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  • CLASSES

    Gynecological Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Imidazole antifungal agent that is fungicidal in vitro against Candida spp.; available as a vaginal preparation; multiple dose products available OTC; single dose product available by prescription only.

    COMMON BRAND NAMES

    Gynazole-1

    HOW SUPPLIED

    Gynazole-1 Vaginal Cream: 2%

    DOSAGE & INDICATIONS

    For the treatment of vulvovaginal candidiasis (VVC).
    Intravaginal dosage
    Non-pregnant Adults

    1 applicatorful of 2% sustained-release prescription cream intravaginally at bedtime for 1 dose or 1 applicatorful of the 2% OTC cream intravaginally at bedtime for 3 doses for uncomplicated VVC. The CDC recommends intermittent topical treatments as an alternative to fluconazole for maintenance of recurrent VVC.[46358] [59799] For HIV-infected patients, treat for 3 to 7 days for uncomplicated VVC and for at least 7 days for severe or recurrent VVC.[34362]

    Adolescents†

    1 applicatorful of 2% sustained-release prescription cream intravaginally at bedtime for 1 dose or 1 applicatorful of the 2% OTC cream intravaginally at bedtime for 3 doses for uncomplicated VVC. The CDC recommends intermittent topical treatments as an alternative to fluconazole for maintenance of recurrent VVC. For HIV-infected patients, treat for 3 to 7 days for uncomplicated VVC and for at least 7 days for severe or recurrent VVC.

    MAXIMUM DOSAGE

    Adults

    Maximum intravaginal dose is not available.

    Elderly

    Maximum intravaginal dose is not available.

    Adolescents

    Maximum intravaginal dose is not available.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment needed.

    Renal Impairment

    No dosage adjustment needed.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Intravaginal Administration

    Butoconazole preparations are for intravaginal use only; do not apply to the eye, mouth, or skin.
    Butoconazole is usually administered at bedtime; use special applicator supplied by the manufacturer.
    Instruct patient on proper administration and treatment course.
    Therapy should be continued during menstruation. However, instruct patient not to use tampons during the treatment course.
    Instruct patient not to use douches or spermicides during the treatment course and to abstain from sexual activity during treatment. Vaginal butoconazole products may damage condoms, diaphragms, and cervical caps, and cause them to fail.
    If an adequate response is not achieved, the diagnosis should be reconfirmed and other pathogens commonly associated with vulvovaginitis ruled out.

    STORAGE

    Gynazole-1:
    - Avoid temperatures above 86 degrees F
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Onychomycosis

    As with many other topical antifungal drugs, butoconazole cream is not effective for onychomycosis. This condition usually requires treatment with an oral (systemic) antifungal drug.

    Pregnancy

    Butoconazole vaginal preparations are classified as FDA pregnancy risk category C. No adequate, well-controlled studies have been conducted in pregnant humans. In animal studies, fertility was not impaired following oral administration at doses of up to 5—10 times the recommended human dose. Butoconazole, when given intravaginally in excess doses to pregnant rats, did not cause teratogenicity. While oral doses of 5—50 mg/kg did not result in fetal malformations in pregnant rats, oral doses of 100—750 mg/kg/day have resulted in adverse effects such as abdominal wall defects, cleft palate to the fetus; maternal stress was also evident at the higher dosing range. Administer during pregnancy only if the potential benefits justify the potential risks to the fetus.

    Breast-feeding

    There are no data describing the effects of butoconazole during breast-feeding and its' excretion in human milk is unknown. Following vaginal application, approximately 1.7% of the dose is absorbed systemically. According to the manufacturer, caution is advised when administering to nursing mothers. Fluconazole, 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.

    Azole antifungals hypersensitivity

    Butoconazole is contraindicated in patients who are hypersensitive to the drug. Hypersensitivity reactions may be due to the various vehicles present in the different butoconazole formulations. Butoconazole should be used with caution in patients with azole antifungals hypersensitivity as there may be cross sensitivity with other azole derivatives.

    Contraceptive devices, menstruation

    Patients who are using intravaginal butoconazole preparations should abstain from sexual intercourse during the treatment course. Butoconazole contains mineral oil, which may weaken contraceptive devices, including condoms, diaphragms, and cervical caps and may lead to contraceptive failure. Use of these products within 72 hours following treatment with butoconazole is not recommended. Although butoconazole may be used during menstruation, instruct patients not to use tampons.

