Lamisil (Terbinafine)

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The allylamine derivative terbinafine can be used orally or topically. It is active against a broad range of fungi, including filamentous fungi and, to a lesser extent, yeastlike fungi. However, probably because of irreversible protein binding, its clinical usefulness is limited to the treatment of dermatophyte infections and perhaps lymphocutaneous sporotrichosis. Terbinafine acts by inhibiting the synthesis of fungal ergosterol at the level of squalene oxidase, leading to depletion of ergosterol and accumulation of toxic squalenes in the fungal cell membrane.

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Theophylline is largely metabolized by CYP1A2 and terbinafine increases its half-life. In a randomized, crossover study in 12 healthy volunteers, terbinafine increased theophylline exposure by 16%, with a 14% reduction in clearance and a 24% increase in half-life. These pharmacokinetic changes may predispose individuals to accumulation of theophylline and unwanted toxicity. Caution should be taken in prescribing terbinafine for patients taking long-term theophylline.

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The pharmacokinetics of terbinafine and five known metabolites have been investigated in 12 children, (mean age 8 years; range 5-11 years), who took terbinafine 125 mg/day for 6-8 weeks for tinea capitis. The metabolism of terbinafine was similar to that observed in adults, and there were comparable steady-state plasma concentrations after administration of the same oral dose. Steady state was reached by day 21 with no further accumulation up to day 56.

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Taste disturbance is a rare adverse effect of terbinafine. It is usually reversible, with a median time to recovery of 42 days. However, a 46-year-old woman had complete loss of taste after taking oral terbinafine, with persistent taste disturbances for 3 years after stopping the drug. The projected rate of all blood dyscrasias associated with terbinafine has been estimated to be 32 per million patient-years.