Entecavir is mainly used to treat chronic hepatitis B infection in adults and children two years and older with active viral replication and evidence of active disease with elevations in liver enzymes.[3] It is also used to prevent hepatitis B virus reinfection after liver transplant[9] and to treat HIV patients infected with hepatitis B virus. 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[10] as it may select for resistance to lamivudine and emtricitabine in HIV.[11]
The efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Entecavir by mouth is effective and generally well tolerated treatment.[12]
Pregnancy and breastfeeding
No adequate and well-controlled studies exist in pregnant women.[1]
Side effects
The majority of people who use entecavir have little to no side effects.[13] The most common side effects include headache, fatigue, dizziness, and nausea.[3] Less common effects include trouble sleeping and gastrointestinal symptoms such as sour stomach, diarrhea, and vomiting.[14]
Entecavir reduces the amount of hepatitis B virus in the blood by reducing its ability to multiply and infect new cells.[16]
Administration
Entecavir is taken by mouth as a tablet or solution. Doses are based on a person's weight.[3] 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.[3]
History
1992: SQ-34676 at Squibb as part of anti-herpes virus program[17]
1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against hepatitis B virus, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza[18]
Superior activity observed against hepatitis B virus pushed research towards BMS 200475, its base analogues and its enantiomer against hepatitis B virus in HepG2.2.15 cell line[18]
Comparison to other NAs, proven more selective potent inhibitor of hepatitis B virus by virtue of being Guanine NA[19]
1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP[20]
Metabolic studies showed more efficient phosphorylation to triphosphate active form[21]
3-year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance[22]
Efficacy # LVD resistant hepatitis B virus replication in vitro[23]
Superior activity compared to LVD in vivo for both HBeAg+ & HBeAg− patients[24][25]
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.[28][29]
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 in June 2014, by the US Court of Appeals for the Federal Circuit (752 F.32d 967).
^World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Slusarchyk, WA, Field AK, Greytok JA, Taunk P, Tooumari AV, et al. (1992). "4-Hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl purines and pyrimidines, a new class of anti-herpesvirus agents". Antiviral Research. 17: 98. doi:10.1016/0166-3542(92)90200-o.
^ abBisacchi GS, Chao ST, Bachard C, Daris JP, Innaimo SF, Jacobs JA, et al. (1997). "BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro". Bioorganic & Medicinal Chemistry Letters. 7 (2): 127–132. doi:10.1016/s0960-894x(96)00594-x.
