Telbivudine is a nucleoside analogue and antiviral inhibitor of hepatitis B virus (HBV) replication which is used alone and in combination with other agents in the therapy of the hepatitis B. Telbivudine does not appear to be a significant cause of drug induced liver injury, but can be associated with flares of the underlying hepatitis B either during therapy or upon withdrawal.
Telbivudine (tel biv' ue deen) is the L-enantiomer of deoxythymidine (LdT) and has antiviral activity against HBV replication both in vitro and in vivo. Telbivudine is phosphorylated intracellularly to the triphosphate which inhibits the HBV polymerase and competes with deoxythymidine for incorporation into the growing viral DNA, causing inhibition of polymerase activity and DNA chain termination. Telbivudine has little or no activity against HIV replication. Telbivudine was approved for use in the United States in 2006. Telbivudine is indicated for the treatment of chronic hepatitis B either alone or in combination with other agents. Telbivudine is available as 600 mg tablets under the brand name Tyzeka. The recommended adult dose is 600 mg orally once daily. Side effects of telbivudine are uncommon. Limited studies of telbivudine therapy during pregnancy suggest that it is safe for pregnant women.
Telbivudine shares many features with the other L-nucleosides (lamivudine, emtricitabine) and has been linked to transient flares of hepatitis B during and after treatment of chronic hepatitis B. Serum ALT elevations above 3 times normal occurred in 5% to 10% of patients on telbivudine, which was comparable to other nucleoside analogues. Three types of lfars due to nucleoside analogue therapy have been described: transient and usually asymptomatic flares around the time of initiation of therapy (treatment flares), exacerbations of disease after development of antiviral resistance to telbivudine (breakthrough flares) and after stopping treatment (withdrawal flares). Cases of exacerbation of hepatitis B after development of antiviral resistance or upon telbivudine withdrawal can be severe and some cases have qualified as acute liver failure. No instances of lactic acidosis with hepatic steatosis have been reported with telbivudine therapy of hepatitis B, but isolated cases of suspected mitochondrial injury with myopathy have been reported.
Mechanism of Injury
The apparent absence of significant hepatotoxicity from telbivudine may be due to its lack of hepatic metabolism. In vitro, telbivudine has little activity against mitochondrial polymerase gamma, inhibition of which has been implicated in the syndrome of hepatic mitochondrial injury with lactic acidosis, steatosis and hepatic failure.
Outcome and Management
Flares of hepatitis B during and after telbivudine therapy can range in severity from mild, transient ALT elevations to severe acute liver injury resulting in hepatic failure and death. Flares occurring at initiation of therapy are usually mild and not associated with symptoms or jaundice. Flares associated with development of antiviral resistance and withdrawal flares can be severe. As a result, patients who develop evidence of antiviral resistance to telbivudine should be monitored carefully and switched to or have added another agent with a different pattern of resistance. Upon withdrawal of telbivudine, patients should be monitored carefully and promptly restarted on antiviral therapy if signs of severe injury arise.
[Agents used in therapy of HBV infection include adefovir, emtricitabine,
entecavir, lamivudine, telbivudine, tenofovir, interferon alfa and
Drug Class: Antiviral Agents,
Antiretroviral Agents, Hepatitis B Agents
REPRESENTATIVE TRADE NAMES
Telbivudine – Tyzeka®
Product labeling at DailyMed, National Library of Medicine, NIH
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