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Drugs 2007Telbivudine, the unmodified L-enantiomer of the naturally occurring nucleoside D-thymidine, is a potent synthetic nucleoside analogue. It acts as a hepatitis B virus... (Review)
Review
Telbivudine, the unmodified L-enantiomer of the naturally occurring nucleoside D-thymidine, is a potent synthetic nucleoside analogue. It acts as a hepatitis B virus (HBV) polymerase inhibitor and preferentially inhibits HBV second strand (DNA-dependent) compared with first strand (RNA-dependent) DNA synthesis. More telbivudine than lamivudine recipients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and similar proportions of telbivudine or lamivudine recipients with HBeAg-negative disease achieved a therapeutic response at 52 weeks in the large 2-year GLOBE trial. In a phase III trial in Chinese patients, greater reductions in serum HBV DNA occurred with telbivudine than lamivudine at 52 weeks. Reductions in serum HBV DNA at 24 weeks were greater with telbivudine than adefovir in the 1-year switching trial. A lower residual viral load at 52 weeks was seen in patients who received telbivudine or who switched from adefovir to telbivudine at 24 weeks than in patients receiving adefovir. In the 1-year lamivudine switching trial in patients with serum HBV DNA levels >3 log10 copies/mL despite having received prior treatment with lamivudine for a mean of [almost equal or equal to]7 months, those randomised to telbivudine therapy achieved greater reductions in serum HBV DNA levels at 24 weeks than patients randomised to continue lamivudine therapy. Telbivudine was generally well tolerated and most adverse events were of mild or moderate severity. The incidence of severe ALT flares with telbivudine was half that seen with lamivudine at both 52 and 104 weeks in the GLOBE trial.
Topics: Antiviral Agents; Hepatitis B virus; Hepatitis B, Chronic; Humans; Nucleic Acid Synthesis Inhibitors; Nucleosides; Pyrimidinones; Telbivudine; Thymidine
PubMed: 17722961
DOI: 10.2165/00003495-200767130-00011 -
The American Journal of the Medical... Feb 2014We performed a meta-analysis to compare the efficacies of entecavir and telbivudine in treatment-naive hepatitis B e-antigen (HBeAg)-positive Asian patients with chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed a meta-analysis to compare the efficacies of entecavir and telbivudine in treatment-naive hepatitis B e-antigen (HBeAg)-positive Asian patients with chronic hepatitis B (CHB).
METHODS
Randomized controlled trials (January 1, 2000 to March 30, 2012) directly comparing entecavir 0.5 mg/d and telbivudine 600 mg/d, used for a minimum of 12 weeks in nucleos(t)ide-naive Asian patients with HBeAg-positive CHB, were searched in the PubMed, Embase, OVID, Cochrane Library, CNKI, VIP and WanFang databases. Publication quality was assessed using the Jadad quality scale. The rates of viral response, biochemical response, HBeAg loss and HBeAg seroconversion were analyzed using forest plots.
RESULTS
Seven eligible articles (867 patients in total) were included in this meta-analysis. With regard to the rates of hepatitis B virus DNA suppression, there were no significant differences between patients treated with entecavir or telbivudine at 12 and 48 weeks, but telbivudine was superior at 24 weeks. Twelve, 24 and 48 weeks after the start of therapy, the rates of alanine aminotransferase normalization were similar between the 2 drugs, and patients treated with telbivudine had higher HBeAg loss and seroconversion rates than patients treated with entecavir.
CONCLUSIONS
In nucleos(t)ide-naive Asian patients with HBeAg-positive CHB, assessed 12, 24, and 48 weeks after beginning treatment, telbivudine was as potent as entecavir in viral suppression, but superior with regard to HBeAg loss and seroconversion. Telbivudine seems to be more effective and suitable for these patients.
Topics: Antiviral Agents; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Telbivudine; Thymidine
PubMed: 23563307
DOI: 10.1097/MAJ.0b013e318286878d -
Advances in Therapy Feb 2009The treatment of chronic hepatitis B virus (HBV) infection has been revolutionized in the past decade by the increased availability of effective antiviral agents.... (Review)
Review
INTRODUCTION
The treatment of chronic hepatitis B virus (HBV) infection has been revolutionized in the past decade by the increased availability of effective antiviral agents. Telbivudine is an L-nucleoside that is structurally related to lamivudine and has recently been approved for use in patients with chronic HBV infection. Telbivudine is highly selective for HBV DNA and inhibits viral DNA synthesis with no effect on human DNA or other viruses. This article reviews the pharmacology, pharmacokinetics, therapeutic efficacy and safety of telbivudine, and discusses its place in the current armamentarium against HBV.
