MLリソース：エイズ治療剤[個別製品]
本頁は、●MLリソース:エイズ治療剤 のうち個別製品部分を独立させたもの。Supported by Nobelpharma Co.Ltd.
in a part.
■個別収録製品[1288]●エトラビリンetravirine(Intelence － Tibotec)インテレンス[ティボテック]日本語版註）エトラビリンetravirine(Intelence － Tibotec)インテレンス[ティボテック]
【別名】TMC125 【開発元】Tibotec Pharmaceuticals, Ltd [DBR_ID]
【化学名】4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-benzonitrile ;CAS REGISTRY NUMBER:269055-15-4
【承認】FDA申請=17-Jul-2007、FDA承認=18-Jan-2008; (Tibotec Therapeutics, Division of Ortho Biotech Products, L.P.,); 【製剤】１錠中etravirine 100mg 【適応】治療歴があり、HIV-1 に感染している成人において抗レトロウイルス剤との併用。 【用法用量】200mg を1 日2 回食後に経口投与する。
【作用】 【特徴】NNRTI耐性HIV変異株に有効な次世代の非核酸系逆転写酵素阻害剤(NNRTI)
【製品情報】www.intelence-info.com 【添付文書】Intelence-PI
【提携】 【EU】Intelence[Janssen-Cilag]CHMP承認勧告26-JUn-2008；MA=28-Aug-2008
【日本】TMC125/INTELENCE(R)[ヤンセンファーマ]申請準備中(HIV-I感染症) 【その他】
●[1277]Raltegravir (Isentress － Merck)ラルテグラビル(アイセントレス錠)日本語版註）Raltegravir potassium(Isentress － Merck)ラルテグラビル(アイセントレス錠4)
【別名】MK-0518; RAL, L-000900612-003E 【開発元】Merck & Co.
【化学名】4-Pyrimidinecarboxamide, N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-, monopotassium salt; CAS_REG 871038-72-1
【承認】FDA申請=Apr 13, 2007、FDA承認=Oct 12, 2007 ; 【製剤】1錠中ラルテグラビルを400mg含有 【適応】HIV-1 の複製が認められ、多剤耐性のHIV-1 を保有している治療経験のある患者にアイセ ントレスは他の抗HIV 薬と併用する。 【用法用量】400mgを１日２回
【作用】初のインテグラーゼ阻害薬a human immunodeficiency virus integrase strand transfer inhibitor (HIV-1 INSTI) インテグラーゼは、HIV-1の複製に必要な3つの酵素のうちの1つであり、HIV-1のDNAを宿主細胞の遺伝子に組み込む過程を触媒する。非臨床試験のデータから、ラルテグラビルが種々のHIV-1変異株（既存の抗HIV薬に耐性を示すHIV-1変異株を含む）に対して広い活性を有することが示されている。 【特徴】既存の抗HIV薬に耐性があるウイルスを検出不能レベルにまで効果的に低下させ、エファビレンツより有効ウイルス量を70％減少 【製品情報】www.isentress.com 【添付文書】ISENTRESS(TM) (raltegravir) -PI
【EU】EMEAではIsentress INN: raltegravir[Merck Sharp & Dohme]承認20 Dec 2007; 2007年にメキシコで承認されて以来、2008年現在30カ国以上でMerck & Co.及びその関連会社からISENTRESSの名称で承認されている。
【日本】「アイセントレス錠400mg」MK-0518[万有製薬]第二部会審議2008.4.30、承認日2008.6.24、薬価収載2008.6.27、発売2008.7.7 【製剤～日本】1錠中にラルテグラビルとして400mgを含有 【適応～日本】HIV感染症 【用法用量～日本】通常、成人にはラルテグラビルとして400 mg を1 日2 回経口投与する。本剤は、食事の有無にかかわらず投与できる。なお、投与に際しては、必ず他の抗HIV薬と併用すること。 【製品情報～日本】アイセントレス(R)錠400mg 【添付文書～日本】アイセントレス(R)錠400mg - インタビューフォーム 【その他】
●[1277]Maraviroc (Selzentry － Pfizer) 日本語版註）Maraviroc (Selzentry － Pfizer)マラビロック
【別名】UK-427857 【開発元】Pfizer
【化学名】4,4-difluoro-N-{(1S)-3-[exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclohexanecarboxamide
【承認】FDA申請=Dec 19, 2006、FDA承認=Aug 6, 2007 ; 【製剤】film-coated tablets for oral administration containing either 150 or 300 mg of maraviroc 【適応】ウイルス複製が証明され、かつ複数の抗レトロウイルス薬耐性のHIV-1菌株を有する、CCR5指向性のHIV-1が検出された成人感染者 indicated for combination antiretroviral treatment of adults infected with only CCR5-tropic HIV-1detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents 【用法用量】1)PIs(except tipranavir/ritonavir), delavirdineを含むCYP3A阻害薬服用時、１日150mgを２回 2)NRTIs, tipranavir/ritonavir, nevirapineおよび非強力なCYP3A阻害薬・誘発薬の服用時、１日300mgを２回 3)efavirenzを含むCYP3A誘発剤(強力CYP3A阻害剤非服用時)服用時、１日600mgを２回
【作用】CCR5拮抗薬として知られ、同クラスにおける初めての製品。CCR5拮抗薬は、ウイルスがT細胞に入り込む際の主要経路であるCCR5コレセプターを遮断。他クラスの経口HIV治療薬はいずれもT細胞内でウイルスと戦うが、Selzentryは細胞表面でR5ウイルスを阻止して侵入を防ぐ。 【特徴】10余年ぶりに登場する新しいクラスの経口HIV治療薬で、特定のタイプのHIVに感染した他剤治療歴のある患者の白血球へのウイルス侵入を遮断し、ウイルス量を有意に減少させるとともに、T細胞の数を増やす。 【製品情報】www.selzentry.com 【添付文書】SELZENTRY-PI
【提携】 【EU】Celsentri INN: maraviroc [Pfizer]承認18 Sep 2007 【日本】UK-427,857[ファイザー]申請準備中(HIV-1 感染症（CCR5陽性）) 【その他】
●[1244]Atripla Tablet (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) [Gilead/BMS]日本語版註）Atripla Tablet (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) [Gilead/BMS]
【別名】 【開発元】Gilead Science [DBR_ID]
【化学名】
【承認】FDA申請=Apr 25,2006、FDA承認=July 12, 2006 ; 【製剤】(efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) 【適応】for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. 【用法用量】１日１回１錠 【作用】 【特徴】 【製品情報】http://www.atripla.com/ 【添付文書】Atripla Full Prescribing Information 【EU】Atripla[Gilead/BMS/Merck３社]EMEA申請2006.10.9 承認2007.12.13。 【日本】未開発 【その他】●[1243]darunavir ethanolate (PREZISTA[TM] [Tibotec, Inc.])ダルナビル(プレジスタ)
日本語版註）darunavir ethanolate (PREZISTA[TM] [Tibotec, Inc.])ダルナビル(プレジスタ)
【別名】TMC-114 【開発元】Tibotec, Inc., A Division of Ortho Biotech Products, LP [DBR_ID]
【化学名】[(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester monoethanolate. m.f.=C27H37N3O7S . C2H5OH and m.w.=593.73.
【承認】FDA申請=22-Dec-2005、FDA承認=23-Jun-2006 ; 【製剤】錠剤－darunavir ethanolate equivalent to 300 mg of darunavir. 【適応】HIV感染症（抗レトロウイルス薬による既治療患者の成人）リトナビル 100mgと併用する。 【用法用量】成人の場合、600mgを１日２回、ritonavir 100mgずつと一緒に服用 【作用】HIV-1 protease阻害剤。 It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in infected cells, thereby preventing the formation of mature virus particles. 【特徴】交叉耐性ウイルスに有効 【製品情報】http://www.prezista.com/ 【添付文書】Full Prescribing Information
【EU】Prezista[Janssen-Cilag] EMEA申請2006.2.11 承認2007.2.12 【日本】プリジスタ錠300mg[製造販売元／ヤンセンファーマ株式会社 提携／TibotecPharmaceuticalsLtd]PREZISTA 申請2006.11、承認承認2007.11.22、薬価収載2007.11.30、発売2007.12.10; 【製剤～日本】１錠中ダルナビル エタノール付加物325.23mg（ダルナビルとして300mg） 【適応～日本】HIV感染症 【用法用量～日本】通常、成人にはダルナビルとして1回600mgとリトナビル1回100mgをそれぞれ1日2回食事中又は食直後に併用投与する。投与に際しては、必ず他の抗HIV薬と併用すること。 【製品情報～日本】プリジスタ 【添付文書～日本】プリジスタ添付文書 | プリジスタインタビューフォーム 【その他】
●[1219]Tipranavir Disodium (Aptivus [Boehringer Ing])チプラナビル(アプチバス)
日本語版註）Tipranavir Disodium (Aptivus [Boehringer Ing])チプラナビル(アプチバス)
【別名】PNU-140690E 【開発元】Pfizerが創製し、Boehringer-Ingにライセンス(2000) [DBR_ID]
【化学名】3'-[(1R)-1-[(6R)-5,6-Dihydro-4-hydroxy-2-oxo-6-phenethyl-6-propyl-2H-pyran-3-yl]propyl]-5-(trifluoromethyl)-2-pyridinesulfonanilide, disodium salt. CAS-174484-41-4(Tipranavir).;CAS-191150-83-1(Tipranavir Disodium)
【承認】FDA申請=December 21, 2004,、FDA承認=Jun 22, 2005 ; 【製剤】カプセル中250mg 【適応】(高度な治療経験があり又は多数のプロテアーゼ阻害剤に耐性のHIV-1 ウイルスを有し、ウイルス複製の証拠のあるHIV-1 感染症患者におけるリトナビルとの併用)for the use of Aptivus (tipranavir) capsules, 250 mg, coadministered with 200 mg of ritonavir, for combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. 【用法用量】500mg（２カプセル）を１日２回経口投与 【作用】非ペプチド系プロテアーゼ阻害剤（NPPI）；チプラナビルは非ペプチド系化学構造を持つことで、よりフレキシブルにHIVプロテアーゼ活性部位に結合。 ペプチド系プロテアーゼ阻害剤（PI）と異なり、チプラナビルが薬剤耐性を獲得したHIVに有効で、かつチプラナビルに対しHIVの感受性が低下することが非常にまれという薬剤耐性特性はこのためだと考えられる。 【特徴】 【製品情報】Aptivus(R) (tipranavir) Capsules 【添付文書】Aptivus(R) Capsules 250mg (tipranavir) 【EU】Aptivus[Boehringer Ingelheim]EU申請=2004.10.25,CHMP承認勧告=2005.7.28,EU承認=2005.10.25 【日本】日本ベーリンガーインゲルハイムで開発検討中 【その他】
●[1203]emtricitabine/tenofovir(Truvada[Gilead]) エムトリシタビンとフマル酸テノホビル ジソプロキシル配合剤(ツルバダ(TM)錠)
日本語版註）emtricitabine/tenofovir(Truvada[Gilead])(tru-VAH-dah) エムトリシタビンとフマル酸テノホビル ジソプロキシル配合剤(ツルバダ(TM)錠)
【別名】 【開発元】Gilead Science [DBR_ID]
【化学名】
【承認】FDA申請=March 11, 2004、FDA承認=Aug.02/2004 ; 【製剤】1錠中emtricitabine 200mg and tenofovir disoproxil fumarate 300mg 【適応】TRUVADA is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults. 【用法用量】１錠を１日１回 【作用】逆転写酵素阻害剤。 nucleoside reverse transcriptase inhibitors(NRTI) 【特徴】他の抗HIV剤と併用した場合、複製プロセスを妨害することによりHIV量や人体の負担を低減、免疫システム細胞T cells / CD4 cellsを増加させる。 【製品情報】http://www.truvada.com/ 【添付文書】http://www.truvada.com/fpi.pdf 【提携】ギリアド・サイエンシズ社 【EU】諮問委CHMPは2004.11.18に承認勧告、2005.2.23EU25カ国承認。 Gilead's Access Programにより、68の低資源国ヘ非営利価格で提供。 【日本】ツルバダ(TM)錠(製造販売元／日本たばこ産業株式会社 販売元／鳥居薬品株式会社 提携／GILEAD)承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19(鳥居薬品)。：「ツルバダ(TM)錠」製品概要 【製剤～日本】1錠中エムトリシタビン200mg及びフマル酸テノホビル ジソプロキシル300mg（テノホビル ジソプロキシルとして245mg） 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人には1回1錠（エムトリシタビンとして200mg及びフマル酸テノホビル ジソプロキシルとして300mgを含有）を1日1回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること 【添付文書～日本】ツルバダ錠添付文書 | ツルバダ錠インタビューフォーム 【その他】
