It is thought that protease inhibitors, which are renally cleared to only a small degree, require no dosage adjustment for patients with renal insufficiency and those on hemodialysis (HD). However, few studies have been conducted to evaluate this assumption.
A recent study of atazanavir (ATV) in HIV-uninfected patients with kidney disease, performed by the manufacturer, found that patients with severe renal impairment (who were not on HD) had higher mean serum ATV exposure (AUC) and minimum concentrations (Cmin) than did matched controls with normal kidney function. Surprisingly, although ATV was not cleared by HD, subjects on HD had substantially lower ATV levels than controls (AUC 42% lower on HD days, 28% lower on non-HD days). The mechanism for this effect is not known. Pending further study, the manufacturer recommends that treatment-experienced patients on HD should not be treated with ATV, and that patients with severe renal impairment who are not on HD should be treated with ritonavir-boosted ATV at usual doses.
- Agarwala S, Eley T, Child M, et al. Pharmacokinetics of atazanavir in severely renally impaired subjects including those on hemodialysis. In: Program and abstracts of the 8th International Workshop on Clinical Pharmacology of HIV Therapy; April 16-18, 2007; Budapest. Abstract 2.
- Reyataz [patient information]. Princeton, NJ: Bristol-Myers Squibb. December 2007. Available at: http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed February 27, 2008.