DESCRIPTION SECTION.

11 DESCRIPTION ERTACZO (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 racemic mixture of equal amounts of and enantiomers.Sertaconazole nitrate is designated chemically as (+-)-1-[2,4-dichloro--[(7-chlorobenzo-[b]thien-3-yl)methoxy]phenethyl]imidazole nitrate. It has molecular weight of 500.8. The molecular formula is C20H15Cl3N2OS HNO3, and the structural formula is as follows:Sertaconazole nitrate is 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 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.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION oApply ERTACZO cream, 2% twice daily for weeks. Apply sufficient amount of ERTACZO cream, 2% to cover both the affected areas between the toes and the immediately surrounding healthy skin.oUse ERTACZO cream, 2% for the full treatment time recommended by the physician, even though symptoms may have improved.oDry the affected area(s) thoroughly before application, if using ERTACZO cream, 2% after bathing.oWash hands after use.oAvoid the use of occlusive dressings or wrappings.oFor topical use. oNot for ophthalmic, oral, or intravaginal use.. oApply ERTACZO cream, 2% twice daily for weeks. Apply sufficient amount of ERTACZO cream, 2% to cover both the affected areas between the toes and the immediately surrounding healthy skin.. oUse ERTACZO cream, 2% for the full treatment time recommended by the physician, even though symptoms may have improved.. oDry the affected area(s) thoroughly before application, if using ERTACZO cream, 2% after bathing.. oWash hands after use.. oAvoid the use of occlusive dressings or wrappings.. oFor topical use. oNot for ophthalmic, oral, or intravaginal use.. oApply ERTACZO cream, 2% to the affected and immediate surrounding area(s) twice daily for weeks. (2)oNot for ophthalmic, oral, or intravaginal use. (2). oApply ERTACZO cream, 2% to the affected and immediate surrounding area(s) twice daily for weeks. (2). oNot for ophthalmic, oral, or intravaginal use. (2).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS Most common adverse reactions observed in clinical trials (incidence >2%) were contact dermatitis, dry skin, burning skin, application site skin tenderness. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.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 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 dermal sensitization trial, of 202 evaluable subjects tested with ERTACZO cream, 2%, and of 202 evaluable subjects tested with vehicle exhibited erythematous reaction in the challenge phase. There was no evidence of cumulative irritation or contact sensitization in 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 population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Cutaneous adverse events: erythema, pruritus, vesiculation, desquamation, and hyperpigmentation.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In 2-year rat dermal carcinogenicity study, topical administration of sertaconazole nitrate cream did not increase the number of neoplastic lesions compared to control animals, at sertaconazole nitrate doses of up to 800 mg/kg/day (200 times the MRHD based on BSA comparison).No clastogenic potential was observed in mouse micronucleus test. Sertaconazole nitrate was nonclastogenic in the in vivo mouse sister chromatid exchange assay. There was no evidence that sertaconazole nitrate induced unscheduled DNA synthesis in primary rat hepatocyte cultures.Rats treated orally with up to 160 mg/kg/day of sertaconazole nitrate (40 times the MRHD based on BSA comparison), exhibited no toxicity or adverse effects on reproductive performance or fertility in male or female rats.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sertaconazole nitrate is an azole antifungal [see Clinical Pharmacology (12.4)].. 12.3 Pharmacokinetics In multiple-dose pharmacokinetic trial that included male subjects with interdigital tinea pedis (range of diseased area, 42 140 cm2; mean, 93 cm2), ERTACZO cream, 2%, was topically applied every 12 hours for total of 13 doses to the diseased skin (0.5 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.. 12.4 Microbiology Mechanism of ActionSertaconazole, 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 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 Clinical InfectionsSertaconazole nitrate has been shown to be active against isolates of the following microorganisms in clinical infections [see Indications and Usage (1)]: Trichophyton rubrum Trichophyton mentagrophytes Epidermophyton floccosum. Trichophyton rubrum. Trichophyton mentagrophytes. Epidermophyton floccosum.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES In two randomized, double-blind clinical trials, subjects 12 years and older with interdigital tinea pedis applied either ERTACZO cream, 2%, or vehicle, twice daily for weeks. Subjects with moccasin-type (plantar) tinea pedis and/or onychomycosis were excluded from the trial. Two weeks after completion of therapy (6 weeks after beginning therapy), subjects 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 with Interdigital Tinea PedisTrial 1Trial 2SertaconazoleVehicleSertaconazoleVehicleComplete Cure (PrimaryEfficacy Variable)13/99 (13.1%)3/92 (3.3%)28/103 (27.2%)5/103 (4.9%)Effective Treatment32/99 (32.3%)11/92 (12.0%)52/103 (50.5%)16/103 (15.5%)Mycological Cure49/99 (49.5%)18/92 (19.6%)71/103 (68.9%)20/103 (19.4%) 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 negative fungal culture. In clinical trials, complete cure in ERTACZO cream, 2%-treated subjects was achieved in 32 of 160 (20%) subjects with Trichophyton rubrum, in of 28 (25%) subjects with Trichophyton mentagrophytes, and in of 13 (15%) subjects with Epidermophyton floccosum.. 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 negative fungal culture. In clinical trials, complete cure in ERTACZO cream, 2%-treated subjects was achieved in 32 of 160 (20%) subjects with Trichophyton rubrum, in of 28 (25%) subjects with Trichophyton mentagrophytes, and in of 13 (15%) subjects with Epidermophyton floccosum.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).Instruct the patient of the following:Administration InstructionsoERTACZO cream, 2% is for topical use only. oAvoid contact with the eyes, mouth, vagina, and other mucous membranes.oDry the affected area(s) thoroughly before application, if using ERTACZO cream, 2% after bathing.oWash hands after use. oUse the medication for the full treatment time recommended by the physician, even though symptoms may have improved.oAvoid the use of occlusive dressings unless otherwise directed by the physician [see Dosage and Administration (2)]. Local Adverse ReactionsoInform the physician if the area of application shows signs of increased irritation, redness, itching, burning, blistering, swelling, or oozing [see Warnings and Precautions (5.1)].Distributed by:Bausch Health US, LLCBridgewater, NJ 08807 USAManufactured by:DPT Laboratories, Ltd.San Antonio, TX 78215ERTACZO is trademark of Bausch Health Companies Inc. or its affiliates.(C) 2020 Bausch Health Companies Inc. or its affiliates 9378102. oERTACZO cream, 2% is for topical use only. oAvoid contact with the eyes, mouth, vagina, and other mucous membranes.. oDry the affected area(s) thoroughly before application, if using ERTACZO cream, 2% after bathing.. oWash hands after use. oUse the medication for the full treatment time recommended by the physician, even though symptoms may have improved.. oAvoid the use of occlusive dressings unless otherwise directed by the physician [see Dosage and Administration (2)]. oInform the physician if the area of application shows signs of increased irritation, redness, itching, burning, blistering, swelling, or oozing [see Warnings and Precautions (5.1)].

