Entecavir treatment

Liver transplant recipients - Safety and efficacy in liver transplant recipients are unknown. If entecavir treatment is necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function (eg, cyclosporine, tacrolimus), renal function must be carefully monitored before and during treatment with entecavir. 

Observational study Long-term safety data from the roll-over open label study ETV-901, concentrating on the adverse events with a potential nucleotide association, have been reviewed by Manns et al. [91 ]. From 1051 patients enrolled from 10 prior studies, the overall median time on entecavir was 184 weeks with 512 patients completing more than 5 years of entecavir treatment. The analysis demonstrated that no adverse events potentially associated... 

As previously published, multiple further retrospective studies have been performed that demonstrate the good side effect profile with no or minimal drug-related adverse events or early study drug discontinuations with ente-cavir in the treatment of chronic hepatitis B [92-94 ]. Furthermore, several studies [95 96 ] have specifically looked for and not detected any cases of lactic acidosis in their patients on entecavir treatment, while one review article has commented on the lactic acidosis being more attributable to the severity of tire xmderlying hepatic pathology as opposed to the entecavir therapy [97 ]. 

Pan CQ, Tong M, Kowdley KV, Hu KQ, Chang TT, Lai CL, et al. FHghrates of viral suppression after long-term entecavir treatment of Asian patients with hepatitis B e antigen-positive chronic hepatitis B. CUn Gastroenterol Hepatol 2012 10(9) 1047-50. 

Saadah Ol, Sindi HH, Bin-Talib Y, Al-Harthi S, Al-Mughales J. Entecavir treatment of children 2-16 years of age with chronic hepatitis B infection. Arab J Gastroenterol 2012 13(2) 41-4. 

All the nucleoside (and nucleotide) analogues that have entered the clinic for the treatment of HBV infections (i.e., nucleoside analogues lamivudine, entecavir, tel-bivudine nucleotide analogues adefovir and tenofovir) are fairly well tolerated without side effects that would preclude their long-term usage. The nucleoside analogues in (pre)clinical development for the treatment of HCV infections are not yet sufficiently advanced to assess their tolerability and/or safety. 

In addition to the NRTI lamivudine (3TC) and the NtRTI adefovir dipivoxU and tenofovir disoproxil fumarate (which has been recently licensed for the treatment of chronic hepatitis B), two other nucleoside analogues, that is, entecavir and L-dT (tel-bivudine) (Fig.4aa), have been licensed for the treatment of HBV infections. Two other compounds 3 -Val-L-dC (valtorcitabine) and L-FMAU (clevudine) (Fig. 4aa) are in clinical development for the treatment of HBV infections, and yet two other compounds, that is, racivir and elvucitabine (Fig. 3), yield potential for the treatment of both HBV and HIV infections. 

The 5 -triphosphate metabolite of entecavir has been shown to accumulate in-tracellularly at concentrations that are inhibitory to 3TC-resistant HBV DNA polymerase (Levine et al. 2002). This would imply that entecavir should be active against HBV infections that have become resistant to treatment with lamivudine. Yet, it should be taken into account that treatment with lamivudine leads to the same... 

Zoulim F (2006) Entecavir a new treatment option for chronic hepatitis B. J Clin Virol 36 8-12... 

Persons with confirmed chronic hepatitis B should be evaluated for treatment, which may include interferon, pegylated interferon, lamivudine, adefovir dipivoxil, or entecavir. The drug of choice for chronic hepatitis B depends on the patient s past medical history, aminotransferase level, HBV DNA level, and most importantly, HBeAg status. 

Patients who develop resistance to lamivudine have significant improvement in histology while receiving entecavir, but higher doses (1 mg daily) are required. Additionally, 19% of lamivudine-resistant patients had undetectable HBV DNA levels compared to 1% of those who continued treatment with lamivudine.36 At present, no resistance has been associated with entecavir in patients treated for 1 year, but the data beyond 1 year of therapy are unknown. Entecavir resistance has only been seen in patients who already had lamivudine resistance.37... 

Drug therapy is used to suppress viral replication by immune mediating or antiviral effects. Interferon 2b lbN-fb1 lamivudine, telbivudine, ade-fovir entecavir, and pegylated IFN-a2a (PEG-IFN) are approved in the United States for first-line treatment of chronic HBV. 

Duration of therapy The optimal duration of treatment with entecavir for patients with chronic HBV infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown. 

