6.1 Clinical Trial Experience

During controlled clinical studies conducted in the United States, patients with vulvovaginal candidiasis were treated with terconazole vaginal cream, 0.8% for 3 days. Based on comparative analyses with placebo (Table 1), the adverse experiences considered most likely related to terconazole vaginal cream, 0.8% were headache (21% vs. 16% with placebo) and dysmenorrhea (6% vs. 2% with placebo). Other adverse experiences reported with terconazole vaginal cream 0.8% were abdominal pain (3.4% vs. 1% with placebo), fever (1% vs. 0.3% with placebo), and genital burning and itching (5% vs. 6%-9% with placebo). The therapy-related dropout rate was 2.0% for terconazole vaginal cream 0.8%. The adverse drug experience most frequently causing discontinuation of terconazole vaginal cream, 0.8% therapy was vulvovaginal itching (0.7% vs. 0.3% placebo).

Table 1

Photosensitivity reactions were observed in some normal volunteers following repeated dermal application of terconazole 2.0% 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 terconazole suppositories or vaginal cream, 0.8%.

8.1 Pregnancy

Terconazole vaginal cream, 0.8% should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus. There are no adequate and well-controlled clinical trials of terconazole vaginal cream, 0.8% in pregnant women.

Animal data

There was no evidence of teratogenicity when terconazole was administered orally up to (10 times the recommended intravaginal human dose based on body surface area comparisons) in rats, or rabbits.

There was a delay in fetal ossification at 10 mg/kg/day in rats (about 2 times the recommended intravaginal human dose based on body surface area comparisons). Higher doses, up to 10 times the recommended intravaginal human dose based on body surface area comparisons, resulted in decreased litter size, decreased number of viable young and reduced fetal weight in rats. There was also 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. Since terconazole is absorbed from the human vagina, it should not be used in the first trimester of pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.

8.2 Nursing Mothers

It is not known whether terconazole is excreted in human milk. Caution should be exercised when terconazole is administered to a nursing woman.

8.3 Pediatric Use

The safety and effectiveness of terconazole vaginal cream, 0.8% have not been established in pre-menarchal females.

8.4 Geriatric Use

Clinical studies of terconazole vaginal cream, 0.8% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

12.1 Mechanism of Action

Terconazole is an antifungal agent [see Clinical Pharmacology, Microbiology (12.4)].

12.3 Pharmacokinetics

Following intravaginal administration of terconazole vaginal cream, 0.8% in females, absorption ranged from 5-8% in three hysterectomized subjects and 12-16% in two non-hysterectomized subjects with tubal ligations.

Following daily intravaginal administration of 0.8% terconazole 40 mg (0.8% cream x 5 g) for seven days to healthy female subjects, plasma concentrations were low and gradually rose to a daily peak (mean of 5.9 ng/mL or 0.006 mcg/mL) at 6.6 hours. Results from similar studies in female patients with vulvovaginal candidiasis indicate that the slow rate of absorption, the lack of accumulation, and the mean peak plasma concentration of terconazole was not different from that observed in healthy females. The absorption characteristics of terconazole vaginal cream, 0.8% in pregnant or non-pregnant patients with vulvovaginal candidiasis were also similar to those found in healthy subjects.

Following oral (30 mg) administration of 14C-labelled terconazole, the mean half-life of elimination from the blood for the parent terconazole was 6.9 hours (range 4.0-11.3). Terconazole is extensively metabolized; the plasma AUC for terconazole compared to the AUC for total radioactivity was 0.6%. Total radioactivity was eliminated from the blood with a mean elimination half-life of 52.2 hours (range 44-60). Excretion of radioactivity was both by renal (32-56%) and fecal (47- 52%) routes.

In vitro, terconazole is highly protein bound (94.9%) and the degree of binding is independent of drug concentration.

