and tenofovir. Entecavir reduces the amount of HBV in the blood by reducing its ability to multiply and infect new cells. Administration 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. Food and Drug Administration (FDA) in March 2005. Patent information Bristol-Myers Squibb 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 US between Bristol Myers Squibb (the patent owner) and Teva Pharmaceuticals USA (a generic manufacturer). 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 (752 F.32d 967). 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. References External links