GRISEOFULVIN- griseofulvin suspension
Qualitest Pharmaceuticals
DESCRIPTION
Griseofulvin microsize contains 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??-methylspiro[benzofuran-2(3H), 1'-[2]cyclohexane]-3-4?-dione. Its structural formula is:
Structural Formula of griseofulvin
(click image for full-size original)
Griseofulvin occurs as a white to creamy white, bitter tasting powder which is very slightly soluble in water and sparingly soluble in alcohol. Griseofulvin microsize contains particles of approximately 2 to 4 �m in diameter.
Griseofulvin Oral Suspension, USP is orange in color with orange and coconut flavor. Each 5 mL of Griseofulvin Oral Suspension, USP contains 125 mg of griseofulvin microsize and also contains alcohol 0.2%, coconut flavor, docusate sodium, FD&C Red No. 40, FD&C Yellow No. 6, magnesium aluminum silicate, menthol, methylparaben, orange flavor, propylene glycol, propylparaben, purified water, saccharin sodium, simethicone emulsion (silicon dioxide, carboxymethylcellulose sodium, and sorbic acid), sodium alginate, and sucrose. Griseofulvin Oral Suspension, USP may contain dibasic sodium phosphate or potassium phosphate monobasic for pH adjustment.
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 G.I. 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 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.
Drug Resistance:
Although there have been reports of dermatophyte resistance to griseofulvin, the clinical significance is unknown.
INDICATIONS AND USAGE
Griseofulvin is 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 is not effective in the following:
Bacterial infections
Coccidioidomycosis
Candidiasis (Moniliasis)
North American Blastomycosis
Histoplasmosis
Cryptococcosis (Torulosis)
Actinomycosis
Tinea versicolor
Sporotrichosis
Nocardiosis
Chromoblastomycosis
The use of this drug is not justified in minor or trivial dermatophyte infections which will respond to topical agents alone.
