Allylamine Antifungals

Allylamine antifungals (terbinafine and naftifine) inhibit squalene epoxidase, blocking ergosterol synthesis and causing toxic squalene accumulation. They are fungicidal against dermatophytes and are the most effective drugs for tinea of the nails and skin. Butenafine is a related benzylamine with the same mechanism.

Pharmacokinetics. Oral terbinafine is more than 70% absorbed regardless of food, highly protein bound, accumulates in skin, nails and sebum, and is hepatically metabolised, with a terminal half-life of 200 to 400 hours. It is a strong CYP2D6 inhibitor.

• Oral terbinafine: dermatophyte infections, some Sporothrix infections; poor activity against Candida and non-dermatophyte moulds.
• Topical terbinafine 1%: cream once or twice daily; naftifine 1% cream or gel once or twice daily.
• Compared with itraconazole, terbinafine is fungicidal and gives higher cure rates in onychomycosis. Compared with griseofulvin, it is faster for tinea capitis caused by Trichophyton but less effective against Microsporum.

Adult oral terbinafine 250 mg once daily.

• Tinea corporis and cruris: 2 to 4 weeks. Tinea pedis: 2 to 6 weeks.
• Fingernail onychomycosis: 6 weeks. Toenail onychomycosis: 12 weeks.
• Tinea capitis: 4 weeks for Trichophyton; 6 to 8 weeks for Microsporum, where griseofulvin or itraconazole is preferred.

Child doses (tinea capitis, once daily). Under 20 kg 62.5 mg; 20 to 40 kg 125 mg; over 40 kg 250 mg.

Topical. Localised tinea: terbinafine cream once or twice daily for 1 to 2 weeks. Pityriasis versicolor: terbinafine solution or a topical azole.

Region. In East Africa, tinea capitis in school-age children is common and caused by anthropophilic Trichophyton and Microsporum species; terbinafine and griseofulvin are the usual choices, and household contacts need screening. Griseofulvin supply varies.

Confirm the diagnosis. Nail disease requires microscopy or culture before a 12-week course, since many dystrophic nails are not fungal.

Contraindications. Chronic or active liver disease; hypersensitivity.

Serious adverse effects. Hepatotoxicity (rare, but liver failure has occurred); neutropenia; severe cutaneous reactions; lupus-like syndromes; taste and smell disturbance that may persist; depression.

Interactions. Raises levels of CYP2D6 substrates: tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers (metoprolol, propranolol), flecainide, propafenone and codeine (reduced analgesia). Rifampicin lowers terbinafine levels substantially; cimetidine raises them.

Monitoring. Baseline liver enzymes for courses over 4 weeks; repeat at 4 to 6 weeks. Stop for jaundice, dark urine, pale stool or persistent nausea. Full blood count if a course is prolonged or infection arises.

Special groups.

• Pregnancy and breastfeeding: avoid oral terbinafine; use topical agents only for superficial disease.
• Kidney impairment: halve the dose when creatinine clearance is under 50 mL/min if treatment is essential.
• Liver disease: avoid. Older adults: review interactions.
• Children: weight-banded dosing.

Referral and escalation. Refer for treatment failure after full course (confirm species and adherence), for extensive or deep fungal infection, and for suspected drug-induced liver injury.