Griseofulvin

Griseofulvin is an oral fungistatic antibiotic that is deposited in keratin, used mainly for tinea capitis (including Microsporum infection) and for dermatophyte infection when other oral options are unsuitable. Treatment is long, absorption needs fat, and it induces CYP3A4, so interactions are common. It is teratogenic.

Class. Antifungal antibiotic; oral dermatophyte agent.

Mechanism. Binds fungal tubulin, disrupting the mitotic spindle and arresting cell division. It is incorporated into newly formed keratin, which resists infection.

Pharmacokinetics. Absorption variable and increased by a fatty meal; micronised and ultramicronised forms differ in dose. Half life 9 to 24 hours, hepatic metabolism, urinary excretion of metabolites. Induces CYP3A4 and CYP2C9.

Tinea capitis (children).

• Micronised: 10 to 20 mg/kg once daily (or in two divided doses), usually 20 mg/kg for Microsporum, maximum 1 g daily.
• Ultramicronised: 5 to 10 mg/kg daily.
• Duration: 6 to 8 weeks, continued for 2 weeks after clinical and mycological clearance.

Tinea corporis and cruris (adults). Micronised 500 mg to 1 g daily for 2 to 4 weeks.

Tinea pedis. 500 mg to 1 g daily for 4 to 8 weeks.

Onychomycosis. 500 mg to 1 g daily for 6 months (fingernails) to 12 to 18 months (toenails); second-line because of cure rates.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 1 g daily in adults (2 g in severe infection, specialist).

Main alternative. Terbinafine, or itraconazole.

Contraindications. Pregnancy, porphyria, hepatocellular failure, systemic lupus erythematosus, hypersensitivity.

Serious adverse effects. Hepatotoxicity, leucopenia and neutropenia, severe skin reactions, photosensitivity, lupus-like syndrome and exacerbation of porphyria.

Common adverse effects. Headache, nausea, diarrhoea, rash, fatigue and photosensitivity.

Interactions.

• Reduces effectiveness of warfarin, combined oral contraceptives, ciclosporin and theophylline.
• Alcohol: flushing and tachycardia (disulfiram-like effect).
• Phenobarbital reduces its absorption.

Common prescribing errors. Stopping before clearance, taking it without fat, prescribing in pregnancy or to those planning conception, and missing contraceptive interaction.

Special groups.

• Pregnancy: contraindicated; effective contraception during treatment and for 1 month after in women, and for 6 months after in men who may father children.
• Breastfeeding: avoid.
• Children: suitable from 1 year; weight-based dosing.
• Older adults: usual dose with liver tests.
• Kidney impairment: no adjustment.
• Liver impairment: contraindicated in failure; caution otherwise.

Regional points. Tinea capitis is common in school-age children in many African settings, and griseofulvin remains widely used because it covers Microsporum when terbinafine is unavailable.

Formulations. Tablets 125 mg and 500 mg; oral suspension 125 mg/5 mL.

Administration. With a fatty meal or full-fat milk. Treat household contacts and shared combs and caps.

Baseline. Liver tests (long courses), full blood count, pregnancy test in women of childbearing age.

Monitoring. Liver tests and full blood count every 4 to 6 weeks on prolonged treatment; clinical and scalp culture review at 4 and 8 weeks.

Stopping thresholds. Stop for hepatitis, neutropenia, severe skin reaction or pregnancy.

Referral and escalation. Specialist review for treatment failure, kerion or extensive disease.