gynazole 1 Dailymed

Contraindications

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.

Clinical Studies

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 butoconazole 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.

Warnings

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.

Precautions

General -

If clinical symptoms persist, tests should be repeated to rule out other pathogens, to confirm the original diagnosis, and to rule out other conditions that may predispose a patient to recurrent vaginal fungal infections.

Carcinogenesis, Mutagenesis, Impairment of Fertility -

Carcinogenesis - Long term studies in animals have not been performed to evaluate the carcinogenic potential of this drug.

Mutagenicity - Butoconazole nitrate was not mutagenic when tested in the Ames bacterial test, yeast, chromosomal aberration assay in CHO cells, CHO/HGPRT point mutation assay, mouse micronucleus, and rat dominant lethal assays.

Impairment of Fertility - No impairment of fertility was seen in rabbits or rats administered butoconazole nitrate in oral doses up to 30 mg/kg/day (5 times the human dose based on mg/m²) or 100 mg/kg/day (10 times the human dose based on mg/m²), respectively.

Pregnancy:

Pregnancy Category C -

In pregnant rats administered 6 mg/kg/day of butoconazole nitrate intravaginally during the period of organogenesis, there was an increase in resorption rate and decrease in litter size; however, no teratogenicity was noted. This dose represents a 130- to 353-fold margin of safety based on serum levels achieved in rats following intravaginal administration compared to the serum levels achieved in humans following intravaginal administration of the recommended therapeutic dose of butoconazole nitrate.

Butoconazole nitrate has no apparent adverse effect when administered orally to pregnant rats throughout organogenesis at dose levels up to 50 mg/kg/day (5 times the human dose based on mg/m²). Daily oral doses of 100, 300 or 750 mg/kg/day (10, 30 or 75 times the human dose based on mg/m² respectively) resulted in fetal malformations (abdominal wall defects, cleft palate), but maternal stress was also evident at these higher dose levels. There were, however, no adverse effects on litters of rabbits who received butoconazole nitrate orally, even at maternally stressful dose levels (e.g., 150 mg/kg, 24 times the human dose based on mg/m²).

Butoconazole nitrate, like other azole antifungal agents, causes dystocia in rats when treatment is extended through parturition. However, this effect was not apparent in rabbits treated with as much as 100 mg/kg/day orally (16 times the human dose based on mg/m²).

There are, however, no adequate and well-controlled studies in pregnant women. GYNAZOLE • 1^® Butoconazole Nitrate Vaginal Cream USP, 2% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers -

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when butoconazole nitrate is administered to a nursing woman.

Pediatric Use -

Safety and effectiveness in children have not been established.

Adverse Reactions

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.

Dosage And Administration

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.

How Supplied

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).

Manufactured By Padagis

Yeruham, Israel

Distributed By

Padagis_TM

Allegan, MI 49010 • www.padagis.com

Rev 05-22

8F200 RC J2

Patient Package Insert

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 not remove tip; do not use 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

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

Manufactured By Padagis

Yeruham, Israel

Distributed By

Padagis_TM

Allegan, MI 49010 • www.padagis.com

Rev 05-22

8F200 RC J2