GYNAZOLE•1® (butoconazole nitrate) vaginal cream, 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® 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.

Last updated on RxList: 7/17/2008

GYNAZOLE•1® (butoconazole nitrate) vaginal cream, 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® 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.)

The recommended dose of GYNAZOLE •1® 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, 2% is available in cartons containing one single-dose prefilled disposable applicator (NDC 64011-001-08).

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 for Ther-Rx Corporation by KV Pharmaceutical Co. St. Louis, MO 63044. 08/03. FDA Rev date: 7/24/2003

Last updated on RxList: 7/17/2008

Of the 314 patients treated with GYNAZOLE •1® 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.

No information provided.

Last updated on RxList: 7/17/2008

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® 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.

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 anti-fungal 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® 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.

Last updated on RxList: 7/17/2008

No information provided.

GYNAZOLE•1® is contraindicated in patients with a history of hypersensitivity to any of the components of the product.

Last updated on RxList: 7/17/2008

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.

Microbiology

The exact mechanism of the antifungal action of butoconazole nitrate is unknown; however, it is presumed to function as other imidazole derivatives via inhibition of steroid synthesis. lmidazoles generally inhibit the conversion of lanosterol to ergosterol, resulting in a change in fungal cell membrane lipid composition. This structural change alters cell permeability and, ultimately, results in the osmotic disruption or growth inhibition of the fungal cell.

Butoconazole nitrate is an imidazole derivative that has fungicidal activity in vitro against Candida spp. and has been demonstrated to be clinically effective against vaginal infections due to Candida albicans. Candida albicans has been identified as the predominant species responsible for vulvovaginal candidiasis.

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 is defined by a 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. The therapeutic cure rate was 67% in the butoconazole group and 61% in the clotrimazole group.

Table 1

	2% butoconazole nitrate cream	500-mg clotrimazole vaginal tablet
Enrolled	161	161
Evaluable at Late Follow-up	118	116
Clinical Cure	95/118 (81%)	93/116 (80%)
Mycologic Eradication*	87/118 (74%)	77/116 (66%)
Therapeutic Cure	79/118 (67%)	71/116 (61%)
*=C. albicans in the vaginal culture was proven at admission in all of these patients.

Last updated on RxList: 7/17/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 7/17/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BUTOCONAZOLE NITRATE CREAM - VAGINAL

(byoo-toe-CON-uh-zole NYE-trate)

COMMON BRAND NAME(S): Femstat, Gynazole-1, Mycelex

USES: This medication is used to treat vaginal yeast infections. Butoconazole reduces vaginal burning, itching, and discharge that may occur with this condition. This medication is an azole antifungal. It works by stopping the growth of yeast (fungus) that causes the infection.

HOW TO USE: Read the Patient Information Leaflet available with this product. Consult your doctor or pharmacist if you have any questions.

If you are pregnant, follow your doctor's instructions on how to use the applicator to insert this medication.

Use the medication once daily, usually at bedtime or as directed by your doctor. Wash your hands before using the medication. Use the applicator (either prefilled or disposable). Follow the package instructions on how to fill the disposable applicator with the cream. Lie on your back with your knees toward your chest. Insert one applicator full of cream into the vagina as far as it will comfortably go. Slowly press the plunger of the applicator all the way down to apply the cream. If you have itching/burning around the outside of the vagina (vulva), apply some cream to that area as well. After use, discard the applicator and wash your hands.

Continue to use this medication every day for the full time prescribed, even if symptoms disappear after a few days or if your menstrual period starts. Stopping the medication too soon may allow the yeast infection to return. Do not use tampons or douches while using this medication. Unscented sanitary napkins may be used for your menstrual period or to protect your clothing from leakage of the medication.

Inform your doctor if your condition persists or returns 1 week after completing the treatment.

SIDE EFFECTS: Headache, burning/itching/pain in the vagina or urinary opening, or lower abdominal cramps may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

If your doctor has prescribed this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fever, chills, flu-like symptoms, stomach/abdominal pain.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using butoconazole, tell your doctor or pharmacist if you are allergic to it; or to other azole antifungal agents (e.g., clotrimazole, fluconazole); or to mineral oil; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, immune system problems, 4 or more vaginal yeast infections per year.

Ask your doctor whether you can have sexual intercourse while using this product. Avoid using a diaphragm, cervical cap, or latex condoms for birth control while using this product and for 3 days after treatment is finished. Some ingredients in the cream may damage these products, possibly causing them to break. Use other forms of birth control such as polyurethane condoms.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: oral antibiotics, corticosteroids (e.g., prednisone), drugs that suppress the immune system (e.g., cyclosporine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This product may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., KOH smear, culture) may be performed periodically to monitor your progress. Consult your doctor for more details.

Dry the genital area thoroughly after showering, bathing, or swimming. Avoid wearing tight jeans, nylon underwear, pantyhose, a wet bathing suit, or damp/sweaty exercise clothes for long periods. Wear cotton underwear, and change your underwear daily. This may help to prevent the growth of yeast.

If your sexual partner experiences symptoms, they should contact their doctor immediately.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the cream at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.