Adefovir dipivoxil (
Hepsera) is an oral
prodrug of the
nucleotide analogue
adefovir. It is indicated for the treatment of
chronic hepatitis B in adults.
Adefovir dipivoxil 10 mg/day significantly improved histological, biochemical and virological outcomes in
hepatitis B e antigen (
HBeAg)-positive and -negative patients, and serological outcomes in
HBeAg-positive patients. In two trials, the proportion of
adefovir dipivoxil recipients showing histological improvement in the liver was approximately twice that for placebo recipients. In two trials in patients chronically infected with
lamivudine-resistant hepatitis B virus (HBV), switching to or adding
adefovir dipivoxil was significantly more effective at reducing serum HBV
DNA levels than continuing
lamivudine monotherapy. In treatment-naive patients, 1 year's treatment with
adefovir dipivoxil plus
lamivudine had similar efficacy to
lamivudine plus placebo; however,
lamivudine-resistant HBV emerged in significantly more patients receiving
lamivudine plus placebo.
Adefovir dipivoxil has also shown efficacy in noncomparative trials in patients with decompensated
liver disease, patients co-infected with HIV and patients pre- or post-
liver transplantation. Within 96 weeks of treatment with
adefovir dipivoxil, a resistance-conferring mutation emerged in viral isolates from 1.6% of patients. In vitro, these isolates remained sensitive to
lamivudine, while
lamivudine-resistant HBV isolates remained sensitive to
adefovir dipivoxil.
Adefovir dipivoxil 10 mg/day is generally well tolerated. In a pooled analysis of 48-week data from two trials, there was no marked difference in adverse events or laboratory abnormalities between
adefovir dipivoxil and placebo recipients. Within 96 weeks of treatment with
adefovir dipivoxil, >1% of patients with adequate renal function developed an increase in serum
creatinine levels of >/=0.5 mg/dL above baseline. Within 48 weeks of treatment, increases in serum
creatinine levels of >/=0.5 mg/dL above baseline were observed in 13% of pre- and post-
liver transplantation patients who generally had
renal insufficiency or risk factors for renal dysfunction at baseline. Most patients continued treatment with dosage adjustments.
CONCLUSION: Oral
adefovir dipivoxil is effective and generally well tolerated in
HBeAg-positive and -negative patients chronically infected with wild-type or
lamivudine-resistant HBV. Few resistant HBV mutants have emerged to date. Data from ongoing long-term studies are awaited with interest. Existing treatment options for patients with
chronic hepatitis B are limited in both number and effectiveness; the proven efficacy, good tolerability profile and apparently low potential for resistance of
adefovir dipivoxil make it a promising new option in the management of this disease.