Ertaczo

Valeant Pharmaceutials North America LLC

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use ERTACZO cream safely and effectively. See full prescribing information for ERTACZO cream. ERTACZO (sertaconazole nitrate) cream, 2%, for topical use Initial U.S. Approval: 2003INDICATIONS AND USAGEERTACZO cream 2% is an azole antifungal indicated for the topical treatment of interdigital tinea pedis in immunocompetent patients 12 years of age and older, caused by: Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. (1)DOSAGE AND ADMINISTRATIONERTACZO cream should be applied to the affected and immediate surrounding area(s) twice daily for 4 weeks. (2)Not for ophthalmic, oral, or intravaginal use. (2)DOSAGE FORMS AND STRENGTHSCream, 2%. (3)CONTRAINDICATIONSNone. (4)Side EffectsMost 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 Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 ERTACZO INDICATIONS AND USAGE
• 2 ERTACZO DOSAGE AND ADMINISTRATION
• 3 DOSAGE FORMS AND STRENGTHS
• 4 ERTACZO CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Local Adverse Reactions
• 6 ERTACZO ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing Experience
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 11 ERTACZO DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.3 Pharmacokinetics
  • 12.4 Microbiology
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

ERTACZO^® (sertaconazole nitrate) cream, 2%, is indicated for the topical treatment of interdigital tinea pedis in immunocompetent patients 12 years of age and older, caused by: Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum [see Clinical Studies (14) ].

2 DOSAGE AND ADMINISTRATION

In the treatment of interdigital tinea pedis, ERTACZO cream, 2%, should be applied twice daily for 4 weeks. Sufficient amount of ERTACZO cream, 2%, should be applied to cover both the affected areas between the toes and the immediately surrounding healthy skin of patients with interdigital tinea pedis.

Not for ophthalmic, oral, or intravaginal use.

3 DOSAGE FORMS AND STRENGTHS

Cream, 2%. Each gram of ERTACZO cream, 2%, contains 17.5 mg of sertaconazole (as sertaconazole nitrate, 20 mg) in a white cream base.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Local Side Effects

If irritation develops, treatment should be discontinued and appropriate therapy instituted.

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

6 ADVERSE REACTIONS

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 7 of 297 (2%) subjects (2 of them severe) receiving ERTACZO^® cream, 2%, and in 7 of 291 (2%) subjects (2 of them severe) receiving vehicle. These reported cutaneous adverse events included contact dermatitis, dry skin, burning skin, application site skin tenderness.

In a dermal sensitization trial, 8 of 202 evaluable subjects tested with ERTACZO^® cream, 2%, and 4 of 202 evaluable subjects tested with vehicle, exhibited a slight 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.

In post-marketing surveillance for ERTACZO cream, 2%, the following were reported:

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.

There are no adequate and well-controlled studies conducted with ERTACZO cream in pregnant women. ERTACZO cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Reproduction studies have not been performed with ERTACZO cream. Sertaconazole nitrate did not produce any evidence of maternal toxicity, embryotoxicity or teratogenicity in rats and rabbits at an oral dose of 160 mg/kg/day (40 times (rats) and 80 times (rabbits) the maximum recommended human dose based on a body surface area comparison). A reduction in live birth indices and an increase in the number of still-born pups were seen at doses of 80 and 160 mg/kg/day sertaconazole nitrate in an oral peri- and post-natal development study in rats.

8.3 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.

8.4 Pediatric Use

The efficacy and safety of ERTACZO cream, 2%, have not been established in pediatric patients below the age of 12 years.

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.

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 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, glyceryl isostearate, glycolized saturated glycerides, light mineral oil, methylparaben, polyethylene glycol palmitostearate, polyoxyethylened saturated glycerides, sorbic acid and purified water.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

ERTACZO cream is an azole antifungal [see Clinical Pharmacology (12.4) ].

12.3 Pharmacokinetics

In a multiple dose pharmacokinetic trial that included 5 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 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.

12.4 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 Clinical Infections:
Sertaconazole 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

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a rat dermal carcinogenicity study, topical administration of sertaconazole nitrate cream for up to 102 weeks did not increase the number of neoplastic lesions compared to control animals, at sertaconazole nitrate doses of up to 800 mg/kg/day (approximately 200 times the maximum recommended human dose based on a body surface area comparison).