●[1219]tenofovir disoproxil fumarate(Viread Tabs[Gilead])フマル酸テノホビル ジソプロキシル(ビリアード)
日本語版註）tenofovir disoproxil fumarate(Viread Tabs[Gilead])フマル酸テノホビル ジソプロキシル(ビリアード)
【別名】GS-4331-05 【開発元】Gilead Science [DBR_ID]
【化学名】9-[(R)-2-[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1); C19H30N5O10P.C4H4O4; m.w.635.52.; CAS-202138-50-9
【承認】FDA申請=April 30, 2001、FDA承認=10/26/2001 ; 【製剤】錠剤－300mg of tenofovir disoproxil fumarate(eq. to 245 mg of tenofovir disoproxil) 【適応】VIREAD is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 【用法用量】1日1回１錠(300mg)を食事と共に服用。 【作用】HIV reverse transcriptase inhibitor 【特徴】 【製品情報】http://www.viread.com/ 【添付文書】http://www.gilead.com/pdf/viread_pi.pdf 【提携】 【EU】Viread[Gilead Sciences]承認2002.2.5; 【日本】ビリアード錠300mg(製造販売元／日本たばこ産業株式会社 販売元／鳥居薬品株式会社 提携／GILEAD)承認申請2004.1.19、輸入承認2004.3.25、薬価収載2004.4.2、発売2004.4.12(鳥居薬品)；抗HIV薬「ビリアード(R)錠300mg」製品概要 【製剤～日本】錠-フマル酸テノホビル ジソプロキシル300mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはフマル酸テノホビル ジソプロキシルとして1回300mg（テノホビル ジソプロキシルとして245mg）を1日1回経口投与する。なお、投与に際しては必ず他の抗ＨＩＶ薬と併用すること。 【添付文書～日本】ビリアード錠300mg 添付文書[html]|[pdf] - インタビューフォーム[pdf] 【その他】a prodrug of tenofovir; an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5’-monophosphate
●[1203]abacavir/lamivudine(Epzicom[GSK])
日本語版註）abacavir sulfate/lamivudine(Epzicom[GSK])
【別名】 【開発元】GSK [DBR_ID]
【化学名】
【承認】FDA申請=2003.10.7、FDA承認=Aug.02/2004 ; 【製剤】Each orange, film-coated tablet contains the active ingredients 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine and the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. 【適応】indicated for the treatment of HIV-1 infection 【用法用量】成人で１日１回１錠を他のantiretroviral agentsと併用して用いる。 【作用】 【特徴】 【製品情報】 【添付文書】Epzicom Tablet -PI 【EU】Kivexa INN:Abacavir/Lamivudine[GSK] - CHMP=2004.9.7承認勧告,MA=2004.12.17 【日本】エプジコム錠[グラクソ・スミスクライン株式会社]薬価基準収載年月=2005年1月;販売開始年月=2005年1月7日 【製剤～日本】1錠中にラミブジン300mg、硫酸アバカビル702mg（アバカビルとして600mg） 【適応～日本】HIV感染症 【用法用量～日本】通常、成人には1回1錠（ラミブジンとして300mg及びアバカビルとして600mg）を1日1回経口投与する。 【添付文書～日本】エプジコム錠 添付文書 - インタビューフォーム【その他】
●lamivudine(Epivir[GSK])ラミブジン(エピビル錠)日本語版註）lamivudine(Epivir[GSK])ラミブジン(エピビル錠)
【別名】3TC 【開発元】GSK [DBR_ID]
【化学名】(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one.; C8H11N3O3S ; m.w.229.3 daltons.
【承認】FDA申請=、FDA承認=Nov 17, 1995; 【製剤】錠150mg,300mg、経口液10mg/mL 【適応】indicated for the treatment of HIV infection 【用法用量】成人は１日300mgを１回または２分服、３ヵ月～１６才は１日4mg/Kgを２回 【作用】核酸系逆転写酵素阻害剤 【特徴】 【製品情報】 【添付文書】Epivir 【EU】Epivir[Glaxo]MA=1996.8.8 【日本】エピビル錠150,300(GSK): [150mg]薬価収載1997.2、販売開始1997.2 [300mg]薬価収載2003.9、販売開始2003.10.8 【製剤～日本】１錠中ラミブジン150mg,300mg 【適応～日本】下記疾患における他の抗HIV 薬との併用療法：HIV 感染症 【用法用量～日本】通常、成人には他の抗HIV 薬と併用して、ラミブジンとして1日量300mgを1日1回又は2回（150mg×2）に分けて経口投与する。 【添付文書～日本】エピビル錠150,300 -インタビューフォーム 【その他】
●[1169]emtricitabine (Emtriva [Gilead])エムトリバ(R)カプセル
日本語版註）emtricitabine エムトリシタビン(Emtriva [Gileadギリアド社])エムトリバ(R)カプセル
【別名】(－)-FTC; 524W91; BW-524W91; FTC-(－) 【開発元】Gilead Science [DBR_ID]43322 [625A]
【化学名】5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.m
【承認】FDA申請=2002.9.3、FDA承認=02-Jul-2003、発売=2003.7 ;【製剤】Capsule; Oral 200MG 【適応】indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults. 【用法用量】18才以上、１日１回200mg 【作用】HIVの増殖に関わる逆転写酵素の働きを阻害する核酸系逆転写酵素阻害剤 【特徴】1日1回1カプセル（200mg）の投与で有効性を示すため、患者の服薬負担が少なく、長期的な服薬遵守の促進につながる 【製品情報】www.emtriva.com 【添付文書】http://www.gilead.com/pdf/emtriva_pi.pdf 【EU】Emtriva[Gilead Sciences]; 諮問委CPMP勧告=2003.7.24; 承認ECMA=2003.10.28 【日本】エムトリバカプセル200mg(製造販売元／日本たばこ産業株式会社 販売元／鳥居薬品株式会社 提携／GILEAD)契約2003.7.31、承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19。 【製剤～日本】1カプセル中エムトリシタビンとして200mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常，成人にはエムトリシタビンとして1回200mgを1日1回経口投与する。なお，投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】エムトリバ添付文書 | エムトリバインタビューフォーム 【その他】nucleoside reverse transcriptase inhibitor (NRTI)抗HIV（逆転写酵素阻害）
●[1169]硫酸アタザナビルatazanavir sulfate(レイアタッツREYATAZ[BMS])
日本語版註）硫酸アタザナビルatazanavir sulfate(レイアタッツREYATAZ[BMS])
【別名】BMS-232632-05 【開発元】Novartisが創製しBMSにライセンス [DBR_ID]x
【化学名】dimethyl(3S,8S,9S,12S)-9-benzyl-3,12,di-tert-butyl-8-hydroxy-4,11-dioxo-6-(p-2-pyridylbenzyl)-2,5,6,10,13-pentaazatetradecanedioate, sulfate (1:1)(salt); CAS-229975-97-7
【承認】FDA申請=2002.12.20、FDA承認=20-Jun-2003、米国発売=2003.7 ;【製剤】Capsules - 100 mg, 150 mg, or 200 mg 【適応】indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 【用法用量】 【作用】HIVプロテアーゼ阻害剤 【特徴】レイアタッツカプセルは他の抗ＨＩＶ薬との併用療法で用いられるプロテアーゼ阻害剤で、この系統の薬剤としては日本で初めて１日１回投与を実現。 1回２カプセル（1カプセル200mg x 2）と服用量が少ない上、脂質への影響も少ないことが大きな特徴。 また、耐性変異出現率は低く、未治療患者に対する使用において耐性が出現した場合には、独自の耐性変異（Ｉ５０Ｌ）が現れることにより、他のプロテアーゼ阻害剤に対するウイルス感受性を向上させ、将来の治療に柔軟性をもたらす可能性がある。 既存のプロテアーゼ阻害剤と同等の効果があるが、①投与法が１日１回②脂質代謝異常の出現頻度が少ない③他のプロテアーゼ阻害剤の耐性ウイルスにも効果がある――などの特徴を持つ。
【製品情報】www.reyataz.com 【添付文書】Reyataz Full Prescribing Information
【EU】Reyataz[BMS]; 申請2002.5.29; CPMP承認勧告 21/Nov/03、承認2004.3.2 【日本】レイアタッツカプセル150mg,200mg[発売元／ブリストル・マイヤーズ株式会社 製造販売元／ブリストル製薬有限会社 ]申請2003.10、薬事・食品衛生審議会医薬品第二部会承認了承2003.11.21 薬価収載2003.12.25,販売開始年月=2004年１月6日 【製剤～日本】１カプセル中，硫酸アタザナビル170.84mg(アタザナビルとして150mgに相当)または227.79mg(アタザナビルとして200mgに相当)を含有する。【適応～日本】HIV-1感染症 【用法用量～日本】通常成人には，アタザナビルとして400mgを１日１回食事中又は食直後に経口投与する。 投与に際しては必ず他の抗HIV薬と併用すること。 なお，中等度の肝障害患者には300mgを１日１回に減量して投与することが推奨される。 【添付文書～日本】レイアタッツカプセル150mg,200mg 【その他】
●[1159]enfuvirtide(Fuzeon [Trimeris/Roche]エンフューヴィルタイド「フューゼオン」
日本語版註）enfuvirtide(Fuzeon [Trimeris/Roche]
(en fyoo' vir tide)エンフューヴィルタイド「フューゼオン」
【別名】T-20; DP178; Ro 29-9800;pentafuside 【開発元】Trimeris[US]トライメリス社 [DBR_ID]48270(TC=625A)
【化学名】CH3CO-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu-Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn-Trp-Phe-NH2; CAS-159519-65-0
【承認】FDA申請=17-Sept-2002、FDA承認=3-Mar-2003、発売=27-Mar-2003[Roche] ;【製剤】Injectable; Subcutaneous 90MG/VIAL;１日２回 【適応】FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. 【用法用量】 【作用】現在唯一の融合阻害剤。細胞侵入時におきるGp41の構造変化の段階を阻害すると考えられる。36個のアミノ酸からなる合成ペプチドであり、半減期は3.8時間と短いため、冷蔵庫保存が必要であり、1日2回の皮下注射が必要である。 【特徴】初のHIV-細胞融合阻害剤。T-20は多剤耐性HIVに感染している患者においても強い抗HIVを示すが、問題点も多い。例えば、経口投与ができないこと(注射部位反応98%)やその治療費が高いことなどである。そのため、経口投与ができる小分子化合物の開発が期待されている。 【製品情報】http://www.fuzeon.com/ 【添付文書】http://www.rocheusa.com/products/fuzeon/ 【EU】FuzeonINN:Enfuvirtide[Roche]申請=20-Sept-2002; 諮問委CPMP勧告=19-Mar-2003; 承認=27-May-2003 【日本】未開発 【その他】Antiviral(blockade of gp-41 mediated membrane fusion); FUZEON (enfuvirtide) is an inhibitor of the fusion of HIV-1 with CD4+ cells. Enfuvirtide is a linear 36-amino acid synthetic peptide with the N-terminus acetylated and the C-terminus is a carboxamide. It is composed of naturally occurring L-amino acid residues.
