Entecavir is mainly used to treat chronic hepatitis B infection in adults and children 2 years and older with active viral replication and evidence of active disease with elevations in liver enzymes. It is also used to prevent HBV reinfection after liver transplant and to treat HIV patients infected with HBV. Entecavir is weakly active against HIV, but is not recommended for use in HIV-HBV co-infected patients without a fully suppressive anti-HIV regimen as it may select for resistance to lamivudine and emtricitabine in HIV. The efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Entecavir by mouth is effective and generally well tolerated treatment.
Pregnancy and breastfeeding
It is considered pregnancy category C in the United States, and currently no adequate and well-controlled studies exist in pregnant women.
Side effects
The majority of people who use entecavir have little to no side effects. The most common side effects include headache, fatigue, dizziness, and nausea. Less common effects include trouble sleeping and gastrointestinal symptoms such as sour stomach, diarrhea, and vomiting. Serious side effects from entecavir include lactic acidosis, liver problems, liver enlargement, and fat in the liver. Laboratory tests may show an increase in alanine transaminase, hematuria, glycosuria, and an increase in lipase. Periodic monitoring of hepatic function and hematology are recommended.
Entecavir is taken by mouth as a tablet or solution. Doses are based on a person's weight. The solution is recommended for children more than 2 years old who weigh up to 30 kg. Entecavir is recommended on an empty stomach at least 2 hours before or after a meal, generally at the same time every day. It is not used in children less than 2 years old. Dose adjustments are also recommended for people with decreased kidney function.
History
1992: SQ-34676 at Squibb as part of anti-herpes virus program
1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against HBV, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza
Superior activity observed against HBV pushed research towards BMS 200475, its base analogues and its enantiomer against HBV in HepG2.2.15 cell line
Comparison to other NAs, proven more selective potent inhibitor of HBV by virtue of being Guanine NA
1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP
Metabolic studies showed more efficient phosphorylation to triphosphate active form
3-year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance
Efficacy # LVD resistant HBV replication in vitro
Superior activity compared to LVD in vivo for both HBeAg+ & HBeAg− patients
Efficacy in LVD refractory CHB patients
Entecavir was approved by the U.S. FDA in March 2005.
Patent information
was the original patent holder for Baraclude, the brand name of entecavir in the US and Canada. The drug patent expiration for Baraclude was in 2015. Entecavir patents were a subject of litigation in the USA between Bristol-Myers-Squibb Co. and Teva Pharmaceuticals USA. The lawsuit resulted in a relatively rare in the pharmaceutical field patent invalidation for obviousness, which was affirmed on 12 June 2014 by the US Court of Appeals for the Federal Circuit. On August 26, 2014, Teva Pharmaceuticals USA gained FDA approval for generic equivalents of Baraclude 0.5 mg and 1 mg tablets; Hetero Labs received such approval on August 21, 2015; and Aurobindo Pharma on August 26, 2015.