No clastogenic potential was observed in a mouse micronucleus test. Sertaconazole nitrate was considered 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.

At oral doses up to 60 mg/kg/day (16 times the maximum recommended human dose based on a body surface area comparison), sertaconazole nitrate exhibited no toxicity or adverse effects on reproductive performance or fertility in male or female rats.

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 four weeks. Subjects with moccasin-type (plantar) tinea pedis and/or onychomycosis were excluded from the trial. Two weeks after completion of therapy (six weeks after beginning therapy), subjects were evaluated for signs and symptoms related to interdigital tinea pedis.

Treatment outcomes are summarized in the table below.

In clinical trials, complete cure in sertaconazole treated subjects was achieved in 32 of 160 (20%) subjects with Trichophyton rubrum, in 7 of 28 (25%) subjects with Trichophyton mentagrophytes and in 1 of 13 (15%) subjects with Epidermophyton floccosum.

16 HOW SUPPLIED/STORAGE AND HANDLING

ERTACZO cream, 2%, is white in color and supplied in tubes in the following size:

Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

See FDA-approved Patient Labeling (Patient Information)

The patient should be instructed to:

• 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, mouth, vagina and other mucous membranes. ERTACZO cream, 2%, is for external use only.
• Dry the affected area(s) thoroughly before application, if you wish to use ERTACZO cream, 2%, after bathing.
• Use the medication for the full treatment time recommended by the physician, even though symptoms may have improved.
• Inform the physician if the area of application shows signs of increased irritation, redness, itching, burning, blistering, swelling or oozing.
• Avoid the use of occlusive dressings unless otherwise directed by the physician.
• Do not use this medication for any disorder other than that for which it was prescribed.

PATIENT INFORMATION

ERTACZO (er-tack-zo)
(sertaconazole nitrate) cream, 2%

What is ERTACZO cream?

ERTACZO cream is a prescription medicine used on the skin (topical) to treat athlete's foot that is between the toes (interdigital tinea pedis) in people 12 years of age and older with normal immune systems.

It is not known if ERTACZO cream is safe and effective in children under 12 years of age.

What should I tell my healthcare provider before using ERTACZO cream?

Before using ERTACZO cream, tell your healthcare provider about all of your medical conditions, including if you:

• have any allergies
• are pregnant or plan to become pregnant. It is not known if ERTACZO cream will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if ERTACZO cream passes into your breast milk.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use ERTACZO cream?

• Use ERTACZO cream exactly as your healthcare provider tells you to use it.
• Use ERTACZO cream for the full treatment time, even if your symptoms improve.
• If you take a bath or shower, dry the affected skin areas well before you apply ERTACZO cream.
• Apply ERTACZO cream 2 times a day for 4 weeks to the affected skin areas between your toes and to the healthy skin around the affected areas.
• Wash your hands after you apply ERTACZO cream
• Do not cover the treated skin areas with bandages unless your healthcare provider tells you to.

What are the possible side effects of ERTACZO cream?

The 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 I store ERTACZO cream?

• Store ERTACZO cream at room temperature, between 68°F to 77°F (20°C to 25°C).
• Keep ERTACZO cream and all medicines out of the reach of children.

General information about the safe and effective use of ERTACZO cream

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your healthcare provider or pharmacist for information about ERTACZO cream that is written for health professionals. Do not use ERTACZO cream for a 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.

What are the ingredients in ERTACZO cream?

Active ingredient: sertaconazole nitrate

Inactive ingredients: ethylene glycol, glyceryl isostearate, glycolized saturated glycerides, light mineral oil, methylparaben, polyethylene glycol palmitostearate, polyoxyethylened saturated glycerides, sorbic acid and purified water

Distributed by: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Product of Spain

For more information call 1-800-321-4567.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Issued 01/14

PRINCIPAL DISPLAY PANEL - 60 g Tube

NDC 0187-5115-60

ERTACZO^®
(sertaconazole nitrate) cream, 2%

For Topical Use Only – Not for Oral, Ophthalmic, or Intravaginal Use