●[1095]Kaletra(lopinavir/ritonavir) Capsules &Oral sol.[Abbott Labs]
日本語版註） Kaletra(lopinavir/ritonavir) Capsules &Oral sol.[Abbott Labs]
【別名】 【開発元】Abbott(創製者Triangle Pharmaceuticals,Incを買収) [DBR_ID]
【承認～カプセル・液】FDA申請=31-May-2000優先審査、FDA承認=15-Sep-2000 【承認～錠】FDA申請=Apr 28,2005優先審査、FDA承認=28-Oct-2005; 【製剤】Capsules -133.3 mg lopinavir and 33.3 mg ritonavir; Oral solution -80 mg lopinavir and 20 mg ritonavir per milliliter; Tablets -200mg lopinavir and 50mg ritonavir or 100mg lopinavir and 25mg iitonavir
【適応】indicated in combination with other antiretroviral agents for the treatment of HIV-1 infections in adults and pediatric patients age six months
【用法用量】成人(未治療)は800/200mg(200/50mg４錠または10mL経口液)を１日１回または分２ 成人(治療経験者)は400/100mg(200/50mg２錠または5mL経口液)を１日２回 ６ヵ月以上の小児は１日２回体重に応じて 【作用】本剤はロピナビルとリトナビルの配合剤である． ロピナビルはHIVプロテアーゼの活性を阻害し，HIVプロテアーゼによるgag-polポリ蛋白質の開裂を抑制することで，感染性を持つ成熟したHIVの産生を抑制する．リトナビルは，CYP3Aによるロピナビルの代謝を競合的に阻害し，ロピナビルの血中濃度の上昇をもたらす．本剤の抗ウイルス活性は，ロピナビルによるものである． 本剤はHIVプロテアーゼに対する選択的親和性を有し，ヒトのアスパルティックプロテアーゼに対してはほとんど阻害作用を示さない． 【特徴】 【製品情報】http://www.kaletra.com 【添付文書】http://www.rxabbott.com/pdf/kaletratabpi.pdf
【EU】Kaletra[Abbott]MA=20 March 2001
【日本】カレトラ・ソフトカプセル／カレトラ・リキッド[アボットジャパン]承認2000.12.12薬価2000.12.15発売2000.12.25 カレトラ・リキッド[アボットジャパン]承認2000.12.12薬価2000.12.15発売2000.12.25 カレトラ錠[アボットジャパン]承認2006.9.1薬価2006.9.4発売2006.9.15 【製剤～日本】1カプセル中 ロピナビル133.3mg・リトナビル33.3mg；内用液－1mL中 ロピナビル80mg・リトナビル20mg；1錠中 ロピナビル200mg・リトナビル50mg 【適応～日本】HIV感染症 【用法用量～日本】通常，成人にはロピナビル・リトナビルとして1回400mg・100mg（5mLまたは3カプセルまたは2錠）を1日2回食後に経口投与する． なお，体重40kg以上の小児には成人と同用量投与できる． 通常，小児には，体重7kg以上15kg未満で1kgあたり12mg・3mg，15kg以上40kg以下で１kgあたり10mg・2.5mgを1日2回食後に経口投与する．最大投与量は 400mg・100mg（5mL）1日2回投与とする． 【製品情報～日本】 【添付文書～日本】カレトラ錠添付文書|カレトラ・ソフトカプセル添付文書|カレトラ・リキッド添付文書 カレトラ錠・カレトラ・リキッドインタビューフォーム|カレトラ・ソフトカプセルインタビューフォーム 【その他】
●ritonavir (Norvir[Abbott])ノービア
;【別名】Norvir; ABT-538 【開発元】Abbott(創製者Triangle Pharmaceuticals,Incを買収) [DBR_ID]45128
;【化学名】10-Hydroxy-2-methyl-5-(1-methylethyl)-1- [2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, [5S-(5R*,8R*,10R*,11R*)]
【承認】FDA申請=、FDA承認=1-Mar-1996; 【製剤】ソフトカプセル－100mg ritonavir： 内用液－80mg/mL of ritonavir 【適応】 indicated in combination with other antiretroviral agents for the treatment of HIV-infection【用法用量】通常，成人にはリトナビルとして1回600mg（6カプセルまたは7.5mL）を1日2回食後に経口投与する．ただし，投与初日は1回300mg以上を1日2回，2～3日目毎に1回100mg単位で増量する。 【作用】本剤は、HIV-1及びHIV-2のプロテアーゼの活性を競合的に阻害し，HIVプロテアーゼによるgag-pol蛋白質前駆体の産生を抑制することで抗ウイルス作用を示す．Ｘ線結晶解析で，本剤は基質遷移状態アナログとしてHIVアスパルティックプロテアーゼの活性部位Asp-Thr-Gly配列に直接的に結合することが示されている． 本剤は，HIVプロテアーゼに対する選択的親和性を有し，ヒトのアスパルティックプロテアーゼに対してはほとんど阻害作用を示さない． 【特徴】 【製品情報】http://www.norvir.com/ 【添付文書】http://www.rxabbott.com/pdf/norpi2a.pdf#page=1
【提携】 【EU】Norvir[Abbott]MA=26 August 1996
【日本】ノービアカプセル100mg(硬カプセル)申請1996.7.23承認1997.11.20発売1997.12.18→販売中止； ノービア・ソフトカプセル100mg[アボットジャパン]承認1999.8.25薬価1999.9.10発売1999.9.17 ノービア・リキッド[アボットジャパン]承認1998.9.25薬価1998.9.25発売1998.12.14 【製剤～日本】1カプセル中リトナビル・100mg；内用液1mL中リトナビル・80mg 【適応～日本】下記疾患におけるヌクレオシド系HIV逆転写酵素阻害剤との併用療法 1.後天性免疫不全症候群（エイズ） 2.治療前のCD4リンパ球数500/mm3以下の症候性及び無症候性HIV感染症 【用法用量～日本】通常，成人にはリトナビルとして1回600mg（6カプセルまたは7.5mL）を1日2回食後に経口投与する．ただし，投与初日は1回300mgを1日2回，2日目， 3日目は1回400mgを1日2回，4日目は1回500mgを1日2回，5日目以降は1回600mgを1日2回食後に経口投与する． 【製品情報～日本】 【添付文書～日本】ノービア・ソフトカプセル100mg添付文書|ノービア・リキッド添付文書 インタビューフォーム 【その他】
●[1041]abacavir (Ziagen [GSK])ザイアジェン[GSK]
日本語版註）abacavir sulfate (Ziagen Tabs & Oral Sol [GSK])
【別名】1592U89;GW592 【開発元】GSK [DBR_ID]
【化学名】(-)-[(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopenta-2- enyl]methanol hemisulfate ;CAS188062.50.2
【承認～錠・内服液】FDA申請=24-Jun-1998、FDA承認=17-Dec-1998 【製剤】錠EQ 300MG BASE ；内服液EQ 20MG BASE/ML 【適応】For the treatment of HIV-1 infection in adults and children (ages 3 months and above). This indication is based on analyses of surrogate markers in controlled studies up to 24 weeks in duration. 【用法用量】成人には他の抗HIV薬と併用して、アバカビルとして1日量600mgを1日2回経口投与。 ３ヵ月～１６才小児は8mg/kg(最大300mg)を1日2回経口投与する。 【作用】ヌクレオシド系逆転写酵素阻害薬（NRTI）；アバカビルは細胞内で細胞性酵素によって活性代謝物のカルボビル三リン酸に変換される。カルボビル三リン酸は天然基質dGTPと競合し、ウイルスDNAに取り込まれることによって、HIV-1逆転写酵素（RT）の活性を阻害する。取り込まれたヌクレオシド誘導体には3'-OH基が存在しないため、DNA鎖の伸長に不可欠な5'-3'ホスホジエステル結合の形成が阻害され、ウイルスのDNA複製が停止する。 【特徴】 【製品情報】US-Product :Ziagen 【添付文書】Ziagen Tablets-PI | Ziagen Oral Solution-PI
【EU】Ziagen[GSK]MA=8 July 1999 ； 2004 年12 月現在、世界70 ヵ国以上で承認されている。
【日本】ザイアジェン錠300mg[GSK]承認1999.9.10、薬価収載1999.9.10、発売1999.9.17 【製剤～日本】1錠中にアバカビル硫酸塩351mg（アバカビルとして300mg）を含有する。 【適応～日本】HIV感染症 【用法用量～日本】通常、成人には他の抗HIV薬と併用して、アバカビルとして1日量600mgを1日1回又は2回に分けて経口投与する。 【添付文書～日本】ザイアジェン錠 添付文書情報 - インタビューフォーム - 製品情報(詳細) 【その他】
●[1041]efavirenz [SUSVETA, DMP 266; BMS]ストックリン[万有]
日本語版註）エファビレンズ efavirenz [SUSVETA, Dupont] ストックリン
【別名】DMP 266 【開発元】DuPont Pharm→現BMS [DBR_ID]
【化学名】(-)-(S )- 6-Chloro-4-(cyclopropylethynyl)-1, 4-dihydro-4-(trifluoromethyl)-2H - 3,1-benzoxazin-2-one
【承認～カプセル】FDA申請=11-Jun-1998、FDA承認=17-SEP-1998[DuPont Pharmaceuticals] 【承認～錠】FDA申請=30-Mar-2001、FDA承認=1-Feb-2002[BMS] ;【製剤】カプセル100MG; 200MG; 50MG efavirenz；錠600mg efavirenz 【適応】Treatment of HIV-1 infection 【用法用量】推奨用量は600mg 経口、１日１回である。投与に際しては、プロテアーゼ阻害剤およびまたはヌクレオシド系逆転写酵素阻害剤と併用する。小児は体重40kg 以上の患児に対する本剤の推奨用量は、600mg １日１回である。3 歳以上と体重10～40kgの患児の用量は添付文書参照 【作用】本剤は、ヒト免疫不全ウイルス1型(HIV-1)の選択的非ヌクレオシド系逆転写酵素阻害剤である。本剤は、HIV-1逆転写酵素(RT)のテンプレート (鋳型)、プライマー又はヌクレオシド三リン酸に対する非拮抗的阻害剤であり、混合型非拮抗阻害形式を示し、拮抗的阻害作用をわずかに併せ持つ。本剤は、臨床における血中濃度を十分に上回る濃度においても、HIV-2RT及びヒトDNAポリメラーゼα、β、γ及びδを阻害しない。 【特徴】 【製品情報】http://www.sustiva.com/ 【添付文書】Sustiva-PI
【EU】Stocrin[Merck Sharp & Dohme]MA=28 May 1999 Sustiva[Bristol-Myers Squibb]MA=28 May 1999；2006年現在、世界100の国と地域で承認
【日本】ストックリンカプセル２００[萬有製薬]承認1999.9.10、薬価収載1999.9.10、発売1999.9.14/STOCRIN 【製剤～日本】１カプセル中200mgエファビレンツ 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはエファビレンツとして600mgを1日1回経口投与する。本剤は、食事の有無にかかわらず投与できる。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】ストックリンカプセル200 添付文書 インタビューフォーム 【その他】米国、カナダ、一部の欧州ではBMS社がSustivaの製品名で販売し、それ以外の地域では、Merck & Co., Inc.,によってStocrinの製品名で発売
●[1057]amprenavir (Agenerase: Glaxo Wellcome)プローゼProzei［キッセイ］
日本語版註）amprenavir (Agenerase [GSK]) アムプレナビル（アジェネラーゼ［GSK社］
