Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: Two double-blind, randomized, placebo-controlled studies

Background. The incidence of adefovir dipivoxil (ADV) nephrotoxicity has been previously reported with the 60 and 120 mg daily dose in human immunodeficiency virus (HIV). We report a complete analysis on the renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B. Methods. To investigate the efficacy, safety, and the tolerability of two dosing regimens of ADV (10 mg daily or 30 mg daily), two double-blind, placebo-controlled studies were performed in patients with chronic hepatitis B and compensated liver disease who were not undergoing current treatment and who had evidence of hepatitis B virus (HBV) replication. Results. There was no overall median change from baseline at week 48 in serum creatinine or serum phosphorus levels in the ADV 10 mg group. In the ADV 30 mg group there was a slight increase of 0.2 mg/dL in median serum creatinine levels, and decrease of 0.1 mg/dL in serum phosphorus levels at week 48. Serum creatinine increase and hypophosphatemia were more frequently observed in patients receiving ADV 30 mg daily compared with ADV 10 mg and placebo. There were no grade 4 proteinuria, hematuria, or glycosuria events. Conclusion. Mild nephrotoxicity was demonstrated with the dose of 30 mg daily. Nephrotoxicity, as defined by an increase greater than or equal to0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of <1.5 mg/dL on two consecutive occasions, was not observed in patients treated with ADV 10 mg for a median follow-up period of approximately 64 weeks.