Terconazole Vaginal Cream 0.8%

1 INDICATIONS AND USAGE Terconazole Vaginal Cream, is indicated for the treatment of vulvovaginal candidiasis in adult females. Terconazole Vaginal Cream is an azole antifungal indicated for the treatment of vulvovaginal candidiasis in adult females. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dose is one applicator full of Terconazole Vaginal Cream (5 grams of cream containing 40 mg terconazole) administered intravaginally once daily at bedtime for three consecutive days. Terconazole Vaginal Cream is not for oral or ophthalmic use. • One full applicator (5 grams) of Terconazole Vaginal Cream administered intravaginally once daily at bedtime for three (3) consecutive days. ( 2 ) • Not for oral or ophthalmic use. ( 2 )

5 WARNINGS AND PRECAUTIONS Risk of Skin Irritation and Flu-Like Symptoms: Discontinue Terconazole Vaginal Cream and do not retreat if skin irritation, fever, chills or flu-like symptoms are reported during use. ( 5 ) 5.1 Risk of Skin Irritation and Flu-Like Symptoms Discontinue Terconazole Vaginal Cream and do not retreat, if skin irritation, fever, chills or flu-like symptoms are reported during use. 5.2 Hypersensitivity There is no information regarding cross-hypersensitivity between terconazole and other azole antifungal agents. Monitor patients with a history of hypersensitivity to azoles.

4 CONTRAINDICATIONS Terconazole Vaginal Cream, 0.8% is contraindicated in patients with known hypersensitivity to terconazole or to any of the components of the cream. Known hypersensitivity to terconazole or any other component of the cream ( 4 )

7 DRUG INTERACTIONS Oral Contraceptives: There is no known interaction with the concomitant use of this product and oral contraceptives.

8.1 Pregnancy Risk Summary There are no available data on Terconazole Vaginal Cream use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Available data from observational studies with terconazole use in pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies with oral terconazole, no adverse development effects were observed at clinically relevant systemic exposures (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data There was no evidence of malformations when terconazole was administered orally in rats, or rabbits. There was a delay in fetal ossification at an oral dose of 10 mg/kg/day in rats. Higher doses resulted in decreased litter size, decreased number of viable young and reduced fetal weight in rats. There was also a delay in ossification and an increase incidence of skeletal variants. The 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 30 times the mean peak plasma level (0.006 mcg/mL) seen in normal subjects after intravaginal administration of terconazole vaginal cream 0.8%. 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.

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 2%) were headache, dysmenorrhea, genital burning and itching, and abdominal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fougera at 1-800-645-9833 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use and estimating their relative rates. During a controlled clinical trial conducted in the United States, patients with vulvovaginal candidiasis were treated with Terconazole Vaginal Cream, 0.8% for 3 days (n=231) or Terazol®3 for 3 days (n=229) [see Clinical Studies (14)]. Table 1 lists the adverse reactions occurring in ≥2% of patients receiving Terconazole Vaginal Cream in the trial. The therapy-related discontinuation rate was 2.0% for Terconazole Vaginal Cream. The adverse reaction most frequently causing discontinuation of Terconazole Vaginal Cream therapy was vulvovaginal itching (0.7%). Table 1: Adverse Reactions Occurring in ≥2% of Patients Receiving Terconazole Vaginal Cream in a Randomized, Double-Blind Active Controlled Trial Terconazole Vaginal Cream, 0.8% n=231 (%) Terazol ® 3 n=229 (%) Headache 49 (21) 37(16) Dysmenorrhea 14 (6) 5 (2) Genital Burning and Itching 12 (5) 15-21 (6-9) Abdominal Pain 8 (3.4) 2 (1) Other adverse reactions reported in less than 2% of patients receiving Terconazole Vaginal Cream was fever (1%). Photosensitivity reactions were observed in some normal volunteers following repeated dermal application of terconazole 2.0% (not an approved strength) and 0.8% creams under conditions of filtered artificial ultraviolet light. Photosensitivity reactions were not observed in U.S. and foreign clinical trials in patients who were treated with other terconazole formulations (i.e., terconazole suppositories or vaginal cream, 0.8%).