Telbivudine for the management of chronic hepatitis B virus infection

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Telbivudine for the management of chronic hepatitis B virus infection

S. s RPh, PharmD

aDepartment of Pharmacy Practice, School of Pharmacy, Bouv¨¦ College of Health

Sciences, Northeastern University, Boston, Massachusetts

Accepted 10 September 2007. Available online 15 January 2008.

Abstract

Background: Telbivudine (LdT) is an L-nucleoside that is structurally related to

lamivudine. It is highly selective for hepatitis B virus (HBV) and inhibits

viral DNA synthesis. LdT was approved by the US Food and Drug Administration on

October 25, 2006, for the treatment of chronic HBV infection in adults who have

active viral replication and either elevations in liver transaminases or signs

of active liver disease on histologic examination.

Objective: This article reviews the pharmacology, pharmacokinetics, and

therapeutic efficacy of LdT. Potential drug interactions and adverse events

associated with the use of LdT are also reviewed.

Methods: Relevant publications were identified from searches of MEDLINE

(1996-June 2007), the Cochrane Library, and BIOSIS (1993-June 2007). Search

terms included, but were not limited to, telbivudine, ¦Â-L-thymidine, LdT,

pharmacology, pharmacokinetics, adverse events, resistance, drug interactions,

hepatitis B, and therapeutic use. Additional publications were identified from

the reference lists of the identified papers, meeting abstracts, and

correspondence with the manufacturer of LdT.

Results: After 52 weeks of therapy in the Phase III GLOBE study, HBV resistance

(breakthrough and resistance mutations) to LdT occurred in 3% of patients who

were hepatitis B e antigen (HBeAg) positive and 2% of patients who were HBeAg

negative. After 104 weeks of therapy, 17.8% to 21.6% of HBeAg-positive and 7.3%

to 8.6% of HBeAg-negative LdT-treated patients had a rebound in HBV DNA

associated with breakthrough and resistance mutations. After 24 weeks of

treatment, the risk of resistance was greater in patients with HBV DNA titers>3

log10 copies/mL than in those with lower numbers of copies. LdT is not active

against lamivudine-resistant HBV. The proportion of HBeAg-positive patients with

undetectable HBV DNA (by polymerase chain reaction assay) after 104 weeks of

therapy in the GLOBE study was significantly greater with LdT compared with

lamivudine (56% vs 39%, respectively; P < 0.05). After 104 weeks of therapy, the

corresponding proportions of HBeAg-negative patients with undetectable HBV DNA

were 82% and 57% (P < 0.05). Patients who failed lamivudine therapy in the GLOBE

study showed cross-resistance to LdT. The most common adverse events associated

with LdT are upper respiratory tract infection (14%¨C17%), fatigue and malaise

(12%¨C14%), nasopharyngitis (11%¨C15%), headache (11%¨C12%), and abdominal pain

(6%¨C12%). Grade 3/4 adverse events included elevations in serum creatine

kinase, which were more common in patients receiving LdT than in those receiving

lamivudine (9% vs 3%, respectively). Elevations in creatine kinase are typically

asymptomatic; however, myopathy has been reported in 3 of 680 patients receiving

LdT.

Conclusions: LdT joins the increasing number of antiviral agents for the

management of chronic HBV infection. Questions concerning the optimal length of

therapy and long-term efficacy await the results of on-going clinical trials.

Concerns about increasing resistance over time may relegate LdT to second-line

status in the management of chronic HBV infection. The role of LdT in

combination therapy is under investigation.

Address correspondence to: S. s, RPh, PharmD, Division of Clinical

Pharmacy, Department of Pharmacy Practice, School of Pharmacy, Bouv¨¦ College of

Health Sciences, Northeastern University, 237 Mugar Hall, 360 Huntington Avenue,

Boston, MA 02115.

Clinical Therapeutics

Volume 29, Issue 12 December 2007, Pages 2635-2653

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