Adefovir

Adefovir is a prescription medicine used to treat (chronic) infections with hepatitis B virus. A prodrug form of adefovir was previously called bis-POM PMEA, with trade names Preveon and Hepsera. It is an orally administered nucleotide analog reverse-transcriptase inhibitor (ntRTI). It can be formulated as the pivoxil prodrug adefovir dipivoxil.

Adefovir
Clinical data
Trade namesHepsera
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    administration
    Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability59%
    Protein binding<4%
    Elimination half-life7.5 hours
    ExcretionUrine
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    CompTox Dashboard (EPA)
    ECHA InfoCard100.106.235
    Chemical and physical data
    FormulaC8H12N5O4P
    Molar mass273.186 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Uses

    It is used for treatment of hepatitis B [1][2] and herpes simplex virus infection. [3][4]

    Trials of adefovir in patients with HIV have not shown any clear benefits.[3][5]

    History

    Adefovir was invented in the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic by Antonín Holý, and the drug was developed by Gilead Sciences for HIV with the brand name Preveon. However, in November 1999, an expert panel advised the U.S. Food and Drug Administration (FDA) not to approve the drug due to concerns about the severity and frequency of kidney toxicity when dosed at 60 or 120 mg. The FDA followed that advice, refusing to approve adefovir as a treatment for HIV.

    Gilead Sciences discontinued its development for HIV treatment in December 1999, but continued to develop the drug for hepatitis B (HBV), where it is effective with a much lower dose of 10 mg. FDA approval for use in the treatment of hepatitis B was granted on September 20, 2002, and adefovir is sold for this indication under the brand name Hepsera. Adefovir became an approved treatment for HBV in the European Union in March 2003.

    Mechanism of action

    Adefovir dipivoxil

    Adefovir works by blocking reverse transcriptase, an enzyme crucial for the HBV to reproduce in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (primarily ALT) or histologically active disease.

    The main benefit of adefovir over lamivudine (the first NRTI approved for the treatment of HBV) is that it takes a much longer period of time for the virus to develop resistance to it.

    Adefovir dipivoxil contains two pivaloyloxymethyl units, making it a prodrug form of adefovir.

    References

    1. Marcellin P; Chang TT; Lim SG; et al. (February 2003). "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B". N. Engl. J. Med. 348 (9): 808–16. doi:10.1056/NEJMoa020681. PMID 12606735.
    2. Manolakopoulos S; Bethanis S; Koutsounas S; et al. (February 2008). "Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine". Aliment. Pharmacol. Ther. 27 (3): 266–73. doi:10.1111/j.1365-2036.2007.03567.x. PMID 17988233.
    3. ADHOC International Steering Committee (October 2002). "A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial". HIV Med. 3 (4): 229–38. doi:10.1046/j.1468-1293.2002.00111.x. PMID 12444940.
    4. "US Adefovir Dipivoxil label" (PDF). FDA. April 2013. Retrieved 12 February 2017.
    5. Fisher EJ; Chaloner K; Cohn DL; et al. (September 2001). "The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial". AIDS. 15 (13): 1695–700. doi:10.1097/00002030-200109070-00013. PMID 11546945.
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