Telbivudine Tablets (Tyzeka™)
Pharmacology Update
Telbivudine Tablets (Tyzeka™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has approved an oral, once-daily drug for the treatment of chronic hepatitis B. Telbivudine is the β-L enantiomer of thymidine with potent antiviral activity against hepatitis B virus. Telbivudine is manufactured by Novartis Pharma Stein AG in Switzerland and co-marketed by Idenix Pharmaceuticals, Incorporated and Novartis as "Tyzeka.™"
Indications
Telbivudine is indicated for the treatment of adult patients with chronic hepatitis B with evidence of viral replication and either persistent elevation in ALT or AST or histologically active disease.1
Dosage
The recommended dose is 600 mg once daily and may be taken with or without food. Dose should be reduced with impaired renal function.1
Telbivudine is available as 600 mg tablets.
Potential Advantages
Telbivudine has been reported to have more antiviral activity than adefovir in HBeAg positive patients.2 In contrast to adefovir, renal toxicity is not a major concern. The activated form of telbivudine (telbivudine-5' triphosphate) is not a substrate for human polymerase.3 One-year resistance rate was 4.4% compared to 10- 40% for lamivudine.4
Potential Disadvantages
Lactic acidosis and severe hepatomegaly with steatosis, including death has been associated with nucleoside analogs. Myopathy has been reported with telbivudine. Mutation associated with drug resistance and some cross-resistance among nucleosides has been reported.1
Comments
Telbivudine is a potent and specific inhibitor of hepatitis B virus with limited or no activity against herpes simplex virus or HIV.3 Efficacy has been shown in nucleoside treatment-naïve adults who are HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease.1 FDA approval was based on the GLOBE study involving 1,367 nucleoside treatment-naïve patients randomized to telbivudine (600 mg daily) or lamivudine 100 mg daily. The primary end point of therapeutic response at 52 weeks was a combination of suppression of HBV DNA to < 5 log10 copies/ml with either loss of serum HBeAg or ALT normalization. Response rate in HBeAg positive patients was 75% for telbivudine and 67% for lamivudine. Rates were 75% and 77% in HBeAg negative patients respectively. Since severe acute exacerbation of the disease may occur after discontinuation of therapy, patients should be monitored for at least several months after discontinuation of therapy and resumption of therapy may be required. Tebivudine is generally well tolerated, as adverse events are similar to lamivudine; however, elevation of creatine kinase is more likely with telbivudine. Grade 3 or 4 elavation occurred in 9% of telbivudine patients compared to 3% for lamivudine. Common side effects include upper respiratory tract infection (14%), fatigue/malaise (12%), abdominal pain (12%), nasopharyngitis (11%) and headache (11%). There appears to be no advantage in combining telbivudine with lamivudine.5 Telbivudine has been reported to have greater antiviral activity compared to adefovir,2 however the rate of ALT normalized and HBeAg loss were similar with the two drugs. There are no published comparative studies between telbivudine and entecavir. In similarly designed phase III trials, compared to lamivudine, entecavir appears to be numerically better.1,6 Efficacy in lamivudine or adefovir-resistant virus has not been reported. The cost of telbivudine was not available at the time of this review.
Clinical Implications
Chronic hepatitis B is a significant health problem, affecting about 5% of the world's population. Up to 40% of these individuals will develop cirrhosis or hepatocellular carcinoma in their lifetime. Current oral treatment includes lamivudine, adefovir, entecavir and now telbivudine. Lamivudine is associated with a high rate of development of viral resistance. Adefovir is associated with renal toxicity and potential development of HIV resistance. Entecavir has been reported to be effective against lamivudine-resistant virus and such has not been reported for telbivudine. Telbivudine may be an alternative to lamivudine in treatment-naïve patients but not an alternative for entecavir for lamivudine-resistant virus.
References
1. Tyzeka Product Information. Idenix and Novartis. October 2006.
2. Heathcote E, et al. Abstract 479. DDW 2006. May 20-25, 2006. Los Angeles, CA.
3. Han SH. Telbivudine: a new nucleoside analogue for the treatment of chronic hepatitis B. Expert Opin Investing Drugs. 2005;14:511-519.
4. Marcellin P, et al. Treatment of chronic hepatitis B J Viral Hepat. 2005;12:333-345.
5. Lai CL, et al. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology. 2005;129:528-536.
6. Baraclude Product Information. Bristol-Myers Squibb Company. March 2005.
The FDA has approved an oral, once-daily drug for the treatment of chronic hepatitis B. Telbivudine is the β-L enantiomer of thymidine with potent antiviral activity against hepatitis B virus.Subscribe Now for Access
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