Terbinafine 250 mg Film Coated · Tablets

Terbinafine is an allylamine antifungal [see Clinical Pharmacology ( 12.4)] .

Following oral administration, terbinafine is well absorbed (greater than 70%) and the bioavailability of terbinafine tablets as a result of first-pass metabolism is approximately 40%. Peak plasma concentrations of 1 mcg/mL appear within 2 hours after a single 250 mg dose; the AUC is approximately 4.56 mcg•h/mL. An increase in the AUC of terbinafine of less than 20% is observed when terbinafine tablets are administered with food.

In plasma, terbinafine is greater than 99% bound to plasma proteins and there are no specific binding sites. At steady-state, in comparison to a single dose, the peak concentration of terbinafine is 25% higher and plasma AUC increases by a factor of 2.5; the increase in plasma AUC is consistent with an effective half-life of ~36 hours.Terbinafine is distributed to the sebum and skin. A terminal half-life of 200 to 400 hours may represent the slow elimination of terbinafine from tissues such as skin and adipose. Prior to excretion, terbinafine is extensively metabolized by at least 7 CYP isoenzymes with major contributions from CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19. No metabolites have been identified that have antifungal activity similar to terbinafine. Approximately 70% of the administered dose is eliminated in the urine.

In patients with renal impairment (creatinine clearance less than or equal to50 mL/min) or hepatic cirrhosis, the clearance of terbinafine is decreased by approximately 50% compared to normal volunteers. No effect of gender on the blood levels of terbinafine was detected in clinical trials. No clinically relevant age-dependent changes in steady-state plasma concentrations of terbinafine have been reported.