Tioconazole, 1-[2-{(2-chloro-3-thienyl)methoxy}-2(2,4-dichlorophenyl)ethyl]1,H-imidazole, is a topical antifungal agent. Its chemical formula is C₁₆H₁₃Cl₃N₂OS with a molecular weight of 387.7.

VAGISTAT-1 (tioconazole 6.5%) is formulated in a base of white, soft paraffin and aluminum magnesium silicate with butylated hydroxyanisole (BHA) added as a preservative. Each applicator-full of VAGISTAT-1 provides approximately 4.6 grams of ointment containing 300 mg of tioconazole.

VAGISTAT-1 is indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As VAGISTAT-1 has been shown to be effective only for candidal vulvovaginitis, the diagnosis should be confirmed by KOH smears and/or cultures. Other pathogens commonly associated with vulvovaginitis should be ruled out by appropriate methods.

Studies have shown that women taking oral contraceptives have a cure rate similar to those not taking such agents when treated with VAGISTAT-1.

Safety and effectiveness in pregnant and diabetic patients have not been established (see PRECAUTIONS).

VAGISTAT-1 has been found to be effective as a single- dose treatment for vulvovaginal candidiasis. Using the prefilled applicator, insert one applicator- full intravaginally. Administration of VAGISTAT-1 just prior to bedtime may be preferred.

VAGISTAT-1 is supplied in a ready-to-use, prefilled, single-dose vaginal applicator (NDC 0087-0657-40). Each applicator-full will deliver approximately 4.6 grams of VAGISTAT-1 containing 65 mg of tioconazole per gram of ointment.

Storage: Store at controlled room temperature 15°-30° C (59°-86° F).

WARNING: Manufactured with 1,1,1-trichloroethane, a substance which harms public health and environment by destroying ozone in the upper atmosphere.

The incidence of adverse reactions to VAGISTAT-1 is based on clinical trials involving 1000 patients. Burning and itching were the most frequent side effects occurring in approximately 6% and 5% of the patients, respectively. In most instances these did not interfere with the course of therapy.

There were occasional reports (less than 1%) of other side effects including irritation, discharge, vulvar edema and swelling, vaginal pain, dysuria, nocturia, dyspareunia, dryness of vaginal secretions, desquamation, and burning sensation.

No information provided.

General

VAGISTAT-1 is intended for intravaginal administration only. Applicators should be opened just prior to administration to prevent contamination. Administration of VAGISTAT-1just prior to bedtime may be preferred. The VAGISTAT-1 ointment base may interact with rubber or latex products such as condoms or vaginal contraceptive diaphragms; therefore, use of such products within 72 hours following treatment is not recommended.

If clinical symptoms persist, appropriate microbiological tests should be repeated to rule out other pathogens and to confirm the diagnosis.

Carcinogenesis

No long-term studies in animals have been performed to evaluate the carcinogenic potential of tioconazole.

Mutagenesis

Tioconazole did not demonstrate mutagenic activity at the levels examined in tests at either the chromosomal or subchromosomal level.

Impairment of Fertility

No impairment of fertility was seen in male rats administered tioconazole hydrochloride in oral doses up to 150 mg/kg/day. However, there was evidence of preimplantation loss in female rats at oral dose levels above 35 mg/kg/day.

Pregnancy

Pregnancy Category C: Tioconazole hydrochloride had no adverse effects on fetal viability or growth when administered orally to pregnant rats at doses of 55, 110, and 165 mg/kg/day during the period of organogenesis. A drug- related increase in the incidence of dilated ureters, hydroureters, and hydronephrosis observed in the fetuses of this study was transient and no longer evident in pigs raised to 21 days of age. These effects did not occur following intravaginal administration of approximately 10 mg/kg/day in a 2% cream. There was no evidence of major structural anomalies. No embryotoxic or teratogenic effects were observed in rabbits receiving oral dose levels as high as 165 mg/kg/day or daily intravaginal application of approximately 2-3 mg/kg in a 2% tioconazole cream during organogenesis. Tioconazole hydrochloride, like other azole antimycotic agents, causes dystocia in rats when treatment is extended through parturition. Associated effects in rats include prolongation of pregnancy, in utero deaths, and impaired pup survival. The ''no-effect'' level for this phenomenon is 20 mg/kg/day orally and approximately 9 mg/kg/day intravaginally. No effect on parturition occurred in rabbits at 50 mg/kg/day orally.

There are no adequate and well-controlled studies in pregnant women. VAGISTAT® -1 (tioconazole 6.5%) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, nursing should be temporarily discontinued while VAGISTAT-1 is administered.

Pediatric Use

Safety and effectiveness in children have not been established.

VAGISTAT-1 is contraindicated in individuals who have been shown to be sensitive to imidazole antifungal agents or to other components of the ointment.

Tioconazole is a broad-spectrum antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata.

Pharmacokinetics

Systemic absorption of tioconazole after a single intravaginal application of VAGISTAT-1 in nonpregnant patients is negligible.

The VAGISTAT-1 ointment base may interact with rubber or latex products such as condoms or vaginal contraceptive diaphragms; therefore, use of such products within 72 hours following treatment is not recommended.