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Tenofovir alafenamide

(Redirected from GS-7340)

Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease[8] and is given in combination with other medications for the prevention and treatment of HIV. It is taken by mouth.[6]

Tenofovir alafenamide
Clinical data
Pronunciation/ˌtəˈnoʊfəvɪər ˌæləˈfɛnəmaɪd/
Trade namesVemlidy
Other namesGS-7340
AHFS/Drugs.comMonograph
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding~80%[6]
Elimination half-life0.51 hour
ExcretionFeces (31.7%), urine (<1%)
Identifiers
  • Isopropyl (2S)-2-[[[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H29N6O5P
Molar mass476.474 g·mol−1
3D model (JSmol)
  • C[C@H](CN1C=NC2=C(N=CN=C21)N)OC[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC3=CC=CC=C3
  • InChI=1S/C21H29N6O5P/c1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24)/t15-,16+,33+/m1/s1
  • Key:LDEKQSIMHVQZJK-CAQYMETFSA-N
Tenofovir alafenamide fumarate, the salt used in drug formulations

Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor and is a prodrug of tenofovir. It was developed by Gilead Sciences based on the protide technology of Chris McGuigan and is applied in the form of tenofovir alafenamide fumarate (TAF). Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (TDF), TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent.[9][10] It was approved for use in the US for HIV in 2015,[11] and for hepatitis B in 2016.[12] Although the US Food and Drug Administration (FDA) has approved tenofovir alafenamide for manufacture as a generic medication,[13] it is not available.[14]

Fixed-dose combinations containing tenofovir alafenamide

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Research

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Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir[44] and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.[45][46][47] In a 48-week study comparing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (Stribild) to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya), the results showed the newer drug's effects to be non-inferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function.[48][49][50] The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015.[11] Genvoya is the first TAF-based regimen to receive approval.[11]

References

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  1. ^ "Tenofovir alafenamide (Vemlidy) Use During Pregnancy". Drugs.com. 26 December 2018. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  2. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
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  4. ^ "Liver disease". Health Canada. 9 May 2018. Retrieved 13 April 2024.
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  9. ^ Eisenberg EJ, He GX, Lee WA (2001). "Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood". Nucleosides Nucleotides Nucleic Acids. 20 (4–7): 1091–8. doi:10.1081/NCN-100002496. PMID 11562963. S2CID 24652157.
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  48. ^ "Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild". AIDSmeds. 1 November 2012. Archived from the original on 20 September 2015.
  49. ^ Highleyman L (6 March 2013). "CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated". hivandhepatitis.com. Archived from the original on 25 October 2020. Retrieved 25 July 2024.
  50. ^ Horn T (13 June 2013). "Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead". Treatment Action Group. Archived from the original on 19 November 2019.
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