Terbinafine

Terbinafine is an allylamine antifungal that is fungicidal against dermatophytes and the first-line oral drug for onychomycosis and for tinea corporis, cruris and pedis that need systemic therapy. It accumulates in skin, hair and nails and persists for weeks after the course. It is weak against Candida and ineffective against pityriasis versicolor by the oral route. Taste disturbance and, rarely, liver injury are the key adverse effects.

Class. Allylamine antifungal.

Mechanism. Inhibits squalene epoxidase, depleting ergosterol and accumulating toxic squalene.

Pharmacokinetics. About 70% absorbed, extensive first-pass metabolism (about 40% bioavailable), highly protein bound and lipophilic, terminal half life 200 to 400 hours in skin and nail. Strong inhibitor of CYP2D6; eliminated in urine as metabolites.

Onychomycosis (adults). 250 mg orally once daily for 6 weeks (fingernails) or 12 weeks (toenails).

Tinea corporis and cruris. 250 mg once daily for 2 to 4 weeks.

Tinea pedis. 250 mg daily for 2 weeks (interdigital) to 6 weeks (moccasin type).

Tinea capitis. Children by weight, once daily for 4 weeks (Trichophyton) and often 8 weeks or longer for Microsporum: under 20 kg 62.5 mg; 20 to 40 kg 125 mg; over 40 kg 250 mg.

Topical. Cream 1% once or twice daily for 1 to 2 weeks.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 250 mg daily.

Main alternatives. Itraconazole for onychomycosis; griseofulvin for tinea capitis (including Microsporum); topical azoles for limited skin disease.

Contraindications. Active or chronic liver disease, hypersensitivity, and history of terbinafine liver injury.

Serious adverse effects. Hepatotoxicity (rarely liver failure), neutropenia, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis), lupus erythematosus exacerbation, depression and visual disturbance.

Common adverse effects. Taste disturbance (rarely permanent), nausea, diarrhoea, headache and rash.

Interactions. Inhibition of CYP2D6 raises tricyclic antidepressants, SSRIs, beta blockers (metoprolol), flecainide and propafenone, and reduces the activation of tamoxifen and codeine. Rifampicin lowers terbinafine levels; cimetidine raises them.

Common prescribing errors. No baseline liver tests, using it for pityriasis versicolor, stopping early in nail disease, and missing CYP2D6 interactions.

Special groups. - Pregnancy: avoid unless essential; delay treatment. - Breastfeeding: excreted in milk; avoid. - Children: weight-banded dosing for tinea capitis; over 2 years. - Older adults: usual dose with liver tests. - Kidney impairment: with CrCl under 50 mL/min, halve the dose. - Liver impairment: avoid in active or chronic disease.

Formulations. Tablets 125 mg and 250 mg; granules for children; cream 1%.

Administration. Once daily with or without food.

Baseline. Liver tests (all patients), pregnancy test, drug review.

Monitoring. Counsel to report jaundice, dark urine, pruritus, fever or rash; repeat liver tests and full blood count after 4 to 6 weeks on prolonged courses. Nail clearance lags treatment by months.

Stopping thresholds. Stop for ALT over three times the upper limit of normal with symptoms, jaundice, neutropenia or severe skin reaction.

Referral and escalation. Specialist review for treatment failure, hepatic injury, or extensive or nail disease with resistant organisms.