Terconazole

INDICATIONS AND USAGE Terconazole Vaginal Suppositories, 80 mg are indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As this product 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 Terconazole Vaginal Suppository (80 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 suppositories is not affected by menstruation.

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

ADVERSE REACTIONS Adverse Reactions from Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. During controlled clinical studies conducted in the United States, 284 patients with vulvovaginal candidiasis were treated with terconazole 80 mg vaginal suppositories. Based on comparative analyses with placebo (295 patients), the adverse experiences considered adverse reactions most likely related to terconazole 80 mg vaginal suppositories were headache (30.3% vs. 20.7% with placebo) and pain of the female genitalia (4.2% vs. 0.7% with placebo). Adverse reactions that have also been reported but were not statistically significantly different from placebo were burning (15.2% vs. 11.2% with placebo) and body pain (3.9% vs. 1.7% with placebo). Fever (2.8% vs. 1.4% with placebo) and chills (1.8% vs. 0.7% with placebo) have also been reported. The adverse drug experience on terconazole most frequently causing discontinuation was burning (2.5% vs. 1.4% with placebo) and pruritus (1.8% vs. 1.4% with placebo). Post-marketing Experience The following adverse drug reactions have been first identified during post-marketing experience with terconazole:. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General: Asthenia, Influenza-Like Illness consisting of multiple listed reactions including fever and chills, nausea, vomiting, myalgia, arthralgia, malaise Immune: Hypersensitivity, Anaphylaxis, Face Edema Nervous: Dizziness Respiratory: Bronchospasm Skin: Rash, Toxic Epidermal Necrolysis, Urticaria To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions - The therapeutic effect of terconazole is not affected by oral contraceptive usage. The levels of estradiol and progesterone did not differ significantly when 0.8% terconazole vaginal cream was administered to healthy female volunteers established on a low dose oral contraceptive.

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.

DESCRIPTION Terconazole Vaginal Suppositories are white to off-white suppositories for intravaginal administration containing 80 mg of the antifungal agent terconazole, cis -1-[ p -[[2-(2,4-Dichlorophenyl)-2-(1 H -1,2,4-triazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methoxy]phenyl]-4-isopropylpiperazine, in triglycerides derived from coconut and/or palm kernel oil (a base of hydrogenated vegetable oils) and butylated hydroxyanisole. The structural formula of terconazole is as follows: TERCONAZOLE C 26 H 31 Cl 2 N 5 O 3 Terconazole, a triazole derivative, is a white to almost white powder with a molecular weight of 532.47. It is insoluble in water; sparingly soluble in ethanol; and soluble in butanol. Chemical Structure

OVERDOSAGE In the rat, the oral LD 50 values were found to be 1741 and 849 mg/kg for the male and female, respectively. The oral LD 50 values for the male and female dog were ≅1280 and ≥640 mg/kg, respectively. In the event of oral ingestion of suppository or cream, supportive and symptomatic measures should be carried out. If the cream is accidentally applied to the eyes, wash with clean water or saline and seek medical attention if symptoms persist.

HOW SUPPLIED Terconazole Vaginal Suppositories 80 mg are available as 2.5 g, elliptically-shaped white to off-white suppositories in packages of three with a vaginal applicator. NDC 0713-0552-73 Store at 20°- 25°C (68°- 77°F) [see USP Controlled Room Temperature].