Two year safety and tolerability of tenofovir disoproxil fumarate treatment in HBeAg negative and HBeAg positive patients with chronic hepatitis B.

Tenofovir disoproxil fumarate (TDF) has a long term safety profile in HIV-1 infected patients with more than 2 million patient years of exposure. TDF is approved for the treatment of chronic hepatitis B (CHB) and the safety and tolerability of 2 years of TDF treatment in CHB patients is reported. Method(s): In the Phase 3 studies 102 and 103, HBeAg negative or HBeAg positive patients were randomized 2:1 to double-blind, once daily TDF 300 mg or adefovir dipivoxil (ADV) 10 mg. At Week (W) 48, patients with a W48 biopsy continued on open-label (OL) TDF for up to 7 years. Included in this W96 analysis are 389 patients who initiated OL TDF and were treated for up to 2 years. Result(s): The following occurred at a low frequency during OL TDF treatment in Year 2: SAEs (4%), Grade (G) 3 or G4 AEs (5%), AEs considered related to TDF (6%), and AEs resulting in discontinuation (<1%). One death occurred due to cholangiocellular carcinoma. The patient had been diagnosed with adrenal gland and lymph node metastases at weeks 40-42. Individual G3 or G4 AEs and SAEs occurred at a frequency of <1%. SAEs considered related to TDF included facial spasm and renal impairment (peak creatinine 1.4 mg/dL with improvement to 1.2 mg/dL at W96). Three patients discontinued due to AEs: HCC, increased creatinine (peak 1.3 mg/dL) and disturbance in attention, fatigue, and dizziness. No patient had bone fractures considered pathological, related to TDF, or associated with abnormalities in calcium, phosphorus, alkaline phosphatase or renal laboratory parameters. G3-4 laboratory abnormalities occurring in >1% of patients during OL TDF included glucosuria (3%), elevated serum amylase (2%) and elevated prothrombin time (2%). All patients with glucosuria had elevated serum glucose and most were diabetics. During OL TDF, no TDF patient had a confirmed decrease in creatinine clearance <50 mL/min or confirmed increase in serum creatinine >=0.5 mg/dL. Conclusion(s): TDF was well tolerated for 2 years in C