WARNING: SEVERE ACUTE EXACERBATIONS OF HEPATITIS, NEPHROTOXICITY, HIV RESISTANCE, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS
Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-Hepatitis B therapy including HEPSERA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-Hepatitis B therapy. If appropriate, resumption of anti-Hepatitis B therapy may be warranted [see Warnings and Precautions].
In patients at risk of or having underlying renal dysfunction, chronic administration of HEPSERA may result in nephrotoxicity. These patients should be monitored closely for renal function and may require dose adjustment [see Warnings and Precautions and Dosage and Administration].
HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated Human Immunodeficiency Virus (HIV) infection treated with anti-hepatitis B therapies, such as therapy with HEPSERA, that may have activity against HIV [see Warnings and Precautions].
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [see Warnings and Precautions].
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HEPSERA SUMMARY
HEPSERA is the tradename for adefovir dipivoxil, a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV).
HEPSERA is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and in adult patients with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.
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NEWS HIGHLIGHTS
Published Studies Related to Hepsera (Adefovir Dipivoxil)
HBV DNA level as an important determinant of E antigen seroconversion of chronic hepatitis B during adefovir dipivoxil therapy. [2009.05]
CONCLUSIONS: Low pre-treatment HBV DNA level is predictive of HBeAg seroconversion in patients treated with Adefovir dipivoxil or placebo. Adefovir dipivoxil may provide additional benefits for HBeAg seroconversion in patients with pre-treatment HBV DNA levels between 10(7) and 10(8) copies/mL. Profound early HBV DNA reduction may contribute to HBeAg seroconversion.
Impact of adefovir dipivoxil on liver fibrosis and activity assessed with biochemical markers (FibroTest-ActiTest) in patients infected by hepatitis B virus. [2009.03]
SUMMARY: The aim was to assess the utility of FibroTest-ActiTest (FT-AT) as noninvasive markers of histological changes in patients with chronic hepatitis. Patients with chronic hepatitis B (HBeAg+ and HBeAg-) randomized in two trials of adefovir (ADV) vs placebo, with available paired liver biopsies and FT-AT at baseline and after 48 weeks of treatment were included...
Complex dynamics of hepatitis B virus resistance to adefovir. [2009.01]
In patients with hepatitis B e antigen-negative chronic hepatitis B, adefovir dipivoxil administration selects variants bearing reverse transcriptase rtN236T and/or rtA181V/T substitutions in 29% of cases after 5 years. The aim of this study was to characterize the dynamics of adefovir-resistant variant populations during adefovir monotherapy in order to better understand the molecular mechanisms underlying hepatitis B virus resistance to this class of nucleotide analogues...
Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. [2008.12.04]
BACKGROUND: Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase... CONCLUSIONS: Among patients with chronic HBV infection, tenofovir DF at a daily dose of 300 mg had superior antiviral efficacy with a similar safety profile as compared with adefovir dipivoxil at a daily dose of 10 mg through week 48. (ClinicalTrials.gov numbers, NCT00116805 and NCT00117676.) 2008 Massachusetts Medical Society
A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post-liver transplantation hepatitis B prophylaxis. [2008.11]
CONCLUSION: Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost.
Clinical Trials Related to Hepsera (Adefovir Dipivoxil)
Hepsera Versus Hepsera Plus Lamivudine for Treatment of Chronic Hepatitis B in Patients With Normal ALT [Completed]
This project is a randomized, open-label trial of adefovir dipivoxil (Hepsera) and lamivudine
combination therapy versus adefovir dipivoxil (Hepsera) monotherapy. Both adefovir dipivoxil
and lamivudine are nucleoside analogues approved by the U. S. FDA for the treatment of chronic
hepatitis B.
The primary hypothesis is that subjects treated with combination therapy will see their viral
DNA count decrease in an amount greater than subjects treated with monotherapy. The
secondary hypothesis is that subjects treated with combination therapy will have a higher
HBeAg conversion rate compared to historical controls of subjects treated with lamivudine or
adefovir dipivoxil monotherapy.
A Study to Compare Tenofovir Versus Hepsera (Adefovir) for the Treatment of HBeAg Negative Chronic Hepatitis B [Active, not recruiting]
This study is designed to evaluate the safety and antiviral activity of tenofovir disoproxil
fumarate (DF) compared to Hepsera for the treatment of HBeAg negative chronic hepatitis B.
Patients will either receive tenofovir or the approved hepatitis B therapy, Hepsera.
A Study to Compare Tenofovir Versus Hepsera (Adefovir) for the Treatment of Hepatitis Be Antigen (HBeAg) Positive Chronic Hepatitis B [Active, not recruiting]
This study is designed to evaluate the safety and antiviral activity of tenofovir compared to
Hepsera for the treatment of HBeAg positive chronic hepatitis B. Patients will either receive
tenofovir or the approved hepatitis B therapy, Hepsera.
Open Label Study of Pharmacokinetics and Safety of Dose of Adefovir Dipivoxil in Children and Adolescents With HBV [Completed]
Open-label study of the pharmacokinetics of adefovir dipivoxil in children and adolescents
infected with chronic hepatitis B.
Peg-Intron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (Study P04498) [Active, not recruiting]
This is an open label, randomized, comparative, multi-center study. Subjects will be
screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all
the selection criteria will be randomly assigned 1: 1 to (1) once-a-week, subcutaneous
Peg-Intron (1. 5 mg/kg body weight) or (2) oral adefovir 10 mg daily. The treatment phase
will be 24 weeks for Peg-Intron and 48 weeks for adefovir. All subjects completing the
assigned treatment phase will be followed up for an additional 48 weeks for Peg-Intron and 24
weeks for adefovir as observation phase. The primary objective is to establish the efficacy
profile of Peg-Intron. Secondary objectives are to compare the efficacy profile of
Peg-Intron with that of adefovir, compare efficacy of Peg-Intron in lamivudine-naïve and
lamivudine-experienced subjects, and to establish the safety profile of Peg-Intron in
treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
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Page last updated: 2009-10-20
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