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Mycelex®-G 500 mg is an effective antifungal containing 500 mg of clotrimazole (the active ingredient). Clotrimazole is a broad spectrum antifungal which exhibits fungicidal activity in vitro against Candida albicans and other species of the genus Candida. No single-step or multiple-step resistance to clotrimazole has developed during successive passages of Candida albicans.
Mycelex®-G 500 mg has proved to be clinically effective for local treatment of vulvovaginal candidiasis when one day therapy is felt warranted. In the case of severe vulvovaginal candidiasis longer antimycotic therapy such as Mycelex®-G 100 mg tablets or Mycelex®-G Cream is recommended.
Mycelex®-G 500 Vaginal Tablets are contraindicated in women who have shown hypersensitivity to any components of the compound. If there is a lack of response to treatment with Mycelex®-G 500 mg, appropriate microbiological studies should be performed to confirm the diagnosis and rule out other pathogens before instituting another course of antimycotic therapy. There are, however, no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy.
Each Mycelex®-G 500 mg Vaginal Tablet contains 500 mg clotrimazole (the active ingredient) dispersed in lactose, microcrystalline cellulose, lactic acid, corn starch, crospovidone, calcium lactate, magnesium stearate, silicon dioxide and hydroxypropyl methylcellulose. Chemically, clotrimazole is [1-(o-Chloro-(alpha), (alpha)-diphenylbenzyl) imidazole], a synthetic antifungal agent having the chemical formula C 22 H 17 ClN 2 ; a molecular weight of 344.84; and the following chemical structure:
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Clotrimazole is an odorless, white crystalline substance, practically insoluble in water, sparingly soluble in ether, soluble in carbon tetrachloride, and very soluble in ethanol and chloroform.
Serum levels and levels in vaginal secretions of clotrimazole were measured in six healthy volunteers who had one 500 mg vaginal tablet inserted. Although serum levels of clotrimazole were higher than those in other volunteers given 100 mg and 200 mg vaginal tablets these levels did not exceed 10 nanograms/mL. It has been estimated that three to ten percent of a vaginal dose of clotrimazole may be absorbed, but the drug rapidly and efficiently degrades to microbiologically inactive metabolites. The clotrimazole concentrations remaining in vaginal secretions were still in the mg/mL range for 48 hours and in two of the six subjects at 72 hours.
The findings of high clotrimazole concentrations in vaginal secretions for up to 72 hours and low concentrations in the serum suggest that nearly all the clotrimazole given in the 500 mg vaginal tablet remains in the vagina for 48 hours, and in some cases 72 hours, in fungicidal concentrations.
Clotrimazole is a broad-spectrum antifungal agent. It has been postulated that the compound affects the permeability characteristics of the membrane allowing the leakage of essential intracellular components with a consequent inhibition of the synthesis of such macromolecules as protein, lipid, DNA, and polysaccharides.
At concentrations as low as 2-5 µg/mL, clotrimazole exhibits fungicidal activity in vitro against Candida albicans and other species of the genus Candida.
No single-step or multiple-step resistance to clotrimazole has developed during successive passages of Candida albicans.
Mycelex-G 500 mg Vaginal Tablets are indicated for the local treatment of vulvovaginal candidiasis when one day therapy is felt warranted. In the case of severe vulvovaginitis due to candidiasis, longer antimycotic therapy is recommended. The diagnosis should be confirmed by KOH smears and/or cultures. Other pathogens commonly associated with vulvovaginitis, Trichomonas and Gardnerella (Haemophilus) vaginalis, should be ruled out by appropriate laboratory methods.
Mycelex-G 500 mg Vaginal Tablets are contraindicated in women who have shown hypersensitivity to any components of the preparation.
None.
If there is a lack of response to Mycelex-G 500 mg Vaginal Tablets, appropriate microbiological studies should be repeated to confirm the diagnosis and rule out other pathogens before instituting another course of antimycotic therapy.
No long term studies in animals have been performed to evaluate the carcinogenic potential of Mycelex-G 500 mg Vaginal Tablets intravaginally. A long term study in rats (Wistar strains) where clotrimazole was administered orally provided no indication of carcinogenicity.
Pregnancy Category B: The disposition of 14 C-clotrimazole has been studied in humans and animals. Clotrimazole is poorly absorbed following intravaginal administration to humans, whereas it is rather well absorbed after oral administration.
In clinical trials, use of vaginally applied clotrimazole in pregnant women in their second and third trimesters has not been associated with ill effects. There are, however, no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy.
Studies in pregnant rats given repeated intravaginal doses up to 100 mg/kg/day have revealed no evidence of harm to the fetus due to clotrimazole.
Repeated high oral doses of clotrimazole in rats and mice ranging from 50 to 120 mg/kg resulted in embryotoxicity (possibly secondary to maternal toxicity), impairment of mating, decreased litter size and number of viable young and decreased pup survival to weaning. However, clotrimazole was not teratogenic in mice, rabbits and rats at oral doses up to 200, 180 and 100 mg/kg, respectively. Oral absorption in the rat amounts to approximately 90% of the administered dose.
Because animal reproduction studies are not always predictive of human response, this drug should be used only if clearly indicated during the first trimester of pregnancy.
Of 297 patients in double-blind studies with the 500 mg vaginal tablet, 3 of 149 patients treated with active drug and 3 of 148 patients treated with placebo reported complaints during therapy that were possibly drug related. In the active drug group, vomiting occurred in one patient, vaginal soreness with coitus in another, and complaints of vaginal irritation, itching, burning and dyspareunia in the third patient. In the placebo group, clitoral irritation occurred in one patient and dysuria, described as remotely related to drug, in the other. A third patient in the placebo group developed bacterial vaginitis which the investigator classed as possibly related to drug.
Eighteen (1.6%) of the 1116 patients treated with Mycelex-G in other formulations in double-blind studies reported complaints during therapy that were possibly drug-related. Mild burning occurred in six patients while other complaints such as skin rash, itching, vulval irritation, lower abdominal cramps and bloating, slight cramping, slight urinary frequency, and burning or irritation in the sexual partner, occurred rarely.
No data available.
Drug abuse and dependence with Mycelex-G 500 mg Vaginal Tablets has not been reported.
The recommended dose is one tablet inserted intravaginally one time only, preferably at bedtime. In the event of treatment failure, that is, persistence of signs and symptoms of vaginitis after five days, other pathogens commonly responsible for vaginitis should be ruled out before instituting another course of antimycotic therapy.
Mycelex-G 500 mg Vaginal Tablets are white, bullet shaped, uncoated tablets, coded with Mycelex on one side and 500 on the other, supplied as a single 500 mg tablet with plastic applicator and patient instructions, or in twin pack with Mycelex 1% cream 7g tube.
U.S. Patent Numbers 3,660,577; 3,705,172; 3,839,573; 4,457,938.
Manufactured by
Bayer Corporation
Pharmaceutical Division
West Haven, CT 06516 USA
PD500056 5/95 BAY 5097
© 1995 Bayer Corporation 5213