Chemistry:Telbivudine
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| Trade names | Tyzeka, Sebivo |
| Other names | 1-(2-deoxy-β-L-ribofuranosyl)-5-methyluracil β-L-2-deoxythymidine β-L-thymidine (LdT) 1-[(2S,4R,5S)-4-hydroxy-5-hydroxymethyltetrahydrofuran-2-yl]-5-methyl-1H-pyrimidine-2,4-dione |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a607045 |
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| Routes of administration | By mouth |
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| Protein binding | Low (3.3% in vitro) |
| Metabolism | Nil |
| Elimination half-life | 40 to 49 hours (terminal phase) |
| Excretion | Kidney |
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| Formula | C10H14N2O5 |
| Molar mass | 242.231 g·mol−1 |
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Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (European Union) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance.[1][2][3] However, HBV signature resistance mutation M204I (a change from methionine to isoleucine at position 204 in the reverse transcriptase domain of the hepatitis B polymerase) or L180M+M204V have been associated with Telbivudine resistance.[4]
Telbivudine is a synthetic thymidine β-L-nucleoside analogue; it is the L-isomer of thymidine. Telbivudine impairs hepatitis B virus (HBV) DNA replication by leading to chain termination. It differs from the natural nucleotide only with respect to the location of the sugar and base moieties, taking on an levorotatory configuration versus a dextrorotatory configuration as do the natural deoxynucleosides.[4] It is taken orally in a dose of 600 mg once daily with or without food.[5]
Telbivudine has no in vitro activity against HIV-1,[6] and in a case-series of three HIV-HBV co-infected patients, telbivudine did not produce sustained HIV-1 virologic suppression or induce any resistance mutations in HIV-1.[7]
Phase III clinical trials suggested that telbivudine put patients at greater risk for myopathy and peripheral neuropathy than the comparator drug lamivudine.[8] FDA required a required a risk evaluation and mitigation strategy (REMS) aiming to increase awareness of peripheral neuropathy by requiring distribution of a medication guide.[9]
In 2016, Novartis posted a discontinuation notice.[10][11] Efficacy or safety concerns were not cited as rationale for discontinuation, but rather "availability of alternative medications"; presumably this refers to tenofovir disoproxil, which became available as a generic medication in 2017, and is a safe and effective treatment for chronic HBV infection.
References
- ↑ "A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B". Gastroenterology 129 (2): 528–536. August 2005. doi:10.1016/j.gastro.2005.05.053. PMID 16083710.
- ↑ "Telbivudine versus lamivudine in patients with chronic hepatitis B". The New England Journal of Medicine 357 (25): 2576–2588. December 2007. doi:10.1056/NEJMoa066422. PMID 18094378.
- ↑ "Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial". Annals of Internal Medicine 147 (11): 745–754. December 2007. doi:10.7326/0003-4819-147-11-200712040-00183. PMID 17909201.
- ↑ 4.0 4.1 "Safety and efficacy of telbivudine for the treatment of chronic hepatitis B". Therapeutics and Clinical Risk Management 5: 789–798. 2009. doi:10.2147/tcrm.s5318. PMID 19851526.
- ↑ Drugs.com. "Tyzeka: Package Insert / Prescribing Information". Drugs.com. https://www.drugs.com/pro/tyzeka.html. Retrieved 2023-06-01.
- ↑ "Telbivudine exhibits no inhibitory activity against HIV-1 clinical isolates in vitro". Antimicrobial Agents and Chemotherapy 54 (6): 2670–2673. June 2010. doi:10.1128/AAC.01703-09. PMID 20308377.
- ↑ "Telbivudine in the treatment of chronic hepatitis B: experience in HIV type-1-infected patients naive for antiretroviral therapy". Antiviral Therapy 14 (6): 869–872. 2009. doi:10.3851/IMP1303. PMID 19812451.
- ↑ Drugs.com. "Tyzeka: Package Insert / Prescribing Information". Drugs.com. https://www.drugs.com/pro/tyzeka.html. Retrieved 2023-06-01.
- ↑ FDA. "Risk Evaluation and Mitigation Strategy". https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022011s001REMS.pdf. Retrieved 2023-06-01.
- ↑ "HBV drug Tyzeka discontinued". https://www.healio.com/news/hepatology/20161007/hbv-drug-tyzeka-discontinued.
- ↑ "FDA: Hepatitis B Drug Discontinued". 2016-10-05. https://www.empr.com/home/news/fda-hepatitis-b-drug-discontinued/.
External links
- "Telbivudine". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/telbivudine.
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