【別名】KVX-478, VX-478, 141W94 【開発元】Vertex Pharm [DBR_ID]46082
【化学名】4-Amino-N-[2(R)-Hydroxy-4-phenyl-3(S) -{tetrahydrofuran-3 (S)-yloxycarbonamylamino}butyl} -N-isobutylbenzenesulfonamide [CAS Registry Number] 161814-49-9
【承認】FDA申請=15-Oct-1998(カプセル)7-Dec-1998(内服液)、FDA承認=15-Apr-1999、発売=99.6.23[GSK] ;【製剤】カプセル50mg,150mg amprenavir、内服液15mg/mL amprenavir 【適応】for the treatment of HIV-1 infection 【用法用量】通常他の抗HIV 薬と併用し，成人にはアンプレナビルとして1回1200mgを1日2回経口投与する。 リトナビルと併用時、本剤1200mg+R 200mgを１日１回または本剤600mg+R 100mgを１日２回。 体重50Kg以上の１３～１６才は成人と同じ。 体重50Kg未満の１３～１６才児童および4-12才児は20mg/Kgを１日２回または15mg/Kgを１日３回。 【作用】HIV‐1 プロテアーゼの阻害剤。アンプレナビルは，HIV‐1 プロテアーゼの活性部位に結合し，ウイルスのgag及びgag‐pol 前駆体ポリ蛋白質の切断を阻害し，その結果，感染性をもたない未成熟なウイルスにする。 【特徴】 【製品情報】 【添付文書】Agenerase Capsules-PI | Agenerase Oral Solution-PI
【EU】Agenerase[GSK]承認=2000.10.20
【日本】プローゼProzei[キッセイ]99.7.2申請; 承認=1999/9/10、薬価収載=1999/9/10、発売=1999/10/1、プローゼカプセル販売中止～最終出荷2005.9末、経過措置期間 2006年3月末迄、提携：ヴァーテックス・ファーマスーティカルズ・インコーポレイティッド 【製剤～日本】1 カプセル中 アンプレナビル150mg 含有 【適応～日本】HIV-1 感染症 【用法用量～日本】通常，成人にはアンプレナビルとして1回1200mgを1日2回経口投与する。投与に際しては，必ず他の抗HIV 薬と併用すること。なお，肝機能低下の程度により減量を考慮する。 【製品情報～日本】プローゼカプセル 【添付文書～日本】プローゼカプセル添付文書[pdf] - インタビューフォーム 【その他】[US Pat] 5,585,397: HIVプロテアーゼ阻害剤
●Fosamprenavir calcium(Lexiva[GSK])ホスアンプレナビルカルシウム水和物(レクシヴァ錠700)
日本語版註）Fosamprenavir calcium(Lexiva[GSK])ホスアンプレナビルカルシウム水和物(レクシヴァ錠700)
【別名】VX-175;旧称GW433908 【開発元】Vertex Pharm [DBR_ID]
【化学名】(3S)-tetrahydrofuran-3-yl (1S,2R)-3-[[(4-aminophenyl) sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy) propylcarbamate monocalcium salt
【承認～錠】FDA申請=19-Dec-2002、FDA承認=20-Ot-2003[GSK] ; 【承認～内服液】FDA申請=13-Dec-2006、FDA承認=14-Jun-2007[GSK] ; 【製剤】700 mg tablets and 50 mg/mL oral suspension 【適応】indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 【用法用量】(未治療成人)1,400mg１日２回または本剤1400mg+リトナビル100mg/200mgを１日１回または本剤700mg+リトナビル100mgを１日２回 (プロテアーゼ阻害剤経験者)本剤700mg+リトナビル100mgを１日２回 (小児2-18才)体重Kg別投与 【作用】an HIV protease inhibitor; アンプレナビル（APV）のプロドラッグであり、１日の服薬剤数を４錠または２錠（リトナビル２カプセル併用時）に低減した。。 【特徴】本剤はDHHS（Department of Health and Human Services）のHIV感染症治療ガイドライン（2005.4.7改訂版）や、HIV感染症「治療の手引き」＜第８版＞２）にも初回治療に推奨される多剤併用療法の１薬剤として掲載。 【製品情報】http://www.lexiva.com/ 【添付文書】Lexiva -PI 【提携】 【EU】Telzir[GSK]承認12 July 2004 ；2005年7月現在米国、EU加盟国を含む30カ国以上で承認 【日本】レクシヴァ錠700[GSK]承認2004.12.24薬価2005.1.7発売2005.1.7 【製剤～日本】1錠中にホスアンプレナビルカルシウム水和物をホスアンプレナビルとして700mg含有する。 【適応～日本】HIV感染症 【用法用量～日本】通常、成人には以下の用法・用量に従い経口投与する。投与に際しては、必ず他の抗HIV薬と併用すること。
[(1) 抗HIV薬の治療経験がない患者]・ホスアンプレナビルとして1回700mgとリトナビル1回100mgをそれぞれ1日2回併用投与 ・ホスアンプレナビルとして1回1400mgとリトナビル1回200mgをそれぞれ1日1回併用投与 ・ホスアンプレナビルとして1回1400mgを1日2回投与
[(2) HIVプロテアーゼ阻害剤の投与経験がある患者] ・ホスアンプレナビルとして1回700mgとリトナビル1回100mgをそれぞれ1日2回併用投与 【添付文書～日本】レクシヴァ錠700添付文書 | インタビューフォーム 【その他】
●[]Delavirdine mesylate(Rescriptor : Pfizer)レスクリプター[ファイザー、第一三共]
日本語版註）Delavirdine mesylate(Rescriptor [Pfizer])メシル酸デラビルジン(レスクリプター錠[[ファイザー、第一三共]])
【別名】U90152S 【開発元】Agouron社→現在Pfizerの100%子会社 [DBR_ID]
【化学名】1-[3-[(1-methyl-ethyl)amino]-2-pyridinyl]-4-[[5-[(methylsulfonyl)amino]-1H-indol-2-yl]carbonyl]-piperazine,monomethanesulfonate.
【承認】FDA申請=、FDA承認=4-Apr-1997 ;【製剤】１錠中100mg or 200 mg of delavirdine mesylate 【適応】indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. 【用法用量】通常、成人にはデラビルジンメシル酸塩として1回400mgを1日3回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【作用】a synthetic non-nucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1).デラビルジンはHIV-1の非ヌクレオシド系逆転写酵素阻害剤である。デラビルジンは逆転写酵素に直接結合し、RNA依存性及びDNA依存性のDNAポリメラーゼ活性を阻害する。デラビルジンはテンプレートであるプライマー又はデオキシヌクレオシド三リン酸と競合しない。HIV-2逆転写酵素及びヒト細胞DNAポリメラーゼ（α、γ、δ）はデラビルジンによって阻害されない。また、HIV-1グループ0（北米では少ないが、高度の多様性を示す株の一群）もデラビルジンによる阻害を受けないと考えられる。 【特徴】 【製品情報】 【添付文書】http://media.pfizer.com/files/products/uspi_rescriptor.pdf
【EU】
【日本】レスクリプター錠200mg [製造販売元／ファイザー株式会社 販売元／第一三共株式会社]承認=2000.2.25、薬価収載2000.4.3、発売 【製剤～日本】1錠中デラビルジンメシル酸塩 200.00mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはデラビルジンメシル酸塩として1回400mgを1日3回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】レスクリプター錠200mg 添付文書 【その他】
Agouron Pharmaceuticals, Inc.; RESCRIPTOR is a registered trademark of Pharmacia & Upjohn Company.日本語版註）Delavirdine mesylate(Rescriptor [Pfizer])メシル酸デラビルジン(レスクリプター錠[[ファイザー、第一三共]])
【別名】U90152S 【開発元】Agouron社→現在Pfizerの100%子会社 [DBR_ID]
【化学名】1-[3-[(1-methyl-ethyl)amino]-2-pyridinyl]-4-[[5-[(methylsulfonyl)amino]-1H-indol-2-yl]carbonyl]-piperazine,monomethanesulfonate.
【承認】FDA申請=、FDA承認=4-Apr-1997 ;【製剤】１錠中100mg or 200 mg of delavirdine mesylate 【適応】indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. 【用法用量】通常、成人にはデラビルジンメシル酸塩として1回400mgを1日3回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【作用】a synthetic non-nucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1).デラビルジンはHIV-1の非ヌクレオシド系逆転写酵素阻害剤である。デラビルジンは逆転写酵素に直接結合し、RNA依存性及びDNA依存性のDNAポリメラーゼ活性を阻害する。デラビルジンはテンプレートであるプライマー又はデオキシヌクレオシド三リン酸と競合しない。HIV-2逆転写酵素及びヒト細胞DNAポリメラーゼ（α、γ、δ）はデラビルジンによって阻害されない。また、HIV-1グループ0（北米では少ないが、高度の多様性を示す株の一群）もデラビルジンによる阻害を受けないと考えられる。 【特徴】 【製品情報】 【添付文書】http://media.pfizer.com/files/products/uspi_rescriptor.pdf
【EU】
【日本】レスクリプター錠200mg [製造販売元／ファイザー株式会社 販売元／第一三共株式会社]承認=2000.2.25、薬価収載2000.4.3、発売 【製剤～日本】1錠中デラビルジンメシル酸塩 200.00mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはデラビルジンメシル酸塩として1回400mgを1日3回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】レスクリプター錠200mg 添付文書 【その他】
Agouron Pharmaceuticals, Inc.; RESCRIPTOR is a registered trademark of Pharmacia & Upjohn Company. ●[1160]HIV検査薬日本語版註）OraQuick Rapid HIV-1 Antibody Test[OraSure Technologies, Inc.]
【別名】 【開発元】OraSure Technologies, Inc [DBR_ID]x
【化学名】A kit contsains 1)Test device 2)Absorbent packet 3)Developer solution vial など
【承認】FDA申請=、FDA承認=7-Nov-2002、CLIA (Clinical Laboratory Improvements Amendments of 1988) waiver for the test受取=2003.1.31 ;【製剤】方法 Rapid EIA 検体 全血(指先穿刺) 【適応】a rapid, point-of-care test designed to detect antibodies to HIV-1 within 20 minutes 【製品情報】http://www.orasure.com/products/default.asp?sec=2&subx=2&cid=2&prd=134 【添付文書】http://www.orasure.com/uploaded/331.pdf?134&sec=2&subsec=2 【EU】 【日本】未開発 【その他】
日本語版註）Reveal Rapid HIV-1 Antibody Test[MedMira Laboratories, Inc.]
