Tyzeka is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV) DNA polymerase. Tyzeka inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate. Incorporation of Tyzeka into viral DNA causes DNA chain termination, resulting in inhibition of HBV replication.
Tyzeka is specifically indicated for the treatment of chronic hepatitis B in adult subjects with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Tyzeka is supplied as a white to slightly yellowish film-coated, ovaloid-shaped tablet for oral administration. The recommended initial dose of the drug is 600 mg once daily, taken orally with or without food.
FDA approval of Tyzeka was based on the results of one clinical trial. This randomized, double-blind, multinational trial, dubbed 007 GLOBE, enrolled 1,367 nucleoside-naïve chronic hepatitis B HBeAg-positive and HBeAg-negative subjects. The trial was designed to compare 600 mg of Tyzeka once daily to 100 mg of lamivudine once daily, for a treatment period of up to 104 weeks. The primary endpoint was a composite serologic endpoint requiring suppression of HBV DNA to < 5 log10 copies/mL in conjunction with either loss of serum HBeAg or ALT normalized. Secondary endpoints included histologic response, ALT normalization, and various measures of antiviral efficacy. In HBeAg-positive patients, 75% of the telbivudine subjects and 67% of the lamivudine subjects had a therapeutic response. In HBeAg-negative patients, 75% of the telbivudine subjects and 77 % of the lamivudine subjects had a therapeutic response. Secondary analysis indicated that treatment with Tyzeka reduced HBV DNA levels by 6.45 log10, versus 5.54 log10 for treatment with lamivudine (p<0.001) and led to improvements in ALT normalization (77% versus 75%), HBeAg Seroconversion (23% versus 22%) and HBeAg Loss (26% versus 23%).
Ongoing Study Commitments
Adverse events associated with the use of Tyzeka may include, but are not limited to, the following:
In addition Tyzeka was shown to cause myopathy in conjunction with increases in creatine kinase (CK) values, several weeks to several months after starting therapy. Among patients with telbivudine-associated myopathy, there has not been a uniform pattern with regard to the degree or timing of CK elevations and predisposing factors are unknown. Patients should be advised to report promptly unexplained muscle aches, pain, tenderness or weakness. Treatment should be interrupted if myopathy is suspected, and discontinued if myopathy is diagnosed.
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Tyzeka is the unmodified ß-L enantiomer of the naturally occurring nucleoside, thymidine.It inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'-triphosphate. Incorporation of Tyzeka into viral DNA causes DNA chain termination, resulting in inhibition of HBV replication. Tyzeka is an an inhibitor of both HBV first strand and second strand synthesis.
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Zhou XJ, Fielman BA, Lloyd DM, Chao GC, Brown NA Pharmacokinetics of telbivudine in healthy subjects and absence of drug interaction with lamivudine or adefovir dipivoxil. Antimicrobial agents and chemotherapy 2006 Jul;50(7):2309-15.
Lai CL, Leung N, Teo EK, Tong M, Wong F, Hann HW, Han S, Poynard T, Myers M, Chao G, Lloyd D, Brown NA; Telbivudine Phase II Investigator Group A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005 Aug;129(2):528-36.
Lai CL, Lim SG, Brown NA, Zhou XJ, Lloyd DM, Lee YM, Yuen MF, Chao GC, Myers MW A dose-finding study of once-daily oral telbivudine in HBeAg-positive patients with chronic hepatitis B virus infection. Hepatology 2004 Sep;40(3):719-26.
For additional information regarding Tyzeka or hepatitis B virus, please visit the Tyzeka web page.