Clinical medicine profile
Griseofulvin
Tubulin Inhibiting Agent [EPC]
- Route
- ORAL / TOPICAL / IV
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- 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.
Precautions
- 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).
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION Accurate diagnosis of the 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 tinea pedis, yeasts and bacteria may be involved as well as dermatophytes. Griseofulvin tablets, USP will not eradicate hese associated bacterial or yeast infections. ADULTS : 0.5 g daily (125 mg q.i.d., 250 mg b.i.d., or 500 mg/day). Patients with less severe or 300 extensive infections may require less, whereas those with widespread lesions may require a starting dose of 0.75 g to 1 g/day. This may be reduced gradually to 0.5 g or less after a response has been noted. In all cases, the dosage should be individualized. PEDIATRIC PATIENTS (older than 2 years): A dosage of 10 mg/kg daily is usually adequate (pediatric patients from 30 to 50 lb, 125 mg to 250 mg daily; pediatric patients over 50 lb, 250 mg to 500 mg daily, in divided doses). Dosage should be individualized, as with adults. Clinical relapse will occur if the medication is not continued until the infecting organism is eradicated. Safety is not established at higher doses than recommended.
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.
Fluconazole dose-adjust in CKD; amphotericin nephrotoxicity high-alert.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Monitor LFTs for courses >14 days or higher-risk patients.
Use, effects & interactions
Indications
- 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.
Adverse effects
- 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
Open multi-drug checker ↗- Match agent to site and species.
- For tinea, continue topical beyond clearance.
- Invasive fungal disease needs ID/specialist input and source control.
Mechanism & disposition
Griseofulvin inhibits fungal mitosis by disrupting the mitotic spindle through interaction with polymerized microtubules.
Read complete mechanism
Griseofulvin inhibits fungal mitosis by disrupting the mitotic spindle through interaction with polymerized microtubules. Azoles inhibit fungal CYP51 (lanosterol 14α-demethylase), depleting ergosterol and disrupting membrane integrity. Terbinafine inhibits squalene epoxidase. Polyenes bind ergosterol creating membrane pores. Echinocandins inhibit β-glucan synthase (cell wall).
Days for clinical response (varies)
Days–weeks per indication
ORAL / TOPICAL / IV
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 th...
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...
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 t...
Pregnancy, lactation & diet
Systemic azoles often avoided in pregnancy (fluconazole high-dose teratogenicity signal); topical clotrimazole commonly used for VVC.
Nursing Mothers It is not known if griseofulvin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for griseofulvin in animal studies (see PRECAUTIONS, Carcinogenesis, Mutagenesis, Impairment of Fertility ), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| GRISEOFULVIN | DAIMA BIASHARA / Wholesale Import | 500MG 100`S(GRISACTIN) | KES 564.38Daima Chemist price-list reference ↗ Source date not recorded · verify current price |
| GRISOZEN 125 | ZAIN PHARMA LIMITED | Tablet | Unavailable |
| GRISOZEN 250 | ZAIN PHARMA LIMITED | Tablet | Unavailable |
| GRISOZEN 500 | ZAIN PHARMA LIMITED | Tablet | Unavailable |
| Itramet | Afya Index / Retail Reference | tabs 4's | KES 250.00afya_index_book |
| Special Information: It is selectively concen- | Afya Index product / manufacturer unverified | tabs 4's | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.