【別名】 【開発元】MedMira Inc. [DBR_ID]x
【化学名】次のものを含むキット。 1)Test cartridge(免疫反応性膜を含む) 2)Disposable pipette 3)Desiccant packet 4)MedMira Colorimetric Detection Agent比色定量検出剤 (a proprietary protein A-colloidal gold conjugate) 5)MedMira HIV-1 Human Test Control 6)MedMira Universal Buffer
【承認】FDA申請=、FDA承認=16-Apr-2003、発売=2003.5.15 ;【製剤】方法 Rapid Immunoassay 検体 血清/血漿 【適応】 【製品情報】http://www.reveal-hiv.com/ 【添付文書】http://www.reveal-hiv.com/pdf/Reveal_Pa.pdf 【EU】 【日本】未開発 【その他】FDA承認を受けた最初で唯一のrapid, point-of-care test designed to detect HIV-1 antibodies。３分で検査終了
[1288]●製品 エトラビリンetravirine(Intelence － Tibotec)インテレンス[ティボテック]
日本語版註）エトラビリンetravirine(Intelence － Tibotec)インテレンス[ティボテック]
【別名】TMC125 【開発元】Tibotec Pharmaceuticals, Ltd [DBR_ID]
【化学名】4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-benzonitrile ;CAS REGISTRY NUMBER:269055-15-4
【承認】FDA申請=17-Jul-2007、FDA承認=18-Jan-2008; (Tibotec Therapeutics, Division of Ortho Biotech Products, L.P.,); 【製剤】１錠中etravirine 100mg 【適応】治療歴があり、HIV-1 に感染している成人において抗レトロウイルス剤との併用。 【用法用量】200mg を1 日2 回食後に経口投与する。
【作用】 【特徴】NNRTI耐性HIV変異株に有効な次世代の非核酸系逆転写酵素阻害剤(NNRTI)
【製品情報】www.intelence-info.com 【添付文書】Intelence-PI
【提携】 【EU】Intelence[Janssen-Cilag]CHMP承認勧告26-JUn-2008；MA=28-Aug-2008
【日本】TMC125/INTELENCE(R)[ヤンセンファーマ]申請準備中(HIV-I感染症) 【その他】
US Pharmacopeial Commission AMA: United States Adopted Names - etravirine.doc BIAM --- BIAM -ABC順|BIAM -会社順 NLM: MeSH HOme ---MeSH Online search
【日本語版コメント1288】
抗ＨＩＶ薬の世界市場規模は2007年約１．２５兆円。 グラクソ・スミスクライン社とブリストル・マイヤーズスクイブ社がHIV市場の50％以上を占め、ファイザー社、ジョンソン・エンド・ジョンソン社、メルク社、ギリアド社らは開発後期にある有望な新薬候補薬剤を持つ。
NRTIが29.4%を占め、製剤としてはコンビビルCombivir[GSK]が依然トップ999億円、プロテアーゼ阻害剤PI(シェア29.1%)ではカレトラが依然トップ1,461億円だが、新薬のレイアタッツが急速な伸びで既に二番手1,240億円で２強を形成。 NNRTI(シェア12.3%)では、Sustiva[BMS](日本ではストックリン[万有])1,054億円。 配合剤(シェア22.4%)はツルバダ1,753億円、Atripla[Gilead] 996億円。 因みに日本市場規模は2007年年間80億円と小さい。 新薬開発の現在の中心はCCR5拮抗薬で数多く開発途上にあるが、昨2007年に二つの新規系統の新薬がFDA承認を受けた。 初のインテグラーゼ阻害薬ラルテグラビル(Isentress)と初のCCR5拮抗薬マラビロック(Selzentry)であるが、2008年1-6月売上はIsentress $124mと順調だが、Selzentryは低迷。
ラルテグラビル(アイセントレス錠400mg[万有])は日本でも2008.7.7発売。 他にプロテアーゼ阻害剤「プリジスタ(R)錠300mg」(ダルナビル)[ヤンセンファーマ]は2007.12.10発売。 「ストックリン(R)錠600mg」」（一般名：エファビレンツ）[万有製薬]は新剤型として2008.6.20発売。→詳細は参考資料●MLリソース：エイズ治療剤●MLリソース:エイズ治療剤[個別製品]に纏めた。＜日本語版コメント要約＞
・新しいNNRTIのエトラビリンが、前治療歴のある成人HIV-1感染症患者に対する併用薬として、優先審査によりFDAに承認された。
・臨床試験では、他のNNRTIおよびプロテアーゼ阻害薬に抵抗性のHIV-1感染症患者において、ウイルス量をプラセボに比し有意に低下させた。
・本剤には多くの薬物-薬物間相互作用があるため、併用には注意が必要である。
●承認データ：FDA ●FDA Newsroom - FDA Press Releases FDA Approves New HIV Drug After Priority Review[FDA News 2008.1.18] ●Index to Drug-Specific Information ●2004.5.1 以降 Drugs@FDA
★Drug Name(s) =INTELENCE (ETRAVIRINE) FDA Application No. =(NDA) 022187 Active Ingredient(s)=ETRAVIRINE Company =TIBOTEC Inc Dosage Form/Route =TABLET; ORAL Strength =100MG - Approval Date=01/18/2008[000][Approval]:Label[添付文書]|Letter[承認書]|Review|Summary Review 申請17-Jul-2007 適応for the use of IntelenceTM (etravirine) 100mg tablets in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a nonnucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents. Original Approval or Tentative Approval Date January 18, 2008 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug
●Electronic Orange Book Application Number: 022187 Active Ingredient : ETRAVIRINE Proprietary Name : INTELENCE [TIBOTEC] TABLET; ORAL 100MG Approval Date : Jan 18, 2008 Exclusivity Data : NCE Jan 18, 2013 Patent Data : 6878717 Nov 5, 2019 U-256 7037917 Nov 5, 2019 Y Y U-256
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Intelence INN: etravirine 04/09/08 1. Summary for the public 2. All Authorised Presentations 3. Public assessment report Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet Name of the Medicinal Product Intelence Marketing Authorisation Holder Janssen-Cilag International NV Turnhoutseweg 30,BE-2340 Beerse,Belgium Active Substance etravirine International Nonproprietary Name or Common Name etravirine Pharmaco-therapeutic Group Non-nucleoside reverse transcriptase inhibitors ATC Code (J05AGXX) [Therapeutic Indication ] INTELENCE, in combination with a boosted protease inhibitor and other antiretroviral medicinal products, is indicated for the treatment of human immunodeficiency virus type 1 (HIV?1) infection in antiretroviral treatment?experienced adult patients (see sections 4.4, 4.5 and 5.1).
This indication is based on week 24 analyses from 2 randomised, double?blind, placebo?controlled Phase III trials in highly pre?treated patients with viral strains harbouring mutations of resistance to non?nucleoside reverse transcriptase inhibitors and protease inhibitors, where INTELENCE was investigated in combination with an optimised background regimen (OBR) which included darunavir/ritonavir (see section 5.1).
Date of issue of Marketing Authorisation valid throughout the European Union 28 August 2008 Orphan medicinal product designation date Not applicable ●CHMP Press Releases Meeting highlights from the Committee for Medicinal Products for Human Use, 23-26 June 2008[2008.6.26] - CHMPの承認勧告 ●Summaries of Opinion - List of Products - CHMP Opinions諮問委員会審議品目一覧 ---Substance/INN Trade Name Pharmaceuticalform Strength OpinionAdoption Date [CHMP]SUMMARY OF POSITIVE OPINION for INTELENCE[2008.6.26] 26 June 2008に承認勧告 Intelence (etravirine), from Janssen-Cilag International NV, for use in combination with a boosted protease inhibitor and other antiretroviral medicines for the treatment of human immunodeficiency virus (HIV-1) infection in antiretroviral treatment-experienced adult patients. EMEA review began on 15 August 2007 with an active review time of 178 days.
●Johnson & Johnson ■Products ●Products - Diseases & Conditions www.intelence-info.com ■J&J Investors Relations ●J&J - Annual reports Annual Report 2007 [html] [pdf](82p) ●J&J Financial Reports - Pharmaceutical pipeline ●Financial nformation - 四半期報 Sales of Key Products/Franchises 4Q 2007[pdf,2008.1.24] - 個別製品売上高 ●SEC Filings ★10K and 10Q 10-K Annual Report[2008.2.26] - [pdf,128p] During 2007, the Company launched INVEGA(TM)(paliperidone) Extended-Release Tablets, in both the U.S. and Europe.
Additionally, in 2007 the Company launched the antibacterial, DORIBAX(TM)(doripenem for injection) in the U.S. and the antiretroviral, PREZISTA(TM)(darunavir), in Europe. The Company submitted five new molecular entities for approval: paliperidone palmitate for schizophrenia in the U.S., ustekinumab, or CNTO 1275, for psoriasis in both the U.S. and Europe, dapoxetine for premature ejaculation in several countries in Europe, antibacterial ceftobiprole in the U.S. and Europe and anti-HIV medication, TMC 125 in the U.S. and Europe. TMC 125 was approved by the U.S. FDA in January 2008 and will be marketed as INTELENCE(TM)(etravirine).●J&J Investors Relations- News release -http://www.investor.jnj.com/releases.cfm ■News -http://www.jnj.com/news/index.htm - Press Releases & Statements[10件毎] -http://www.jnj.com/news/jnj_news/index.htm - News Archives -http://www.jnj.com/news/archive/index.htm INTELENCETM (etravirine) RECEIVES MARKETING AUTHORISATION IN THE EUROPEAN UNION FOR HIV COMBINATION THERAPY[2008.8.29] - The EMEA decision follows similar approvals earlier in the year in Switzerla nd, Russia, Argentina, Canada, South Korea and the U.S. Commercial launches will vary from country to country, based on local price and reimbursement discussions with national authorities. FDA Approves INTELENCE(TM) (etravirine) for HIV Combination Therapy[2008.1.18]
●ヤンセン ファーマ株式会社 ●医療従事者 - 医薬品情報 - CNSネット～精神神経分野★要ID 医療関係者限定 - Pain Relief★要ID 医療関係者限定 ●病気に関する情報 メンタル・ナビwww.mental-navi.net ～一般用・医療関係用(要ID) 水虫ちゃんねる フケ・脂漏性皮膚炎 こころのこと あしのこと フケのこと ●プレスリリース
●Tibotec Pharmaceuticals, Ltd -http://www.tibotec.com/ Division of Ortho Biotech Products, LP 1994 設立。 HIV/AIDSやunmet medical needの感染症分野の創薬企業として設立。アイルランド Tibotec Inc.として。 1995 VircoがSpin-off 2001 TibotecとVircoが合併し、Tibotec-Virco(本社ベルギー)に。 2002.4 両社ともJohnson & Johnsonに買収。 ●開発中の新薬 * TMC114, a protease inhibitor (PI), PREZISTA[TM] (darunavir)。FDA承認されTibotec Therapeutics, a division of Ortho Biotech Products, L.P. により販売。 EUではTibotec, a division of Janssen-Cilagが承認後販売する予定。 * TMC125/Intelence(etravirine), a non-nucleoside reverse transcriptase inhibitor (NNRTI), * TMC278, a non-nucleoside reverse transcriptase inhibitor (NNRTI). * TMC120, Tibotec's first NNRTI in clinical development。as a vaginal microbicide 2004.3 International Partnership for Microbicides にライセンス。 * TMC207, a novel anti-TB compound was transferred from Johnson & Johnson PRD to Tibotec for clinical development. * VX-950 C型肝炎 P2 Vertexからライセンス。. an investigational oral inhibitor of hepatitis C virus protease in Phase II development ●News INTELENCE(TM) (etravirine) Receives Marketing Authorisation In the European Union For HIV Combination Therapy[2008.8.29]
INTELENCE (etravirine) Receives Positive Opinion from European Committee For Human Medicinal Products (CHMP) for Treatment of HIV[2008.6.26]
48-Week data for ETRAVIRINE (TMC125) Presented at Major U.S. Medical Meeting[2008.2.7]
FDA Approves INTELENCE(TM) (etravirine) for HIV Combination Therapy[2008.1.18]
FDA Accepts New Drug Application for Priority Review of Investigational HIV treatment TMC125[2007.9.20]
Tibotec Submits Marketing Authorisation Application for Investigational HIV Treatment TMC125 in Europ[2007.7.26]
New Drug Application for Investigational HIV Treatment TMC125[2007.7.18]
TMC125 Demonstrates Significant Efficacy in Treatment-Experienced Patients with NNRTI Resistance in Phase III trials[2007.7.6]16 August 2006★48 Week Data On Investigational Antiretroviral TMC125 From Tibotec★TMC125 a next-generation NNRTI
14 August 2006★Analysis provides additional data for PREZISTA (TM) as part of HIV Combination Therapy★Presented Tuesday, 14 August, at the 16th International AIDS Conference (AIDS 2006) in Toronto, Canada
30 June 2006★Tibotec reinforces its commitment in the field of hepatitis★Separate announcements today from both Vertex and Medivir further reinforce Tibotec's commitment to finding innovative treatments for global viral diseases
28 June 2006★PREZISTA (TM) Receives FDA Approval in USA as part of HIV Combination Therapy★PREZISTA is the first compound in the company's research pipeline to receive regulatory approval.
23 June 2006★FDA Approves New HIV Treatment for Patients Who Do Not Respond to Existing drugs★The Food and Drug Administration (FDA) today approved PREZISTA (darunavir), a new drug for adults whose infection with HIV has not responded to treatment with other antiretroviral drugs.
06 March 2006★Tibotec Announces FDA Acceptance for Review of NDA for TMC114★The Prescription Drug User Fee Act (PDUFA) user fee goal date for the NDA will be June 23, 2006
16 February 2006★New Data on Tibotec HIV/AIDS Investigational Product Portfolio★Following the 13th Conference on Retroviruses and Opportunistic Infections (CROI)
11 January 2006★Tibotec Submits Marketing Authorisation Application for Investigational HIV Protease Inhibitor TMC114 in Europe★Follows Recent Submission of New Drug Application to the US FDA★本日EMEA申請を行ったことを発表。 POWER 2研究によると、TMC114 600mg/ ritonavir 100mgの比較試験を行い、TMC114は患者の64%でウイルス濃度が低下(1 log10 以上)しritonavirは14%、一方もっとも一般的な副作用は頭痛・吐き気で両剤とも17%に発生。 一つ以上の副作用発生率はTMC114が15%、Ritonavirが8%。
27 December 2005★New Drug Application for Investigational HIV Protease Inhibitor TMC114 Submitted to U.S. Food & Drug Administration★HIV/AIDS compound marks first regulatory submission by Tibotec Pharmaceuticals Ltd.
