Terconazole

INDICATIONS AND USAGE Terconazole Vaginal Suppositories, 80 mg is 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.

WARNINGS Anaphylaxis and toxic epidermal necrolysis have been reported during terconazole therapy. Terconazole 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.

Drug Interactions The therapeutic effect of this product is not affected by oral contraceptive usage.

Pregnancy Teratogenic Effects Pregnancy Category C There was no evidence of teratogenicity when terconazole was administered orally up to 40 mg/kg/day (25× the recommended intravaginal human dose of the suppository formulation) in rats, or 20 mg/kg/day in rabbits, or subcutaneously up to 20 mg/kg/day in rats. Dosages at or below 10 mg/kg/day produced no embryotoxicity; however, there was a delay in fetal ossification at 10 mg/kg/day in rats. There was some evidence of embryotoxicity in rabbits and rats at 20 to 40 mg/kg. In rats, this was reflected as a decrease in litter size and number of viable young and reduced fetal weight. There was also delay in ossification and an increased incidence of skeletal variants. The no-effect dose of 10 mg/kg/day resulted in a mean peak plasma level of terconazole in pregnant rats of 0.176 mcg/mL which exceeds by 17 times the mean peak plasma level (0.010 mcg/mL) seen in normal subjects after intravaginal administration of terconazole 80 mg vaginal suppository. This safety assessment does not account for possible exposure of the fetus through direct transfer to terconazole from the irritated vagina by diffusion across amniotic membranes. Since terconazole is absorbed from the human vagina, it should not be used in the first trimester of pregnancy unless the physician considers it essential to the welfare of the patient. Terconazole may be used during the second and third trimester if the potential benefit outweighs the possible risks to the fetus.

Nursing Mothers It is not known whether this drug is excreted in human milk. Animal studies have shown that rat offspring exposed via the milk of treated (40 mg/kg/orally) dams showed decreased survival during the first few post-partum days, but overall pup weight and weight gain were comparable to or greater than controls throughout lactation. Because many drugs are excreted in human milk, and because of the potential for adverse reaction in nursing infants from terconazole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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