Tenofovir alafenamide

Source: Wikipedia, the free encyclopedia.

Tenofovir alafenamide
Clinical data
Pronunciation/ˌtəˈnfəvɪər ˌæləˈfɛnəmd/
Trade namesVemlidy
Genvoya (with elvitegravir, cobicistat and emtricitabine)
Odefsey (with emtricitabine and rilpivirine)
Descovy (with emtricitabine)
Symtuza (with darunavir, cobicistat, and emtricitabine)
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%[5]
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, 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[7] and is given in combination with other medications for the prevention and treatment of HIV. It is taken by mouth.[5]

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.[8][9] It was approved for use in the US against HIV in 2015[10] and against hepatitis B in 2016.[11] Although the FDA has approved tenofovir alafenamide for manufacture as a generic medication[12], it is not currently available as a generic medication[13].

Fixed-dose combinations containing tenofovir alafenamide

Research

Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir[40] and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.[41][42][43] 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.[44][45][46] The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015.[10] Genvoya is the first TAF-based regimen to receive approval.[10]

References

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  2. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  3. ^ "Product Monograph: Vemlidy (tenofovir alafenamide) tablets" (PDF). Government of Canada: The Drug and Health Product Register. 20 August 2020. Archived (PDF) from the original on 10 June 2022. Retrieved 7 June 2022.
  4. ^ "Vemlidy 25 mg film coated tablets - Summary of Product Characteristics (SmPC)". (emc). 8 September 2020. Archived from the original on 11 July 2021. Retrieved 12 November 2020.
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  6. ^ "Vemlidy EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 13 July 2021. Retrieved 12 November 2020.
  7. ^ Childs-Kean LM, Egelund EF, Jourjy J (October 2018). "Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection". Pharmacotherapy. 38 (10): 1051–1057. doi:10.1002/phar.2174. PMID 30120841. S2CID 52033420.
  8. ^ 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.
  9. ^ Markowitz M, Zolopa A, Ruane P, Squires K, Zhong L, Kearney BP, Lee W (March 2011). GS-7340 demonstrates greater declines in HIV-1 RNA than tenofovir disoproxil fumarate during 14 days of monotherapy in HIV-1 infected subjects (PDF). 18th Conference on Retroviruses and Opportunistic Infections. Archived from the original (PDF) on 25 April 2012.
  10. ^ a b c "U.S. Food and Drug Administration Approves Gilead's Single Tablet Regimen Genvoya (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection" (Press release). Gilead. 5 November 2015. Archived from the original on 8 November 2015.
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  12. ^ "First Generic Drug Approvals 2023". U.S. Food and Drug Administration (FDA). 30 May 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
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  21. ^ "Stribild EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  22. ^ "Odefsey- emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide tablet". DailyMed. U.S. National Library of Medicine. 6 December 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  23. ^ "Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) Tablets". U.S. Food and Drug Administration (FDA). 29 November 2016. Archived from the original on 13 April 2021. Retrieved 28 July 2020.
  24. ^ "Odefsey EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  25. ^ "Drug Approval Package: (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) NDA #202123". U.S. Food and Drug Administration (FDA). 6 September 2012. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  26. ^ "Summary Review: Complera" (PDF). US Food and Drug Administration. 19 July 2011. Archived (PDF) from the original on 1 April 2021. Retrieved 29 July 2020.
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  32. ^ "Symtuza- darunavir, cobicistat, emtricitabine, and tenofovir alafenamide tablet, film coated". DailyMed. U.S. National Library of Medicine. 6 March 2020. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  33. ^ "Drug Approval Package: Symtuza (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide)". U.S. Food and Drug Administration (FDA). 11 December 2018. Archived from the original on 9 July 2021. Retrieved 19 August 2020.
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External links