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  • CLASSES

    Topical Dermatological Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Oxaborole antifungal for onchomycosis of toenails
    Effective against Trichophyton rubrum or Trichophyton mentagrophytes
    Available as topical solution

    COMMON BRAND NAMES

    KERYDIN

    HOW SUPPLIED

    KERYDIN/Tavaborole Topical Sol: 5%

    DOSAGE & INDICATIONS

    For the treatment of onychomycosis of the toenail(s) caused by Trichophyton rubrum and Trichophyton mentagrophytes.
    Topical dosage
    Adults

    Apply solution topically to the affected toenail(s) once daily for 48 weeks. Ensure the entire toenail (toenail beds, folds, hyponychium, and undersurface of the toenail plate) is completely covered. Avoid contact with skin, other than the skin immediately surrounding the affected toenail(s). Wipe away excess solution from surrounding skin.

    Children and Adolescents 6 years and older

    Apply solution topically to the affected toenail(s) once daily for 48 weeks. Ensure the entire toenail (toenail beds, folds, hyponychium, and undersurface of the toenail plate) is completely covered. Avoid contact with skin, other than the skin immediately surrounding the affected toenail(s). Wipe away excess solution from surrounding skin.

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information not available.

    Geriatric

    Specific maximum dosage information not available.

    Adolescents

    Specific maximum dosage information not available.

    Children

    6 to 12 years: Specific maximum dosage information not available.
    1 to 5 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 use on toenails only; not for ophthalmic, oral, or intravaginal use.
    Instruct patients to avoid pedicures, and use of nail polish or cosmetic nail products during treatment.
    Solution is flammable. Avoid heat, flame, and tobacco smoking during and immediately following application.

    Other Topical Formulations

    Topical Nail Solution:
    Clean and dry toenails prior to application.
    Use the manufacturer supplied dropper assembly to apply solution onto each toenail requiring treatment.
    Spread the drop(s) around the affected toenail(s). Ensure the entire toenail (toenail bed, folds, hyponychium, and undersurface of the toenail plate) is completely covered. Also apply to skin immediately surrounding the treated nail(s). Wipe away any excess solution from surrounding skin.
    Allow solution to dry completely.
    Wash hands with soap and water after the application process.

    STORAGE

    KERYDIN:
    - Flammable, keep away from heat and flame
    - Product should be used within 3 months after opening
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Ocular exposure, ophthalmic administration, vaginal administration

    Tavaborole is only approved for external use on toenails; it is not for ophthalmic administration, oral administration, or vaginal administration. During topical application, take care to avoid accidental ocular exposure.

    Pregnancy

    There are no adequate or well-controlled studies regarding use of tavaborole during pregnancy. Animal studies involving rats revealed embryofetal toxicities, skeletal malformations, and delayed development following oral administration of doses 570-times the maximum recommended human dose (MRHD). In rabbits, excessive embryofetal mortality due to post-implantation loss was noted following administration of oral doses 155-times MRHD. Of note for both animal species, these embryofetal toxicities occurred in the presence of maternal toxicities. Although no drug related fetal malformations were observed in rabbits following topical administration, decreased fetal body weights were noted in offspring of mother exposed to 10% topical solution. Administer during pregnancy only if the potential benefits justify the potential risks to the fetus.

    Breast-feeding

    Data are limited regarding use of tavaborole during breast-feeding, and its' excretion into human milk is unknown. 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 administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Tobacco smoking

    Tavaborole solution is flammable. Avoid heat, flame, and tobacco smoking during and immediately following application.

    ADVERSE REACTIONS

    Moderate

    erythema / Early / 1.6-1.6
    contact dermatitis / Delayed / Incidence not known

    Mild

    skin irritation / Early / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Tavaborole products.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate or well-controlled studies regarding use of tavaborole during pregnancy. Animal studies involving rats revealed embryofetal toxicities, skeletal malformations, and delayed development following oral administration of doses 570-times the maximum recommended human dose (MRHD). In rabbits, excessive embryofetal mortality due to post-implantation loss was noted following administration of oral doses 155-times MRHD. Of note for both animal species, these embryofetal toxicities occurred in the presence of maternal toxicities. Although no drug related fetal malformations were observed in rabbits following topical administration, decreased fetal body weights were noted in offspring of mother exposed to 10% topical solution. Administer during pregnancy only if the potential benefits justify the potential risks to the fetus.

    Data are limited regarding use of tavaborole during breast-feeding, and its' excretion into human milk is unknown. 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 administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Tavaborole prevents fungal protein biosynthesis by inhibiting leucyl-transfer ribonucleic acid (tRNA) synthetase (LeuRS), an aminoacyl-tRNA synthetase (AARS) that ensure correct translation of the genetic code by catalyzing the attachment of an amino acid to its corresponding tRNA. Inhibition of LeuRS occurs when the boron atom contained within the oxaborole ring of tavaborole binds to the 2' and 3'-oxygen atoms of tRNALEU 3'-terminal adenosine. This tavaborole-tRNALeu binding blocks tRNALeu active site, thereby preventing translation of tRNA by LeuRS.
     
    Resistance was not observed during clinical trials following repeated exposure of Trichophyton rubrum and T. mentagrophytes to tavaborole.

    PHARMACOKINETICS

    Tavaborole is applied topically to toenails. Following administration of a single dose to 6 healthy volunteers, the drug was found to undergo extensive metabolism and be excreted primarily in the urine. Specific data regarding distribution and half-life are not available from the manufacturer.
    Affected cytochrome P450 isoenzymes: None
    Based on data from in vitro studies, therapeutic concentrations of tavaborole do NOT inhibit nor induce cytochrome P450 (CYP450) enzymes.

    Topical Route

    Pharmacokinetic parameters of tavaborole were evaluated in 24 patients with onychomycosis involving at least 4 toenails. The drug was administered topically once daily for 14 days to patients' 10 toenails and 2 mm of adjacent skin. Upon administration of a single dose, the mean plasma Cmax was 3.54 +/- 2.26 ng/ml and the mean AUC was 44.4 +/- 25.5 ng x hr/ml. After 14 daily treatments, the mean plasma Cmax increased to 5.17 +/- 3.47 ng/ml and the mean AUC increased to 75.8 +/- 44.5 ng x hr/ml. Steady state was achieved after 14 days.