Telbivudine

NOVARTIS

Synthetic thymidine nucleoside analogue approved for the treatment of chronic HBV

Telbivudine was approved on October 25, 2006, for the treatment of chronic hepatitis B virus (HBV) in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This agent is phosphorylated by cellular kinases to its active triphosphate form, which inhibits HBV DNA polymerase, thus inhibiting HBV replication.

Safety. Lactic acidosis and severe hepato-megaly with steatosis, including fatal cases, have been reported in patients using nucleoside analogues alone or in combination with antiretroviral drugs. Severe acute exacerbations of HBV have been reported in patients who have discontinued anti-HBV therapy. Hepatic function should therefore be monitored closely with clinical and laboratory follow-up for at least several months in patients discontinuing anti-HBV therapy. Uncomplicated myalgia has been reported in patients treated with telbivudine. Cases of myopathy have been reported in telbivudine-treated patients several weeks to months after therapy initiation. If myopathy is suspected, telbivudine therapy should be interrupted; if myopathy is diagnosed, telbivudine therapy should be discontinued. The most common adverse events reported in association with telbivudine treatment include fatigue and malaise, abdominal pain, headache, cough, nausea and vomiting, influenza-like symptoms, and diarrhea. Increases in creatine kinase levels also have been reported. Periodic monitoring of hepatic function during treatment is recommended.

Dosing. The recommended dosage of telbivudine for the treatment of chronic HBV in patients with creatinine clearance ≥50 mL/min is 600 mg once daily. In patients with creatinine clearance 30 to 49 mL/min, telbivudine 600 mg should be administered once every 48 hours, and in patients with creatinine clearance <30 mL/min, telbivudine 600 mg should be administered once every 72 hours. In patients with end-stage renal disease, telbivudine 600 mg should be administered after hemodialysis once every 96 hours.