griseofulvin 165 MG Oral Tablet [Fulvicin P/G]

INDICASTIONS AND USAGE Griseofulvin tablets, USP are indicated for the treatment of dermatophyte infections of the skin not adequately treated by topical therapy, hair and nails, namely: Tinea corporis Tinea pedis Tinea cruris Tinea barbae Tinea capitis Tinea unguium when caused by one or more of the following species of fungi: Epidermophyton floccosum Microsporum audouinii Microsporum canis Microsporum gypseum Trichophyton crateriform Trichophyton gallinae Trichophyton interdigitalis Trichophyton megnini Trichophyton mentagrophytes Trichophyton rubrum Trichophyton schoenleini Trichophyton sulphureum Trichophyton tonsurans Trichophyton verrucosum Note: Prior to therapy, a dermatophyte should be identified as responsible for the infection. Prior to initiating treatment, appropriate specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis. Griseofulvin tablets, USP are not effective in the following: Bacterial infections Candidiasis (Moniliasis) Histoplasmosis Actinomycosis Sporotrichosis Chromoblastomycosis Coccidioidomycosis North American Blastomycosis Cryptococcosis (Torulosis) Tinea versicolor Nocardiosis The use of this drug is not justified in minor or trivial dermatophyte infections which will respond to topical agents alone.

DOSAGE AND ADMINISTRATION Accurate diagnosis of infecting organism is essential. Identification should be made either by direct microscopic examination of a mounting of infected tissue in a solution of potassium hydroxide or by culture on an appropriate medium. Medication must be continued until the infecting organism is completely eradicated as indicated by appropriate clinical or laboratory examination. Representative treatment periods are tinea capitis, 4 to 6 weeks; tinea corporis, 2 to 4 weeks; tinea pedis, 4 to 8 weeks; tinea unguium–depending on rate of growth–fingernails, at least 4 months; toenails, at least 6 months. General measures in regard to hygiene should be observed to control sources of infection or reinfection. Concomitant use of appropriate topical agents is usually required, particularly in treatment of tinea pedis. In some forms of athlete’s foot, yeasts and bacteria may be involved as well as fungi. Griseofulvin will not eradicate the bacterial or monilial infection. Ultramicrosize griseofulvin tablets may be swallowed whole or crushed and sprinkled onto 1 tablespoonful of applesauce and swallowed immediately without chewing. Adults: Daily administration of 375 mg (as a single dose or in divided doses) will give a satisfactory response in most patients with tinea corporis, tinea cruris, and tinea capitis. For those fungus infections more difficult to eradicate, such as tinea pedis and tinea unguium, a divided dose of 750 mg is recommended. Pediatric Use : Approximately 7.3 mg per kg of body weight per day of ultramicrosize griseofulvin is an effective dose for most pediatric patients. On this basis, the following dosage schedule is suggested: 16 to 27 kg: 125 mg to 187.5 mg daily. Over 27 kg: 187.5 mg to 375 mg daily Children and infants 2 years of age and younger–dosage has not been established. Clinical experience with griseofulvin in children with tinea capitis indicates that a single daily dose is effective. Clinical relapse will occur if the medication is not continued until the infecting organism is eradicated.

Warnings Prophylactic Usage: Safety and efficacy of prophylactic use of this drug has not been established. Chronic feeding of griseofulvin, at levels ranging from 0.5-2.5% of the diet, resulted in the development of liver tumors in several strains of mice, particularly in males. Smaller particle sizes result in an enhanced effect. Lower oral dosage levels have not been tested. Subcutaneous administration of relatively small doses of griseofulvin once a week during the first three weeks of life has also been reported to induce hepatomata in mice. Although studies in other animal species have not yielded evidence of tumorigenicity, these studies were not of adequate design to form a basis for conclusions in this regard. In subacute toxicity studies, orally administered griseofulvin produced hepatocellular necrosis in mice, but this has not been seen in other species. Disturbances in porphyrin metabolism have been reported in griseofulvin-treated laboratory animals. Griseofulvin has been reported to have a colchicine-like effect on mitosis and cocarcinogenicity with methylcholanthrene in cutaneous tumor induction in laboratory animals. Reports of animal studies in the Soviet literature state that a griseofulvin preparation was found to be embryotoxic and teratogenic on oral administration to pregnant Wistar rats. Rat reproduction studies done in the United States and Great Britain were inconclusive in this regard. Pups with abnormalities have been reported in the litters of a few bitches treated with griseofulvin. Because the potential for adverse effects on the human fetus cannot be ruled out, additional contraceptive precautions should be taken during treatment with griseofulvin and for a month after termination of treatment. Griseofulvin Oral Suspension, USP should not be prescribed to women intending to become pregnant within one month following cessation of therapy. Suppression of spermatogenesis has been reported to occur in rats but investigation in man failed to confirm this. Griseofulvin interferes with chromosomal distribution during cell division, causing aneuploidy in plant and mammalian cells. These effects have been demonstrated in vitro at concentrations that may be achieved in the serum with the recommended therapeutic dosage. Since griseofulvin has demonstrated harmful effects in vitro on the genotype in bacteria, plants, and fungi, males should wait at least six months after completing griseofulvin therapy before fathering a child.

