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.
Efficacy. The efficacy of telbivudine was evaluated in the 007 GLOBE study, which enrolled 1,367 nucleoside-naïve patients with chronic
HBV, evidence of HBV infection with viral replication (HBsAg-positive, HBeAg-positive or HBeAg-negative, HBV DNA detectable
by PCR assay), elevated ALT levels ≥1.3 times the upper limit of normal, and chronic inflammation on liver biopsy compatible
with chronic viral hepatitis. Patients were randomized to receive either telbivudine 600 mg once daily or lamivudine 100 mg
once daily for up to 104 weeks. The primary data analysis was performed at Week 52. The primary outcome for evaluating therapeutic
response was a composite serologic end point requiring suppression of HBV DNA to <5 log10 copies/mL plus either loss of serum HBeAg or normalization of ALT. At Week 52, 75% of both HBeAg-positive and HBeAg-negative
patients treated with telbivudine had achieved a therapeutic response, whereas 67% of HBeAg-positive and 77% of HBeAg-negative
patients treated with lamivudine had achieved a therapeutic response. HBeAg-positive and HBeAg-negative patients who were
treated with telbivudine achieved mean HBV DNA reduction from baseline of –6.45 and –5.23 log10 copies/mL, respectively, compared with –5.54 and –4.40 log10 copies/mL among lamivudine-treated HBeAg-positive and HBeAg-negative patients, respectively. 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.
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