Ketek and Renal dysfunction

Telithromycin is eliminated by both renal and hepatic routes. In a multiple-dose study of subjects with varying degrees of renal impairment, patients classified as having severely impaired renal function (CrCl < 30 mL/min) had a 1.4-fold increase in steady-state peak plasma concentration (Cmax) and a 1.9-fold increase in systemic exposure (AUC) of telithromycin compared to healthy volunteers following administration of 800 mg once daily for 5 days. Renal excretion may serve as a compensatory elimination pathway for telithromycin in situations where metabolic clearance is impaired. In one study, coadministration of ketoconazole (which inhibits metabolism of telithromycin via CYP450 3A4) in 2 patients with severe renal impairment resulted in a 4- to 5-fold increase in telithromycin AUC compared to that in healthy subjects with normal renal function receiving telithromycin alone. Since patients with severe renal impairment are prone to conditions that may impair their metabolic clearance, telithromycin dosage should be reduced to 600 mg once daily in patients with severe renal impairment (CrCl < 30 mL/min), including those undergoing dialysis. The dosage should be further reduced to 400 mg once daily if there is coexisting hepatic impairment.