19 December 2005★Tibotec Presents Phase 2b Data on 2 Investigational HIV Compounds at ICAAC★TMC114 and TMC125 demonstrate activity against drug resistant HIV
●Tibotec Therapeutics - http://www.tibotectherapeutics.com/ Division of Ortho Biotech Products, LP 2003.3 設立。 本社Bridgewater, N.J. ●Our Products PREZISTA(TM)(darunavir) Tablets Dear Health Care Professional Letter (Issued: March 2008) See Full U.S. Prescribing Information Visit www.PREZISTA.com INTELENCE(TM)(etravirine) Tablets See Full U.S. Prescribing Information Visit www.INTELENCE-info.com ●News Center
● [独立行政法人 国立病院機構 大阪医療センター] 医学倫理委員会 - [審議内容]2008年6月25日 「新規抗HIV 薬Etravirine を用いた先進的HIV/AIDS 医療の実施」 申請者 免疫感染症科白阪琢磨部長より以下のように説明がなされた。 新規抗HIV 薬Etravirine は2008 年1 月18 日にFDA にて認可された非ヌクレオチド系逆転写酵素 阻害剤(NNRTI)である。本邦で使用可能なNNRTI であるefavirenz やnevirapine とは異なる薬剤耐 性変異を示すことから、過去にNNRTI が投与された症例においても高い治療効果が期待される。 現在、日本では未承認の段階であるため、本製剤の使用経験は本邦では未だ少なく、有効性およ び安全性の評価等の課題が残されている。当計画ではEtravirine の有効性および安全性を評価しつ つ、新規の抗HIV 療法を実施する。
[1277]●製品 Raltegravir (Isentress － Merck) & Maraviroc (Selzentry － Pfizer)
日本語版註）Raltegravir potassium(Isentress － Merck)ラルテグラビル(アイセントレス錠4)
【別名】MK-0518; RAL, L-000900612-003E 【開発元】Merck & Co.
【化学名】4-Pyrimidinecarboxamide, N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-, monopotassium salt; CAS_REG 871038-72-1
【承認】FDA申請=Apr 13, 2007、FDA承認=Oct 12, 2007 ; 【製剤】1錠中ラルテグラビルを400mg含有 【適応】HIV-1 の複製が認められ、多剤耐性のHIV-1 を保有している治療経験のある患者にアイセ ントレスは他の抗HIV 薬と併用する。 【用法用量】400mgを１日２回
【作用】初のインテグラーゼ阻害薬a human immunodeficiency virus integrase strand transfer inhibitor (HIV-1 INSTI) インテグラーゼは、HIV-1の複製に必要な3つの酵素のうちの1つであり、HIV-1のDNAを宿主細胞の遺伝子に組み込む過程を触媒する。非臨床試験のデータから、ラルテグラビルが種々のHIV-1変異株（既存の抗HIV薬に耐性を示すHIV-1変異株を含む）に対して広い活性を有することが示されている。 【特徴】既存の抗HIV薬に耐性があるウイルスを検出不能レベルにまで効果的に低下させ、エファビレンツより有効ウイルス量を70％減少 【製品情報】www.isentress.com 【添付文書】ISENTRESS(TM) (raltegravir) -PI
【EU】EMEAではIsentress INN: raltegravir[Merck Sharp & Dohme]承認20 Dec 2007; 2007年にメキシコで承認されて以来、2008年現在30カ国以上でMerck & Co.及びその関連会社からISENTRESSの名称で承認されている。
【日本】「アイセントレス錠400mg」MK-0518[万有製薬]第二部会審議2008.4.30、承認日2008.6.24、薬価収載2008.6.27、発売2008.7.7 【製剤～日本】1錠中にラルテグラビルとして400mgを含有 【適応～日本】HIV感染症 【用法用量～日本】通常、成人にはラルテグラビルとして400 mg を1 日2 回経口投与する。本剤は、食事の有無にかかわらず投与できる。なお、投与に際しては、必ず他の抗HIV薬と併用すること。 【製品情報～日本】アイセントレス(R)錠400mg 【添付文書～日本】アイセントレス(R)錠400mg - インタビューフォーム 【その他】
日本語版註）Maraviroc (Selzentry － Pfizer)マラビロック
【別名】UK-427857 【開発元】Pfizer
【化学名】4,4-difluoro-N-{(1S)-3-[exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclohexanecarboxamide
【承認】FDA申請=Dec 19, 2006、FDA承認=Aug 6, 2007 ; 【製剤】film-coated tablets for oral administration containing either 150 or 300 mg of maraviroc 【適応】ウイルス複製が証明され、かつ複数の抗レトロウイルス薬耐性のHIV-1菌株を有する、CCR5指向性のHIV-1が検出された成人感染者 indicated for combination antiretroviral treatment of adults infected with only CCR5-tropic HIV-1detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents 【用法用量】1)PIs(except tipranavir/ritonavir), delavirdineを含むCYP3A阻害薬服用時、１日150mgを２回 2)NRTIs, tipranavir/ritonavir, nevirapineおよび非強力なCYP3A阻害薬・誘発薬の服用時、１日300mgを２回 3)efavirenzを含むCYP3A誘発剤(強力CYP3A阻害剤非服用時)服用時、１日600mgを２回
【作用】CCR5拮抗薬として知られ、同クラスにおける初めての製品。CCR5拮抗薬は、ウイルスがT細胞に入り込む際の主要経路であるCCR5コレセプターを遮断。他クラスの経口HIV治療薬はいずれもT細胞内でウイルスと戦うが、Selzentryは細胞表面でR5ウイルスを阻止して侵入を防ぐ。 【特徴】10余年ぶりに登場する新しいクラスの経口HIV治療薬で、特定のタイプのHIVに感染した他剤治療歴のある患者の白血球へのウイルス侵入を遮断し、ウイルス量を有意に減少させるとともに、T細胞の数を増やす。 【製品情報】www.selzentry.com 【添付文書】SELZENTRY-PI
【提携】 【EU】Celsentri INN: maraviroc [Pfizer]承認18 Sep 2007 【日本】UK-427,857[ファイザー]申請準備中(HIV-1 感染症（CCR5陽性）) 【その他】
US Pharmacopeial Commission AMA: United States Adopted Names - raltegravir potassium - raltegravir - BIAM --- BIAM -ABC順|BIAM -会社順 NLM: MeSH HOme ---MeSH Online search
【日本語版コメント】
日本に関しては、エイズ動向委員会報告によると、(2007.12.末現在)HIV感染者9,392人、エイズ患者4,450人、凝固因子製剤による感染者1,438人 合計15,280人 死亡251人。 新規患者は2007年間でHIV 1048,エイズ400人。
抗HIV薬は最もドラッグラグの少ない領域で、欧米で承認された新薬の大半が日本でも優先的に承認されてきた。
薬物療法の標準は作用機序の異なる抗HIV-1薬を併用する多剤併用療法(HAART;Highly Active Anti-retroviral Therapy)であり、実態調査によると、服薬率95%以上でのHAART治療成功率は78.3%と比較的高いが、一方副作用頻度の合計は34～59％と高率であり、軽微な副作用も含めると「どの組み合わせを選んでも何らかの副作用が生じる」のが問題。 更に多剤耐性変異株の出現と慢性毒性の蓄積が課題として残る。 そのため優れた新薬の出現は歓迎される
新薬開発については1995年以降はプロテアーゼ阻害剤を中心に次々と開発されてきたが、昨2007年に二つの新規系統の新薬がFDA承認を受けた。 初のインテグラーゼ阻害薬ラルテグラビルと初のCCR5拮抗薬マラビロックである。→詳細は参考資料●リソース：エイズ治療剤●MLリソース:エイズ治療剤[個別製品]に纏めた。<日本語版コメント要約＞
・2種類の新規HIV治療薬が承認された。
・ インテグラーゼ阻害薬ラルテグラビルは、治療抵抗性のHIV-1感染患者において他の抗レトロウイルス薬との併用により有効性を示した。
・CCR5拮抗薬のマラビロックも他の抗レトロウイルス薬無効の患者に有効だが、その使用はCCR5指向性HIV-1に感染した成人に限定される。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =ISENTRESS (RALTEGRAVIR POTASSIUM) FDA Application No. =(NDA) 022145 Active Ingredient(s)=Raltegravir potassium Company =MERCK AND CO INC Dosage Form/Route =TABLET; ORAL Strength =EQ 400MG BASE Original Approval or Tentative Approval Date October 12, 2007 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=10/12/2007[000][Approval]:Label[添付文書]|Letter[承認書]|Review|Summary Review Drug Name(s) =SELZENTRY (MARAVIROC) FDA Application No. =(NDA) 022128 Active Ingredient(s)=Maraviroc Company =PFIZER Dosage Form/Route =TABLET; ORAL Strength =150MG, 300MG Original Approval or Tentative Approval Date August 6, 2007 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=08/06/2007[000][Approval] :Label[添付文書]|Letter[承認書]|
●Electronic Orange Book Application Number: 022145 Active Ingredient : Raltegravir potassium Proprietary Name : ISENTRESS [MERCK AND CO INC] TABLET; ORAL EQ 400MG BASE Approval Date : Oct 12, 2007 Exclusivity Data : NCE OCT 12,2012 Patent Data : 7169780 OCT 09,2023 Y Y 7217713 OCT 21,2022 U-257 Application Number: 022128 Active Ingredient : Maraviroc Proprietary Name : SELZENTRY [PFIZER] TABLET; ORAL 150MG,300MG Approval Date : Aug 6, 2007 Exclusivity Data : NCE AUG 06,2012 Patent Data : 6586430 DEC 01,2019 Y Y U-824 6667314 MAY 25,2021 Y Y U-824
●FDA Advisory Committees 参考●ML資料：FDA諮問委員会～議題 FDA Advisory Committees FDAAdvisorycommittee.com CDER■Antiviral Drugs - http://www.fda.gov/ohrms/dockets/ac/cder07.htm#AntiviralDrugs Antiviral Drugs 2006 - 2005 | 2004 | 2003 FDAAdvisorycommittee.com: Antiviral Drugs
ML 開催日 議題 備考 1277 2007.9.5 抗HIV薬raltegravir potassium(Isentress[Merck])
※資料Briefing Information |raltegravir potassium(Isentress[Merck]) 1277 2007.4.24 抗HIV薬Maraviroc (Selzentry － Pfizer)
※資料Briefing Information | 【審議結果/Minutes】 1)承認可否12-0 2)CCR5 co-receptor拮抗剤の安全性問題(lymphomas and infection, hepatotoxicity, and tropism switching)=議事録に論議収録したが、要約すると起立性低血圧とQT延長増強の問題により用量制限が必要とされ添付文書明記、市販後調査でデータ収集すべきこと。 3)申請用量の可否12-0 4)Monogram Trofile assayを被験者の選定や被験者の宿主指向性切り換え(tropism switching)モニターに用いる。この臨床使用の妥当性。～一般論としては決定不可、しかしMaravirocによる治療への必要性には同意できない。 5)(略)Maraviroc(Selzentry[Pfizer])
●他のFDA ●FDA Approves Novel Antiretroviral Drug[FDA News 2007.8.6] - maraviroc ●New HIV Drug for Adults[Consumer Update 2007.8.6] ●FDA HIV/AIDS E-mail List - ●Drugs Used in the Treatment of HIV Infection
Entry Inhibitors - CCR5 co-receptor antagonist
Brand Name Generic Names Manufacturer Name Approval Date Time to Approval Selzentry maraviroc Pfizer 06-August-07 8 months HIV integrase strand transfer inhibitors
Brand Name Generic Names Manufacturer Name Approval Date Time to Approval Isentress raltegravir Merck & Co., Inc. 12--Oct-07 6 months
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Isentress INN: raltegravir /14/01/08 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product ] Isentress [Marketing Authorisation Holder ] Merck Sharp & Dohme Ltd. Hertford Road ,Hoddesdon, Hertfordshire EN11 9BU,United Kingdom [Active Substance ] raltegravir (as potassium) [International Nonproprietary Name or Common Name ] raltegravir [Pharmaco-therapeutic Group ] Antiviral [ATC Code ] J05AX08 [Therapeutic Indication ] ISENTRESS is indicated in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in treatment -experienced adult patients with evidence of HIV-1 replication despite ongoing anti-retroviral therapy. This indication is based on safety and efficacy data from two double-blind, placebo-controlled trials of 24 weeks duration in treatment-experienced patients (see SPC section 5.1). [Date of issue of Marketing Authorisation valid throughout the European Union ] 20 December 2007 [Orphan medicinal product designation date ] Not applicable ★Celsentri INN: maraviroc /15/10/07 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product ] Celsentri [Marketing Authorisation Holder ] Pfizer Limited Ramsgate Road ,Sandwich ,Kent CT13 9NJ,United Kingdom [Active Substance ] maraviroc [International Nonproprietary Name or Common Name ] maraviroc [Pharmaco-therapeutic Group ] Other antivirals [ATC Code ] J05AX09 [Therapeutic Indication ] CELSENTRI, in combination with other antiretroviral medicinal products, is indicated for treatment-experienced adult patients infected with only CCR5 -tropic HIV-1 detectable (see section 4.2). This indication is based on safety and efficacy data from two double-blind, placebo-controlled trials in treatment-experienced patients (see section 5.1). [Date of issue of Marketing Authorisation valid throughout the European Union ] 18 September 2007 [Orphan medicinal product designation date ] Not applicable ●CHMP Press Releases ●Summaries of Opinion - List of Products - CHMP Opinions諮問委員会審議品目一覧 ---Substance/INN Trade Name Pharmaceuticalform Strength OpinionAdoption Date
