Hepatitis tenofovir

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. 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Tenofovir is not indicated for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of tenofovir have not been established in patients coinfected with HBV and human immunodeficiency virus (HIV). Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV and have discontinued tenofovir. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who discontinue tenofovir and are coinfected with HBV and HIV. If appropriate, initiation of anti-hepatitis B therapy may be warranted. 

Tenofovir is not indicated for chronic hepatitis B virus (HBV) infection. Safety and efficacy have not been established in patients with HBV and HIV. Severe acute exacerbation of HBV infection has been reported in co-infected patients. 

All NRTI agents, as well as tenofovir, carry the risk of lactic acidosis with hepatic steatosis as a potential adverse event. 

Several anti-HBV agents have anti-HIV activity as well, including lamivudine, adefovir dipivoxil, and tenofovir. Emtricitabine, an antiretroviral NRTI, is under clinical evaluation for HBV treatment. Because NRTI agents may be used in patients co-infected with HBV and HIV, it is important to note that acute exacerbation of hepatitis may occur upon discontinuation or interruption of these agents. 

In 2001, tenofovir disoproxil fumarate 61, a prodrug of tenofovir was approved for treatment of HIV, subsequently being preregistered in the USA for treatment of hepatitis B. Emtricitabine 62, a reverse transcriptase inhibitor, was approved in 2003 for HIV. What is of import is that these compounds are now part of fixed dose combination therapies for treatment of HIV, either two drug (tenofovir disoproxil fumarate/emtricitabine) or three drug Atripla (tenofovir disoproxil fumarate/emtricitabine/efavirenz) formulations. Thus, even 50 + years after Bergmann s discovery of bioactive arabinose nucleosides, small molecules synthesised as result of his discoveries are still in clinical use and others are in clinical trials for treatment of viral diseases. 

All but one of the drugs in this class are nucleosides that must be triphosphorylated at the 5 -hydroxyl to exert activity. The sole exception, tenofovir, is a nucleotide monophosphate analog that requires two additional phosphates to acquire full activity. These compounds inhibit both HIV-1 and HIV-2, and several have broad-spectrum activity against other human and animal retroviruses emtricita-bine, lamivudine, zalcitabine, and tenofovir are active against hepatitis B virus (HBV) in vitro, and tenofovir also has activity against herpes viruses. 

Tenofovir disoproxil fumarate 300 mg daily did not alter the pharmacokinetics of a single 600-mg dose of ribavirin in 22 subjects, and the pharmacokinetics of tenofovir did not appear to be changed by ribavirin when compared with historical data. Note that, there is evidence that HIV-pos-itive patients co-infected with hepatitis C and treated with interferon alfa and ribavirin may be at increased risk of lactic acidosis and hepatic decompensation when receiving any NRTF, (p.805), including tenofovir, and increased monitoring is recommended. ... 

Adenine itself was successfully incorporated into a number of pharmaceuticals, Adefovir dipivoxil, also known as bis-POM PMEA, with trade names Preveon and Hepsera, is used for the treatment of hepatitis B and herpes simplex virus infection. It is an orally administered nucleotide analog as a reverse transcriptase inhibitor (NRTI). Reverse transcriptase is an enzyme crucial to viral production. A second NRXI that contains adenine is Tenofovir disoproxil fumarate (TDF), which has been used in the treatment of HIV/AIDS and hepatitis B. TDF is a prodrug of tenofovir (also known as PMPA) designed to improve absorption and cell permeability of the active moiety under the trade name Viread. Both adefovir dipivoxil and TDF are marketed by Gilead Sciences. 

Tenofovir Gilead Sciences 9.3 129 Reverse transcriptase inhibitor HIV, hepatitis B... 

Tan LK, Gilleece Y, Mandalia S, Murungi A, Grover D, Fisher M, Atkins M, Nelson M. Reduced glomerular filtration rate but sustained virologic response in HIV/hepatitis B co-infected individuals on long-term tenofovir. J Viral Hepat 2009 16(7) 471-8. 

Neurological Neuropsychiatric effects have been reported in a man receiving telaprevir based triple therapy, raltegravir, emtricitabine (FTC)/tenofovir (TDF) and bosentan for pulmonary arterial hypertension (PAH) with hepatitis C (HCV), hepatitis B (HBV) and HIV coinfection [81 ]. 

A 55-year-old male patient with chronic hepatitis B was started on TDF. One month after starting treatment he developed odynophagia and a painful tongue. Tenofovir was continued but topical corticoid therapy was added for symptom control. 

Gara N, Zhao X, Collins MT, Chong WH, Kleiner DE, Jake Laing T, et al. Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B. Aliment Pharmacol Ther 2012 35(ll) 1317-25. 

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. 

Gish RG, Clark MD, Kane SD, Shaw RE, Mangahas MF, Baqai S. Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol 2012 10(8) 941-6. 

Pol S, Lampertico. First-line treatment of chronic hepatitis B with entecavir or tenofovir in real-life settings from clinical trials to clinical practice. J Viral Hepat 2012 19(6) 377-86. 

Qa)fyum S, Dong H, Kovadc D, Sohail S, Waters B, Thornton C, et al. Combination therapy efavirenz/emtridtabine/tenofovir disoproxil fumarate assodated with hepatic failure. Curr Drug Saf 2012 7(5) 391-3. 

---