Griseofulvin is a metabolite of Penicillium griseofulvum and Penicillium janczewskii. It binds to and disrupts both the α and β tubulin subunits inducing conformational changes which disrupts the fungal mitotic spindle. As microtubules are involved in the transport of secretory material through the cytoplasm this has a profound cellular effect. As a consequence, griseofulvin is a potent mutagen in multiple mammalian cell test assays.
Dose & Delivery
Griseofulvin is formulated as both microsize and ultramicrosize preparations given orally. In adults, the dose of the microsize preparation is 0.5–1 g daily administered once or twice daily. Microsize griseofulvin should be administrated with a fatty food such as cheese or other dairy product, chocolate, fried food or nuts. The dosages of the ultramicrosize preparation are 330–660 mg daily. In children, the dose of microsize griseofulvin is 10 mg/kg daily and for the ultramicrosize preparation 5.5 mg/kg daily.
Fungi - the drug is active against
The dermatophytes Microsporum spp., Trichophyton spp. and Epidermophyton spp. are susceptible to griseofulvin. Griseofulvin is not active against Candida spp. Aspergillus spp., Fusarium spp, Mucorales spp, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Histoplasma capsulatum or Coccidioides immitis.
In children with tinea capitis, oral griseofulvin 500 mg/day had an efficacy of 88% over 6 weeks.
For tinea corporis topical therapy with griseofulvin may be effective (less than terbinafine of itraconazole), and oral therapy, 500mg daily for 3-6 weeks, results in a 60% response rate.
Griseofulvin is relatively ineffective for onychomycosis and not recommended.
Griseofulvin may be effective at the elevated dose of 500mg three times daily for 12 months for eumycetoma caused by Madurella spp.
Drug / Drug interactions
Griseofulvin reduces the anticoagulant effect of warfarin and ciclosporin levels, probably through CYP P450 enzyme induction. Griseofulvin may impair the performance of skilled tasks (e.g. driving) and enhances the effects of alcohol. Griseofulvin administration leads to accelerated estrogen and progestogen metabolism possibly reducing the efficacy of contraceptives. Griseofulvin reduces serum salicylate concentrations.
Link to drug interaction database.
Griseofulvin is sometimes not well tolerated. The most common side-effects are nausea, vomiting, diarrhoea, heartburn, flatulence, cracking at the side of the mouth, soreness and/or blackening of the tongue and thirst. Headache is a frequent side-effect (<15%), but may resolve on continued therapy. Other neurological side effects such as peripheral neuropathy may occur. Maculopapular, urticarial or photosensitivity rashes occasionally occur. Cutaneous lupus erythematosus lesions occurred in several patients with circulating antibodies to SSA/Ro and SSB/La autoantigens (nuclear and cytoplasmic polypeptides) and is contraindicated in systemic lupus erythematosus (SLE). Hepatotoxicity is infrequent but pre-existing liver disease may be exacerbated by griseofulvin.
Griseofulvin is contraindicated in pregnancy (class C). As griseofulvin induces abnormalities in murine sperm, fertile men should be advised not to father children during therapy or for six months after the drug is stopped.
Structure of griseofulvin
Penicillium griseofulvum, A-C. 7-day-old colonies on three different media (from Samson RA & J.C. Frisvad JC. Stud. Mycol 2004; 49: 1-174).