12.4 Microbiology

Mechanism of Action

Terconazole inhibits the enzyme cytochrome P450 14α-demethylase which leads to inhibition of ergosterol synthesis, an essential component of the fungal cell membrane

Activity in vitro

Terconazole exhibits fungicidal activity in vitro against Candida albicans.

Drug Resistance

Studies showed no development of resistance to terconazole during successive passages of C. albicans. However, the clinical significance of such an effect is not known.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to determine the carcinogenic potential of terconazole have not been performed. Terconazole was not mutagenic when tested in vitro for induction of microbial point mutations (Ames test), or for inducing cellular transformation, or in vivo for chromosome breaks (micronucleus test) or dominant lethal mutations in mouse germ cells. No impairment of fertility occurred when female rats were administered terconazole orally up to 40 mg/kg/day (about 10 times the recommended intravaginal human dose based on body surface area comparisons) for a three-month period.

17.1 Instructions for Use

Patients using terconazole vaginal cream, 0.8% should receive the following information and instructions:

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Terconazole vaginal cream, 0.8% is for intravaginal use only. Avoid contact with eyes and inside the nose and mouth.

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This medication should be used for three days as directed, even if you feel better quickly.

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Do not use this medication for any disorder other than the one for which it was prescribed.

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Terconazole vaginal cream, 0.8% should be used once a day as directed.

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If your sexual partner has itching, redness or discomfort in the genital area, tell your partner to consult a physician and that you are being treated for a yeast infection.

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Terconazole vaginal cream, 0.8% can be used during a menstrual period but external pads should be used until the medication treatment has been completed. Tampons may absorb the medication and should not be used. You may wish to wear an absorbent panty liner while using terconazole vaginal cream, 0.8%.

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Don’t scratch the vaginal area. Scratching can cause more irritation and spread the infection.

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Wash hands before and after applying terconazole vaginal cream, 0.8%.

Patients prone to vaginal yeast infections should receive the following instructions:

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Dry the genital area thoroughly after showering, bathing, or swimming. Change out of a wet bathing suit or damp exercise clothes as soon as possible. A dry environment is less likely to encourage the growth of yeast.

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Wipe from front to rear (away from the vagina) after a bowel movement.

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Don’t douche unless the healthcare provider specifically tells you to do so. Douching may disturb the balance of normal bacterial flora and the pH of secretions.

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See FDA-Approved Patient Labeling (17.2)

17.2 FDA-Approved Patient Labeling

PATIENT INFORMATION

TERCONAZOLE

(ter kon ah zol)

VAGINAL CREAM, 0.8%

Read the Patient Information that comes with terconazole vaginal cream, 0.8% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment.

What is terconazole vaginal cream, 0.8%?

Terconazole vaginal cream, 0.8% is prescription medicine used to treat vaginal yeast infections caused by a fungus called Candida (KAN di duh).

It is not known if terconazole vaginal cream, 0.8% is safe or effective in females who have not reached puberty.

Who should not use terconazole vaginal cream, 0.8%?

Do not use terconazole vaginal cream, 0.8% if you are allergic to terconazole or any of the other ingredients of the cream. See the end of this leaflet for a complete list of ingredients in terconazole vaginal cream, 0.8%.

What should I tell my doctor before using terconazole vaginal cream, 0.8%?

Before using terconazole vaginal cream, 0.8%, tell your doctor if you:

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Have had an allergic reaction to another antifungal medicine.

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If you are pregnant or plan to become pregnant. Terconazole vaginal cream, 0.8% is absorbed from the vagina. You should not use terconazole during pregnancy without first talking to your doctor.

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If you are breastfeeding or plan to breastfeed. It is not known if terconazole vaginal cream, 0.8% passes into your breast milk.

Tell your doctor about all the medicines that you take including prescription and non-prescription medicines, vitamins and herbal supplements. Certain types of medicines can increase the chance of getting vaginal infections.

How should I use terconazole vaginal cream, 0.8%?

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Use terconazole vaginal cream, 0.8% exactly as prescribed.

