Butoconazole is an imidazole antifungal agent. It is fungicidal in vitro against Candida spp. and is clincally effective in treating vulvovaginal candidiasis. Butoconazole is available as a vaginal preparation. Butoconazole was FDA-approved in 1985 for the treatment of vulvovaginal candidiasis. In December 1995, multiple-dose butoconazole formulations were approved for over-the-counter (OTC) use. A single dose vaginal product (Gynazole-1(R)) was FDA-approved in July 2000 as a prescription-only product.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
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.
Of the 314 patients treated with butoconazole intravaginally for 1 day in controlled clinical trials, 18 patients (5.7%) experienced an adverse event; however, these events were considered treatment-related in only 3 patients (1%). Butoconazole-associated adverse events consist primarily of localized vaginal irritation including burning, pruritus, swelling, and vaginal pain or soreness. Systemic events include pelvic pain, abdominal pain, and abdominal cramping.
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.
No adequate, well-controlled studies have been conducted with butoconazole in human pregnancy. Guidelines recommend the use of butoconazole intravaginally in pregnant persons. Following vaginal application, approximately 1.7% of the dose is absorbed systemically. In animal studies, fertility was not impaired following oral administration at doses of up to 5 to 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 to 50 mg/kg did not result in fetal malformations in pregnant rats, oral doses of 100 to 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.
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.
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.
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.
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.
Safety and efficacy of butoconazole have not been established in neonates, infants, or children < 12 years of age.
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.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Candida albicans, Candida sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Candida glabrata, Candida tropicalis, Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton sp., Trichophyton tonsurans
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of vulvovaginal candidiasis (VVC):
-for the treatment of uncomplicated VVC in persons without HIV:
Intravaginal dosage:
Adults: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally as a single dose.
Pregnant Adults*: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally once daily for 7 days.
Adolescents*: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally as a single dose.
Pregnant Adolescents*: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally once daily for 7 days.
-for the treatment of uncomplicated VVC in persons living with HIV*:
Intravaginal dosage:
Adults: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally once daily for 3 to 7 days.
Adolescents: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally once daily for 3 to 7 days.
-for the treatment of severe or recurrent VVC*:
Intravaginal dosage:
Adults: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally once daily for 7 to 14 days. Subsequent intermittent topical treatment may be considered for maintenance of recurrent VVC as an alternative to fluconazole.
Adolescents: 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally once daily for 7 to 14 days. Subsequent intermittent topical treatment may be considered for maintenance of recurrent VVC as an alternative to fluconazole.
Maximum Dosage Limits:
-Adults
1 applicatorful (100 mg butoconazole/5 g cream) intravaginally/day.
-Geriatric
1 applicatorful (100 mg butoconazole/5 g cream) intravaginally/day.
-Adolescents
Safety and efficacy have not been established; however, 1 applicatorful (100 mg butoconazole/5 g cream) intravaginally/day has been used off-label.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment needed.
Patients with Renal Impairment Dosing
No dosage adjustment needed.
*non-FDA-approved indication
There are no drug interactions associated with Butoconazole products.
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.
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.
-Route-Specific Pharmacokinetics
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.