TelbivudineOther Names: Beta-L-Thymidine, Telbivudina Drug Class: Opportunistic Infections and Coinfections
Telbivudine, also known as Tyzeka, is a thymidine nucleoside analogue with activity against hepatitis B virus (HBV). 
Telbivudine is used for the treatment of hepatitis B virus (HBV); telbivudine is not active against HIV-1 and has not been approved for use in patients who are coinfected with HIV and HBV.  However, telbivudine is being studied in patients who are coinfected with HIV and HBV. 
 HIV and Hepatitis.com HIV and AIDS articles: Selected Highlights from the New EACS Guidelines for Treatment of HIV Coinfection with Chronic Hepatitis C and Hepatitis B, October 30, 2007. Available at: http://www.hivandhepatitis.com/recent/2007/103007_c.html. Accessed 11/22/08.
Mode of Delivery
Film-coated tablets that contain telbivudine 600 mg. 
Store tablets in original container at 25 C (77 F). Excursions are permitted to controlled room temperature of 15C to 30 C (59F to 86F). 
 Idenix Pharmaceuticals Inc. News Releases, 2006: TYZEKA(TM) (telbivudine) Approved by U.S. Food and Drug Administration (FDA) as a New Treatment for Patients with Chronic Hepatitis B [press release], October 25, 2006. Available at: http://ir.idenix.com/phoenix.zhtml?c=131556&p=irol-newsArticle&ID=921371&highlight=. Accessed 11/22/08.
Telbivudine is a potent and selective nucleoside analogue antiviral medication that specifically inhibits HBV. Telbivudine belongs to a group of compounds, the beta-L-nucleosides, that have been shown to be highly specific and potent inhibitors of HBV polymerase and HBV replication in vitro. Lamivudine is a well known example of the class of beta-L-nucleoside analogues.   Unlike lamivudine, telbivudine does not have activity against HIV-1. 
Telbivudine is metabolized by cellular kinases that phosphorylate telbivudine to telbivudine monophosphate (telbivudine-MP), to telbivudine diphosphate (telbivudine-DP), and to its major active metabolite, telbivudine-triphosphate (telbivudine-TP). Telbivudine-TP inhibits DNA reverse transcriptase by competing with and replacing the natural substrate, thymidine 5'-triphosphate to cause DNA chain termination and inhibition of viral replication. Telbivudine inhibits both HBV first-strand and second-strand synthesis. 
Telbivudine-TP does not inhibit cellular DNA polymerases and does not appear toxic to mitochondria in HepG2 cells at concentrations up to 10 microM.  A mean peak plasma concentration (Cmax) of 3.69 ug/mL and a mean area under the concentration-time curve of 26.1 ug(h)/mL are achieved with once-daily administration of telbivudine 600 mg. Steady-state concentrations are achieved in approximately 1 week and provide an effective half-life of approximately 15 hours. Telbivudine is only slightly bound to plasma proteins (3.3%) and is highly distributed into tissues. Telbivudine is eliminated, unchanged, renally by passive diffusion. 
Telbivudine is in pregnancy category B; there are no adequate and well-controlled studies of telbivudine in pregnant women, so the drug should only be used during pregnancy if potential benefits outweigh risks. In pregnant rats and rabbits, telbivudine crossed the placenta, but no evidence of developmental toxicity occurred at doses up to 1,000 mg/kg/day (rougly equivalent six and 37 times higher, respectively, than the 600-mg dose administered to humans).  Interim analyses of the Phase III GLOBE and other studies of telbivudine compared with lamivudine or adefovir for the treatment of chronic HBV show that clearance within the first 6 months of therapy is associated with better outcomes at 1 and 2 years of treatment, that patients treated with telbivudine achieved greater viral clearance at 24 weeks of treatment than patients treated with either lamivudine or adefovir, and that patients who switched to telbivudine achieved greater viral suppression than those who continued on lamivudine or adefovir. 
In Phase III studies, the following amino acid substitutions were associated with virologic failure of telbivudine: rtM204I, rtL80I/V, rtA181T, rtL180M, and rtL229W/V; the rtM204I mutation occurred most often and was associated with greater than 10-fold virologic rebound in 34 or 36 patients who exhibited this mutation.  Cross resistance of telbivudine with other nucleoside analogues has been observed with the rtM204I mutation as well and with the lamivudine resistance-associated mutations rtM204V and rtL180M/rtM204V. The adefovir resistance-associated mutation rtA181V reduced viral susceptibility to telbivudine as well. 
 Idenix Pharmaceuticals Inc. News releases - New Telbivudine Data From Three Clinical Trials to be Presented at the 57th Annual Meeting of the American Association for the Study of Liver Diseases [press release], October 27, 2006. Available at: http://ir.idenix.com/phoenix.zhtml?c=131556&p=irol-newsArticle&ID=922689&highlight=. Accessed 11/22/08.
In studies with HBV infected patients, telbivudine was well tolerated. No serious adverse events and no dose-limiting toxicities were reported in study participants.  Adverse events data was collected in the Phase III GLOBE study, which enrolled more than 1,200 participants who received telbivudine 600 mg daily. In this study, the most common adverse events included fatigue, abdominal pain, headache, cough, nausea and vomiting, flu-like symptoms, diarrhea, fever, rash, and myalgia. Increased creatine kinase levels seven or more times the upper limit of normal occurred more frequently in patients treated with telbivudine than those treated in the control group with lamivudine 100 mg.  Myopathy (muscle pain with increased creatine kinase levels) has been reported with telbivudine within several weeks to months after the start of therapy. Telbivudine should be discontinued if myopathy is diagnosed. 
Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported with the use of nucleoside analogues alone or in combination with antiretroviral therapy. Severe acute exacerbations of HBV have been reported in patients who discontinue telbivudine. Hepatic function should be monitored closely for several months after such discontinuation. 
Drug and Food Interactions
Telbivudine may be taken with or without food. Absorption of telbivudine 600 mg remains the same during fasting or high-fat food coadministration. 
Telbivudine is not a substrate or inhibitor of the cytochrome P450 (CYP450) liver enzyme system. Therefore, telbivudine is not affected by, and does not affect, drugs that are metabolized by that system. At concentrations up to 12 times those in humans, telbivudine did not affect the following CYP 450 metabolism pathways: 1A2, 2C9, 2C19, 2D26, 2E1, or 3A4, so the potential for interactions is extremely low. 
Lamivudine, adefovir dipivoxil, cyclosporine, and pegylated interferon-alfa 2a do not alter telbivudine concentrations, nor does telbivudine affect the concentrations of lamivudine, adefovir dipivoxil, or cyclosporine. Telbivudine's effect on pegylated interferon-alfa 2a is unknown. 
Telbivudine is not antagonistic to the antiretroviral activity of the anti-HIV medications abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, or zidovudine. 
Telbivudine should not be administered to patients who have a hypersensitivity to any components of the tablet. 
Click here to search ClinicalTrials.gov for trials that use Telbivudina.
Dieterich DT. Special considerations and treatment of patients with HBV-HIV coinfection. Antivir Ther. 2007;12 Suppl 3:H43-51. Review.
Garcia-Gasco P, Sheldon J, Soriano V. Treatment of chronic hepatitis B in HIV-infected patients in 2007. J HIV Ther. 2007 Mar;12(1):19-23. Review.
Keam SJ. Telbivudine. Drugs. 2007;67(13):1917-29. Review.
Matthews SJ. Telbivudine for the management of chronic hepatitis B virus infection. Clin Ther. 2007 Dec;29(12):2635-53. Review.