●Pfizer ●Products～全製品の添付文書 ●Research & Development～The Pfizer Pipeline ■Investors ●SEC Filings 10-K Annual report[2008.2.29; pdf,141p] - [xls] - [doc] 10-K Annual report[2007.3.1; pdf,188p] -[xls] -[doc] ●Financial Report Annual Review 2007[pdf] Financial Report 2007[pdf] Annual Review 2006 - [pdf] Financial Report 2006 - [pdf] ●News Release Pfizer Achieves Key 2006 Financial Targets[2007.1.23] Feb 7, 2008★Pfizer Presents New Data from HIV/AIDS Portfolio at Conference on Retroviruses and Opportunistic Infections
Dec 22, 2007★Pfizer Statement on Results of Comparative Analysis of Tropism Assays
09/24/2007★Pfizer's Celsentri(R) Approved in the European Union, Providing a Novel Treatment Option for Treatment-Experienced HIV Patients★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
09/18/2007★Long-Term Data Reinforce Safety and Efficacy Profile of Pfizer's New HIV Drug Selzentry(TM) (Maraviroc)★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
08/06/2007★Pfizer's SelzentryTM (Maraviroc) Tablets, Novel Treatment for HIV, Approved by FDA★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
07/25/2007★Maraviroc Reduces HIV Viral Load in Treatment-Naive Patients, 48 Week Data Show★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
07/19/2007★Pfizer Receives Positive Opinion from CHMP for Celsentri(R) (maraviroc) for Treatment-Experienced Patients Infected with CCR5-Tropic HIV-1★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
06/20/2007★Pfizer Receives Approvable Letter From FDA For Maraviroc★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
04/30/2007★Pfizer Foundation's ConnectHIV Initiative Provides $7.5 Million in Grants to Community-Based AIDS Service Organizations Across 10 States
04/24/2007★FDA Advisory Committee Recommends Accelerated Approval of Pfizer's Maraviroc for Treatment-Experienced Patients Infected with CCR5-tropic HIV-1★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
03/01/2007★Pfizer's Maraviroc, Novel Medicine For HIV, Significantly Reduces Viral Load, in Combination Therapy Across Range of Treatment-Experienced Patients★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
02/13/2007★Pfizer's Maraviroc to Receive Accelerated Regulatory Reviews in the U.S. and Europe★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
12/01/2006★Pfizer Announces Plans to Establish Expanded Access Program for Maraviroc, Investigational HIV CCR5 Antagonist★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
05/08/2006★Pfizer and Monogram to Make HIV Co-Receptor Tropism Assay Available Globally★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
10/14/2005★New HIV/AIDS Care Center--Big Boost for the AIDS Support Organization (TASO) and Uganda Infrastructure
07/13/2004★Patent Protection Crucial for Next Generation of HIV/AIDS Medicines★抗HIV薬Maraviroc(Selzentry(TM)/Celsentri(R))
★Selzentry/Celsentri (maraviroc) FDA承認Aug 2007
[2007]
Selzentry/Celsentri (maraviroc) is the first in a new class of oral HIV medicines in more than a decade known as CCR5 antagonists. CCR5 antagonists work by blocking the CCR5 co-receptor, the virus' predominant entry route into T-cells. Selzentry/Celsentri stops the R5 virus on the outside surface of the cells before it enters, rather than fighting the virus inside, as do all other classes of oral HIV medicines. Selzentry/Celsentri was approved in the U.S. in August 2007 and in Europe in September 2007, and is indicated for combination anti-retroviral treatment of treatment-experienced adults infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and have HIV-1 strains resistant to multiple anti-retroviral agents. A diagnostic test confirms whether a patient is infected with CCR5-tropic HIV-1, which is also known as "R5-virus."
●ファイザー株式会社 - 2003.8.1 ファルマシア社と経営統合、ファィザー製薬→ファイザー（株）に ●プレスリリース ファイザー社2007年度第4四半期および2007年度通期の決算報告[2008.2.4] ファイザー株式会社 2006年度の業績を発表[2007.2.28] ファイザー社2006年度決算報告[2007.1.31] ★ファイザー社のHIV治療薬SELZENTRY(TM)をFDAが承認[2007.8.9] ニューヨーク、2007年8月6日 - ファイザー社は本日、米食品医薬品局（FDA）がSelzentryTM（一般名：マラビロック）錠剤を承認したと発表しました。Selzentryは10余年ぶりに登場する新しいクラスの経口HIV治療薬で、特定のタイプのHIVに感染した他剤治療歴のある患者さんの白血球へのウイルス侵入を遮断し、ウイルス量を有意に減少させるとともに、T細胞の数を増やします。
Selzentryは、CCR5拮抗薬として知られ、同クラスにおける初めての製品です。CCR5拮抗薬は、ウイルスがT細胞に入り込む際の主要経路であるCCR5コレセプターを遮断します。他のクラスの経口HIV治療薬は、いずれもT細胞内でウイルスと戦いますが、Selzentryは、細胞の表面でR5ウイルスを阻止して侵入を防ぎます。
Selzentryは9月中旬までに米国で発売となる予定です。また、ファイザー社はSelzentryの承認申請を世界各国で提出しており、最近、欧州連合（EU）の医薬品委員会（CHMP-Committee for Medical Products for Human Use）から肯定的意見を受けました。ファイザー社では、Selzentryを米国外では、Celsentriという製品名で発売する予定です。
●医療従事者
●Merck & Co. ● ---Products - The product information[全製品] ● ---Disease ●Investor Information ★SEC Filings 10-K 2007 Annual Report[2008.2.28] - [pdf] - 10-K 2006 Annual Report[2007.2.28] - [pdf] [pdf]はコピー不可のため[html]がうまくいかない時→こちら ★Financial News - Newsroom [万有製薬ニュースリリース] - 2007年度通年および第4四半期業績に関するお知らせ[2008.2.5] - 2006年度通年および第4四半期業績に関するお知らせ[2007.2.2] - Merck Announces 2007 Financial Results Reflecting Revenue Growth from Key Products[2008.1.30] - Merck Announces 2006 Financial Results that Demonstrate Solid Revenue Growth[2007.1.30] - Merck Announces Strong Full-Year and Fourth-Quarter 2005 Earnings; Reserves an Additional $295 Million for VIOXX Legal Defense Costs[2006.1.31] ★Annual and other Financial Reports - Annual Review 2006 - [pdf] - [2006 10-K] ★開発品目 ---- なし？(AR=x) ---Research& development ★ニュースhttp://www.merck.com/newsroom/ Merck's ISENTRESS(R) (raltegravir) Tablets in Combination with other Anti-HIV Medicines Maintained Reductions
in HIV-1 Viral Load and Increased CD4 Cell Counts Through 48 Weeks of Therapy in Treatment-
Experienced Adults[2008.2.6] FDA Approves ISENTRESS(TM) (raltegravir) Tablets, First-in-Class Oral HIV-1 Integrase Inhibitor[2007.12.2] ISENTRESS(TM) (raltegravir), in Combination with Optimized Background Therapy (OBT),
Provided Sustained Viral Suppression in Highly Treatment-Experienced Patients Infected with HIV,
through 48 Weeks[2007.9.18] FDA Advisory Committee Unanimously Recommends Accelerated Approval of
ISENTRESS(TM) (raltegravir), Merck's Investigational Oral Integrase Inhibitor, for Treatment of HIV[2007.9.5] ISENTRESS(TM) (raltegravir), an Investigational Oral HIV Integrase
Inhibitor, in Combination Therapy Demonstrated HIV RNA Reduction Comparable to Efavirenz in Treatment
-Naive HIV-Positive Patients[2007.7.24] ★ISENTRESS(TM) (raltegravir) 抗HIV薬
[2007]
On October 12, 2007, the FDA granted Isentress accelerated approval for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Isentress is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors. Isentress works by inhibiting the insertion of HIV DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. The FDA’s decision was based on a 24-week analysis of clinical trials in which Isentress, in combination with optimized background therapy in treatment-experienced patients, provided significant reductions in HIV RNA viral load and increases in CD4 cell counts. In February 2008, the Company announced 48 week data that demonstrated Isentress, in combination with other anti-HIV medicines, maintained significant HIV-1 viral load suppression and increased CD4 cell counts through 48 weeks of therapy compared to placebo in combination with anti-HIV medicines, in two Phase III studies of treatment-experienced patients failing antiretroviral therapies. Patients in the studies had HIV resistant to at least one drug in each of three classes of oral antiretroviral medicines. By the end of 2007, the medicine was approved for use in the EU, Canada and Mexico. Merck is also conducting Phase III clinical trials of Isentress in the treatment-naive (previously untreated) HIV population. Potent antiretroviral activity has been demonstrated with no significant changes in serum lipids at week 48 and Isentress was generally well tolerated in patients. The Company anticipates making a supplemental filing with the FDA for the treatment-naive indication in 2008.
