Companies:

Idenix and Novartis

Antiviral (nucleoside analogue reverse transcriptase inhibitor)

Telbivudine 600mg; tabs.

Treatment of chronic hepatitis B in patients with evidence of viral replication and either evidence of persistent elevations of ALT/AST or histologically active disease.

Telbivudine is a thymidine nucleoside analogue that has activity against hepatitis B virus (HBV) reverse transcriptase. Its active form is incorporated into viral DNA, causing DNA chain termination and inhibition of HBV replication.

In a trial involving 1,367 nucleoside-naive patients with chronic hepatitis B infection, telbivudine 600mg once daily was compared to lamivudine 100mg once daily for up to 104 weeks; the primary data analysis was conducted after week 52. Clinical and virological endpoints were evaluated separately in HBeAg-positive and HBeAg-negative patients. The percentage of patients who became HBV DNA negative at 52 weeks using telbivudine was 60% in the HBeAg-positive cohort and 88% in the HBeAg-negative cohort compared with 40% and 71% respectively in the lamivudine treated group. Telbivudine treated patients who achieved non-detectable HBV DNA levels at 24 weeks were more likely to under go e-antigen seroconversion, normalize ALT and minimize resistance at one year.

Telbivudine has not been studied in patients co-infected with other viruses, but it has not been shown to be active against hepatitis C or HIV-1. It was shown to have no antagonistic activity against other antiretroviral agents such as abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. Telbivudine has not shown to be effective in patients with hepatitis B infection that isresistant to either lamivudine or adefovir.

≥16yrs (CrCl ≥50mL/min): 600mg once daily. Renal impairment: CrCl 30–49mL/min: 600mg once every 48 hrs; CrCl < 30mL/min (not on dialysis): 600mg once every 72 hrs; end-stage renal disease: 600mg every 96 hrs (give after dialysis session).

<16yrs: not recommended.

Renal impairment. Monitor for lactic acidosis and for myopathy; suspend therapy if myopathy is suspected, discontinue if confirmed. Risk of hepatitis B reactivation (monitor after discontinuing therapy). Elderly. Pregnancy (Cat.B). Nursing mothers: not recommended.

Risk of myopathy may be increased with statins, fibrates, corticosteroids, chloroquine, hydroxychloroquine, penicillamine, zidovudine, cyclosporine, erythromycin, niacin, azole antifungals. Caution with drugs that affect renal elimination (may need to extend telbuvidine dosing interval); monitor renal function with cyclosporine, tacrolimus.

Fatigue, malaise, fever, joint pain, upper respiratory symptoms, headache, abdominal pain, myalgia/ myopathy, elevated CPK levels, GI upset, dizziness, insomnia, post-treatment exacerbation of hepatitis B; lactic acidosis, severe hepatomegaly with steatosis.

Register pregnant patients exposed to telbivudine by calling (800) 258-4263.

Tabs—30

1/4/07