Telbivudine prevents vulnerable cells from dying by reversing the deregulation of BIRC3 brought on by B19V, interfering with the apoptotic process[2].

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 (Europe) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. Telbivudine is a synthetic thymidine nucleoside analogue, it is the L-isomer of thymidine. It is taken once daily. Telbivudine is a potent antiviral that provides effective and sustained viral suppression in patients with compensated CHB. In clinical trials, treatment outcomes were improved significantly more with telbivudine 600 mg once daily than with lamivudine 100 mg or adefovir 10 mg once daily, and telbivudine-treated patients had significantly less viral resistance than lamivudine-treated patients. Telbivudine is associated with a medium genetic barrier to resistance and, as patients with undetectable HBV DNA levels have significantly improved outcomes, it is recommended that HBV DNA levels are monitored at week 24 (and 6 monthly thereafter), with the addition of a nucleoside/nucleotide analogue without cross resistance (such as adefovir dipivoxil) if viraemia is present to reduce the risk of resistance (Roadmap concept). Telbivudine was generally well tolerated in clinical trials for periods of up to 4 years, and has a similar tolerability profile to that of lamivudine.

Absorption, Distribution and Excretion
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.
Telbivudine is eliminated primarily by urinary excretion of unchanged drug.
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)]

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Metabolism / Metabolites
No metabolites of telbivudine were detected following administration of [14C]–telbivudine in humans. Telbivudine is not a substrate, or inhibitor of the cytochrome P450 (CYP450) enzyme system.

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Biological Half-Life
Approximately 15 hours.

Hepatotoxicity
Telbivudine shares many features with the other L-nucleosides (lamivudine, emtricitabine) and has been linked to transient flares of hepatitis B during and after treatment of chronic hepatitis B. Serum ALT elevations above 3 times normal occurred in 5% to 10% of patients on telbivudine, which was comparable to other nucleoside analogues. Three types of flares can arise with nucleoside analogue therapy: transient and usually asymptomatic flares around the time of initiation of therapy (treatment flares), exacerbations of disease after development of antiviral resistance to telbivudine (breakthrough flares) and after stopping treatment (withdrawal flares). Cases of exacerbation of hepatitis B after development of antiviral resistance or upon telbivudine withdrawal can be severe and some cases have qualified as acute liver failure. No instances of lactic acidosis with hepatic steatosis have been reported with telbivudine therapy of hepatitis B, but isolated cases of suspected mitochondrial injury with myopathy have been reported. In trials of telbivudine therapy in pregnant women with HBsAg and HBeAg in serum and high levels of HBV DNA, therapy appeared to lessen if not eliminate maternal infant transmission, but withdrawal flares of hepatitis B occurred in some women with active disease and ALT elevations before therapy. In women with “immune tolerant” hepatitis B with high levels of HBV DNA without serum aminotransferase elevations, withdrawal flares are uncommon and levels of HBV DNA rise to previous levels on stopping therapy but without a concurrent flare of disease.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Telbivudine has been discontinued from the US market. It has not been studied in nursing mothers being treated for hepatitis B infection. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
No difference exist in infection rates between breast-fed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
In vitro binding of telbivudine to human plasma proteins is low (3.3%).

[1]. Telbivudine: a novel nucleoside analog for chronic hepatitis B. Ann Pharmacother. 2006;40(3):472-478.

[2]. Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells. Viruses. 2019;11(3):227. Published 2019 Mar 6.

Telbivudine is a pyrimidine 2'-deoxyribonucleoside that is the L-enantiomer of thymine. A synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. It has a role as an antiviral drug and an EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor. It is functionally related to a thymine. It is an enantiomer of a thymidine.
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.
Telbivudine is a Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor. The mechanism of action of telbivudine is as a Nucleoside Reverse Transcriptase Inhibitor.
Telbivudine is a nucleoside analogue and antiviral inhibitor of hepatitis B virus (HBV) replication which is used alone and in combination with other agents in the therapy of the hepatitis B. Telbivudine does not appear to be a significant cause of drug induced liver injury, but can be associated with flares of the underlying hepatitis B either during therapy or upon withdrawal.
Telbivudine is a synthetic thymidine nucleoside analogue with antiviral activity highly specific for the treatment of hepatitis B virus (HBV). Intracellularly, telbivudine is phosphorylated to its active metabolite, telbivudine triphosphate. The dideoxy telbivudine triphosphate competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). This results in the blockade of HBV DNA replication and viral propagation.
A thymidine derivative and antiviral agent that inhibits DNA synthesis by HEPATITIS B VIRUS and is used for the treatment of CHRONIC HEPATITIS B.
See also: Thymidine (annotation moved to).

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Drug Indication
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.
Sebivo is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis. Initiation of Sebivo treatment should only be considered when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate.
Treatment of chronic hepatitis B

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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.

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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.

C10H14N2O5

242.23

242.09

3424-98-4

Granisetron-d3 (1-methyl-d3);1224925-76-1;Telbivudine-d4;1134182-00-5

159269

White to off-white solid powder

1.5±0.1 g/cm3

188-190ºC

1.584

-1.11

3

5

2

17

381

3

CC1=CN(C(=O)NC1=O)[C@@H]2C[C@H]([C@@H](O2)CO)O

IQFYYKKMVGJFEH-CSMHCCOUSA-N

InChI=1S/C10H14N2O5/c1-5-3-12(10(16)11-9(5)15)8-2-6(14)7(4-13)17-8/h3,6-8,13-14H,2,4H2,1H3,(H,11,15,16)/t6-,7+,8+/m1/s1

1-((2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 3.25 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.25 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.25 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10 mg/mL (41.28 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)