FDA gives nod to new hepatitis B treatment

December 11, 2006

The Centers for Disease Control & Prevention (CDC) estimates that 1.25 million Americans are chronically infected with hepatitis B virus (HBV). Now a new, oral, once-daily treatment has been approved by the Food & Drug Administration and is indicated for the treatment of the illness in adult patients with both evidence of viral replication and either persistent elevations in serum aminotransferases or histologically active disease.

Telbivudine (Tyzeka), from Novartis, is a synthetic thymidine nucleoside analog. "Like other nucleoside analogs currently used to treat chronic hepatitis B infection, telbivudine is incorporated into the viral DNA, causing termination of viral DNA chain elongation and inhibiting HBV," said Jiwon Kim, Pharm.D., assistant professor of clinical pharmacy at the University of Southern California School of Pharmacy. What is different about telbivudine, he went on to explain, is its ability to preferentially inhibit anticomplement or second-stand DNA-versus lamivudine, for example, which inhibits complement DNA synthesis.

"The elimination half-life is significantly increased in patients with moderate to severe renal impairment," stated Kim. Therefore, the dosage reduction recommendation in these patients is as follows: For creatinine clearance (CrCl) = 30-49 ml/min, the dose should be 600 mg Q48h; for CrCl <30 ml/min (not requiring dialysis), a dose of 600 mg q72h; and for patients on dialysis, the dosing interval should be extended to q96h, given after dialysis. No adjustment is necessary for hepatic impairment.

The prescribing information contains a black box warning alerting pharmacists to the potential for lactic acidosis and severe hepatomegaly with steatosis that can occur with the use of nucleoside analogs alone or in combination with antiretrovirals. In addition, the black box also contains a reminder that severe acute exacerbations of hepatitis B have been reported in patients who have discontinued antihepatitis B therapy. Therefore, hepatic function should be monitored for at least several months after discontinuation of therapy.

Other adverse effects of concern include muscle pain, tenderness, or weakness. "The rate of creatine kinase (CK) elevation and associated myopathy was significantly higher with telbivudine compared with lamivudine," explained Kim.

According to Novartis, cases of myopathy have been reported with telbivudine use several weeks to months after starting therapy. The persistent, unexplained muscle aches and/or muscle weakness were found in conjunction with increases in CK values. If myopathy is suspected, therapy with telbivudine should be interrupted and, if diagnosed, telbivudine should be discontinued. During clinical trials, 9% of patients receiving telbivudine experienced grade 3-4 CK elevations versus only 3% in the lamivudine group. "Any patient who experiences these symptoms should inform their prescriber promptly," Kim said.

TIPS TO REMEMBER... Tyzeka