Tenofovir alafenamide

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Tenofovir alafenamide
Tenofovir alafenamide structure.svg
Names
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
  • Isopropyl (2S)-2-[[[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate
Clinical data
Drug classReverse transcriptase inhibitor[1]
Main usesChronic hepatitis B[1]
Side effectsHeadache, nausea, tiredness[1]
Pregnancy
category
  • AU: B3[2]
  • US: N (Not classified yet)[2]
Routes of
use
By mouth (tablets)
Typical dose25 mg OD[1]
External links
AHFS/Drugs.comMonograph
US NLMTenofovir alafenamide
Legal
License data
Legal status
  • UK: POM (Prescription only) [3]
  • US: ℞-only [4]
  • EU: Rx-only [1]
  • In general: ℞ (Prescription only)
Pharmacokinetics
Protein binding~80%[4]
Elimination half-life0.51 hour
ExcretionFeces (31.7%), urine (<1%)
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, sold under the brand name Vemlidy, is a medication for the treatment of chronic hepatitis B in those with compensated liver disease.[5] It is taken by mouth.[5] It can be used in people over the age of 11.[1] Hepatitis B may worsen after stopping the medication.[5]

Common side effects include headache, nausea, and tiredness.[1] Other side effects may include lactic acidosis.[5] It is not recommended in severe liver problems.[5] Tenofovir alafenamide is converted by the body to tenofovir, by which it works.[1] This than blocks reverse transcriptase which prevents the virus from multiplying.[1]

Tenofovir alafenamide was approved for use in the United States in 2016 and Europe in 2017.[5][1] In the United States it costs about 1,300 USD per month as of 2021.[6] In the United Kingdom this amount costs the NHS about £325 and in Canada it is about 600 CAD.[7][8]

Medical uses

It is used for chronic hepatitis B.[1]

Dosage

It is taken by mouth once a day at a dose of 25 mg for usually 6 to 12 months.[1]

History

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.[9][10]

Combinations

Tenofovir alafenamide fumarate, the salt used in drug formulations.

Gilead announced a Phase III trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir[11] and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.[12][13][14] 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 to be noninferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function.[15][16][17] The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015.[18] Genvoya is the first TAF-based regimen to receive approval.[18]

Fixed-dose combinations

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 "Vemlidy EPAR". European Medicines Agency (EMA). Archived from the original on 13 July 2021. Retrieved 26 January 2021.
  2. 2.0 2.1 "Tenofovir alafenamide (Vemlidy) Use During Pregnancy". Drugs.com. 26 December 2018. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  3. "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.
  4. 4.0 4.1 "Vemlidy- tenofovir alafenamide tablet". DailyMed. 11 February 2020. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 "Tenofovir Alafenamide Monograph for Professionals". Drugs.com. Archived from the original on 18 January 2021. Retrieved 26 September 2021.
  6. "Vemlidy Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 28 January 2021. Retrieved 26 September 2021.
  7. BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 659. ISBN 978-0-85711-369-6.
  8. "Pharmacoeconomic Review Report TENOFOVIR ALAFENAMIDE (VEMLIDY)" (PDF). Archived (PDF) from the original on 18 October 2018. Retrieved 26 September 2021.
  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.
  10. 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 Archived 25 April 2012 at the Wayback Machine. 18th Conference on Retroviruses and Opportunistic Infections 2 Mar 2011. Paper # 152LB
  11. "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.
  12. "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.
  13. GS-7340 Packs Greater HIV Punch, Potentially Better Safety, Versus Viread Archived 8 September 2015 at the Wayback Machine Horn, Tim. 15 Mar 2012. AIDSmeds.com
  14. Pharmacokinetics of a Novel EVG/COBI/FTC/GS-7340 Single Tablet Regimen Archived 28 November 2020 at the Wayback Machine. 13th International Workshop on Clinical Pharmacology of HIV Therapy. Barcelona, Spain. April 16–18, 2012.
  15. Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild Archived 20 September 2015 at the Wayback Machine. AIDSmeds.com 1 Nov 2012.
  16. CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated Archived 25 October 2020 at the Wayback Machine. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.
  17. Horn, T. et al. Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead Archived 19 November 2019 at the Wayback Machine. 13 June 2013. Treatment Action Group.
  18. 18.0 18.1 "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.
  19. "Genvoya- elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide tablet". DailyMed. 11 February 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  20. "Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) fixed-dose combination tablet". U.S. Food and Drug Administration (FDA). 8 December 2015. Archived from the original on 29 July 2020. Retrieved 28 July 2020. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  21. "Genvoya EPAR". European Medicines Agency (EMA). Archived from the original on 8 August 2020. Retrieved 28 July 2020.
  22. "Drug Approval Package: Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Fixed Dose". U.S. Food and Drug Administration (FDA). 10 October 2012. Archived from the original on 29 July 2020. Retrieved 28 July 2020. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  23. "Stribild- elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate tablet, film coated". DailyMed. 28 January 2019. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  24. "Stribild EPAR". European Medicines Agency (EMA). Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  25. "Odefsey- emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide tablet". DailyMed. 6 December 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  26. "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.
  27. "Odefsey EPAR". European Medicines Agency (EMA). Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  28. "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. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  29. "Complera- emtricitabine, rilpivirine hydrochloride, and tenofovir disoproxil fumarate tablet, film coated". DailyMed. 9 December 2019. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  30. "Descovy- emtricitabine and tenofovir alafenamide tablet". DailyMed. 13 January 2020. Archived from the original on 24 June 2021. Retrieved 18 April 2020.
  31. "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.
  32. Mandavilli, Apoorva (4 October 2019). "F.D.A. Approves New H.I.V.-Prevention Drug, but Not for Everyone". The New York Times. Archived from the original on 9 July 2021. Retrieved 11 October 2019.
  33. "Biktarvy- bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate tablet". DailyMed. 8 August 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  34. "Symtuza- darunavir, cobicistat, emtricitabine, and tenofovir alafenamide tablet, film coated". DailyMed. 6 March 2020. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  35. "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.
  36. "Symtuza EPAR". European Medicines Agency. Archived from the original on 10 July 2021. Retrieved 19 August 2020.
  37. http://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=CCE11C6BC5177A30CA2585AE00423857&agid=(PrintDetailsPublic)&actionid=1[permanent dead link]
  38. "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 9 July 2021. Retrieved 5 December 2020.

External links

Identifiers: