General Information

Lamisil (terbinafine hydrochloride) is an allylamine antifungal.

Lamisil is specifically indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium).

Lamisil is supplied as tablets for oral administration. Prior to initiating treatment, appropriate nail specimens for laboratory testing [potassium hydroxide (KOH) preparation, fungal culture, or nail biopsy] should be obtained to confirm the diagnosis of onychomycosis.

Before administering Lamisil tablets, evaluate patients for evidence of chronic or active liver disease. The recommended dosages are as follows:

• Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks
• Toenail onychomycosis: One 250 mg tablet once daily for 12 weeks

The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.

Mechanism of Action

Lamisil (terbinafine) is an allylamine antifungal. Terbinafine inhibits biosynthesis of ergosterol, an essential component of fungal cell membrane, via inhibition of squalene epoxidase enzyme. This results in fungal cell death primarily due to the increased membrane permeability mediated by the accumulation of high concentrations of squalene but not due to ergosterol deficiency. Depending on the concentration of the drug and the fungal species test in vitro, terbinafine hydrochloride may be fungicidal. However, the clinical significance of in vitro data is unknown.

Side Effects

Adverse effects associate with the use of Lamisil may include, but are not limited to, the following:

• headache
• diarrhea
• rash
• dyspepsia
• liver enzyme abnormalities
• pruritus
• taste disturbance
• nausea
• abdominal pain
• flatulence

Clinical Trial Results

The efficacy of Lamisil tablets was revaluated in three North American placebo-controlled clinical trials.

Results of the first trial in toenail infections assessed at week 48 (12 weeks of treatment with 36 weeks follow-up after completion of therapy), demonstrated mycological cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 70% of subjects. Fifty-nine percent (59%) of subjects experienced effective treatment (mycological cure plus 0% nail involvement or greater than 5mm of new unaffected nail growth); 38% of subjects demonstrated mycological cure plus clinical cure (0% nail involvement). The mean time to overall success was approximately 10 months. In the trial, for subjects evaluated at least 6 months after achieving clinical cure and at least 1 year after completing therapy with Lamisil Tablets, the clinical relapse rate was approximately 15%.

In a second toenail trial of dermatophytic onychomycosis, in which nondermatophytes were also cultured, similar efficacy against the dermatophytes was demonstrated. The pathogenic role of the nondermatophytes cultured in the presence of dermatophytic onychomycosis has not been established. The clinical significance of this association is unknown.

Results of a trial evaluating fingernail infections assessed at week 24 (6 weeks of treatment with 18 weeks follow-up after completion of therapy), demonstrated mycological cure in 79% of subjects, effective treatment in 75% of the subjects, and mycological cure plus clinical cure in 59% of the subjects. The mean time to overall success was approximately 4 months for the fingernail trial.