Introduction
Griseofulvin is an antifungal antibiotic derived from various Penicillium species that has been used clinically since the 1950s. It was one of the first oral antifungal agents developed specifically for the treatment of dermatophyte infections. Griseofulvin exhibits fungistatic activity against various species of Microsporum, Epidermophyton, and Trichophyton, making it particularly valuable for superficial fungal infections of the skin, hair, and nails.
Mechanism of Action
Griseofulvin exerts its antifungal effect through a unique mechanism. It binds to keratin precursor cells, making them resistant to fungal invasion. The drug is then incorporated into newly synthesized keratin, which becomes highly resistant to dermatophyte infection. At the cellular level, griseofulvin disrupts the mitotic spindle by interacting with polymerized microtubules, thereby inhibiting fungal cell mitosis. It also inhibits nucleic acid synthesis and cell wall deposition of chitin. The drug accumulates in the stratum corneum, hair, and nails, where it creates an environment hostile to fungal growth.
Indications
- Tinea capitis (ringworm of the scalp)
- Tinea corporis (ringworm of the body)
- Tinea pedis (athlete's foot)
- Tinea unguium (onychomycosis)
- Tinea barbae (barber's itch)
- Tinea cruris (jock itch)
Griseofulvin is specifically indicated for dermatophyte infections that are resistant to topical therapy or extensive enough to warrant systemic treatment.
Dosage and Administration
Adults: 500 mg daily in divided doses or single dose (microsize formulation) or 330-375 mg daily (ultramicrosize formulation) Children: 10-20 mg/kg/day (microsize) or 5-10 mg/kg/day (ultramicrosize), not to exceed 1 g daily Administration:- Take with a high-fat meal to enhance absorption
- Duration of therapy varies by infection site:
- Tinea capitis: 4-6 weeks - Tinea corporis: 2-4 weeks - Onychomycosis: 4-6 months for fingernails, 6-12 months for toenails
Special Populations:- Hepatic impairment: Use with caution, consider dose reduction
- Renal impairment: No specific dosage adjustment recommended
- Elderly: Consider potential for decreased hepatic function
Pharmacokinetics
Absorption: Variable and incomplete (25-70% of microsize formulation); enhanced by fatty meals; ultramicrosize formulation has improved bioavailability Distribution: Widely distributed throughout body tissues; concentrates in keratin precursor cells, skin, hair, and nails; crosses placenta and enters breast milk Metabolism: Extensively metabolized in the liver primarily by cytochrome P450 enzymes (CYP3A4) Elimination: Half-life of 9-24 hours; primarily excreted in urine (unchanged drug <1%) and feces; also eliminated in sweatContraindications
- Hypersensitivity to griseofulvin or any component of the formulation
- Porphyria or history of porphyria
- Hepatocellular failure
- Pregnancy (FDA Pregnancy Category X)
- Concomitant use with terfenadine, astemizole, cisapride, or pimozide
Warnings and Precautions
- Hepatotoxicity: May cause hepatocellular necrosis; monitor liver function tests
- Blood dyscrasias: Leukopenia, neutropenia, and granulocytopenia have been reported
- Photosensitivity: May cause photosensitivity reactions; advise sun protection
- Lupus erythematosus: May exacerbate or precipitate systemic lupus erythematosus
- Carcinogenicity: Shown to have tumorigenic potential in animal studies
- Drug resistance: Development of resistant strains may occur
Drug Interactions
- Warfarin: Griseofulvin may decrease warfarin efficacy via enzyme induction
- Oral contraceptives: May reduce contraceptive efficacy; recommend alternative contraception
- Cyclosporine: May decrease cyclosporine levels
- Barbiturates: May decrease griseofulvin absorption and efficacy
- Alcohol: May cause disulfiram-like reaction (tachycardia, flushing)
- CYP3A4 inhibitors: May increase griseofulvin concentrations
Adverse Effects
Common (≥1%):- Headache
- Gastrointestinal disturbances (nausea, vomiting, diarrhea)
- Photosensitivity reactions
- Rash
- Fatigue
- Hepatotoxicity
- Blood dyscrasias (leukopenia, neutropenia)
- Stevens-Johnson syndrome
- Angioedema
- Proteinuria
- Peripheral neuropathy
- Mental confusion
Monitoring Parameters
- Liver function tests (baseline and periodically during therapy)
- Complete blood count with differential (baseline and periodically)
- Renal function tests
- Signs of hypersensitivity reactions
- Therapeutic response assessment
- Adverse effect monitoring (especially neurological symptoms)
Patient Education
- Take with fatty meals to enhance absorption
- Complete full course of therapy even if symptoms improve
- Avoid alcohol consumption during treatment
- Use sun protection measures due to photosensitivity risk
- Report any signs of liver problems (yellowing skin/eyes, dark urine)
- Inform all healthcare providers about griseofulvin use
- Use alternative contraception if taking oral contraceptives
- Report any unusual bleeding, bruising, or infections
- Notify provider if pregnancy is suspected or planned
References
1. Gupta AK, Drummond-Main C. Meta-analysis of randomized, controlled trials comparing particular doses of griseofulvin and terbinafine for the treatment of tinea capitis. Pediatr Dermatol. 2013;30(1):1-6. 2. Elewski BE. Griseofulvin and terbinafine in the treatment of dermatophyte infections. Int J Dermatol. 1999;38(Suppl 2):24-28. 3. Griseofulvin [package insert]. U.S. Food and Drug Administration. 4. Katzung BG, Trevor AJ. Basic & Clinical Pharmacology. 14th ed. McGraw-Hill Education; 2018. 5. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020. 6. Lexicomp Online. Griseofulvin: Drug Information. Wolters Kluwer Clinical Drug Information, Inc.; 2023. 7. American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021.