Tenofovir Disoproxil Fumarate
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▴ Tenofovir disoproxil fumarate (tenofovir DF) is an orally administered ester prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor that shows potent in vitro activity against both hepatitis B virus (HBV) and HIV-1.
▴ As a component of antiretroviral combination therapy regimens, tenofovir DF is well established in the treatment of adults with HIV-1 infection. Tenofovir DF, administered once daily, is also used in the treatment of adults with chronic hepatitis B (CHB) [the main focus of this profile].
▴ In CHB, the efficacy of tenofovir DF against HBV has been evaluated in two large randomized, phase III clinical studies in hepatitis B e antigen (HBeAg)-negative or HBeAg-positive adults, with compensated liver function. The trials (planned duration 8 years) were double-blind for the first 48 weeks; thereafter, patients received open-label tenofovir DF. Results at 48 and 96 weeks are available.
▴ In these studies, at week 48, a significantly greater proportion of recipients of tenofovir DF 300 mg once daily than oral adefovir dipivoxil 10 mg once daily achieved a complete response (primary endpoint). A complete response was defined as a reduction from baseline in plasma HBV DNA level to <400 copies/mL and histological improvement (reduction of 2 or more points in Knodell necroinflammatory score without worsening of fibrosis).
▴ The efficacy of tenofovir DF in the treatment of CHB was also demonstrated over a 96-week treatment period in both studies.
▴ Tenofovir DF was generally well tolerated by adults with CHB in the two phase III trials.
- 1.Lok ASF, McMahon BJ. AALSD practice guidelines. Chronic hepatitis B: update 2009 [online]. Available from URL: http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Chronic_Hep_B_Update_2009 [Accessed 2009 Sep 30]
- 7.National Institute for Health and Clinical Excellence. Single technology appraisal TA 173. Tenofovir disoproxil for the treatment of chronic hepatitis B [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/TA173Guidance.pdf [Accessed 2009 Sep 30]
- 8.National Institute for Health and Clinical Excellence. Hepatitis B: entecavir [online]. Available from URL: http://www.nice.org.uk/TA153 [Accessed 2009 Sep 30]
- 9.National Institute for Health and Clinical Excellence. Hepatitis B (chronic): adefovir dipivoxil and pegylated interferon alpha-2a [online]. Available from URL: http://www.nice.org.uk/TA96 [Accessed 2009 Sep 30]
- 10.European Medicines Agency. Summary of product characteristics. Viread (tenofovir disoproxil fumarate) [online]. Available from URL: http://www.emea.europa.eu/humandocs/Humans/EPAR/viread/viread.htm [Accessed 2009 Sep 14]
- 11.Gilead Sciences Inc. Viread® (tenofovir disoproxil fumarate) US prescribing information [online]. Available from URL: http://www.gilead.com/pdf/viread_pi.pdf [Accessed 2009 Sep 14]
- 18.Snow-Lampart A, Chappell B, Curtis M, et al. Week 96 resistance surveillance for HBeAg positive and negative subjects with chronic HBV infection randomized to receive tenofovir DF 300 mg QD [poster no. 977]. 59th Annual Meeting of the American Association for the Study of Liver Diseases; 2008 Oct 31–Nov 4; San Francisco (CA)Google Scholar
- 23.Fung S, Mazzulli T, Sherman M. Presence of rtA194T at baseline does not reduce efficacy to tenofovir (TDF) in patients with lamivudine (LAM)-resistant chronic hepatitis B [poster no. 880]. 59th Annual Meeting of the American Association for the Study of Liver Diseases; 2008 Oct 31–Nov 4; San Francisco (CA)Google Scholar
- 26.van Bommel F, Mauss S, Schurmann D, et al. No evidence for tenofovir resistance in patients with lamivudineresistant HBV infection during long-term treatment for up to 5 years. Hepatology 2006 Oct 1; 44 (4 Suppl. 1): 549AGoogle Scholar
- 27.van Bommel F, Mauss S, Zollner B, et al. Long-term effect of tenofovir in the treatment of lamivudine-resistant hepatitis B virus infections in comparison to adefovir [abstract no. 184 plus poster]. Hepatology 2005 Oct; 42 (4 Suppl. 1): 269AGoogle Scholar
- 28.Audsley J, Arrafin N, Yuen L, et al. Surveillance of hepatitis B virus mutations during tenofovir treatment in HIV/HBV-co-infected individuals [abstract no. 942]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)Google Scholar
- 29.Zhou X, Pietropaolo K, Becker M, et al. Absence of pharmacokinetic drug-drug interaction between telbivudine and tenofovir [abstract no. S1782]. Digestive Disease Week; 2009 May 19–24; Washington, DCGoogle Scholar
- 30.Wang C, Buti M, Hadziyannis S, et al. Tenofovir disoproxil fumarate (TDF) is highly active for treatment of chronic hepatitis B in subjects with cirrhosis [abstract no. M1910]. Gastroenterology 2008 April; 134 (4 Suppl. 1): A808–9Google Scholar
- 31.Younossi ZM, Benhamou Y, Gane EJ, et al. Lack of influence of baseline genotype on antiviral response in subjects with chronic hepatitis B infection receiving tenofovir DF 300mg qd for 1 year [abstract no. M1913]. Gastroenterology 2008 Apr; 134 (4 Suppl. 1): A809Google Scholar
- 34.Lee S, Heathcote E, Sievert W, et al. Tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) in Asians with HBeAg-positive and HBeAg-negative chronic hepatitis B participating in Studies 102 and 103 [abstract no. 980]. 59th Annual Meeting of the American Association for the Study of Liver Diseases; 2008 Oct 31–Nov 4; San Francisco (CA)Google Scholar