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In 2-year rat dermal carcinogenicity study, topical administration of sertaconazole nitrate cream did not increase the number of neoplastic lesions compared to control animals, at sertaconazole nitrate doses of up to 800 mg/kg/day (200 times the MRHD based on BSA comparison).No clastogenic potential was observed in mouse micronucleus test. Sertaconazole nitrate was nonclastogenic in the in vivo mouse sister chromatid exchange assay. There was no evidence that sertaconazole nitrate induced unscheduled DNA synthesis in primary rat hepatocyte cultures.Rats treated orally with up to 160 mg/kg/day of sertaconazole nitrate (40 times the MRHD based on BSA comparison), exhibited no toxicity or adverse effects on reproductive performance or fertility in male or female rats.

PREGNANCY SECTION.

8.1 Pregnancy Risk SummaryThere are no available data on ERTACZO cream, 2% use in pregnant women to evaluate for 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 40 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, reduction in live birth indices and an increase in the number of still-born pups was observed at doses 20 and 40 times the MRHD based on BSA comparison (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have 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.DataAnimal DataAnimal 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 BSA comparison) during the period of organogenesis revealed no malformations or embryofetal developmental toxicity. In pre- and postnatal development study, pregnant rats were administered oral doses of sertaconazole nitrate from pregnancy day to lactation day 20. reduction in live birth indices and an increase in the number of still-born pups were seen at doses 20 and 40 times the MRHD based on BSA comparison.

SPL PATIENT PACKAGE INSERT SECTION.

