AccessPak for HIV PEP Expanded with Kaletra and Renal dysfunction

Tenofovir is primarily eliminated by the kidney via glomerular filtration and active tubular secretion. Renal impairment, including acute renal failure and Fanconi syndrome, has been reported with tenofovir use. Close monitoring of renal function and lengthening the dosing interval are recommended for patients with creatinine clearance less than 50 mL/min. Creatinine clearance should be calculated in all patients before starting tenofovir treatment and during treatment when clinically appropriate. Routine monitoring of serum creatinine and phosphorus is recommended for patients at risk of or with a history of renal dysfunction. Safety and effectiveness have not been evaluated in patients with renal insufficiency using dose adjustments; therefore, the benefit of tenofovir treatment should be weighed against the risk of renal toxicity. Tenofovir should be avoided in patients who are currently using or have recently used nephrotoxic drugs.

Emtricitabine is primarily eliminated by the kidney. Compared to patients with normal renal function (CrCl above 80 mL/min), peak plasma concentration (Cmax) and systemic exposure (AUC) of emtricitabine increased by 45% and 113%, respectively, in patients with moderate renal dysfunction (CrCl 30 to 49 mL/min), and 27% and 186%, respectively, in patients with severe renal dysfunction (CrCl below 30 mL/min). Systemic exposure was increased even further in patients with end-stage renal disease managed on dialysis. These patients had an approximately 3.5-fold increase in emtricitabine AUC compared to patients with normal renal function. Renal clearance of emtricitabine decreased by 68% and 86%, respectively, in patients with moderate and severe renal dysfunction. Dosage adjustment of emtricitabine is recommended for patients with CrCl below 50 mL/min, including patients on dialysis, in accordance with the manufacturer's product labeling. Clinical response to treatment and renal function should be closely monitored.