Skip to main content
SpringerLink
Log in

Tenofovir Disoproxil Fumarate

In Chronic Hepatitis B

  • Adis Drug Profile
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

  • ▴ 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  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]

  2. Papatheodoridis GV, Manolakopoulos S, Dusheiko G, et al. Therapeutic strategies in the management of patients with chronic hepatitis B virus infection. Lancet Infect Dis 2008; 8: 167–78

    Article  PubMed  CAS  Google Scholar 

  3. Liaw Y-F, Leung N, Kao J-H, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2008; 2: 263–83

    Article  PubMed  Google Scholar 

  4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009; 50: 227–42

    Article  Google Scholar 

  5. Reijnders JG, Janssen HL. Potency of tenofovir in chronic hepatitis B: Mono or combination therapy? J Hepatol 2008 Mar; 48(3): 383–6

    Article  PubMed  CAS  Google Scholar 

  6. Hoofnagle JH, Doo E, Liang TJ, et al. Management of hepatitis B: summary of a clinical research workshop. Hepatology 2007 Apr; 45(4): 1056–75

    Article  PubMed  CAS  Google Scholar 

  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]

  12. Lyseng-Williamson KA, Reynolds NA, Plosker GL. Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection. Drugs 2005; 65(3): 413–32

    Article  PubMed  CAS  Google Scholar 

  13. Chapman TM, McGavin JK, Noble S. Tenofovir disoproxil fumarate. Drugs 2003; 63(15): 1597–608

    Article  PubMed  CAS  Google Scholar 

  14. De Clercq E. Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev 2003 Oct; 16(4): 569–96

    Article  PubMed  Google Scholar 

  15. Delaney 4th WE, Ray AS, Yang H, et al. Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother 2006 Jul; 50(7): 2471–7

    Article  PubMed  CAS  Google Scholar 

  16. Cihlar T, Ho ES, Lin DC, et al. Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxocity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids 2001 Apr–Jul; 20(4–7): 641–8

    Article  PubMed  CAS  Google Scholar 

  17. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008 Dec 4; 359(23): 2442–55

    Article  PubMed  CAS  Google Scholar 

  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)

  19. Qi X, Xiong S, Yang H, et al. In vitro susceptibility of adefovir-associated hepatitis B virus polymerase mutations to other antiviral agents. Antivir Ther 2007; 12(3): 355–62

    PubMed  CAS  Google Scholar 

  20. Tan J, Degertekin B, Wong SN, et al. Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovirresistant mutations. J Hepatol 2008 Mar; 48(3): 391–8

    Article  PubMed  CAS  Google Scholar 

  21. Yang H, Qi X, Sabogal A, et al. Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV. Antivir Ther 2005; 10(5): 625–33

    PubMed  CAS  Google Scholar 

  22. Sheldon J, Camino N, Rodes B, et al. Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir. Antivir Ther 2005; 10(6): 727–34

    PubMed  CAS  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)

  24. Lada O, Benhamou Y, Cahour A, et al. In vitro susceptibility of lamivudine-resistant hepatitis B virus to adefovir and tenofovir. Antivir Ther 2004 Jun; 9(3): 353–63

    PubMed  CAS  Google Scholar 

  25. van Bommel F, Wunsche T, Mauss S, et al. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology 2004 Dec; 40(6): 1421–25

    Article  PubMed  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): 549A

    Google 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): 269A

    Google 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)

  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, DC

  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): A808–9

    Google 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): A809

    Google Scholar 

  32. Peters MG, Andersen J, Lynch P, et al. Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A 5127. Hepatology 2006 Nov; 44(5): 1110–6

    Article  PubMed  CAS  Google Scholar 

  33. Dore GJ, Cooper DA, Pozniak AL, et al. Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus. J Infect Dis 2004 Apr 1; 189(7): 1185–92

    Article  PubMed  CAS  Google 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)

  35. Nelson M, Portsmouth S, Stebbing J, et al. An open-label study of tenofovir in HIV-1 and hepatitis B virus coinfected individuals. AIDS 2003 Jan 3; 17(1): F7–10

    Article  PubMed  CAS  Google Scholar 

  36. Nelson MR, Katlama C, Montaner JS, et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS 2007 Jun 19; 21(10): 1273–81

    Article  PubMed  CAS  Google Scholar 

  37. Zimmermann AE, Pizzoferrato T, Bedford J, et al. Tenofovirassociated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis 2006; 42(2): 283–90

    Article  PubMed  CAS  Google Scholar 

  38. Wong SN, Lok AS. Tenofovir disoproxil fumarate: role in hepatitis B treatment. Hepatology 2006 Aug; 44(2): 309–13

    Article  PubMed  Google Scholar 

Download references

Acknowledgements and Disclosures

This manuscript was reviewed by: P. Marcellin, Service d’Hépatologie, Hôpital Beaujon, Clichy, France; M. Nelson, Department of HIV Medicine, Chelsea and Westminster Hospital, London, England.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, Auckland, 0754, New Zealand

    Caroline M. Perry & Dene Simpson

Authors
  1. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dene Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Caroline M. Perry.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perry, C.M., Simpson, D. Tenofovir Disoproxil Fumarate. Drugs 69, 2245–2256 (2009). https://doi.org/10.2165/10482940-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/10482940-000000000-00000

Keywords

Search

Navigation