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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: October 20, 2020.



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 in the United States in 2006 as therapy of chronic hepatitis B, either alone or in combination with other agents. It was withdrawn from the United States market in 2016 largely for economic reasons. Telbivudine was previously available as 600 mg tablets under the brand name Tyzeka. The recommended adult dose was 600 mg orally once daily. Side effects of telbivudine are uncommon. Studies of telbivudine therapy during pregnancy suggest that it is safe for pregnant women and can lower the rate of maternal-infant transmission of hepatitis B if administered in the last trimester. It was never approved for this indication in the United States.


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 flares can arise with nucleoside analogue therapy: 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. In trials of telbivudine therapy in pregnant women with HBsAg and HBeAg in serum and high levels of HBV DNA, therapy appeared to lessen if not eliminate maternal infant transmission, but withdrawal flares of hepatitis B occurred in some women with active disease and ALT elevations before therapy. In women with “immune tolerant” hepatitis B with high levels of HBV DNA without serum aminotransferase elevations, withdrawal flares are uncommon and levels of HBV DNA rise to previous levels on stopping therapy but without a concurrent flare of disease.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

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 peginterferon.

Drug Class: Antiviral Agents, Antiretroviral Agents, Hepatitis B Agents

Other Drugs in the Subclass, Nucleoside Analogues: Abacavir, Adefovir, Didanosine, Emtricitabine, Entecavir, Lamivudine, Stavudine, Tenofovir, Zidovudine



Telbivudine – Tyzeka®


Antiviral Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Telbivudine 3424-98-4 C10-H14-N2-O5 image 135115725 in the ncbi pubchem database


References updated: 20 October 2020

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    (Among 159 HBeAg positive adults with chronic hepatitis B treated with telbivudine, peginterferon or both, neuropathy arose in 14% of those on both agents vs 2% on telbivudine alone and none of the peginterferon alone group, which led to the early discontinuation of the trial).
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    (Among 279 HBeAg positive women with chronic hepatitis B and high levels of HBV DNA treated with telbivudine during the last trimester, rates of transmission were 0% compared to 15% of subjects who refused antiviral therapy; no serious adverse events occurred and there was no mention of on treatment or withdrawal ALT flares).
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    (Among 454 HBeAg positive pregnant women with chronic hepatitis B and normal ALT levels despite high levels of HBV DNA treated with telbivudine or given no therapy starting in the 2nd or 3rd trimester, rates of transmission were none vs 9% [8/86] and 46 of 236 women [20%] who discontinued therapy one month postpartum had a withdrawal flare, although in only 3 [1.3%] did levels rise about 5 times ULN and no woman required therapy as all levels eventually fell into the normal range).
  • Tsai MC, Chen CH, Tseng PL, Hung CH, Chiu KW, Wang JH, Lu SN, et al. Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience. Clin Microbiol Infect. 2016;22:95.e1–95.e7. [PubMed: 26055419]
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  • Hu Y, Xu C, Xu B, Hu L, Liu Q, Chen J, Liu J, et al. Safety and efficacy of telbivudine in late pregnancy to prevent mother-to-child transmission of hepatitis B virus: A multicenter prospective cohort study. J Viral Hepat. 2018;25:429–37. [PubMed: 29193547]
    (Among 328 HBeAg positive pregnant Chinese women who were treated with telbivudine during the last trimester or elected not to receive therapy, there were similar rates of ALT elevations in the postpartum period [21% vs 20%], whereas none of the 128 infants born to treated mothers developed HBV infection compared to 2 of 156 [1.5%] infants of controls ).


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