Tenofovir disoproxil fumarate: in chronic hepatitis B.
Tenofovir disoproxil fumarate (tenofovir DF) is an orally administered ester prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor that shows potent in vitro activity against both hepatitis B virus (HBV) and HIV-1. As a component of antiretroviral combination therapy regimens, tenofovir DF is well established in the treatment of adults with HIV-1 infection. Tenofovir DF, administered once daily, is also used in the treatment of adults with chronic hepatitis B (CHB) [the main focus of this profile]. In CHB, the efficacy of tenofovir DF against HBV has been evaluated in two large randomized, phase III clinical studies in hepatitis B e antigen (HBeAg)-negative or HBeAg-positive adults, with compensated liver function. The trials (planned duration 8 years) were double-blind for the first 48 weeks; thereafter, patients received open-label tenofovir DF. Results at 48 and 96 weeks are available. In these studies, at week 48, a significantly greater proportion of recipients of tenofovir DF 300 mg once daily than oral adefovir dipivoxil 10 mg once daily achieved a complete response (primary endpoint). A complete response was defined as a reduction from baseline in plasma HBV DNA level to <400 copies/mL and histological improvement (reduction of 2 or more points in Knodell necroinflammatory score without worsening of fibrosis). The efficacy of tenofovir DF in the treatment of CHB was also demonstrated over a 96-week treatment period in both studies. Tenofovir DF was generally well tolerated by adults with CHB in the two phase III trials.
Perry
Caroline M
CM
Adis, North Shore, Auckland, New Zealand. demail@adis.co.nz
Simpson
Dene
D
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D063065:Organophosphonates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011355:Prodrugs; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068698:Tenofovir
D063065:Organophosphonates; D011355:Prodrugs; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine