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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2020/05/10 05:07:32」(JST)

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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 for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.^[2] It is taken by mouth.^[2]

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.^[3]^[4] Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016.^[5]

Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir^[6] and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.^[7]^[8]^[9] 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.^[10]^[11]^[12] The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015.^[13] Genvoya is the first TAF-based regimen to receive approval.^[13]

Fixed-dose combinations containing tenofovir alafenamide

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (trade name Genvoya)^[14] — approved November 5, 2015 (compare Elvitegravir/cobicistat/emtricitabine/tenofovir; trade name Stribild)
Emtricitabine/rilpivirine/tenofovir alafenamide (trade name Odefsey)^[15] — approved March 1, 2016 (compare Emtricitabine/rilpivirine/tenofovir; trade name Complera)
Emtricitabine/tenofovir alafenamide (trade name Descovy)^[16] — approved April 4, 2016 (compare Emtricitabine/tenofovir; trade name Truvada). In October 2019, Descovy was approved in the United States for HIV-1 pre-exposure prophylaxis (PrEP).^[17]^[18]
Bictegravir/emtricitabine/tenofovir alafenamide (trade name Biktarvy)^[19] — approved February 2018.
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (trade name Symtuza)^[20] — approved July 17, 2018

References

^ ^a ^b "Tenofovir alafenamide (Vemlidy) Use During Pregnancy". Drugs.com. 26 December 2018. Retrieved 18 April 2020.
^ ^a ^b ^c "Vemlidy- tenofovir alafenamide tablet". DailyMed. 11 February 2020. Retrieved 18 April 2020.
^ 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.
^ 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
^ "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.
^ "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.
^ "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.
^ GS-7340 Packs Greater HIV Punch, Potentially Better Safety, Versus Viread Horn, Tim. 15 Mar 2012. AIDSmeds.com
^ 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.
^ Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild. AIDSmeds.com 1 Nov 2012.
^ CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.
^ Horn, T. et al. Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead. 13 June 2013. Treatment Action Group.
^ ^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.
^ "Genvoya- elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide tablet". DailyMed. 11 February 2019. Retrieved 18 April 2020.
^ "Odefsey- emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide tablet". DailyMed. 6 December 2019. Retrieved 18 April 2020.
^ "Descovy- emtricitabine and tenofovir alafenamide tablet". DailyMed. 13 January 2020. Retrieved 18 April 2020.
^ "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.
^ 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.
^ "Biktarvy- bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate tablet". DailyMed. 8 August 2019. Retrieved 18 April 2020.
^ "Symtuza- darunavir, cobicistat, emtricitabine, and tenofovir alafenamide tablet, film coated". DailyMed. 6 March 2020. Retrieved 18 April 2020.
^ "Comparison of tenofovir prodrugs: TAF vs TDF". DRUG R&D INSIGHT. Retrieved 24 November 2015.
^ Murakami E, Tolstykh T, Bao H, et al. (November 2010). "Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977". J. Biol. Chem. 285 (45): 34337–47. doi:10.1074/jbc.M110.161802. PMC 2966047. PMID 20801890.

External links

"Tenofovir alafenamide". Drug Information Portal. U.S. National Library of Medicine.
"Tenofovir alafenamide fumarate". Drug Information Portal. U.S. National Library of Medicine.

UpToDate Contents

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1. HIV感染症の治療に用いる抗レトロウイルス薬の概要overview of antiretroviral agents used to treat hiv [show details]
…elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide (EVG/c/ FTC/TAF), rilpivirine-emtricitabine-tenofovir alafenamide (RPV/FTC/TAF), tenofovir alafenamide-emtricitabine (TAF/FTC), and bictegra …
2. B型慢性肝炎患者へのテノホビルとアデホビルを用いる抗ウイルス療法tenofovir and adefovir for the treatment of chronic hbv infection [show details]
… Tenofovir disoproxil fumarate, tenofovir alafenamide, and adefovir are nucleotide reverse transcriptase inhibitors (NRTIs) that are used for the treatment of chronic hepatitis B virus (HBV) infection …
3. B型肝炎ウイルス：マネージメントの概要hepatitis b virus overview of management [show details]
…two formulations of tenofovir, tenofovir disoproxil fumarate and tenofovir alafenamide. For most patients, we recommend tenofovir alafenamide (25 mg daily) rather than tenofovir disoproxil fumarate (300 mg …
4. HIV感染患者における慢性B型肝炎の治療treatment of chronic hepatitis b in the hiv infected patient [show details]
…tablets, elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide (EVG/c/FTC/TAF), rilpivirine-emtricitabine-tenofovir alafenamide, and tenofovir alafenamide-emtricitabine. Both TDF and TAF have been found …
5. 妊娠時の抗レトロウイルス剤の安全性および用量safety and dosing of antiretroviral medications in pregnancy [show details]
…settings . There is not enough clinical experience with the newer tenofovir formulation, tenofovir alafenamide, to routinely recommend its initiation during pregnancy. Concerns have been raised regarding …

English Journal

Barriers to the Wider Use of Pre-exposure Prophylaxis in the United States: A Narrative Review.

Mayer KH, Agwu A, Malebranche D.
Advances in therapy. 2020 May;37(5)1778-1811.
Antiretroviral pre-exposure prophylaxis (PrEP) to prevent HIV transmission was first approved by the US Food and Drug Administration in 2012. Despite correlations of decreases in new HIV infections being greatest where PrEP has been deployed, the uptake of PrEP is lagging, particularly among populat
PMID 32232664

The switch from tenofovir disoproxil fumarate to tenofovir alafenamide determines weight gain in patients on rilpivirine-based regimen.

Taramasso L, Berruti M, Briano F, Di Biagio A.
AIDS (London, England). 2020 May;34(6)877-881.
To investigate whether the switch from tenofovir disoproxil fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) to tenofovir alafenamide (TAF)/FTC/RPV is associated with weight gain in people living with HIV (PLWHIV). Retrospective single-centre study. All PLWHIV on TDF/FTC/RPV who switched to TAF/FTC/
PMID 32271252

Adverse events of nucleos(t)ide analogues for chronic hepatitis B: a systematic review.

de Fraga RS, Van Vaisberg V, Mendes LCA, Carrilho FJ, Ono SK.
Journal of gastroenterology. 2020 May;55(5)496-514.
Nucleos(t)ide analogues (NAs) are the main drug category used in chronic hepatitis B (CHB) treatment. Despite the fact that NAs have a favourable safety profile, undesired adverse events (AEs) may occur during the treatment of CHB. Given the eminent number of patients currently receiving NAs, even a
PMID 32185517

Japanese Journal

新規の抗HIV治療薬の尿細管細胞への障害性と有機酸トランスポーターとの相互作用

金子明夏,安西尚彦,霊園良恵,鍬田伸好,満屋裕明
日本薬理学会年会要旨集 93(0), 3-P-300, 2020
… TDF (Tenofovir disoproxil fumarate) and TAF (Tenofovir alafenamide) are nucleoside reverse transcriptase inhibitors that have already been clinically applied. …
NAID 130007811885

Tenofovir nephrotoxicity among Asians living with HIV: review of the literature

Nishijima Takeshi,Gatanaga Hiroyuki,Oka Shinichi
Global Health & Medicine 1(2), 88-94, 2019
… <p>Tenofovir disoproxil fumarate (TDF), prodrug of tenofovir (TFV), is one of the most widely used nucleotide reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infection in resource-rich and resourcelimited settings with proven efficacy and safety, and also for the treatment of hepatitis B infections. …
NAID 130007789711

平成31年3月承認分

新薬紹介委員会
ファルマシア 55(10), 965-969, 2019
本稿では既に「承認薬の一覧」に掲載された新有効成分含有医薬品など新規性の高い医薬品について，各販売会社から提供していただいた情報を一般名，市販製剤名，販売会社名，有効成分または本質および化学構造，効能・効果を一覧として掲載しています．<br>今回は，55巻6号「承認薬の一覧」に掲載した当該医薬品について，表解しています．<br>なお，「新薬のプロフィル」欄においても詳解しま …
NAID 130007722330

