托法替尼

托法替尼
臨床資料
商品名（英語：Drug nomenclature）	捷抑炎/Xeljanz, Jaquinus, Tofacinix, Others
其他名稱	CP-690550
AHFS/Drugs.com	Monograph
MedlinePlus	a613025
核准狀況	美 DailyMed: Tofacitinib;
懷孕分級	澳: D ; ;
給藥途徑	口服給藥
藥物類別（英語：Drug class）	JAK激酶抑制劑
ATC碼	L04AF01 (WHO) ;
法律規範狀態
法律規範	澳：限醫生處方（S4）; 加：處方藥（℞-only）; 歐：Rx-only; 英：處方藥（℞-only） (POM); 美：處方藥（℞-only）; 處方藥（℞-only）;
藥物動力學數據
生物利用度	74%
血漿蛋白結合率	40%
藥物代謝	肝臟（透過CYP3A4和CYP2C19）
生物半衰期	3小時
排泄途徑	Urine
識別資訊
	IUPAC命名法 3-[(3R,4R)-4-Methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile; ;
CAS號	477600-75-2
PubChem CID	9926791;
PubChem SID	347827811;
IUPHAR/BPS	5677;
DrugBank	DB08895 ;
ChemSpider	8102425 ;
UNII	87LA6FU830;
KEGG	D09970 ; as salt: D09783 ;
ChEBI	CHEBI:71200 ;
ChEMBL	ChEMBL221959 ;
PDB配體ID	MI1 (PDBe, RCSB PDB);
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID90197271 ;
ECHA InfoCard	100.215.928
化學資訊
化學式	C16H20N6O
摩爾質量	312.38 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES CC1CCN(C(=O)CC#N)CC1N(C)c1ncnc2[nH]ccc12;
	InChI InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1; Key:UJLAWZDWDVHWOW-YPMHNXCESA-N;

托法替尼（英語：Tofacitinib），商品名捷抑炎（英語：Xeljanz），用於治療類風濕性關節炎、乾癬性關節炎、僵直性脊椎炎、多關節型幼年特發性關節炎和潰瘍性結腸炎的藥物^[9] ^[10]。它是一種JAK激酶抑制劑， ^[9] 由美國國家衛生院和輝瑞公司合作發現和研發。

常見副作用包括腹瀉、頭痛和高血壓^[11]。嚴重的副作用可能包括感染、癌症、血管性水腫和肺栓塞^[11]。高劑量使用時可能會增加死亡風險^[11]。孕期使用可能對胎兒有害^[12]。2019 年，歐洲藥品管理局安全委員會審查後，建議醫師對於肺栓塞高風險族群，暫時不要使用每日兩次 10 毫克劑量^[13]。美國食品藥品監督管理局也發布了有關血栓風險的警告^[14] ^[15] ^[16]。另一個重要副作用是嚴重的細菌、分枝桿菌、真菌和病毒感染。在托法替尼的 III 期臨床試驗中，有 3 例在試驗中得到肺結核，他們在研究進行前的結核病篩查均為陰性^[17]。

托法替尼分別於2012年及2017年在美國及歐洲獲得醫療使用許可^[18] ^[19]。緩釋藥劑是在2016年2月在美國拿到醫療使用許可^[20]。

參考文獻

^ Tofacitinib Use During Pregnancy. Drugs.com. 15 April 2020 [23 October 2020].
^ Xeljanz/Xeljanz XR (Pfizer Australia Pty Ltd). Therapeutic Goods Administration (TGA). 16 February 2023 [10 April 2023].
^ Prescription medicines: registration of new chemical entities in Australia, 2015. Therapeutic Goods Administration (TGA). 21 June 2022 [10 April 2023].
^ Product monograph brand safety updates. 加拿大衛生部. 6 June 2024 [8 June 2024].
^ 10 mg film-coated tablets - Summary of Product Characteristics (SmPC). (emc). 13 October 2020 [3 November 2020].
^ Xeljanz 11 mg prolonged release tablets - Summary of Product Characteristics (SmPC). (emc). [3 November 2020].
^ Xeljanz- tofacitinib tablet, film coated Xeljanz XR- tofacitinib tablet, film coated, extended release Xeljanz- tofacitinib solution. DailyMed. 2 October 2020 [3 November 2020].
^ Xeljanz EPAR. 歐洲藥品管理局 (EMA). 17 September 2018 [3 November 2020]. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ ^9.0 ^9.1 Xeljanz- tofacitinib tablet, film coated Xeljanz XR- tofacitinib tablet, film coated, extended release Xeljanz- tofacitinib solution. DailyMed. 2 October 2020 [3 November 2020].
^ Tofacitinib Citrate. The American Society of Health-System Pharmacists. [1 June 2018].
^ ^11.0 ^11.1 ^11.2 Tofacitinib Monograph for Professionals. Drugs.com. [5 October 2021]. （原始內容存檔於28 September 2021）（英語）.
^ Tofacitinib Use During Pregnancy | Drugs.com. Drugs.com. [5 October 2021]. （原始內容存檔於29 November 2020）.
^ Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2019, May 17, 2019. 歐洲藥品管理局. 17 May 2019 [17 May 2019].
^ Xeljanz, Xeljanz XR (tofacitinib): Drug Safety Communication - Due to an Increased Risk of Blood Clots and Death with Higher Dose. U.S. 美國食品藥品監督管理局 (FDA). 26 July 2019 [10 August 2019]. （原始內容存檔於15 December 2019）.
^ FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) (Podcast). 5 August 2019 [15 December 2019].
^ FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR). U.S. Food and Drug Administration. 15 December 2019 [15 December 2019]. （原始內容存檔於15 December 2019）.
^ O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Annals of the Rheumatic Diseases. April 2013, 72 (Suppl 2): ii111–ii115. PMC 3616338 . PMID 23532440. doi:10.1136/annrheumdis-2012-202576.
^ Tofacitinib Monograph for Professionals. Drugs.com. [5 October 2021]. （原始內容存檔於28 September 2021）（英語）.
^ Xeljanz EPAR. European Medicines Agency (EMA). [3 November 2020]. （原始內容存檔於28 October 2020）. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ Drug Approval Package: Xeljanz (tofacitinib) Extended Release (XR) Tablets NDA #208246. U.S. 美國食品藥品監督管理局 (FDA). 26 June 2017 [30 June 2023].

