Rx Only

Terconazole vaginal cream 0.4% is a white to off-white, water washable cream for intravaginal administration containing 0.4% of the antifungal agent terconazole, cis-1-[p-[[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-isopropylpiperazine, compounded in a cream base consisting of butylated hydroxyanisole, cetyl alcohol, isopropyl myristate, polysorbate 60, polysorbate 80, propylene glycol, stearyl alcohol, and purified water.

The structural formula of terconazole is as follows:

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.

Absorption

Following a single intravaginal application of a suppository containing 240 mg 14C-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 14C-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%).

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.

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

Anaphylaxis and toxic epidermal necrolysis have been reported during terconazole therapy. Terconazole therapy should be discontinued if anaphylaxis or toxic epidermal necrolysis develops.

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, 521 patients with vulvovaginal candidiasis were treated with terconazole 0.4% vaginal cream. Based on comparative analyses with placebo, the adverse experiences considered most likely related to terconazole 0.4% vaginal cream were headache (26% vs. 17% with placebo) and body pain (2.1% vs. 0% with placebo). Fever (1.7% vs. 0.5% with placebo) and chills (0.4% vs. 0.0% with placebo), vulvovaginal burning, itching and irritation have also been reported. The adverse drug experience on terconazole most frequently causing discontinuation was vulvovaginal itching.

Post-marketing Experience

The following adverse drug reactions have been first identified during post-marketing experience with terconazole vaginal cream 0.4%. 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

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 the 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.

One full applicator (5 g) of terconazole vaginal cream 0.4% (20 mg terconazole) should be administered intravaginally once daily at bedtime for seven 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 0.4% is not affected by menstruation.

Terconazole Vaginal Cream 0.4% is available in:

NDC 0168-0346-46     45 gram tube, with a measured dose applicator.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

E. FOUGERA & CO.

A division of

Fougera

PHARMACEUTICALS INC.

Melville, New York 11747

I2346C

R09/14

#22

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Terconazole Vaginal Cream 0.4%

PATIENT INSTRUCTIONS

Filling the applicator:

1.

Remove the cap from the tube.

2.

Use the pointed tip on the top of the cap to puncture the seal on the tube.

3.

Screw the applicator onto the tube.

4.

Squeeze the tube from the bottom and fill the applicator until the plunger stops.

5.

Unscrew the applicator from the tube.

Using the applicator:

1.

Lie on your back with your knees drawn up toward your chest.

2.

Holding the applicator by the ribbed end of the barrel, insert the filled applicator into the vagina as far as it will comfortably go.

3.

Slowly press the plunger of the applicator to release the cream into the vagina.

4.

Remove the applicator from the vagina.

5.

Apply one applicatorful each night for as many days at bedtime, as directed by your doctor.

Cleaning the applicator: After each use, you should thoroughly clean the applicator by following the procedure below:

1.

Pull the plunger out of the barrel.

2.

Wash both pieces with lukewarm, soapy water, and dry them thoroughly.

3.

Put the applicator back together by gently pushing the plunger into the barrel as far as it will go.

NOTE: Store at 20° to 25°C (68° to 77°F)

[see USP Controlled Room Temperature].

See side flap of carton for lot number and expiration date.

A WORD ABOUT YEAST INFECTIONS

Why do yeast infections occur?

Yeast infections are caused by an organism called Candida (KAN di duh). It may be present in small and harmless amounts in the mouth, digestive tract, and vagina. Sometimes the natural balance of the vagina becomes upset. This may lead to rapid growth of Candida, which results in a yeast infection. Symptoms of a yeast infection include itching, burning, redness, and an abnormal discharge.

Your doctor can make the diagnosis of a yeast infection by evaluating your symptoms and looking at a sample of the discharge under the microscope.

How can I prevent yeast infections?

Certain factors may increase your chance of developing a yeast infection. These factors don't actually cause the problem, but they may create a situation that allows the yeast to grow rapidly.

•

Clothing: Tight jeans, nylon underwear, pantyhose, and wet bathing suits can hold in heat and moisture (two conditions in which yeast organisms thrive). Looser pants or skirts, 100% cotton underwear, and stockings may help avoid this problem.

•

Diet: Cutting down on sweets, milk products, and artificial sweeteners may reduce the risk of yeast infections.

•

Antibiotics: Antibiotics work by eliminating disease-causing organisms. While they are helpful in curing other problems, antibiotics may lead to an overgrowth of Candida in the vagina.

•

Pregnancy: Hormonal changes in the body during pregnancy encourage the growth of yeast. This is a very common time for an infection to occur. Until the baby is born, it may be hard to completely eliminate yeast infections. If you believe you are pregnant, tell your doctor.

•

Menstruation: Sometimes monthly changes in hormone levels may lead to yeast infections.

•

Diabetes: In addition to heat and moisture, yeast thrives on sugar. Because diabetics often have sugar in their urine, their vaginas are rich in this substance. Careful control of diabetes may help prevent yeast infections.

Controlling these factors can help eliminate yeast infections and may prevent them from coming back.

Some other helpful tips:

1.

For best results, be sure to use the medication as prescribed by your doctor, even if you feel better very quickly.

2.

Avoid sexual intercourse, if your doctor advises you to do so.

3.

If your partner has any penile itching, redness, or discomfort, he should consult his physician and mention that you are being treated for a yeast infection.

4.

You can use the medication even if you are having your menstrual period. However, you should not use tampons because they may absorb the medication. Instead, use external pads or napkins until you have finished your medication. You may also wish to wear a sanitary napkin if the vaginal medication leaks.

5.

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.

6.

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

7.

Don't douche unless your doctor specifically tells you to do so. Douching may disturb the vaginal balance.

8.

Don't scratch if you can help it. Scratching can cause more irritation and spread the infection.

9.

Discuss with your physician any medication you are already taking. Certain types of medication can make your vagina more susceptible to infection.

10.

Eat nutritious meals to promote your general health.

KEEP OUT OF THE REACH OF CHILDREN.

E. FOUGERA & CO.

A division of

Fougera

PHARMACEUTICALS INC.

Melville, New York 11747

I2346C

R09/14

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 45 GRAM TUBE

NDC 0168-0346-46

Fougera®

TERCONAZOLE

VAGINAL CREAM

0.4%

Rx only

KEEP OUT OF THE REACH OF CHILDREN.

NET WT 45 grams

Quantity by weight not by volume

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 45 GRAM CARTON

NDC 0168-0346-46

Fougera®

Rx only

TERCONAZOLE

VAGINAL CREAM 0.4%

WARNING: Keep out of reach

of children.

NET WT 45 grams