BACKGROUND: Hepatitis B virus (HBV) infection is a major problem worldwide and an important cause of chronic liver disease and cirrhosis. Currently available treatments include interferon alfa-2b, lamivudine, and adefovir dipivoxil. Adefovir dipivoxil is an acyclic nucleotide analogue that was developed in part to improve on the limitations of earlier therapies. OBJECTIVE: This article is a review of available data on the clinical pharmacology, virology, efficacy, tolerability, and clinical use of adefovir dipivoxil. METHODS: A search of the English-language literature indexed on MEDLINE from 1966 to July 2003 was performed using the terms adefovir, PMEA, and Bis-POM PMEA. Pertinent abstracts from scientific meetings on infectious diseases and hepatology were also included. The manufacturer of adefovir dipivoxil provided additional information. These materials were supplemented by US Food and Drug Administration briefing documents and other unpublished materials. In vitro and preclinical studies were included in the review, as were Phase II and III clinical trials. RESULTS: In vitro, adefovir dipivoxil concentrations exceed those necessary to inhibit both wild-type and lamivudine-resistant isolates of HBV. In clinical trials, adefovir dipivoxil was clinically and virologically effective in patients in whom lamivudine therapy had failed due to the presence of lamivudine-resistant HBV. The drug was generally well tolerated. The risk of nephrotoxicity, the most notable adverse effect of adefovir dipivoxil at previously used higher doses, has been substantially reduced at the currently recommended dosage of 10 mg/d. CONCLUSION: Based on the data reviewed adefovir dipivoxil is an effective and well-tolerated alternative for the treatment of HBV infection, including disease that is lamivudine resistant.
BACKGROUND:Hepatitis B virus (HBV) infection is a major problem worldwide and an important cause of chronic liver disease and cirrhosis. Currently available treatments include interferon alfa-2b, lamivudine, and adefovir dipivoxil. Adefovir dipivoxil is an acyclic nucleotide analogue that was developed in part to improve on the limitations of earlier therapies. OBJECTIVE: This article is a review of available data on the clinical pharmacology, virology, efficacy, tolerability, and clinical use of adefovir dipivoxil. METHODS: A search of the English-language literature indexed on MEDLINE from 1966 to July 2003 was performed using the terms adefovir, PMEA, and Bis-POM PMEA. Pertinent abstracts from scientific meetings on infectious diseases and hepatology were also included. The manufacturer of adefovir dipivoxil provided additional information. These materials were supplemented by US Food and Drug Administration briefing documents and other unpublished materials. In vitro and preclinical studies were included in the review, as were Phase II and III clinical trials. RESULTS: In vitro, adefovir dipivoxil concentrations exceed those necessary to inhibit both wild-type and lamivudine-resistant isolates of HBV. In clinical trials, adefovir dipivoxil was clinically and virologically effective in patients in whom lamivudine therapy had failed due to the presence of lamivudine-resistant HBV. The drug was generally well tolerated. The risk of nephrotoxicity, the most notable adverse effect of adefovir dipivoxil at previously used higher doses, has been substantially reduced at the currently recommended dosage of 10 mg/d. CONCLUSION: Based on the data reviewed adefovir dipivoxil is an effective and well-tolerated alternative for the treatment of HBV infection, including disease that is lamivudine resistant.