    Abdominal pain, diabetes mellitus, fever, human immunodeficiency virus (HIV) infection, immunosuppression, vaginal discharge

    Self-administration of butoconazole for longer than 3 days is not recommended. If there is no improvement in the condition after 3 days, the patient should discontinue butoconazole therapy and consult a physician. Some patients should not use non-prescription butoconazole products without the supervision of a health care professional; patients with immunosuppression, diabetes mellitus, human immunodeficiency virus (HIV) infection or those undergoing chemotherapy should discuss use of these products with their health care professional prior to self-treatment. Females should not self-treat with intravaginal butoconazole products if the following signs and symptoms are present: abdominal pain, fever > 100 degrees F, or foul-smelling vaginal discharge. Such symptoms may be an indication of another vaginal infection or pelvic inflammatory disease. Approximately 20% of all vaginal candidal infections co-exist with another infection.

    Children, infants, neonates

    Safety and efficacy of butoconazole have not been established in neonates, infants, or children < 12 years of age.

    Ocular exposure, ophthalmic administration

    Avoid ocular exposure to butoconazole; do not give by ophthalmic administration. If ocular exposure occurs, treat by immediate flushing the affected eye with cool, clean water. Contact an ophthalmologist if eye irritation persists.

    ADVERSE REACTIONS

    Moderate

    vaginal pain / Early / 1.0-1.0

    Mild

    abdominal pain / Early / 1.0-1.0
    vaginal irritation / Early / 1.0-1.0
    pelvic pain / Delayed / 1.0-1.0
    pruritus / Rapid / 1.0-1.0

    DRUG INTERACTIONS

    There are no drug interactions associated with Butoconazole products.

    PREGNANCY AND LACTATION

    Pregnancy

    Butoconazole vaginal preparations are classified as FDA pregnancy risk category C. No adequate, well-controlled studies have been conducted in pregnant humans. In animal studies, fertility was not impaired following oral administration at doses of up to 5—10 times the recommended human dose. Butoconazole, when given intravaginally in excess doses to pregnant rats, did not cause teratogenicity. While oral doses of 5—50 mg/kg did not result in fetal malformations in pregnant rats, oral doses of 100—750 mg/kg/day have resulted in adverse effects such as abdominal wall defects, cleft palate to the fetus; maternal stress was also evident at the higher dosing range. Administer during pregnancy only if the potential benefits justify the potential risks to the fetus.

    There are no data describing the effects of butoconazole during breast-feeding and its' excretion in human milk is unknown. Following vaginal application, approximately 1.7% of the dose is absorbed systemically. According to the manufacturer, caution is advised when administering to nursing mothers. Fluconazole, 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

    As other azole antifungals, butoconazole exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition. Although not fully determined, butoconazole is thought to interfere with ergosterol synthesis through by interacting with 14-alpha demethylase, a cytochrome P-450 enzyme that is necessary for the conversion of lanosterol to ergosterol, an essential component of the membrane. In contrast, amphotericin B binds to ergosterol after it is synthesized. Like imidazole derivatives, the fungicidal activity of butoconazole at high concentrations may result from a direct physiochemical effect of the drug on the fungal cell.

    PHARMACOKINETICS

    Butoconazole is administered intravaginally. The distribution of butoconazole after intravaginal administration has not been determined. The plasma half-life of ranges from 21—24 hours. Metabolism of any systemically-absorbed drug occurs in the liver.

    Other Route(s)

    Intravaginal Route
    When butoconazole is administered intravaginally, small amounts are slowly absorbed systemically. Following intravaginal administration of approximately 5 g of radiolabeled butoconazole nitrate 2% cream (approximately 100 mg of the drug total) to healthy women, peak plasma concentrations 24 hours after administration ranged from 19—44 ng/mL. Following vaginal administration of butoconazole nitrate 2% vaginal cream for one dose to three women, 1.7% (range 1.3—2.2%) of the dose was absorbed on average. Peak plasma levels of the drug and its metabolites are attained between 12 and 24 hours after vaginal administration. Based on limited data, radioactivity was apparent in plasma 2—8 hours after intravaginal administration and persisted for 4—5 days.