|Systematic (IUPAC) name|
|Licence data||EMA: , US FDA:|
|Protein binding||13% (in vitro)|
|Mol. mass||277.279 g/mol|
|(what is this?)|
Entecavir INN // en-TEK-a-vir or en-te-ka-veer, abbreviated ETV, is an oral antiviral drug used in the treatment of hepatitis B virus (HBV) infection. Entecavir is a reverse transcriptase inhibitor. It prevents the hepatitis B virus from multiplying and reduces the amount of virus in the body.
Mechanism of Action
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. It is also used to prevent HBV reinfection after liver transplant and to treat HIV patients infected with HBV. However, entecavir is not active against HIV.
Tablet: 0.5 mg and 1 mg
Oral solution: 0.05 mg/mL
Entecavir should be taken on an empty stomach, at least 2 hours before a meal and 2 hours after a meal.
The most common adverse effects from entecavir include headache, fatigue, dizziness, and nausea. Others adverse effects include diarrhea, dyspepsia, vomiting, somnolence and insomnia. Laboratory abnormalities resulting from treatment include elevated alanine transaminase (ALT) and hematuria. Periodic monitoring of hepatic function and hematology are recommended.
Bristol-Myers Squibb is currently the drug patent holder for Baraclude®, the brand name of entecavir in the US and Canada. The drug patent expiration date for both Baraclude® 0.5 mg and 1 mg tablets is set for February 21, 2015. On August 26, 2014, TEVA Pharms USA gained FDA approval for generic equivalents of Baraclude® 0.5 mg and 1 mg tablets.
The clinical efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Oral entecavir was an effective and generally well tolerated treatment.
- 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.
- “BARACLUDE® (entecavir) Tablets for Oral Use & Oral Solution. U.S. Full Prescribing Information.” Bristol-Myers Squibb Company, 2005. Revised December 2013. 
- "Baraclude Full Prescribing Information". www.baraclude.com. Bristol-Myers Squibb. Retrieved 31 October 2014.
- Sims KA, Woodland AM (December 2006). "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection". Pharmacotherapy 26 (12): 1745–57. doi:10.1592/phco.26.12.1745. PMID 17125436.
- Fung J, Cheung C, Chan SC, et al, "Entecavir Monotherapy is Effective in Suppressing Hepatitis B Virus After Liver Transplantation," Gastroenterology, 2011, 141(4):1212-9.
- "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". www.FDA.gov. FDA. Retrieved 30 October 2014.
- Scott LJ, Keating GM..Drugs 2009;69(8):1003-1033. doi:10.2165/00003495-200969080-00005.
- Slusarchyk, W. A., A. K. Field, J. A. Greytok, P. Taunk, A. V. Tooumari, M. G. Young, and R. Zahler. 4-Hydroxy-3-(hydroxymethyl)-2-methylcyclopentyl purines and pyrimidines, a novel class of anti-herpesvirus agents. Abstract from the Fifth International Conference on Antiviral Research. Antivir Res 1992.17(Suppl. 1):98
- Bisacchi, G. S., S. T. Chao, C. Bachard, J. P. Daris, S. F. Innaimo, J. A. Jacobs, O. Kocy, P. Lapointe, A. Martel, Z. Merchant, W. A. Slusarchyk, J. E. Sundeen, M. G. Young, R. Colonno, and R. Zahler. BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro. Bioorg. Med. Chem. Lett. 1997. 7:127–132
- Innaimo S F, Seifer M, Bisacchi G S, Standring D N, Zahler R, Colonno R J. Identification of BMS-200475 as a Potent and Selective Inhibitor of Hepatitis B Virus. Antimicrob. Agents Chemother. 1997. 41(7): 1444–1448
- Seifer, M., R. K. Hamatake, R. J. Colonno, and D. N. Standring. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob. Agents Chemother. 1998. 42:3200–3208
- Yamanaka, G., T. Wilson, S. Innaimo, G. S. Bisacchi, P. Egli, J. K. Rinehart, R. Zahler, and R. J. Colonno. Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob. Agents Chemother. 1999. 43:190–193
- Colonno, R. J., E. V. Genovesi, I. Medina, L. Lamb, S. K. Durham, M. L. Huang, L. Corey, M. Littlejohn, S. Locarnini, B. C. Tennant, B. Rose, and J. M. Clark. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J. Infect. Dis. 2001.184:1236–1245
- Levine, S., D. Hernandez, G. Yamanaka, S. Zhang, R. Rose, S. Weinheimer, and R. J. Colonno. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob. Agents Chemother. 2002.46:2525–2532
- Chang, T. T. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 2006. 354:1001–1010
- Lai, C. L. et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N. Engl. J.Med. 2006. 354:1011–1020.
- Sherman, M., C. Yurdaydin, J. Sollano, M. Silva, Y. F. Liaw, J. Cianciara, A. Boron-Kaczmarska, P. Martin, Z. Goodman, R. J. Colonno, A. Cross, G. Denisky, B. Kreter, R. Hindes, and the AI463026 Behold Study Group. Entecavir for the treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006. 130:2039–2049.