METHODS
Relevant publications were identified from searches of Medline and PubMed between 2000 and 2008, using the search terms "hepatitis B/HBV," "telbivudine/LdT," "beta-L-thymidine," "pharmacokinetics," "safety," "adverse events," and "resistance." The reference lists of retrieved articles were searched for relevant studies.
RESULTS
Phase 3 clinical studies demonstrate that telbivudine is superior to lamivudine over a 2-year period in hepatitis B e-antigen (HBeAg)-positive and HBeAg-negative patients. Telbivudine was associated with a statistically significantly greater reduction in HBV DNA, greater proportion of alanine aminotransferase normalization, and greater histological response than lamivudine. Furthermore, telbivudine use resulted in fewer cases of treatment failure and less virological resistance than lamivudine. However, after 2 years of therapy, telbivudine resistance was appreciable (25%) and considerably higher than that seen with other new antivirals such as tenofovir and entecavir. Overall, telbivudine was found to be safe, although grade 3 or 4 adverse events, including elevations in creatine kinase, were more commonly found in patients receiving telbivudine than lamivudine. Telbivudine is not active against lamivudine-resistant HBV.
CONCLUSIONS
Telbivudine is a new antiviral agent joining the armamentarium against HBV. It is superior to lamivudine in terms of therapeutic response and resistance profile. However, concerns about resistance with long-term use, along with inferior cost-effective analyses, have relegated telbivudine to a second-line agent in the management of chronic HBV infection.
Topics: Alanine Transaminase; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; DNA, Viral; Drug Evaluation, Preclinical; Drug Interactions; Drug Resistance, Viral; Hepatitis B virus; Hepatitis B, Chronic; Humans; Nucleosides; Pyrimidinones; Safety; Telbivudine; Thymidine; Treatment Outcome; Virus Replication
PubMed: 19225726
DOI: 10.1007/s12325-009-0004-y -
The Journal of International Medical... Dec 2023Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic... (Review)
Review
Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.
Topics: Male; Humans; Telbivudine; Hepatitis B, Chronic; Antiviral Agents; Myoglobin; Thymidine; Rhabdomyolysis; Renal Dialysis; Pain; Muscle Weakness
PubMed: 38140948
DOI: 10.1177/03000605231222244 -
Expert Opinion on Investigational Drugs Apr 2005Telbivudine, beta-L-2'-deoxythymidine (LdT), is a new beta-L-nucleoside analogue with potent inhibitory activity against the hepatitis B virus. In in vitro studies and... (Comparative Study)
Comparative Study Review
Telbivudine, beta-L-2'-deoxythymidine (LdT), is a new beta-L-nucleoside analogue with potent inhibitory activity against the hepatitis B virus. In in vitro studies and animal models, telbivudine has demonstrated potent and specific antiviral activity against hepatitis B. Additionally, in preclinical animal toxicology studies, telbivudine showed no adverse side effects or adverse effects on mitochondrial function. The promising results of the early in vitro and animal telbivudine studies prompted the development and initiation of Phase I and II human clinical trials. The Phase I clinical study demonstrated that end-of-treatment virological response rates were better for telbivudine recipients at multiple dosing levels as compared with placebo patients. The subsequent Phase IIb human clinical study demonstrated superior antiviral efficacy of telbivudine, significantly better ALT normalisation and better hepatitis B e-antigen loss as compared with lamivudine. Telbivudine was well tolerated with no identified safety issues. Virological breakthrough with telbivudine was significantly lower than with lamivudine.
Topics: Animals; Antiviral Agents; Disease Models, Animal; Hepatitis B, Chronic; Humans; Lamivudine; Nucleosides; Pyrimidinones; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors; Telbivudine; Thymidine
PubMed: 15882124
DOI: 10.1517/13543784.14.4.511 -
Expert Opinion on Drug Safety Sep 2010Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient... (Review)
Review
IMPORTANCE OF THE FIELD
Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient non-compliance and adverse effects. Telbivudine is one of the more potent options available, with a 6.5- to 6.6-log copies/ml hepatitis B DNA reduction at 12 weeks in an early viral kinetic study, a potency comparable to entecavir. It is also one of the few drugs in the treatment of CHB under FDA pregnancy Category B.
AREAS COVERED IN THIS REVIEW
The efficacy and safety profile of telbivudine in compensated and decompensated CHB patients compared to other agents are discussed. Viral resistance, characteristic adverse effects including elevation in creatine kinase and peripheral neuropathy in telbivudine treatment are reviewed. Infrequent but significant adverse effects of other nucleoside/nucleotide analogs are highlighted.