Patient Package Insert PATIENT INFORMATIONERTACZO(R) (er-tack-zo)(sertaconazole nitrate) creamImportant information: ERTACZO cream is for use on skin only. Do not use ERTACZO cream in your eyes, mouth, or vagina.What is ERTACZO creamERTACZO cream is prescription medicine used on the skin (topical) to treat athletes foot that is between the toes (interdigital tinea pedis) in adults and children 12 years of age and older with normal immune systems.It is not known if ERTACZO cream is safe and effective in children younger than 12 years of age.Before using ERTACZO cream, tell your healthcare provider about all of your medical conditions, including if you:ohave any allergiesoare pregnant or plan to become pregnant. It is not known if ERTACZO cream will harm your unborn baby.oare breastfeeding or plan to breastfeed. It is not known if ERTACZO cream passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use ERTACZO cream.Tell your healthcare provider about all of the medicinesyou take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How should use ERTACZO creamoUse ERTACZO cream exactly as your healthcare provider tells you to use it.oUse ERTACZO cream for the full treatment time, even if your symptoms improve.oIf you take bath or shower, dry the affected skin areas well before you apply ERTACZO cream.oApply ERTACZO cream times day for weeks to the affected skin areas between your toes and to the healthy skin around the affected areas.oWash your hands after you apply ERTACZO cream.oDo not cover the treated skin areas with bandages unless your healthcare provider tells you to.What are the possible side effects of ERTACZO creamThe most common side effects of ERTACZO cream include: redness, itching, dry skin, burning, blistering, swelling, drainage, and skin tenderness at the treated skin areas. Tell your healthcare provider if you have any of these skin reactions.These are not all the possible side effects of ERTACZO cream. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store ERTACZO creamoStore ERTACZO cream at room temperature between 68F to 77F (20C to 25C).oKeep ERTACZO cream and all medicines out of reach of children.General information about the safe and effective use of ERTACZO creamMedicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use ERTACZO cream for condition for which it was not prescribed. Do not give ERTACZO cream to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about ERTACZO cream that is written for health professionals.What are the ingredients in ERTACZO creamActive ingredient: sertaconazole nitrateInactive ingredients: ethylene glycol, glyceryl isostearate, glycolized saturated glycerides, light mineral oil, methylparaben, polyethylene glycol palmitostearate, polyoxyethylened saturated glycerides, purified water, and sorbic acidDistributed by:Bausch Health US, LLCBridgewater, NJ 08807 USAManufactured by:DPT Laboratories, Ltd.San Antonio, TX 78215ERTACZO is trademark of Bausch Health Companies Inc. or its affiliates. (C) 2020 Bausch Health Companies Inc. or its affiliates 9378102This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: 12/2020. ohave any allergies. oare pregnant or plan to become pregnant. It is not known if ERTACZO cream will harm your unborn baby.. oare breastfeeding or plan to breastfeed. It is not known if ERTACZO cream passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use ERTACZO cream.. oUse ERTACZO cream exactly as your healthcare provider tells you to use it.. oUse ERTACZO cream for the full treatment time, even if your symptoms improve.. oIf you take bath or shower, dry the affected skin areas well before you apply ERTACZO cream.. oApply ERTACZO cream times day for weeks to the affected skin areas between your toes and to the healthy skin around the affected areas.. oWash your hands after you apply ERTACZO cream.. oDo not cover the treated skin areas with bandages unless your healthcare provider tells you to.. oStore ERTACZO cream at room temperature between 68F to 77F (20C to 25C).. oKeep ERTACZO cream and all medicines out of reach of children.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk SummaryThere are no available data on ERTACZO cream, 2% use in pregnant women to evaluate for 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 40 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, reduction in live birth indices and an increase in the number of still-born pups was observed at doses 20 and 40 times the MRHD based on BSA comparison (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have 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.DataAnimal DataAnimal 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 BSA comparison) during the period of organogenesis revealed no malformations or embryofetal developmental toxicity. In pre- and postnatal development study, pregnant rats were administered oral doses of sertaconazole nitrate from pregnancy day to lactation day 20. reduction in live birth indices and an increase in the number of still-born pups were seen at doses 20 and 40 times the MRHD based on BSA comparison.. 8.2 Lactation Risk SummaryThere are no data available on the presence of sertaconazole in human or animal milk, its effects on the breastfed infant, or its effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for ERTACZO cream, 2% and any potential adverse effects on the breastfed infant from ERTACZO cream, 2% or from the underlying maternal condition.. 8.4 Pediatric Use The safety and effectiveness of ERTACZO cream, 2%, have not been established in pediatric patients younger than 12 years of age.. 8.5 Geriatric Use Clinical trials of ERTACZO cream, 2%, did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.