in clinical infections: Trichophyton rubrum Trichophyton mentagrophytes Epidermophyton floccosum.

Most common adverse reactions observed in clinical trials (incidence >2%) were contact dermatitis, dry skin, burning skin, application site skin tenderness.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, cutaneous adverse events occurred in of 297 (2%) subjects (2 of them severe) receiving ERTACZO cream, 2%, and in of 291 (2%) subjects (2 of them severe) receiving vehicle.

These reported cutaneous adverse events included contact dermatitis, dry skin, burning skin, and application site skin tenderness.

In a dermal sensitization trial, 8 of 202 evaluable subjects tested with ERTACZO cream, 2%, and of 202 evaluable subjects tested with vehicle exhibited a erythematous reaction in the challenge phase.

There was no evidence of cumulative irritation or contact sensitization in a repeated insult patch test involving 202 healthy volunteers. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ERTACZO cream, 2%.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cutaneous adverse events: erythema, pruritus, vesiculation, desquamation, and hyperpigmentation.

ERTACZO cream, 2% twice daily for 4 weeks.

Apply a sufficient amount of

ERTACZO cream, 2% to cover both the affected areas between the toes and the immediately surrounding healthy skin.

ERTACZO cream, 2% for the full treatment time recommended by the physician, even though symptoms may have improved.

Dry the affected area(s) thoroughly before application, if using ERTACZO cream, 2% after bathing.

Wash hands after use.

Avoid the use of occlusive dressings or wrappings.

For topical use.

Not for ophthalmic, oral, or intravaginal use.

ERTACZO cream, 2% to the affected and immediate surrounding area(s) twice daily for 4 weeks.

cream, 2%, is white in color and supplied in tubes in the following size: 60-gram tube NDC 73159-004-60 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) .

Risk Summary There are no available data on ERTACZO cream, 2% use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies, there were no adverse developmental effects observed with oral administration of sertaconazole nitrate to pregnant rats and rabbits during organogenesis at doses and 80 times, respectively, the maximum recommended human dose (MRHD) based on body surface area (BSA) comparison.

In rats, when maternal dosing was continued until weaning, a reduction in live birth indices and an increase in the number of still-born pups was observed at doses and 40 times the MRHD based on BSA comparison.

The background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of major birth defects, loss and other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Animal embryofetal development studies have not been conducted with ERTACZO cream, 2%.

Embryofetal development studies performed in pregnant rats and rabbits administered oral doses of sertaconzaole nitrate up to 160 mg/kg/day (40 times [rats] and 80 times [rabbits] the MRHD based on a BSA comparison) during the period of organogenesis revealed no malformations or embryofetal developmental toxicity.

In a pre.

• and postnatal development study, pregnant rats were administered oral doses of sertaconazole nitrate from pregnancy day to lactation day 20.

A reduction in live birth indices and an increase in the number of still-born pups were seen at doses and 40 times the MRHD based on BSA comparison.

The safety and effectiveness of

ERTACZO cream, 2%, have not been established in pediatric patients younger than 12 years of age.

Clinical trials of

ERTACZO cream, 2%, did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.