Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Baraclude (Bristol-Myers Squibb)
0.5 mg and 1 mg tablets
Approved indication: chronic hepatitis B
Australian Medicines Handbook section 5.3.1

Hepatitis B can become chronic particularly if the infection occurs in childhood. While some carriers of the virus have no liver damage, others develop chronic inflammation and cirrhosis. Antiviral drugs, such as lamivudine, adefovir or interferon alfa, can be considered for patients with active inflammation of the liver.

Entecavir is an antiviral drug with activity against hepatitis B viral polymerase. As entecavir is an analogue of the nucleoside guanosine, it competes with the enzyme's usual substrate. This reduces the synthesis of viral DNA. Entecavir is therefore indicated when there is evidence of viral replication. At present it is only approved for adults who have active liver inflammation.

Patients take entecavir once daily. A higher dose is needed if there is resistance to lamivudine because these viral strains are also less susceptible to entecavir. As food reduces absorption, entecavir is taken on an empty stomach. Most of the dose is excreted unchanged in the urine so it should be reduced in people with renal impairment.

Entecavir was compared with placebo in a dose-ranging study of 42 patients with chronic hepatitis B. They took the drug for 28 days and were followed up for a further 24 weeks. All doses of entecavir significantly reduced the concentration of viral DNA.1

Another phase II study randomised 185 patients to take entecavir or lamivudine for 24 weeks. Entecavir had a greater effect on viral load with 26% of the patients taking 0.5 mg having undetectable concentrations of viral DNA compared with 18% of the patients taking 100 mg lamivudine. Concentrations of alanine transaminase (ALT) returned to normal in 69% of those taking entecavir and 59% of those taking lamivudine.2

The phase III studies of entecavir looked at the effect of treatment on liver histology as well as on laboratory tests. Approximately 1600 patients participated with the majority having two liver biopsies. In patients who were positive for hepatitis B e antigen, inflammation improved in 72% with entecavir and in 62% with lamivudine.3The corresponding figures were 70% and 61% in patients without the e antigen.4These differences show a statistical advantage for entecavir. Both treatments resulted in an improvement of liver fibrosis in 35-39% of patients. ALT concentrations were more likely to become normal with entecavir. In a study of 286 patients with lamivudine-refractory infections, switching to entecavir was associated with improved liver histology. After a year of treatment improvements were seen in 55% of the patients given entecavir compared with 28% of those who continued lamivudine.5

During the clinical trials the most common adverse events were headache and fatigue. After treatment stopped in the dose-ranging study the viral load soon increased.1There is a risk that the hepatitis will flare up when the patient stops taking treatment. Safety and efficacy have not been confirmed for more than 48 weeks of treatment and the optimum duration of treatment is unknown. Hepatocellular carcinoma and other cancers have appeared during studies of animals, but the risk in humans is unknown. Like other nucleoside analogues there may be a risk of lactic acidosis.

Resistance to entecavir has been reported. Although there is some cross-resistance with lamivudine, there does not appear to be cross-resistance with adefovir. Currently, there appear to be no published clinical trials comparing lamivudine and adefovir.

Entecavir has efficacy against hepatitis B, but assessing its safety and effectiveness on long-term outcomes will require more study. There is greater certainty that immunisation will prevent more people becoming chronically infected.

Read about The Transparency Score manufacturer provided additional useful information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.