SEBIVO telbivudine NAME OF THE MEDICINE DESCRIPTION PHARMACOLOGY

1 SEBIVO telbivudine NAME OF THE MEDICINE The active ingredient of SEBIVO is telbivudine. The chemical name is: 1-((2S,4R,5S)-4hydroxy-5-hydroxyme...
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SEBIVO telbivudine

NAME OF THE MEDICINE The active ingredient of SEBIVO is telbivudine. The chemical name is: 1-((2S,4R,5S)-4hydroxy-5-hydroxymethyltetrahydrofuran-2-y1)-5-methyl-1H-pyrimidine-2,4-dione or 1-(2Deoxy-β-L-ribofuranosyl)-5-methyluracil; β-L-2′-Deoxythymidine (INN/USAN= telbivudine). Telbivudine is the unmodified -L enantiomer of naturally-occurring thymidine. Alternative name: L-thymidine The chemical structure of telbivudine (CAS number 3424-98-4) is: O CH3

HN O

N

OH

O

OH

DESCRIPTION SEBIVO is available as coated tablets containing 600 mg telbivudine and as oral solution* containing 20mg telbivudine per millilitre. SEBIVO (telbivudine) 600 mg film-coated tablets contain the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet coating contains titanium dioxide, polyethylene glycol, talc and hypromellose. SEBIVO (telbivudine) 20mg/mL oral solution* contain the following inactive ingredients: citric acid anhydrous, benzoic acid, passion fruit flavouring, sodium saccharin, sodium hydroxide and purified water. A 600 mg dose (30 mL) of Sebivo oral solution contains approximately 47 mg of sodium.

PHARMACOLOGY Pharmacotherapeutic group: Antiviral for systemic use.

2 Pharmacodynamics Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. It is efficiently phosphorylated by cellular kinases to the active triphosphate form, which has an intracellular half-life of 14 hours in human hepatocarcinoma cell line HepG2. Telbivudine-5'-triphosphate inhibits HBV DNA polymerase (reverse transcriptase) and thus HBV replication. This inhibition is thought to involve competition with the natural substrate thymidine 5'-triphosphate and incorporation of telbivudine into viral DNA, causing DNA chain termination. Telbivudine is an inhibitor of both HBV first-strand (EC50 = 0.4-3.1 M) and second-strand (EC50 = 0.12-0.47 M) synthesis, and shows a distinct preference for inhibiting second-strand production. By contrast, telbivudine-5'-triphosphate at concentrations up to 100 M did not inhibit human cellular DNA polymerases , , or . In assays relating to human mitochondrial structure, function and DNA content, telbivudine lacked an appreciable toxic effect at concentrations up to 10 M and did not increase lactic acid production in vitro. Antiviral activity: The in vitro antiviral activity of telbivudine was assessed in the HBV-expressing human hepatoma cell line, as well as in primary duck hepatocytes infected with duck hepatitis B virus (DHBV). The concentration of telbivudine that effectively inhibited 50% of viral synthesis (EC50) in both systems was approximately 0.2 M. The antiviral activity of telbivudine is specific to hepatitis B virus and related hepadnaviruses. No activity was noted against multiple other RNA and DNA viruses, including human immunodeficiency virus (HIV) type 1 (EC50 value 200 M). The absence of activity of telbivudine against HIV has not been evaluated in clinical trials. In 4- and 12-week studies of hepadnavirus-infected woodchucks (marmota monax), a relevant animal model for HBV, telbivudine significantly reduced viral DNA levels. Within 28 days, at oral doses of 10 mg/kg/day, serum viral DNA levels decreased by as much as 8 log10 to undetectable levels (80) (n=8) 600 mg

Cmax (g/mL) AUC0-INF (g/h/mL) CLRENAL (L/h)

3.4±0.9 28.5±9.6 7.6±2.9

Renal function (creatinine clearance in mL/min) Mild (50–80) Moderate (30–49) Severe (

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