「テノホビルアラフェナミドフマル酸塩」

Tenofovir alafenamide
Clinical data
Trade names	Vemlidy; Genvoya (with elvitegravir, cobicistat and emtricitabine); Odefsey (with emtricitabine and rilpivirine); Descovy (with emtricitabine); Symtuza (with darunavir, cobicistat, and emtricitabine)
Other names	GS-7340
AHFS/Drugs.com	Monograph
License data	EU EMA: by INN; US DailyMed: Tenofovir_alafenamide;
Pregnancy; category	AU: B3 ; US: N (Not classified yet) ; ;
Routes of; administration	Oral (tablets)
ATC code	J05AF13 (WHO) Combination codes: J05AR17 (WHO) J05AR18 (WHO) J05AR19 (WHO) J05AR20 (WHO) J05AR22 (WHO);
Legal status
Legal status	US: ℞-only ; In general: ℞ (Prescription only);
Pharmacokinetic data
Protein binding	~80%
Elimination half-life	0.51 hours
Excretion	Feces (31.7%), urine (<1%)
Identifiers
	IUPAC name Isopropyl (2S)-2-[[[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate;
CAS Number	379270-37-8;
PubChem CID	9574768;
DrugBank	DB09299;
ChemSpider	7849225;
UNII	EL9943AG5J;
KEGG	D10428;
ChEBI	CHEBI:90926 ;
ChEMBL	ChEMBL2107825;
CompTox Dashboard (EPA)	DTXSID50958941 ;
Chemical and physical data
Formula	C21H29N6O5P
Molar mass	476.466 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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;

　　[★]

英: tenofovir alafenamide fumarate
商: オデフシィ配合、ゲンボイヤ配合、シムツーザ配合、デシコビ配合、ビクタルビ配合、ベムリディ
関: テノホビル

「TAF」

　　[★]

「fumarate」

　　[★]

フマル酸、フマル酸塩、フマル酸エステル

関: fumaric acid

fumaric acid

[Drugs.com_pregnancy-1] "Tenofovir alafenamide (Vemlidy) Use During Pregnancy". Drugs.com. 26 December 2018. Retrieved 18 April 2020.

[Vemlidy_FDA_label-2] "Vemlidy- tenofovir alafenamide tablet". DailyMed. 11 February 2020. Retrieved 18 April 2020.

[3] 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.

[4] 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

[5] "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.

[6] "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.

[7] "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.

[8] GS-7340 Packs Greater HIV Punch, Potentially Better Safety, Versus Viread Horn, Tim. 15 Mar 2012. AIDSmeds.com

[9] 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.

[10] Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild. AIDSmeds.com 1 Nov 2012.

[11] CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.

[12] Horn, T. et al. Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead. 13 June 2013. Treatment Action Group.

[Gilead-13] "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.

[14] "Genvoya- elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide tablet". DailyMed. 11 February 2019. Retrieved 18 April 2020.

[15] "Odefsey- emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide tablet". DailyMed. 6 December 2019. Retrieved 18 April 2020.

[16] "Descovy- emtricitabine and tenofovir alafenamide tablet". DailyMed. 13 January 2020. Retrieved 18 April 2020.

[17] "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.

[18] 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.

[19] "Biktarvy- bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate tablet". DailyMed. 8 August 2019. Retrieved 18 April 2020.

[20] "Symtuza- darunavir, cobicistat, emtricitabine, and tenofovir alafenamide tablet, film coated". DailyMed. 6 March 2020. Retrieved 18 April 2020.

[21] "Comparison of tenofovir prodrugs: TAF vs TDF". DRUG R&D INSIGHT. Retrieved 24 November 2015.

[22] Murakami E, Tolstykh T, Bao H, et al. (November 2010). "Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977". J. Biol. Chem. 285 (45): 34337–47. doi:10.1074/jbc.M110.161802. PMC 2966047. PMID 20801890.

リンク元	「テノホビルアラフェナミドフマル酸塩」「TAF」
関連記事	「fumarate」

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tenofovir alafenamide fumarate