Information for the Patient
Gynazole•1
Pharmacology
GYNAZOLE•1 (butoconazole nitrate) vaginal cream 2%, contains butoconazole nitrate 2%, an imidazole derivative with antifungal activity.
Like other imidazole derivatives, butoconazole nitrate presumably exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition. Although the exact mechanism of action of butoconazole nitrate has not been fully determined, it has been suggested that the fungistatic activity of the drug may result from interference with ergosterol synthesis, probably via inhibition of C-14 demethylation of sterol intermediates (e.g. lanosterol). Like some other imidazole derivatives (e.g. miconazole), the fungicidal activity of butoconazole at high concentrations may result from a direct physicochemical effect of the drug on the fungal cell. This effect may involve hydrophobic interactions between the drug and unsaturated fatty acid components of the membrane.
Butoconazole has some antibacterial activity against gram-positive organisms, but this effect cannot be explained on the basis of inhibition of ergosterol synthesis since bacteria generally do not contain membrane sterols. It has been suggested that the antibacterial effect of butoconazole and other imidazole derivatives may be similar to the physicochemical effect of these agents on fungi or may involve other metabolic sites.
Indications
GYNAZOLE•1 (butoconazole nitrate) vaginal cream 2%, is indicated for the local treatment of vulvovaginal infections caused by C. albicans. The diagnosis should be confirmed by KOH smears and/or cultures.
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).
Precautions
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.
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.
Appropriate microbiologic studies should be performed to confirm the diagnosis and rule out infection caused by non-susceptible pathogens when an adequate response is not achieved following a course of butoconazole therapy. Patients should be instructed not to rely on condoms or diaphragms to prevent sexually transmitted diseases or pregnancy during butoconazole nitrate therapy, since the cream may damage these devices and result in protective failure. Alternative methods of birth control should be used. Patients also should be instructed not to use tampons while using intravaginal butoconazole nitrate vaginal cream.
Butoconazole nitrate vaginal cream should not be applied to the eye nor administered orally. Patients receiving butoconazole nitrate vaginal cream should be instructed to contact their physician or local poison control centre immediately if they accidentally ingest the vaginal cream.
Patients also should be advised to consult a clinician if manifestations of vulvovaginitis recur within 2 months of therapy, or if they think that they may have been exposed to HIV. Recurrent infection may be a sign of pregnancy or a serious underlying condition such as AIDS or diabetes mellitus.
Women with diabetes mellitus, or who are HIV positive or have AIDS, or possible pelvic inflammatory disease (abdominal pain, fever, or a foul-smelling vaginal discharge) should only be treated with butoconazole nitrate while under the care of a physician familiar with their medical history.
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), and 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.
Butoconazole nitrate was not mutagenic when tested in the Ames bacterial test, yeast gene conversion, chromosomal aberration assay in CHO cells, CHO/HGPRT point mutation assay, mouse micronucleus, and rat dominant lethal assays.
No impairment of fertility was seen in rabbits or rats administered butoconazole nitrate in oral doses up to 30 mg/kg/day (3 times the human dose based on mg/m2) or 100 mg/kg/day (10 times the human dose based on mg/m2), respectively.
Long term studies in animals have not been performed to evaluate the carcinogenic potential of this drug.
Safety and effectiveness in children have not been established.
Supplied
Each g of cream contains: butoconazole nitrate 2%. Nonmedicinal ingredients: colloidal silicon dioxide, edetate disodium, glyceryl monoisostearate, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3 oleate, propylene glycol, propylparaben, purified water and sorbitol solution. Cartons of 1 single-dose prefilled disposable applicator (approximately 5 g of the cream). Store at room temperature 15 to 30°C. Avoid heat above 30°C.
Contraindications
GYNAZOLE•1 is contraindicated in patients with a history of hypersensitivity to any of the components of the product.
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 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.
Adverse Effects
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.
Although hepatocellular dysfunction has occurred during systemic treatment with imidazole-derived antifungal agents (e.g. ketoconazole), this adverse event has not been reported to date following intravaginal butoconazole nitrate therapy.
Overdose
There is no specific treatment for butoconazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.
Dosage
The recommended dose of GYNAZOLE•1 is one applicator of cream (approximately 5 g of the cream) intravaginally as a single dose treatment. This amount of cream contains approximately 100 mg of butoconazole nitrate.
Butoconazole nitrate vaginal cream is for intravaginal administration only and should not be administered orally; contact with the eyes should be avoided.
