Griseofulvin

DESCRIPTION Griseofulvin tablets, USP (microsize) contain griseofulvin microsize for oral administration. The active ingredient, griseofulvin, is a fungistatic antibiotic, derived from a species of Penicillium. The chemical name of griseofulvin is 7-chloro-2’,4,6-trimethoxy-6’β-methylspiro[benzofuran-2(3H),1’-[2]cyclohexane]-3-4’-dione. Its structural formula is: Griseofulvin, USP occurs as a white to creamy white, odorless powder which is very slightly soluble in water, soluble in acetone, dimethylformamide, and chloroform and sparingly soluble in alcohol. Each griseofulvin tablet contains 500 mg of microsized griseofulvin. The inactive ingredients for griseofulvin tablets 500 mg, include: magnesium stearate, poloxamer 188, potato starch, and colloidal silicon dioxide. structure

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.

WARNINGS Prophylactic Usage Safety and efficacy of griseofulvin for prophylaxis of fungal infections have not been established. Serious Skin Reactions Severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis) and erythema multiforme have been reported with griseofulvin use. These reactions may be serious and may result in hospitalization or death. If severe skin reactions occur, griseofulvin should be discontinued (see ADVERSE REACTIONS section). Hepatotoxicity Elevations in AST, ALT, bilirubin, and jaundice have been reported with griseofulvin use. These reactions may be serious and may result in hospitalization or death. Patients should be monitored for hepatic adverse events and discontinuation of griseofulvin considered if warranted (see ADVERSE REACTIONS section).

ADVERSE REACTIONS There have been post-marketing reports of severe skin and hepatic adverse events associated with griseofulvin use (see WARNINGS section). When adverse reactions occur, they are most commonly of the hypersensitivity type, such as skin rashes, urticaria, and rarely, angioneurotic edema, and erythema multiforme. These may necessitate withdrawal of therapy and appropriate countermeasures. Peripheral neuropathy and paresthesias of the hands and feet have been reported and may be related to treatment duration. Most patients treated with griseofulvin for less than six months experienced improvement or resolution of their neuropathy upon withdrawal of the griseofulvin. Other side effects reported occasionally are oral thrush, nausea, vomiting, epigastric distress, diarrhea, headache, fatigue, dizziness, insomnia, mental confusion and impairment of performance of routine activities. Proteinuria, nephrosis (sometimes associated with existing systemic lupus erythematosus), leukopenia, coagulopathy, hepatitis, elevated liver enzymes, hyperbilirubinemia, and GI bleeding have been reported rarely. Administration of the drug should be discontinued if granulocytopenia occurs. To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc., at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Griseofulvin has been reported in the literature to interfere with the metabolism of various compounds. Whether this is due to a P-450 mediated enzyme induction effects on sulfurtransferase and/or glucotransferase activity, or some other mechanism is unknown. Griseofulvin decreases the activity of warfarin-type anticoagulants, so that patients receiving these drugs concomitantly may require dosage adjustment of the anticoagulant during and after griseofulvin therapy. Griseofulvin may enhance the hepatic metabolism of estrogens, including the estrogen component of oral contraceptives, thereby reducing the effectiveness of contraception and causing menstrual irregularities. Therefore, an alternate or second form of birth control may be indicated during periods of concurrent use (see also CONTRAINDICATIONS ). Cyclosporine levels may be reduced when administered concomitantly with griseofulvin, resulting in a decrease in the pharmacologic effects of cyclosporine. Serum salicylate concentrations may be decreased when griseofulvin is given concomitantly with salicylates. Barbiturates usually depress griseofulvin activity by decreasing plasma levels and concomitant administration may require a dosage adjustment of the antifungal agent. Nausea, vomiting, flushing, tachycardia, and severe hypotension have been reported following alcohol ingestion during griseofulvin therapy.

Pregnancy Teratogenic Effects Pregnancy Category X See CONTRAINDICATIONS and PRECAUTIONS, Drug Interactions .

Pediatric Use Safety and effectiveness in pediatric patients 2 years of age and younger have not been established. Safety in pediatric patients older than 2 years of age at dosages greater than 10 mg/kg daily has not been established.

OVERDOSAGE There is limited experience on overdose with griseofulvin. In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures as required.