[Drugs.com_Pregnancy-1] Tofacitinib Use During Pregnancy. Drugs.com. 15 April 2020 [23 October 2020].

[2] Xeljanz/Xeljanz XR (Pfizer Australia Pty Ltd). Therapeutic Goods Administration (TGA). 16 February 2023 [10 April 2023].

[3] Prescription medicines: registration of new chemical entities in Australia, 2015. Therapeutic Goods Administration (TGA). 21 June 2022 [10 April 2023].

[4] Product monograph brand safety updates. 加拿大衛生部. 6 June 2024 [8 June 2024].

[5] 10 mg film-coated tablets - Summary of Product Characteristics (SmPC). (emc). 13 October 2020 [3 November 2020].

[6] Xeljanz 11 mg prolonged release tablets - Summary of Product Characteristics (SmPC). (emc). [3 November 2020].

[Xeljanz_FDA_label-7] Xeljanz- tofacitinib tablet, film coated Xeljanz XR- tofacitinib tablet, film coated, extended release Xeljanz- tofacitinib solution. DailyMed. 2 October 2020 [3 November 2020].

[Xeljanz_EPAR-8] Xeljanz EPAR. 歐洲藥品管理局 (EMA). 17 September 2018 [3 November 2020]. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[Xeljanz_FDA_label2-9] 9.0 ^9.1 Xeljanz- tofacitinib tablet, film coated Xeljanz XR- tofacitinib tablet, film coated, extended release Xeljanz- tofacitinib solution. DailyMed. 2 October 2020 [3 November 2020].

[AHFS20182-10] Tofacitinib Citrate. The American Society of Health-System Pharmacists. [1 June 2018].

[AHFS20212-11] 11.0 ^11.1 ^11.2 Tofacitinib Monograph for Professionals. Drugs.com. [5 October 2021]. （原始內容存檔於28 September 2021）（英語）.

[12] Tofacitinib Use During Pregnancy | Drugs.com. Drugs.com. [5 October 2021]. （原始內容存檔於29 November 2020）.

[13] Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2019, May 17, 2019. 歐洲藥品管理局. 17 May 2019 [17 May 2019].

[14] Xeljanz, Xeljanz XR (tofacitinib): Drug Safety Communication - Due to an Increased Risk of Blood Clots and Death with Higher Dose. U.S. 美國食品藥品監督管理局 (FDA). 26 July 2019 [10 August 2019]. （原始內容存檔於15 December 2019）.

[15] FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) (Podcast). 5 August 2019 [15 December 2019].

[16] FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR). U.S. Food and Drug Administration. 15 December 2019 [15 December 2019]. （原始內容存檔於15 December 2019）.

[17] O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Annals of the Rheumatic Diseases. April 2013, 72 (Suppl 2): ii111–ii115. PMC 3616338 . PMID 23532440. doi:10.1136/annrheumdis-2012-202576.

[AHFS2021-18] Tofacitinib Monograph for Professionals. Drugs.com. [5 October 2021]. （原始內容存檔於28 September 2021）（英語）.

[Xeljanz_EPAR2-19] Xeljanz EPAR. European Medicines Agency (EMA). [3 November 2020]. （原始內容存檔於28 October 2020）. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[20] Drug Approval Package: Xeljanz (tofacitinib) Extended Release (XR) Tablets NDA #208246. U.S. 美國食品藥品監督管理局 (FDA). 26 June 2017 [30 June 2023].

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