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Apply one full applicator of terconazole vaginal cream, 0.8% each night at bedtime for as many days as your doctor tells you (usually 3 days in a row).

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Do not stop using terconazole vaginal cream, 0.8% before your doctor tells you to, even if you feel better very quickly. Your infection may not clear up completely.

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Terconazole vaginal cream, 0.8% is not for use in the mouth, eyes, or inside the nose.

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See the end of this leaflet for detailed Instructions for Use about how to use Terconazole vaginal cream correctly.

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Avoid scratching the affected area. Scratching may cause more irritation and spread the infection.

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If your sexual partner has itching, redness, or discomfort in the genital area, tell your partner to see their doctor and tell their doctor that you being treated for a yeast infection.

•

Terconazole vaginal cream, 0.8% can be used during a menstrual period. You should not use tampons because they absorb the medicine. Use external pads until treatment with terconazole vaginal cream, 0.8% has been completed.

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Follow your doctor’s instructions about how to reduce your chances of getting vaginal yeast infections.

What are possible side effects with terconazole vaginal cream, 0.8%?

Tell your doctor if you get any of the following symptoms during treatment with terconazole vaginal cream, 0.8%:

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Skin irritation.

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Fever, chills, or flu-like symptoms

If you have any of the symptoms listed above, your doctor may tell you to stop using terconazole vaginal cream, 0.8% and prescribe a different medicine to treat your fungal infection.

Common side effects of terconazole vaginal cream, 0.8% include

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Headaches

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Painful menstrual periods

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of terconazole vaginal cream, 0.8%. Ask your doctor or pharmacist for more information.

Call your doctor for advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088

How should I store terconazole vaginal cream, 0.8%?

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Store terconazole vaginal cream, 0.8% at room temperature, 68°F to 77°F (20°C to 25°C)

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Keep terconazole vaginal cream, 0.8% and all medicines out of the reach of children

General information about terconazole vaginal cream, 0.8%

Medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use terconazole vaginal cream, 0.8% for a condition for which it was not prescribed. Do not give terconazole vaginal cream, 0.8% to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about terconazole vaginal cream, 0.8%. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about terconazole vaginal cream, 0.8% that is written for healthcare professionals. If you have questions about terconazole vaginal cream, 0.8% you can also call: 1-800-645-9833.

What are the ingredients in terconazole vaginal cream, 0.8%?

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Active Ingredients: terconazole 0.8%

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Inactive Ingredients: butylated hydroxyanisole, cetyl alcohol, isopropyl myristate, polysorbate 60, polysorbate 80, propylene glycol, stearyl alcohol, and purified water.

Instructions for Use Terconazole Vaginal Cream, 0.8% Be sure to read, understand, and follow the instructions below for how to use terconazole vaginal cream, 0.8% correctly. 1. Wash your hands. 2. Fill the Applicator: • Remove the cap from the tube. • Use the pointed tip on the top of the cap to puncture the seal on the tube. • Screw the applicator onto the tube. • Squeeze the tube from the bottom and fill the applicator until the plunger stops. • Unscrew the applicator from the tube.
3. Insert the Cream: • Lie on your back with knees drawn up toward your chest. • Holding the applicator by the ribbed end of the barrel, insert the filled applicator into the vagina as far as it will comfortably go. • Slowly press the plunger of the applicator to release the cream into the vagina. • Remove the applicator from the vagina. Wash the applicator.
4. Wash the Applicator after Use • Wash the applicator after each use. • Pull the plunger out of the barrel. • Wash the applicator pieces with lukewarm, soapy water and then dry them thoroughly. • Put the dry applicator pieces back together by gently pushing the plunger into the barrel as far as it will go. 5. Wash your hands well after you finish washing and drying the applicator.

The brands listed are the registered trademarks of their respective owners and are not trademarks of Fougera Pharmaceuticals Inc.

Revised: December 2024

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