Tenofovir alafenamide

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Tenofovir alafenamide
Tenofovir alafenamide structure.svg
Clinical data
Pronunciation/ˌtəˈnoʊfəvɪər ˌæləˈfɛnəmaɪd/
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 (tablets)
ATC code
Legal status
Legal status
  • UK: POM (Prescription only) [2]
  • US: ℞-only [3]
  • EU: Rx-only [4]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding~80%[3]
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 a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor medication for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.[3] It is taken by mouth.[3]

Tenofovir alafenamide is a prodrug of tenofovir. It was developed by Gilead Sciences based on the protide technology of Chris McGuigan for use in the treatment of HIV/AIDS and chronic hepatitis B, 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.[5][6] Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016.[7]

Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir[8] and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.[9][10][11] In a 48-week study comparing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (trade name Stribild) to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (trade name 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.[12][13][14] The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015.[15] Genvoya is the first TAF-based regimen to receive approval.[15]

Fixed-dose combinations containing tenofovir alafenamide[]

  • Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name Genvoya)[16] — approved both in the United States and in the European Union in November 2015[17][18] (compare Elvitegravir/cobicistat/emtricitabine/tenofovir; brand name Stribild[19][20][21])
  • Emtricitabine/rilpivirine/tenofovir alafenamide (brand name Odefsey)[22] — approved in the United States in March 2016, and in the European Union in June 2016[23][24] (compare Emtricitabine/rilpivirine/tenofovir; brand name Complera[25][26])
  • Emtricitabine/tenofovir alafenamide (brand name Descovy)[27] — approved in the United States in April 2016 (compare Emtricitabine/tenofovir; brand name Truvada). In October 2019, Descovy was approved in the United States for HIV-1 pre-exposure prophylaxis (PrEP).[28][29]
  • Bictegravir/emtricitabine/tenofovir alafenamide (brand name Biktarvy)[30] — approved in the United States in February 2018.
  • Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (brand name Symtuza)[31] — approved in the European Union in September 2017, in the United States in July 2018, and in Australia in November 2019.[32][33][34]
  • Dolutegravir/emtricitabine/tenofovir alafenamide.[35]

References[]

  1. ^ a b "Tenofovir alafenamide (Vemlidy) Use During Pregnancy". Drugs.com. 26 December 2018. Retrieved 18 April 2020.
  2. ^ "Vemlidy 25 mg film coated tablets - Summary of Product Characteristics (SmPC)". (emc). 8 September 2020. Retrieved 12 November 2020.
  3. ^ a b c d "Vemlidy- tenofovir alafenamide tablet". DailyMed. 11 February 2020. Retrieved 18 April 2020.
  4. ^ "Vemlidy EPAR". European Medicines Agency (EMA).
  5. ^ 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.
  6. ^ M Markowitz, A Zolopa, et al. GS-7340 Demonstrates Greater Declines in HIV-1 RNA than Tenofovir Disoproxil Fumarate During 14 Days of Monotherapy in HIV-1 Infected Subjects. 18th Conference on Retroviruses and Opportunistic Infections 2 Mar 2011. Paper # 152LB
  7. ^ "FDA Approves Vemlidy (tenofovir alafenamide) for Chronic Hepatitis B in Adults". United States Department of Health and Human Services. 21 November 2016. Archived from the original on 11 October 2019. Retrieved 11 October 2019.
  8. ^ "Gilead Initiates Phase 3 Clinical Program for Tenofovir Alafenamide, a Novel Low-Dose Prodrug for the Treatment of HIV" (Press release). Gilead. 24 January 2013. Archived from the original on 11 October 2019.
  9. ^ "Gilead Sciences Finalizes Agreement with Tibotec Pharmaceuticals to Develop and Commercialize a Single-Tablet Regimen of Prezista with Emtriva, GS 7340 and Cobicistat". Gilead Sciences (Press release). 15 November 2011. Archived from the original on 11 October 2019. Retrieved 10 October 2019.
  10. ^ GS-7340 Packs Greater HIV Punch, Potentially Better Safety, Versus Viread Horn, Tim. 15 Mar 2012. AIDSmeds.com
  11. ^ Pharmacokinetics of a Novel EVG/COBI/FTC/GS-7340 Single Tablet Regimen. 13th International Workshop on Clinical Pharmacology of HIV Therapy. Barcelona, Spain. April 16–18, 2012.
  12. ^ Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild. AIDSmeds.com 1 Nov 2012.
  13. ^ CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.
  14. ^ Horn, T. et al. Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead. 13 June 2013. Treatment Action Group.
  15. ^ a b "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.
  16. ^ "Genvoya- elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide tablet". DailyMed. 11 February 2019. Retrieved 18 April 2020.
  17. ^ "Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) fixed-dose combination tablet". U.S. Food and Drug Administration (FDA). 8 December 2015. Retrieved 28 July 2020. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  18. ^ "Genvoya EPAR". European Medicines Agency (EMA). Retrieved 28 July 2020.
  19. ^ "Drug Approval Package: Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Fixed Dose". U.S. Food and Drug Administration (FDA). 10 October 2012. Retrieved 28 July 2020. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  20. ^ "Stribild- elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate tablet, film coated". DailyMed. 28 January 2019. Retrieved 28 July 2020.
  21. ^ "Stribild EPAR". European Medicines Agency (EMA). Retrieved 28 July 2020.
  22. ^ "Odefsey- emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide tablet". DailyMed. 6 December 2019. Retrieved 18 April 2020.
  23. ^ "Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) Tablets". U.S. Food and Drug Administration (FDA). 29 November 2016. Retrieved 28 July 2020.
  24. ^ "Odefsey EPAR". European Medicines Agency (EMA). 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. Retrieved 28 July 2020. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  26. ^ "Complera- emtricitabine, rilpivirine hydrochloride, and tenofovir disoproxil fumarate tablet, film coated". DailyMed. 9 December 2019. Retrieved 28 July 2020.
  27. ^ "Descovy- emtricitabine and tenofovir alafenamide tablet". DailyMed. 13 January 2020. Retrieved 18 April 2020.
  28. ^ "FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic". U.S. Food and Drug Administration (FDA). 3 October 2019. Archived from the original on 11 October 2019. Retrieved 11 October 2019.
  29. ^ Mandavilli, Apoorva (4 October 2019). "F.D.A. Approves New H.I.V.-Prevention Drug, but Not for Everyone". The New York Times. Retrieved 11 October 2019.
  30. ^ "Biktarvy- bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate tablet". DailyMed. 8 August 2019. Retrieved 18 April 2020.
  31. ^ "Symtuza- darunavir, cobicistat, emtricitabine, and tenofovir alafenamide tablet, film coated". DailyMed. 6 March 2020. Retrieved 18 April 2020.
  32. ^ "Drug Approval Package: Symtuza (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide)". U.S. Food and Drug Administration (FDA). 11 December 2018. Retrieved 19 August 2020.
  33. ^ "Symtuza EPAR". European Medicines Agency. Retrieved 19 August 2020.
  34. ^ http://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=CCE11C6BC5177A30CA2585AE00423857&agid=(PrintDetailsPublic)&actionid=1
  35. ^ "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 5 December 2020.

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