Entecavir is a nucleoside analogue with selective anti-hepatitis B virus activity. It does not cure the disease nor does it stop its spread to others but it interferes with the ability of the hepatitis B virus to replicate. It is therefore licensed for use in chronic hepatitis B viral infections in adults with compensated liver disease and evidence of active viral replication, persistently elevated serum ALT levels and evidence of active inflammation and/or fibrosis.
Entecavir exerts its antiviral effects once phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. In this form entecavir-triphosphate competes with the natural substrate, deoxyguanosine triphosphate to functionally inhibit three activities of hepatitis B viral polymerase: base priming; reverse transcription of the negative strand DNA from the pregenomic messenger RNA; and synthesis of the positive strand hepatitis B virus DNA.
Following oral administration, entecavir is rapidly absorbed, with peak plasma concentrations observed within 0.5-1.5 hours of dosing. Steady-state is attained between six and 10 days after once daily dosing. The tablets and oral solution are bioequivalent in healthy subjects and both forms can be interchanged as appropriate. Although food is not thought to affect the efficacy of entecavir in nucleoside-naïve patients, it may alter efficacy in lamivudine-refractory patients. Entecavir is predominantly eliminated via the kidneys, undergoing both glomerular filtration and tubular secretion, meaning dose adjustment is required when using the drug in patients with renal impairment.
In clinical trials involving over 1,600 patients with chronic hepatitis B infection and evidence of viral replication, benefit from treatment was judged on histological, virological, biochemical and serological response after 48 weeks. Regardless of baseline characteristics, most patients in these trials showed overall histological and virological responses to treatment.
In HBeAg Negative and HBeAg Positive nucleoside-naïve subjects 70-72% of those given entecavir 0.5mg/day showed histological improvements compared with 61-62% of those treated with lamivudine 100mg/day. The reduction in viral load was significantly greater among those in the entecavir groups compared with the lamivudine groups and the percentage of those with undetectable levels of hepatitis B virus DNA after 48 weeks was again significantly greater for those given entecavir than for those treated with lamivudine. In addition, ALT normalisation was demonstrated in a significantly higher percentage of those given entecavir. In HbeAg positive patients seroconversion was observed in 21% of the entecavir group compared with 18% of the lamivudine group.
Similar benefits were attained in lamivudine refractory patients. In patients co-infected with HIV, entecavir was again associated with significant improvements in all parameters.
Indications: Treatment of chronic hepatitis B in adults with compensated liver disease with evidence of active viral replication, persistently elevated ALT levels and histological evidence of active liver inflammation and fibrosis.
Adult Dose: Nucleoside naive patients, 0·5mg once daily.
Lamivudine-refractory patients, 1mg once daily at least two hours before or after a meal.
Child Dose: Under 18 years, not recommended.
Special Precautions: Renal impairment. Monitor patients regularly for hepatitis B biochemical, virological and serological markers to determine treatment duration. Cirrhosis; monitor closely for hepatic decompensation. Monitor patients closely for several months after stopping therapy for acute exacerbations of hepatitis. Patients (particularly obese women) with hepatomegaly, hepatitis, other risk factors of liver disease; risk of lactic acidosis, sometimes fatal. Co-infection with hepatitis C or D or HIV. Elderly. Pregnancy.
Interactions: Drugs that reduce renal function or compete for active tubular secretion.
Adverse Effects: Headache, fatigue, dizziness, nausea, insomnia, raised ALT, exacerbations of hepatitis.
? Report any adverse reaction to CHM.
Further information: Bristol-Myers Squibb Pharmaceuticals Ltd, Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex UB8 1DH. Tel: (01895) 523000.