Terbinafine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Terbinafine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Terbinafine is an allylamine antifungal [see Clinical Pharmacology ] .
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Terbinafine is an allylamine antifungal [see Clinical Pharmacology ] .
12.2 Pharmacodynamics The pharmacodynamics of Terbinafine tablets is unknown.
12.3 Pharmacokinetics 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 200-400 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 to 50 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.
12.4 Microbiology Terbinafine, an allylamine antifungal, 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.
Terbinafine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: Trichophyton mentagrophytes Trichophyton rubrum The following in vitro data are available, but their clinical significance is unknown.
Pharmacokinetics
12.3 Pharmacokinetics 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 200-400 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 to 50 mL/min) or hepatic cirrhosis, the clearance of terbinafine is decreased by approximately 50% compared to normal volunteers.