Introduction
Telbivudine is a synthetic thymidine nucleoside analog with specific activity against the hepatitis B virus. Telbivudine is orally administered, with good tolerance, lack of toxicity and no dose-limiting side effects.
Uses
Telbivudine is a thymidine nucleoside analog used for the treatment of chronic hepatitis B with clinical evidence of viral replication or persistent elevations in serum aminotransferases (ALT or AST).
For the treatment of chronic hepatitis B in adult and adolescent patients ≥16 years of age with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Associated Conditions
Pharmacodynamics
Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate.
Mechanism of Action
Telbivudine 5'–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine 5'–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine inhibits anticompliment or second-strand DNA.
Absorption
Absorbed following oral administration. Telbivudine absorption and exposure were unaffected when a single 600–mg dose was administered with a high–fat (~55 g), high–calorie (~950 kcal) meal.
Protein Binding
In vitro binding of telbivudine to human plasma proteins is low (3.3%).
Route of Elimination
Telbivudine is eliminated primarily by urinary excretion of unchanged drug.
Half Life
Approximately 15 hours.
Clearance
- 7.6 +/- 2.9 L/h [Normal renal function (Clcr>80 mL/min)]
- 5.0 +/- 1.2 L/h [Mild renal function impairement (Clcr=50-80 mL/min)]
- 2.6 +/- 1.2 L/h [Moderate renal function impairement (Clcr=30-49 mL/min)]
- 0.7 +/- 0.4 L/h [Severe renal function impairement (Clcr<30 mL/min)]
Toxicity
There is no information on intentional overdose of telbivudine, but one subject experienced an unintentional and asymptomatic overdose. Healthy subjects who received telbivudine doses up to 1800 mg/day for 4 days had no increase in or unexpected adverse events. A maximum tolerated dose for telbivudine has not been determined.
Food Interactions
- Take with or without food. The absorption is unaffected by food.
Dosage
For HBeAg-positive patients, HBV DNA should be less than 9 log10 copies per mL and ALT should be greater than or equal to 2x ULN prior to treatment with Telbivudine.
For HBeAg-negative patients, HBV DNA should be less than 7 log10 copies per mL prior to treatment with Telbivudine.
HBV DNA levels should be monitored at 24 weeks of treatment to assure complete viral suppression (HBV DNA less than 300 copies per mL). Alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment. Optimal therapy should be guided by further resistance testing.
The recommended dose of Telbivudine for the treatment of chronic hepatitis B: 600 mg once daily, taken orally, with or without food. Telbivudine Oral Solution (30 mL) may be considered for patients who have difficulty with swallowing tablets.
