Chronic Hepatitis B: Telbivudine is indicated for the treatment of chronic hepatitis B in adult patients with evidence of viral replication and either persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Key points to consider before starting Telbivudine therapy:

• This indication is based on virologic, serologic, biochemical, and histologic responses in nucleoside treatment-naïve adult patients with HBeAg positive or HBeAg negative chronic hepatitis B with compensated liver disease.
• For HBeAg-positive patients, Telbivudine should only be started if HBV DNA is less than 9 log10 copies per mL and ALT is greater than or equal to 2 times the upper limit of normal (ULN).
• For HBeAg-negative patients, Telbivudine should only be started if HBV DNA is less than 7 log10 copies per mL.
• On-treatment response should guide continued therapy.
• Telbivudine has not been evaluated in patients co-infected with HIV, HCV, or HDV.
• Telbivudine has not been evaluated in liver transplant recipients or in patients with decompensated liver disease.
• Telbivudine has not been studied in well-controlled trials for patients with nucleoside analog reverse transcriptase inhibitor-resistant hepatitis B, but it is expected to be cross-resistant with lamivudine.
• The safety and efficacy of Telbivudine have not been evaluated in Black/African American or Hispanic patients.

Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). It is the unmodified β–L enantiomer of the naturally occurring nucleoside thymidine. Telbivudine undergoes phosphorylation through interaction with cellular kinases to form its active metabolite, telbivudine 5'-triphosphate.

Telbivudine 5'-triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate thymidine 5'-triphosphate. This competition leads to termination of DNA chain synthesis, thereby blocking viral replication. Incorporation of telbivudine 5'-triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine does not inhibit human DNA polymerases and has no effect on second-strand DNA.

Adults and Adolescents (16 years of age and older): Due to higher rates of resistance that may develop with longer term treatment among patients with incomplete viral suppression, treatment should only be initiated, if pre-treatment HBV DNA and ALT measurements are known, in the following patient populations-

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.

Plasma levels may be altered when used with medications that affect renal function (such as aminoglycosides, loop diuretics, platinum-based agents, vancomycin, and amphotericin B). Additionally, the risk of myopathy may increase when used concurrently with drugs known to be associated with muscle toxicity, including azole antifungals, cyclosporine, corticosteroids, erythromycin, fibrates, HMG-CoA reductase inhibitors, penicillamine, and zidovudine.

Telbivudine should not be used in patients with hypersensitivity to the drug. The combination of Telbivudine with pegylated interferon alfa-2a is contraindicated due to an increased risk of peripheral neuropathy.

Common side effects of Telbivudine may include cough, dizziness, fatigue, gastrointestinal effects such as abdominal pain, diarrhea, nausea, vomiting, or dyspepsia, rash, joint pain (arthralgia), muscle pain (myalgia), muscle weakness or myopathy, general malaise, back pain, nasopharyngitis, headache, flu or flu-like symptoms, and insomnia. Laboratory findings may show increased levels of serum amylase, lipase, creatine phosphokinase, or alanine aminotransferase. Rare but serious side effects include peripheral neuropathy and rhabdomyolysis.

Telbivudine is classified as Pregnancy Category B. It is not teratogenic and has shown no harmful effects on developing embryos or fetuses in preclinical studies. Animal studies in pregnant rats and rabbits demonstrated that telbivudine crosses the placenta. Developmental toxicity studies in these animals revealed no evidence of harm to the fetus at doses up to 1000 mg per kg per day, which provide exposure levels 6- to 37-times higher than the human 600 mg daily dose. There are no adequate and well-controlled studies of Telbivudine in pregnant women. Because animal reproductive studies may not fully predict human responses, Telbivudine should be used during pregnancy only if the potential benefits outweigh the risks.

Telbivudine may cause severe acute exacerbations of hepatitis B. Patients discontinuing therapy should have their liver function closely monitored. Possible adverse effects include lactic acidosis, severe hepatomegaly with steatosis, myopathy, rhabdomyolysis, and uncomplicated myalgia. Treatment should be discontinued if myopathy is diagnosed. There is an increased risk of peripheral neuropathy when Telbivudine is combined with pegylated interferon alpha-2a. Use caution in patients with decompensated cirrhosis, renal impairment, or those on hemodialysis, as well as in liver transplant recipients or patients on immunosuppressive therapy. Telbivudine may impair the ability to drive or operate machinery. Special populations such as pregnant women, children under 16 years, and the elderly require careful consideration.

Hepatic viral infections (Hepatitis B)

Store Telbivudine in their original container at room temperature between 15° to 30°C. Protect from light and keep out of the reach of children.