WARNINGS: SEVERE ACUTE EXACERBATIONS OF HEPATITIS B, PATIENTS CO-INFECTED WITH HIV AND HBV, and LACTIC ACIDOSIS AND HEPATOMEGALY
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. 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, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions ].
Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic hepatitis B virus (HBV) infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART) [see Warnings and Precautions ].
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals [see Warnings and Precautions ].
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BARACLUDE SUMMARY
Baraclude® (entecavir) Tablets
Baraclude® (entecavir) Oral Solution
BARACLUDE™ is the tradename for entecavir, a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV).
BARACLUDE (entecavir) is indicated for the treatment of chronic hepatitis B virus infection 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 histologic, virologic, biochemical, and serologic responses after one year of treatment in nucleoside-treatment-naive and lamivudine-resistant adult patients with HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver disease and on more limited data in adult patients with HIV/HBV co-infection who have received prior lamivudine therapy.
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NEWS HIGHLIGHTS
Published Studies Related to Baraclude (Entecavir)
Efficacy of entecavir treatment for lamivudine-resistant hepatitis B over 3 years: histological improvement or entecavir resistance? [2009.03]
BACKGROUND AND AIMS: Long-term lamivudine therapy is required for patients with chronic hepatitis B, because hepatitis reappears frequently after it has withdrawn. However, hepatitis B virus (HBV) mutants resistant to lamivudine emerge frequently accompanied by breakthrough hepatitis... CONCLUSION: Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine-resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of entecavir resistance is a concern, and other strategies need to be considered when available.
Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan. [2009.02]
BACKGROUND AND AIM: Entecavir has demonstrated clinical efficacy for chronic hepatitis B. This study evaluated the efficacy and safety of entecavir in nucleoside-naive Japanese chronic hepatitis B patients... CONCLUSIONS: In Japanese nucleoside-naive patients with chronic hepatitis B, 0.1 mg or 0.5 mg entecavir daily provided excellent efficacy and was well tolerated. The 0.5 mg dose was selected for the treatment of nucleoside-naive patients.
Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients with chronic hepatitis B: A randomized international study of entecavir versus adefovir. [2009.01]
This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside-naive adults with chronic hepatitis B (CHB). Sixty-nine nucleoside-naive CHB patients with baseline HBV DNA of 10(8) copies/mL or more were randomized 1:1 to open-label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks...
Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis. [2008.11]
OBJECTIVE: The efficacy and safety of entecavir in patients with chronic hepatitis B and advanced liver fibrosis/cirrhosis was assessed from three large, randomized, multicenter, phase III studies... CONCLUSION: These data confirm that the performance of entecavir relative to that of lamivudine in patients with advanced liver fibrosis/cirrhosis was consistent with the relationship observed in the overall treated population.
Efficacy and safety of entecavir for chronic HBV in HIV/HBV coinfected patients receiving lamivudine as part of antiretroviral therapy. [2008.09.12]
BACKGROUND: Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining suppression of plasma HIV RNA less than 400 copies/ml... CONCLUSION: In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment.
Clinical Trials Related to Baraclude (Entecavir)
Entecavir for Patients With Decompensated Hepatitis B Virus (HBV)-Related Cirrhosis [Enrolling by invitation]
Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B [Recruiting]
The purpose of this study is to evaluate the effectiveness of entecavir plus tenofovir
combination therapy compared with entecavir monotherapy. Safety will also be studied
Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders [Recruiting]
We propose a largely retrospective study with short-term prospective follow-up in a subgroup
of patients who have not yet been treated with 48 weeks of entecavir following partial
response to adefovir. The aim of the study is to describe sequential virologic response to
adefovir and entecavir.
Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Positive Chronic Hepatitis B [Recruiting]
Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with
HBeAg positive CHB, with the overall HBeAg seroconversion far from satisfactory. Therefore,
efforts on the various combinations with the currently available drugs are needed to improve
the overall response rates. The simultaneous combination therapy with oral nucleoside and
peginterferon alfa-2a from large-scaled randomized trials did not show a superior response
rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with
lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown
favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the
assumption that early viral suppression by lamivudine can restore the immune function to
facilitate the later immunomodulatory response by peginterferon alfa-2a. With the recent
introduction of entecavir, the more potent oral nucleoside with few drug resistance,
sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of
treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBeAg
seroconversion. Therefore, we aimed to conduct a placebo controlled randomized control trial
to evaluate of adding entecavir early in the course of therapy can improve the treatment
response.
Pegasys Plus Entecavir Versus Entecavir Alone for Hepatitis Be Antigen-Positive Chronic Hepatitis B [Recruiting]
Although the best treatment choice for chronic hepatitis B is not clarified yet, certain
therapeutic concepts could be derived from the experience of treating patients with chronic
hepatitis C or human immunodeficiency virus (HIV) infection. A major advancement in treating
hepatitis C or HIV infection has been the development of combination therapy. Whether the
combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect
against ETV alone is not clarified. A prior single-arm pilot study suggested that similar
combination therapy may be beneficial in patients with chronic hepatitis B. In this
proposal, we thus hypothesize that the efficacy by using combination therapy with pegylated
IFN alfa-2a plus ETV is superior to that by using ETV alone in that Peg-IFN may restore host
immunity against HBV and prolonged ETV can maximize viral suppression.
The objective of this clinical trial is to evaluate the efficacy of the combination of
Peg-IFN alfa-2a at a dose of 180 mcg administered subcutaneously per week and ETV 0. 5 mg
daily for 24 weeks followed by ETV 0. 5 mg daily monotherapy for an additional 120 weeks
versus ETV 0. 5 mg daily monotherapy for 144 weeks in patients with HBeAg-positive chronic
hepatitis B. It will be an open-label, randomized, comparative, multi-center clinical trial.
The recruited patients will be equally randomized into two treatment groups. Treatment-free
follow-up period will be 48 weeks in both groups of patients. All subjects will be assessed
for loss of HBeAg, presence of anti-HBe, loss of HBsAg, presence of anti-HBs, suppression of
HBV DNA, and normalization of serum ALT at the end of treatment and end of follow-up.
Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of
years 1, 2 and 3. The primary efficacy will be HBeAg seroconversion.
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Page last updated: 2009-10-20
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