CONTRAINDICATIONS Griseofulvin is contraindicated in patients with porphyria or hepatocellular failure, and in individuals with a history of hypersensitivity to griseofulvin. Griseofulvin may cause fetal harm when administered to a pregnant woman. Two published cases of conjoined twins have been reported in patients taking griseofulvin during the first trimester of pregnancy, therefore, griseofulvin is contraindicated in women who are or may become pregnant during treatment. Women taking estrogen-containing oral contraceptives may be at increased risk of becoming pregnant while on griseofulvin (see also PRECAUTIONS, Drug Interactions ) . If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Although no direct causal relationship has been established, spontaneous abortion has been reported rarely coincident with the use of griseofulvin. Note: The Maximum Recommend Human Dose (MRHD) was set at 500 mg/day for the multiple of human exposure calculations performed in this label. If higher doses than 500 mg/day were used clinically, then the multiple of human exposure would be correspondingly reduced for that dose. For example, if a 1,000 mg/day dose was administered to an individual, then the multiple of human exposure would be reduced by a factor of 2. Griseofulvin has been shown to be embryotoxic and teratogenic in pregnant rats when given at a daily oral dose of 250 mg/kg/day [4X the Maximum Recommended Human Dose (MRHD) based on Body Surface Area (BSA)]. Griseofulvin also has been shown to be embryotoxic and teratogenic in pregnant cats treated weekly with griseofulvin at doses of 500 to 1,000 mg/week. There are reports of teratogenicity in a Golden Retriever when doses of 750 mg/day [1.2X the MRHD based on BSA] were administered for four weeks prior to and throughout the pregnancy, and in a study in which beagles were administered 35 mg/kg/day [1.9X the MRHD based on BSA] for intervals from one week up to the entire gestation period. Teratogenicity was also seen in mice when griseofulvin was administered in doses equivalent to 5g/kg/day [40X the MRHD based on BSA] for 2 consecutive days at various stages of the pregnancy.

CLINICAL PHARMACOLOGY Griseofulvin absorption from the gastrointestinal tract varies considerably among individuals mainly because of insolubility of the drug in aqueous media of the upper GI tract. Drug absorption has been estimated to range between 27 and 72%. After an oral dose, griseofulvin is primarily absorbed from the duodenum with some absorption occurring from the jejunum and ileum. The peak serum level in fasting adults given 0.5 g of griseofulvin microsize occurs at about four hours and ranges between 0.5 to 2.0 mcg/mL. The serum level may be increased by giving the drug with a meal with a high fat content. In one study in pediatric patients 19 months to 11 years of age, 10 mg/kg of griseofulvin microsize given with milk resulted in mean peak serum concentrations approximately four-fold greater than the same griseofulvin dose given alone (1.29 mcg/mL versus 0.34 mcg/mL, respectively). Also, the area under the curve value was ten-fold larger when 10 mg/kg griseofulvin and milk were administered simultaneously as compared to the same dosage given to fasting patients. In addition, griseofulvin administered with milk resulted in more consistently detected serum levels across subjects. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. When the drug is discontinued, griseofulvin concentrations in the skin decline less rapidly than those in plasma. Griseofulvin is metabolized by the liver to 6-desmethylgriseofulvin and its glucuronide conjugate. Griseofulvin has a variable elimination half-life in plasma (9 to 24 hours). Approximately 30% of a single oral dose of griseofulvin is excreted in the urine within 24 hours and about 50% of the dose is excreted in the urine within 5 days, mostly in the form of metabolites. Unchanged griseofulvin in the urine accounts for less than 1% of the administered dose. In addition, approximately one-third of a single dose of griseofulvin is excreted in feces within 5 days. Griseofulvin is also excreted in perspiration. Microbiology: Mechanism of Action: The mechanism of griseofulvin consists of binding microtubular proteins, which are required for mitosis. Activity In Vivo: Griseofulvin may be active against most strains of the following dermatophytes as described in the INDICATIONS AND USAGE section: Epidermophyton floccosum, Microsporum audouinii, Microsporum canis, Microsporum gypseum, Trichophyton crateriformis, Trichophyton gallinae, Trichophyton interdigitalis, Trichophyton megnini, Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton sulphureum, Trichophyton schoenleini, Trichophyton tonsurans, and Trichophyton verrucosum. It has no effect on bacteria or on other genera of fungi. Activity In Vitro: In vitro , griseofulvin has been shown to have activity against many dermatophytes, but the clinical significance is unknown. Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC. Drug Resistance: Although there have been reports of dermatophyte resistance to griseofulvin, the clinical significance is unknown.