WHAT THE READER WILL GAIN
Readers are provided the latest update on the clinical profile of long-term use of telbivudine.
TAKE HOME MESSAGE
Long-term telbivudine treatment offers effective viral suppression to CHB patients with certain baseline characteristics and on-treatment virologic response. Creatine kinase elevation is not a good predictor of muscle-related adverse effects with nucleoside/nucleotide analogs. But significant myopathy and neuropathy have been reported in a small number of patients receiving telbivudine.
Topics: Adult; Antiviral Agents; Biomarkers; Creatine Kinase; Double-Blind Method; Drug Resistance, Viral; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Isoenzymes; Male; Multicenter Studies as Topic; Muscular Diseases; Nucleosides; Peripheral Nervous System Diseases; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Infectious; Pyrimidinones; Randomized Controlled Trials as Topic; Telbivudine; Thymidine
PubMed: 20662545
DOI: 10.1517/14740338.2010.507190 -
Journal of Gastroenterology and... Jan 2017Hepatitis B virus (HBV) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. Several antiviral agents have... (Review)
Review
Hepatitis B virus (HBV) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. Several antiviral agents have been approved for the treatment of chronic hepatitis B, leading to a rapid reduction in HBV DNA and normalization of serum alanine aminotransferase levels. Telbivudine, a potent inhibitor of HBV replication, has been shown to be well tolerated. Because of the emergence of drug resistance, optimization strategies for telbivudine therapy have been shown to improve patient responses. Optimal baseline characteristics in so-called super-responders have been used to predict the virological response. Baseline HBV DNA levels < 9 log copies/mL (2 × 10 IU/mL) or alanine aminotransferase levels of more than or equal to twofold the upper limit of normal in HBeAg-positive patients and HBV DNA < 7 log copies/mL (2 × 10 IU/mL) in HBeAg-negative patients were strong predictors for virological response. In addition, the roadmap model, based on early virological response at week 24 of therapy, is considered as a powerful tool to identify patients at risk of treatment failure (HBV DNA ≥ 300 copies/mL, i.e. 60 IU/mL) and to reduce the risk of antiviral resistance. When considering pre-treatment characteristics and on-treatment responses, telbivudine may provide physicians with a wide choice of options to effectively treat patients with chronic hepatitis B, especially those with or at risk of renal impairment, or women of childbearing age.
Topics: Alanine Transaminase; Antiviral Agents; Biomarkers; DNA, Viral; Drug Administration Schedule; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Predictive Value of Tests; Risk; Telbivudine; Thymidine; Treatment Failure; Treatment Outcome
PubMed: 27515408
DOI: 10.1111/jgh.13512 -
Journal of Viral Hepatitis Nov 2017Hepatitis B virus infection is currently the most important cause of chronic viral hepatitis worldwide and is one of the most frequent causes of end-stage liver disease.... (Review)
Review
Hepatitis B virus infection is currently the most important cause of chronic viral hepatitis worldwide and is one of the most frequent causes of end-stage liver disease. With the international implementation of the hepatitis B vaccine and combined prophylaxis for infants born to HBsAg(+) mothers, the prevalence of hepatitis B has decreased remarkably. However, intra-uterine transmission has become a critical bottleneck for eliminating hepatitis B infection. The efficacy of nucleos(t)ide analogs on inhibiting hepatitis B replication has been widely confirmed, and the quality of life and the survival of individuals with chronic hepatitis B (CHB) have improved to a great degree. However, with the availability of long-term antiviral treatment and the ever increasing ageing population, renal disorders should be considered when choosing antiviral medicines. The antiviral efficacy and safety of telbivudine (LdT) have been shown in patients with CHB infection, and LdT is approved as a class B drug for pregnancy. Furthermore, the renal protective function of LdT has been demonstrated recently. In this review, we will focus on the efficacy and safety of LdT in gravidas with CHB infection, as well as the renal protective function of LdT in CHB patients. LdT might provide physicians with a solid option for effectively treating patients with CHB, especially gravidas or those either with or at risk of renal impairment.
Topics: Animals; Antiviral Agents; Female; Hepatitis B, Chronic; Humans; Pregnancy; Pregnancy Complications, Infectious; Renal Insufficiency; Risk; Telbivudine; Thymidine; Treatment Outcome; Viral Load
PubMed: 29082653
DOI: 10.1111/jvh.12787 -
Nature Reviews. Drug Discovery Apr 2007
Topics: Antiviral Agents; Enzyme Inhibitors; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Nucleosides; Pyrimidinones; Randomized Controlled Trials as Topic; Telbivudine; Thymidine
PubMed: 17458000
DOI: 10.1038/nrd2295