Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.
The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.
Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.
The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.
The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:
• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.
• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.
The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.
The changes were made on March 29.
Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.