terconazole 4 MG/ML Vaginal Cream

INDICATIONS AND USAGE Terconazole vaginal cream 0.4% is indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As terconazole vaginal cream 0.4% is effective only for vulvovaginitis caused by the genus Candida , the diagnosis should be confirmed by KOH smears and/or cultures.

DOSAGE AND ADMINISTRATION One full applicatorful (5 g) of terconazole vaginal cream 0.8% (40 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days. Before prescribing another course of therapy, the diagnosis should be reconfirmed by smears and/or cultures and other pathogens commonly associated with vulvovaginitis ruled out. The therapeutic effect of terconazole vaginal cream 0.8% is not affected by menstruation.

WARNINGS Anaphylaxis and toxic epidermal necrolysis have been reported during terconazole therapy. Terconazole Vaginal Suppositories, 80 mg therapy should be discontinued if anaphylaxis or toxic epidermal necrolysis develops.

CONTRAINDICATIONS Patients known to be hypersensitive to terconazole or to any of the components of the suppositories.

CLINICAL PHARMACOLOGY Absorption Following a single intravaginal application of a suppository containing 240 mg 14 C-terconazole to healthy women, approximately 70% (range: 64 to 76%) of terconazole remains in the vaginal area during the suppository retention period (16 hours); approximately 10% (range: 5 to 16%) of the administered radioactivity was absorbed systemically over 7 days. Maximum plasma concentrations of terconazole occur 5 to 10 hours after intravaginal application of the cream or suppository. Systemic exposure to terconazole is approximately proportional to the applied dose, whether as the cream or suppository. The rate and extent of absorption of terconazole are similar in patients with vulvovaginal candidiasis (pregnant or non-pregnant) and healthy subjects. Distribution Terconazole is highly protein bound (94.9%) in human plasma and the degree of binding is independent of drug concentration over the range of 0.01 to 5 mcg/mL. Metabolism Systemically absorbed terconazole is extensively metabolized (>95%). Elimination Across various studies in healthy women, after single or multiple intravaginal administration of terconazole as the cream or suppository/ovule, the mean elimination half-life of unchanged terconazole ranged from 6.4 to 8.5 hours. Following a single intravaginal administration of a suppository containing 240 mg 14 C-terconazole to hysterectomized or tubal ligated women, approximately 3 to 10% (mean ±SD: 5.7 ± 3%) of the administered radioactivity was eliminated in the urine and 2 to 6% (mean ± SD: 4.2 ± 1.6%) was eliminated in the feces during the 7-day collection period. Multiple Dosing There is no significant increase in maximum plasma concentration or overall exposure (AUC) after multiple daily applications of the cream for 7 days or suppositories for 3 days. Photosensitivity reactions have not been observed in U.S. and foreign clinical trials in patients who were treated with terconazole vaginal cream (0.4%). Microbiology Mechanism of action Terconazole, an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of terconazole. Mammalian cell demethylation is less sensitive to terconazole inhibition. Activity in vitro Terconazole exhibits antifungal activity in vitro against Candida albicans and other Candida species. The MIC values of terconazole against most Lactobacillus spp. typically found in the human vagina were ≥ 128 mcg/mL; therefore these beneficial bacteria are not affected by drug treatment.