GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% contains butoconazole nitrate 2%, an imidazole derivative with antifungal activity. Its chemical name is (±)-1-[4-(p-chlorophenyl)-2- [(2,6-dichlorophenyl) thio]butyl] imidazole mononitrate, and it has the following chemical structure:

Butoconazole nitrate is a white to off-white crystalline powder with a molecular weight of 474.79. It is sparingly soluble in methanol; slightly soluble in chloroform, methylene chloride, acetone, and ethanol; very slightly soluble in ethyl acetate; and practically insoluble in water. It melts at about 159°C with decomposition.

GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% contains 2% butoconazole nitrate in a cream of edetate disodium, glyceryl monoisostearate, methylparaben, mineral oil, polyglyceryl-3 oleate, propylene glycol, propylparaben, colloidal silicon dioxide, sorbitol solution, purified water, and microcrystalline wax.

Following vaginal administration of butoconazole nitrate vaginal cream, 2% to 3 women, 1.7% (range 1.3-2.2%) of the dose was absorbed on average. Peak plasma levels (13.6-18.6 ng radioequivalents/mL of plasma) of the drug and its metabolites are attained between 12 and 24 hours after vaginal administration.

GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% is indicated for the local treatment of vulvovaginal candidiasis (infections caused by Candida). The diagnosis should be confirmed by KOH smears and/or cultures (see CLINICAL STUDIES).

Note: GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% is safe and effective in non-pregnant women; however, the safety and effectiveness of this product in pregnant women has not been established (see PRECAUTIONS - Pregnancy).

GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% is contraindicated in patients with a history of hypersensitivity to any of the components of the product.

Vulvovaginal Candidiasis: Two studies were conducted that compared 2% butoconazole nitrate cream with clotrimazole tablets. There were 322 enrolled patients, 161 received 2.0% butoconazole vaginal cream and 161 patients inserted the 500-mg clotrimazole vaginal tablet. At the second follow-up visit (30 days post-therapy), 118 patients in the butoconzole group and 116 in the clotrimazole group were evaluable for efficacy analysis, respectively. All of these patients had infection caused by Candida albicans.

The efficacy of the study drugs was assessed by evaluating clinical, mycologic and therapeutic cure rates, which are summarized in Table 1.

The therapeutic cure was defined as complete resolution of signs and symptoms of vaginal candidiasis (clinical cure) along with a negative KOH examination and negative culture for Candida spp. (microbiologic eradication) at the long term follow-up (30 days). The therapeutic cure rate was 67% in the butoconazole group and 61% in the clotrimazole group.

This cream contains mineral oil. Mineral oil may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms; therefore, use of such products within 72 hours following treatment with GYNAZOLE•1® Butoconazole Nitrate Vaginal Cream USP, 2% is not recommended.

Recurrent vaginal yeast infections, especially those that are difficult to eradicate, can be an early sign of infection with the human immunodeficiency virus (HIV) in women who are considered at risk for HIV infection.

Of the 314 patients treated with GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% for 1 day in controlled clinical trials, 18 patients (5.7%) reported complaints such as vulvar/vaginal burning, itching, soreness and swelling, pelvic or abdominal pain or cramping, or a combination of two or more of these symptoms. In 3 patients (1%) these complaints were considered treatment-related. Five of the 18 patients reporting adverse events discontinued the study because of them.

The recommended dose of GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% is one applicatorful of cream (approximately 5 grams of the cream) intravaginally. This amount of cream contains approximately 100 mg of butoconazole nitrate.

GYNAZOLE•1® Butoconazole Nitrate Vaginal Cream USP, 2% is available in cartons containing one single-dose prefilled disposable applicator (NDC 45802-396-01).

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Avoid heat above 30°C (86°F)

Made in Israel

Manufactured By Perrigo

Yeruham 80500, Israel

Distributed By

Perrigo®

Allegan, MI 49010 • www.perrigo.com

Rev 11-14

:8F200 RC J1

GYNAZOLE•1®

Butoconazole Nitrate Vaginal Cream USP, 2%

IN ONE PREFILLED DISPOSABLE APPLICATOR

Using the GYNAZOLE•1® Butoconazole Nitrate Vaginal Cream USP, 2%

Prefilled Disposable Applicator

3 Easy Steps:

Step 1: Preparing the Applicator

Peel back the protective foil and remove the prefilled applicator. Applicator is designed to be used with tip in place. Do notremove tip; do notuse applicator if tip has been removed.

Do not warm applicator before using. While holding the applicator firmly, pull the ring back to fully extend the plunger (see Figures 1 and 2 ).

Step 2: Inserting the Applicator

Gently insert the applicator into the vagina as far as it will comfortably go (see Figures 3A and 3B ).

Step 3: Applying the Cream

Push the plunger to release the cream (see Figures 4A, 4B and 4C ). Remove the empty applicator from the vagina and throw it away.

Important Instructions

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One prefilled applicator of GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% should be administered.

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This cream contains mineral oil. Mineral oil may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms; therefore, use of such products within 72 hours following treatment with GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% is not recommended.

•

There are no adequate and well-controlled studies in pregnant women. GYNAZOLE • 1® Butoconazole Nitrate Vaginal Cream USP, 2% should be used during pregnancy only under the supervision of a physician.

Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088.

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:8F200 RC J1

Rx Only

NDC 45802-396-01

GYNAZOLE•1®

Butoconazole Nitrate Vaginal Cream USP, 2%

The applicator delivers approximately 5 g cream, containing 100 mg butconazole nitrate.

IN ONE PREFILLED DISPOSABLE APPLICATOR

For Vaginal Use Only.

NET WT 5.8 g

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