Terbinafine (Lamisil, Novartis) is a synthetic allylamine. Clinical studies commenced in the late 1980's and the drug was licensed in 1992. It is now off patent. It is the leading compound for fungal skin and nail infections. It inhibits squalene epoxidase, one of the enzymes in the synthetic pathway of ergosterol, which is the major sterol in cell membranes (unlike in humans in which it is cholesterol).
Dose & Delivery
Terbinafine is only available orally and topically. The standard dose is 250mg daily.
Fungi - the drug is active against
Terbinafine is active against all the skin fungi, including Epidermophyton floccosum, Microsporum species and Trichophyton species. It is also active against Malassezia furfur which causes pityriasis tinea (versicolor). It is active against most Candida species, athough it may not be fungicidal in some species such as Candida albicans. There is some activity demonstrated against Aspergillus, but in combination with amphotericin B was antagonistic in invasive aspergillosis. It has limited activity against other organisms.
The usual dose is 250mg per day. This should be reduced to 50% in those with impaired renal function, and avoided in those with liver disease. Significant skin infections are treated for 3-4 weeks. Nail infections of the fingers require at least 6 weeks of treatment, but toenails require 3-6 months of therapy, depending o the extent of nail involvement. In the treatment of athletes foot, terbinafine cream can be applied between the toes daily for 7 days.
Metabolism distribution and excretion
Terbinafine is well absorbed when taken orally. There is no effect of food on absorption. As it is a fat soluble drug it accumulates in skin, fatty tissue and also the nails. It persists in nails for long periods after the end of treatment. It is metabolised by the liver with a half life of 17 hours. This is prolonged in patients with liver or kidney impairment.
Terbinafine has the advantage over the azoles in not affecting the metabolism of such drugs as cyclosporin and oral diabetic drugs. Its blood levels are reduced if given with rifampicin (rifampin) as this increases the rate of metabolism. Cimetidine, the anti ulcer drug also inhibits its metabolism, so higher blood levels are found if the drugs are given together. Terbinafine inhibits CYP 2D6 and so may increase levels of tricyclic antidepressants, β-blockers, selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors type B. Warfarin may need adjustment if given with terbinafine. View drug interactions database.
Terbinafine is well tolerated. Its common side effects are nausea, mild abdominal discomfort and headache. Allergic skin reactions have been reported, although these are uncommon. Loss of taste or altered taste is also reported. Rarely has liver dysfunction been reported.
Structure of terbinafine