Adefovir dipivoxil: a review of its use in chronic hepatitis B.

UNLABELLED

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.