Monitoring Periodic monitoring of hepatic function is recommended during treatment and for at least several months after treatment in patients who discontinue antihepatitis B therapy. Monitor patients closely for adverse events when entecavir is... 

The nucleoside analogs entecavir and clevudine, the nucleotide analog emtricitabine, and the immunologic modulators theradigm-HBV and thymosin alpha-1 are new agents under evaluation for the treatment of HBV infection. 

Entecavir is a guanosine nucleoside with strong antiviral activity. It is also effective in lamivudine-resistant patients. After 48 weeks of treatment comprising a daily dose of 0.5 or 1.0 mg, there was elimination of HBV DNA in 25 — 30% and normalization of the transaminases in 60—70% of lamivudine-resistant patients. Tolerance is good. Entecavir-induced mutants were not detected. (173)... 

The therapeutic armementarium in this field is enlarging with promising results but at the expense of viral resistance and cost.The drugs used in HBV treatment are mainly interferons (mostly pegylated), and nucleos(t)ide analogs (Lamivudine, Adefovir and the more recent ones Telbivudine, Entecavir and Tenofovir). Different... 

Nucleoside Analogue HIV Reverse Transcriptase Inhibitors as Drugs for the Treatment of HIV and Hepatitis B Zidovudine, Didanosine, Stavudine, Lamivudine, Abacavir, Emtricitabine and Entecavir... 

Entecavir (Baraclude) A Carbocyclic Nucleoside for the Treatment for Chronic Hepatitis B... 

The approval of the nncleotide and nucleoside analogs 1-5 marked a significant advance in the treatment of chronic hepatitis B. In comparison to compounds 2-5, entecavir (1) is a novel carbocychc nucleoside analog with potent and highly selective activity against HBV, as well as a low rate of resistance. In this chapter, the pharmacological profile and syntheses of entecavir (1) will be profiled in detail. 

Acid-base balance Of 16 patients with hepatic cirrhosis and chronic hepatitis B infection, five developed lactic acidosis after 4—240 days of treatment with entecavir all five had highly impaired liver function [13 ]. One patient died, but in the other four the lactic acidosis resolved after withdrawal of entecavir. The serum lactate concentrations were not increased in the other 11 patients, who all had less severe liver impairment. Child-Pugh scores did not correlate with the development of lactic acidosis, but MELD (Model for End-Stage Liver Disease) scores did, as did serum bilirubin, creatinine, and international normalized ratio (INR). The authors suggested that entecavir should be used cautiously in patients with severely impaired liver function. 

Kondo M, Kitada N, Kobayashi M, Morita S, Yoshioka M, Tsuji T, Mori A, Okamoto T, Watari M. A case of drug-induced liver injury caused by entecavir for treatment of hepatitis B virus reactivation during RCHOP in a patient with non-Hodgkin lymphoma. Gan To Kagaku Ryoho 2009 36(7) 1199-201. 

Comparative studies A meta-analysis was performed comparing early antiviral efficacy and safety of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen positive chronic hepatitis [106 ]. Six randomised controlled trials involving 555 patients were included and demonstrated that telbivudine was associated with higher rates of HBeAg disappearance and HBeAg seroconversion than entecavir but had higher adverse events (RR 2.11). No specific details of adverse events were illustrated as pooled risk ratios were used. 

Musculoskeletal A case has been reported of telbivudine-induced myopathy in siblings with chronic hepatitis B who were male, 28 and 25 years of age, treated with 600 mg telbivudine alone for 9 months and combination therapy of 600 mg telbivudine for 13 months in addition to 10 mg of adefovir respectively [110 ]. Both demonstrated symptomatic myopathy with elevated creatine kinase levels which improved on switching to entecavir. This was similarly reported in another case study of a 25-year-old man after 6 months of treatment diagnosed with both serum CK levels and muscle biopsy demonstrating myositis and mitochondrial changes [111 ]. 

Fahrtash-Bahin F, Karinyawasam VC, Gray T, Byth K, George J, Douglas MW. Australian tertiary care outcomes of entecavir monotherapy in treatment naive patients with chronic hepatitis B. World J Gastroenterol 2013 19(5) 721-6. 

Koklu S, Tuna Y, Gulsen MT, Demir M, Koksal AS, Kockar MC, et al. Long-term efiicacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis. Clin Gastroenterol Hepatol 2013 ll(l) 88-94. 

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