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  • CLASSES

    Topical Dermatological Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Topical allylamine antifungal
    Indicated for the interdigital tinea pedis, tinea cruris, and tinea corporis
    Similar efficacy and adverse events profiles to topical azole antifungals

    COMMON BRAND NAMES

    Naftin, Naftin-MP

    HOW SUPPLIED

    Naftifine Hydrochloride/Naftin/Naftin-MP Topical Cream: 1%, 2%
    Naftin Topical Gel: 1%, 2%

    DOSAGE & INDICATIONS

    For the treatment of tinea cruris.
    Topical dosage (1% gel)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Epidermophyton floccosum.

    Adults

    Gently massage into the affected area and surrounding skin twice daily (morning and evening). Therapeutic response may be delayed; reevaluate if no clinical improvement is observed after 4 weeks of treatment. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (1% cream)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

    Adults

    Gently massage into the affected area and surrounding skin once daily. Therapeutic response may be delayed; reevaluate if no clinical improvement is observed after 4 weeks of treatment. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (2% cream)

    NOTE: Indicated for infections caused by Trichophyton rubrum.

    Adults, Adolescents, and Children 12 years and older

    Gently massage into the affected area and approximately 0.5 inches of surrounding skin once daily for 2 weeks. Instruct patients to discontinue treatment if irritation or sensitivity develops. During clinical trials, 25% of patients with tinea cruris were completely cured following 2 weeks of treatment with the 2% cream; mycological cure rate was 72%.

    For the treatment of interdigital tinea pedis.
    Topical dosage (1% gel)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Epidermophyton floccosum.

    Adults

    Gently massage into the affected area and surrounding skin twice daily (morning and evening). Therapeutic response may be delayed; reevaluate if no clinical improvement is observed after 4 weeks of treatment. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (2% gel)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

    Adults, Adolescents, and Children 12 years and older

    Gently massage into the affected area and surrounding skin once daily for 2 weeks. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (1% cream)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

    Adults

    Gently massage into the affected area and surrounding skin once daily. Therapeutic response may be delayed; reevaluate if no clinical improvement is observed after 4 weeks of treatment. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (2% cream)

    NOTE: Indicated for infections caused by Trichophyton rubrum.

    Adults, Adolescents, and Children 12 years and older

    Gently massage into the affected area and approximately 0.5 inches of the surrounding skin once daily for 2 weeks. Instruct patients to discontinue treatment if irritation or sensitivity develops. During clinical trials, 18% of patients with interdigital tinea pedis were completely cured following 2 weeks of treatment with the 2% cream; mycological cure rate was 67%.

    For the treatment of tinea corporis.
    Topical dosage (1% gel)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Epidermophyton floccosum.

    Adults

    Gently massage into the affected area and surrounding skin twice daily (morning and evening). Therapeutic response may be delayed; reevaluate if no clinical improvement is observed after 4 weeks of treatment. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (1% cream)

    NOTE: Indicated for infections caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

    Adults

    Gently massage into the affected area and surrounding skin once daily. Therapeutic response may be delayed; reevaluate if no clinical improvement is observed after 4 weeks of treatment. Instruct patients to discontinue treatment if irritation or sensitivity develops.

    Topical dosage (2% cream)

    NOTE: Indicated for infections caused by Trichophyton rubrum.

    Adults, Adolescents, and Children 2 years and older

    Gently massage into the affected area and approximately 0.5 inches of surrounding skin once daily for 2 weeks. Instruct patients to discontinue treatment if irritation or sensitivity develops. During clinical trials, 46% of patients with tinea cruris were completely cured following 2 weeks of treatment with the 2% cream; mycological cure rate was 63%.

    For the treatment of distal subungual onychomycosis† or white superficial onychomycosis† (tinea unguium) due to susceptible dermatophytes (i.e., Trichophyton rubrum) or Candida species in patients unable to tolerate oral antifungal therapy.
    Topical dosage (1% gel)

    NOTE: Naftifine gel has not been shown to be effective for onychomyosis of the toenail.

    Adults

    Gently massage the 1% topical gel into the affected fingernail area twice a day for at least 6 months. Monthly nail trimming and debridement should accompany topical antifungal nail treatment. Clinical cure has been observed in 40 to 80% of patients.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    No maximum dosage information is available.

    Geriatric

    No maximum dosage information is available.

    Adolescents

    No maximum dosage information is available for the 2% gel or 2% cream; safety and efficacy have not been established for all other formulations.

    Children

    12 years: No maximum dosage information is available for the 2% gel or 2% cream; safety and efficacy have not been established for all other formulations.
    2 to 11 years: No maximum dosage information is available for the 2% cream; safety and efficacy have not been established for all other formulations
    < 2 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Topical Administration

    For topical dermatologic use only; not for ophthalmic, oral, or intravaginal use.
    Wash hands before and after application. When treating hand infections, do not wash patient's hands after application. Use gloves for topical application if required by universal precautions.
    Rub topical cream or gel gently into the affected area(s). Apply an amount sufficient to cover the affected area and the immediate (approximately a 0.5 inch margin) surrounding skin. Avoid getting in the eyes, nose, mouth, or other mucous membranes.
    Avoid occlusive dressing of the affected areas unless otherwise directed by the prescriber.
    Improvement of dermal tinea infection is gradual, and improvements in the treated condition may continue for weeks after naftifine therapy is discontinued. The manufacturer recommends that patients not be considered therapeutic failures until 2 to 4 weeks of therapy have passed.

    STORAGE

    Naftin:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Naftin-MP:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Accidental exposure, ocular exposure

    Naftifine is contraindicated in patients that have a known or suspected hypersensitivity to naftifine or any of the components of the formulation. If irritation, skin rash, or sensitivity occurs during use of naftifine, treatment should be discontinued and appropriate therapy administered. Avoid accidental exposure to unintended areas like the mucus membranes (e.g., mouth, nose, vaginal) or ocular exposure during treatment. Naftifine is for external use only.

    Occlusive dressing

    According to the manufacturer, diagnosis of the mycoses should be performed by a tissue mount in potassium hydroxide and direct microscopic examination or by culture. Naftifine treatment may need to be continued for 4—6 weeks or longer, and patients should be informed to continue treatment for the full treatment period. If no clinical improvement is seen after 4 weeks of using topical naftifine, the patient should be re-evaluated. Patients should be informed to avoid the use of an occlusive dressing with naftifine (unless otherwise directed by their health care professional).

    Pregnancy

    Data are limited regarding use of naftifine during pregnancy. Studies in animals using large oral dosages did not reveal harm to the fetus or impaired fertility. Conclusive studies in humans, however, do not exist. According to the manufacturer, naftifine should only be used in pregnancy if the potential benefit to the mother outweighs the potential risk to the fetus.

    Breast-feeding

    Excretion of topical naftifine into human milk is unknown; caution is advised when administering to nursing women. Based on data that roughly 3% of the drug is adsorbed systemically, it was predicted that a breast-feeding infant might ingest 0.3 mcg/kg from human milk. Instruct nursing mothers to avoid topical application to the breast area. Adverse events in infants have not been reported, because of the half-life of 2—3 days, it may be necessary to withhold nursing if treatment is indicated. Clotrimazole and miconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Children, infants, neonates

    Safety and efficacy of the 1% naftifine gel and 1% naftifine cream have not been established in neonates, infants, children, nor adolescents. The 2% gel formulation is approved for use in pediatric patients as young as 12 years of age; this approval was based on the results of an open label trial, in which 22 pediatric patients (age 12 to 17 years) were exposed to approximately 4 grams of naftifine/day for 14 days. The 2% cream formulation is approved for use in children as young as 2 years of age for the treatment of tinea corporis, and 12 years for the treatment of tinea pedis and tinea cruris.

    ADVERSE REACTIONS

    Severe

    agranulocytosis / Delayed / Incidence not known

    Moderate

    erythema / Early / 0.5-0.5
    contact dermatitis / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known

    Mild

    skin irritation / Early / 2.0-5.0
    rash (unspecified) / Early / 0.5-0.5
    pruritus / Rapid / 1.0
    dizziness / Early / Incidence not known
    headache / Early / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Naftifine products.

    PREGNANCY AND LACTATION

    Pregnancy

    Data are limited regarding use of naftifine during pregnancy. Studies in animals using large oral dosages did not reveal harm to the fetus or impaired fertility. Conclusive studies in humans, however, do not exist. According to the manufacturer, naftifine should only be used in pregnancy if the potential benefit to the mother outweighs the potential risk to the fetus.

    Excretion of topical naftifine into human milk is unknown; caution is advised when administering to nursing women. Based on data that roughly 3% of the drug is adsorbed systemically, it was predicted that a breast-feeding infant might ingest 0.3 mcg/kg from human milk. Instruct nursing mothers to avoid topical application to the breast area. Adverse events in infants have not been reported, because of the half-life of 2—3 days, it may be necessary to withhold nursing if treatment is indicated. Clotrimazole and miconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested or administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Naftifine exerts its antifungal effect by selective inhibition of the enzyme squalene 2,3-epoxidase, a key enzyme in ergosterol biosynthesis in fungi. Typically, squalene is transformed into ergosterol in the fungus. Ergosterol is a component of fungal membranes necessary for normal cell growth and function. The inhibition of the enzyme creates a deficiency in ergosterol and an accumulation of squalene. An abundance of squalene leads to cell death due to a decrease in phospholipid and glycoprotein synthesis and membrane destruction. Naftifine has fungicidal activity against dermatophytes, and exhibits fungistatic activity against Candida sp. At higher concentrations, naftifine can be fungicidal against Candida sp. Naftifine does not inhibit human sterol production. Naftifine has also been shown to possess local bactericidal properties against both gram-positive and gram-negative bacteria. The excellent anti-inflammatory properties of naftifine appear to be due to vasoconstriction via inhibition of inflammatory mediators, such as prostaglandins, leukotrienes, and histamine. Research also suggests that the allylamine antifungals, like naftifine, may enhance selected functions of polymorphonuclear leukocytes.

    PHARMACOKINETICS

    Naftifine is administered topically. Following topical application, measurable concentrations of naftifine are absorbed into the plasma and the drug penetrates the stratum corneum in sufficient quantities to inhibit growth of dermatophytes; however, it is not known if naftifine distributes into human milk or crosses the placenta. Roughly 14 to 29% of the absorbed dose is metabolized in the liver. Up to 64% of an absorbed dose and its metabolites is excreted in the urine and 36% in the bile. The metabolites have no pharmacologic activity. Unlike the imidazoles, the allylamine group of antifungals has limited effect on the cytochrome P450 enzyme system. Naftifine has a half-life of approximately 2 to 3 days.
     
    Affected cytochrome P450 enzymes and drug transporters: None

    Topical Route

    Up to 4.2% and 6% of naftifine gel and cream, respectively, are absorbed after single applications to the skin.