●万有製薬 - http://www.banyu.co.jp/ ●万有について ★Merck & Coパイプライン ●医療用医薬品のページ メルク・マニュアル ●ニュースルーム 「米国で新たな作用機序を持つ経口HIV-1インテグラーゼ阻害剤ラルテグラビルが承認」に関するお知らせ[2007.10.18] Merck & Co., Inc.は、米国食品医薬品局（FDA）が、すでに治療経験のある患者で、複数の抗HIV薬に耐性があり、かつウイルスの増加が認められるHIV-1感染症の治療に対し、他の抗HIV薬との併用でラルテグラビルを使用できるように迅速承認したことを発表しました[1]。
この承認は、ラルテグラビルに関する2つの臨床試験における24週間までの血漿HIV RNA量の分析に基づいています。これらの試験は、3つのクラスの抗HIV薬［ヌクレオシド系逆転写酵素阻害薬（NRTIs）、非ヌクレオシド系逆転写酵素阻害薬（NNRTIs）、プロテアーゼ阻害薬（PIs）］による治療経験があるにもかかわらず、臨床的に進行した成人を対象に実施されました。ラルテグラビルとその他の抗HIV薬との併用は、治療反応性をより高める可能性があります。治療経験のない成人患者や小児患者に対するラルテグラビルの安全性および有効性は確立されていません。また、HIV-1感染の臨床的進展に対するラルテグラビルの効果を証明する治験結果はありません。FDAがラルテグラビルに対する従来のHIV-1感染症に対する適応の承認を検討するためには、より長期にわたるデータが必要になります。
ラルテグラビルは、インテグラーゼ阻害薬と呼ばれる抗HIV薬の新しいクラスで最初に承認された薬剤です[1][2]。ラルテグラビルは、HIV DNAがヒトDNAに入り込む際に作用するインテグラーゼを阻害します[1]。このウイルス増殖に必要なインテグラーゼを阻害することで、ウイルスの複製能と新たな細胞への感染能を抑制します[3]。現在、HIVの複製過程に重要なほかの2種類の酵素‐プロテアーゼと逆転写酵素‐を阻害する薬剤は使われていますが、ラルテグラビルは残るひとつであるインテグラーゼを阻害する、唯一承認された薬剤です[4][2]。
Merck & Co., Inc., 2007年度通年および第4四半期業績に関するお知らせ[2008.2.5] - クラス初のHIVインテグラーゼ阻害薬ISENTRESSTMは、すでに治療経験のある成人患者のHIV-1感染症の治療に対 し、他の抗レトロウイルス薬との併用で使われます。ISENTRESSTMの2007年度通年の全世界での売上は4,100万ドル でした。この中には、米国で発売された2007年度第4四半期の売上2,900万ドルが含まれています。この薬はEU、カ ナダ、及びメキシコでも承認されています。 Merck & Co., Inc., 2007年度業績説明会で戦略計画の進捗状況をレビュー[2007.12.20] - キム社長は、2008年に2件の追加承認申請を行なう予定であることを発表しました。1つは子宮頸がんを予防する ワクチン（HPVワクチン）の、45歳までの成人女性に対する適応拡大、もう1つはHIV-1感染治療薬であるクラス初の インテグラーゼ阻害剤ラルテグラビルの、治療経験のない患者への適応拡大です。
[1244]●製品 Atripla Tablet (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) [Gilead/BMS]
日本語版註）Atripla Tablet (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) [Gilead/BMS]
【別名】 【開発元】Gilead Science [DBR_ID]
【化学名】
【承認】FDA申請=Apr 25,2006、FDA承認=July 12, 2006 ; 【製剤】(efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) 【適応】for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. 【用法用量】１日１回１錠 【作用】 【特徴】 【製品情報】http://www.atripla.com/ 【添付文書】Atripla Full Prescribing Information 【EU】Atripla[Gilead/BMS/Merck３社]EMEA申請2006.10.9 承認2007.12.13。 【日本】未開発 【その他】
【日本語版コメント1244】
2005年、抗ＨＩＶ薬の世界市場規模は約１兆円。 グラクソ・スミスクライン社とブリストル・マイヤーズスクイブ社がHIV市場の50％以上を占め、ファイザー社、ジョンソン・エンド・ジョンソン社、メルク社、ギリアド社らは開発後期にある有望な新薬候補薬剤を持つ。
NRTIが37%を占め、製剤としてはコンビビルCombivir[GSK]が断然トップ、プロテアーゼ阻害剤PI(シェア29%)ではカレトラが依然トップだが、新薬のレイアタッツが急速な伸びで既に二番手に。 NNRTI(シェア13%)では、Sustiva[BMS](日本ではストックリン[万有])、ビラミューン[B-I]の順。 他にビリアードとツルバダは合算すると世界売上高約1600億円(シェア17%)と新薬としてかなり繁用されるようになった。
今回採りあげたのは、ツルバダにNNRTI製剤のストックリンを配合したAtripla錠[Gilead/BMS]。→詳細は参考資料●リソース：エイズ治療剤に纏めた。＜日本語版コメント要約＞
・Atriplaは、1錠中にエファビレンツ、エムトリシタビン、テノフォビルの3種類の抗レトロウイルス剤を含有するHIV感染症の治療薬としては初めての配合錠である。
・用量の調節性は劣るものの、服用が簡便化されることで長期のアドヒアランスが改善する期待が持てる。
・副作用は各成分薬剤を別々に服用した場合と同様で、多くの薬剤との相互作用にも注意する必要がある。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =ATRIPLA FDA Application No. = Active Ingredient(s)=EFAVIRENZ; EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE Company =GILEAD Dosage Form/Route =TABLET; ORAL 600MG;200MG;300MG Strength = - Approval Date=07/12/2006[000] :Label[添付文書]|Letter[承認書]|[Approval]
●Electronic Orange Book Application Number: 021937 Active Ingredient : EFAVIRENZ; EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE Proprietary Name : ATRIPLA [GILEAD] Approval Date : July 12, 2006 Exclusivity Data : - Patent Data : 5210085 MAY 11,2010 U-750 5210085*PED NOV 11,2010 5519021 MAY 21,2013 Y Y 5663169 SEP 02,2014 U-750 5811423 AUG 07,2012 U-750 5814639 SEP 29,2015 Y Y 5814639*PED MAR 29,2016 5914331 SEP 29,2015 Y 5914331*PED MAR 29,2016 5922695 JUL 25,2017 Y U-750 5935946 JUL 25,2017 Y Y U-750 5977089 JUL 25,2017 Y Y U-750 6043230 JUL 25,2017 U-750 6238695 APR 06,2019 Y 6555133 APR 06,2019 U-750 6639071 NOV 13,2021 Y 6642245 NOV 04,2020 U-750 6642245*PED MAY 04,2021 6703396 MAR 09,2021 Y Y 6703396*PED SEP 09,2021 6939964 JAN 20,2018 Y
●FDA Advisory Committees 該当なし 参考●ML資料：FDA諮問委員会～議題 FDA Advisory Committees FDAAdvisorycommittee.com
●Gilead Science ●Products Atripla(TM) - Truvada(R) -http://www.gilead.com/wt/sec/truvada(emtricitabine/tenofovir)[日本]ツルバダ錠(製造販売元／日本たばこ産業 販売元／鳥居薬品) Viread(R) -http://www.gilead.com/wt/sec/viread(FDA承認2001.10,発売2002.2) (tenofovir disoproxil fumarate)[日本]ビリアード錠300mg(製造販売元／日本たばこ産業 販売元／鳥居薬品) AmBisome(amphotericin B liposome)抗真菌剤[日本]アンビゾーム点滴静注用50mg Hepsera(R) -http://www.gilead.com/wt/sec/adefovir(adefovir dipivoxil)B型肝炎[日本]ヘプセラ錠10[GSK]発売=2004.12 Emtriva(R) -http://www.gilead.com/wt/sec/emtriva(emtricitabine)[日本]エムトリバカプセル200mg(製造販売元／日本たばこ産業 販売元／鳥居薬品) Vistide - http://www.gilead.com/wt/sec/vistide(cidofovir)エイズ患者のCMV網膜炎 Tamiflu(R) -http://www.gilead.com/wt/sec/tamiflu ●News October 9, 2006★Bristol-Myers Squibb, Gilead Sciences and Merck & Co. Submit Marketing Authorisation Application for ATRIPLA(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) to European Medicines Agency★HIV配合剤Atripla； 本日Gilead/BMS/Merck３社はEMEA申請。 申請は３社合弁のアイルランドBristol-Myers Squibb Gilead Sciences And Merck Sharp & Dohme Limitedが実施。 FDAは途上国販売にも異なる商品名による承認を行っており またGilead/Merckは2006.8に途上国での販売契約を締結。
September 28, 2006★Bristol-Myers Squibb and Gilead Sciences Establish Agreement to Commercialize ATRIPLA(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) in Canada★HIV配合剤Atripla； Gilead/BMS両社合弁会社の開発・販売を従来の米国にカナダを付加。
August 11, 2006★Gilead Sciences and Merck Establish Agreement for Distribution of ATRIPLA(TM) in Developing Countries★HIV配合剤Atripla
July 12, 2006★U.S. Food and Drug Administration (FDA) Approves ATRIPLA(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg), The First Once-Daily Single Tablet Regimen for Adults with HIV-1 Infection★HIV配合剤Atripla；本日承認、発売は１週間以内；BMS/Gilead両社は2004.12.20開発・販売目的で合弁会社を設立。 本剤はthe first-ever once-daily single tablet regimen (STR) for HIV。 DHHSガイドラインはこの３剤併用をthe preferred agents for use in an NNRTI-based treatment regimenとする。 Study 934によると４８週の比較試験で有効性についてViread/Emtriva/SUSTIVA group (n=244)が84%、１日２回投与のCombivir/SUSTIVA group (n=243) 73%に優り、HIV-1 RNA も400 copies/mL未満を維持。 副作用による中止も前者4%に対し後者9%。
April 27, 2006★Bristol-Myers Squibb and Gilead Sciences Submit New Drug Application to U.S. FDA for a Once-Daily Single Tablet Regimen of Sustiva(R) (Efavirenz) and Truvada(R) (Emtricitabine and Tenofovir Disoproxil Fumarate) for HIV Treatment★HIV配合剤Atripla
January 9, 2006★Bristol-Myers Squibb and Gilead Announce Data Supporting Bioequivalence for Single-Pill Fixed-Dose Regimen of Sustiva(R) (efavirenz) and Truvada(R) (emtricitabine and tenofovir disoproxil fumarate)★HIV配合剤Atripla
August 9, 2005★Gilead Provides Update on Development of Fixed-Dose Regimen of Truvada(R) (Emtricitabine and Tenofovir Disoproxil Fumarate) and Sustiva(R) (Efavirenz) ★HIV配合剤Atripla
April 26, 2005★Gilead Provides Update on Development of Fixed-Dose Regimen of Truvada (emtricitabine and tenofovir disoproxil fumarate) and Sustiva (efavirenz) ★HIV配合剤Atripla
December 20, 2004★Bristol-Myers Squibb and Gilead Sciences Establish U.S. Joint Venture to Develop and Commercialize Fixed-Dose Combination of Three HIV Medicines ★合弁会社名はBristol-Myers Squibb & Gilead Sciences, LLC
●BMS ■製品 Products ATRIPLA^(TM) -http://www.atripla.com/ (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) Tablets；抗HIV薬 Reyataz(R) -http://www.reyataz.com/ (atazanavir sulfate) Capsules；抗HIV薬 Sustiva(R) -http://www.sustiva.com/ (efavirenz) Capsules and Tablets；抗HIV薬 Videx(R) EC -(didanosine, delayed-release capsules)；抗HIV薬 Zerit(R) -(stavudine) Capsules and Oral Solution；抗HIV薬 ■News Room ●News Releases [Investors -News Releasesを含む] Oct 9, 2006★Bristol-Myers Squibb, Gilead Sciences and Merck & Co. Submit Marketing Authorisation Application for ATRIPLA^(TM) (efavirenz 600 mg/ emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) to European Medicines Agency★HIV配合剤Atripla
Sep 28, 2006★Bristol-Myers Squibb and Gilead Sciences Establish Agreement to Commercialize ATRIPLA^(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) in Canada
If Approved, Product Would Be the First Once-Daily Single Tablet Regimen for HIV-1 Infection in Adults in Canada★HIV配合剤Atripla
Jul 12, 2006★U.S. Food and Drug Administration (FDA) Approves ATRIPLA^(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg), the First Once-Daily Single Tablet Regimen For Adults With HIV-1 Infection★- Product Developed Through U.S. Joint Venture between Bristol-Myers Squibb and Gilead Sciences, the First of Its Kind in HIV Treatment -★HIV配合剤Atripla
[1243]●製品 darunavir ethanolate (PREZISTA[TM] [Tibotec, Inc.])ダルナビル(プレジスタ)
日本語版註）darunavir ethanolate (PREZISTA[TM] [Tibotec, Inc.])ダルナビル(プレジスタ)
【別名】TMC-114 【開発元】Tibotec, Inc., A Division of Ortho Biotech Products, LP [DBR_ID]
【化学名】[(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester monoethanolate. m.f.=C27H37N3O7S . C2H5OH and m.w.=593.73.
【承認】FDA申請=22-Dec-2005、FDA承認=23-Jun-2006 ; 【製剤】錠剤－darunavir ethanolate equivalent to 300 mg of darunavir. 【適応】HIV感染症（抗レトロウイルス薬による既治療患者の成人）リトナビル 100mgと併用する。 【用法用量】成人の場合、600mgを１日２回、ritonavir 100mgずつと一緒に服用 【作用】HIV-1 protease阻害剤。 It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in infected cells, thereby preventing the formation of mature virus particles. 【特徴】交叉耐性ウイルスに有効 【製品情報】http://www.prezista.com/ 【添付文書】Full Prescribing Information
【EU】Prezista[Janssen-Cilag] EMEA申請2006.2.11 承認2007.2.12 【日本】プリジスタ錠300mg[製造販売元／ヤンセンファーマ株式会社 提携／TibotecPharmaceuticalsLtd]PREZISTA 申請2006.11、承認承認2007.11.22、薬価収載2007.11.30、発売2007.12.10; 【製剤～日本】１錠中ダルナビル エタノール付加物325.23mg（ダルナビルとして300mg） 【適応～日本】HIV感染症 【用法用量～日本】通常、成人にはダルナビルとして1回600mgとリトナビル1回100mgをそれぞれ1日2回食事中又は食直後に併用投与する。投与に際しては、必ず他の抗HIV薬と併用すること。 【製品情報～日本】プリジスタ 【添付文書～日本】プリジスタ添付文書 | プリジスタインタビューフォーム 【その他】
【日本語版コメント1243】
世界のHIV/AIDS患者数は、2005年末推定3860万人。 毎年410万人の新規感染者が発生。 死亡者数は1998年末までの累計は1390万人、2001年では300万人、2002年310万人、2005年280万人。 日本に関しては、エイズ動向委員会報告によると、(2006.10.1現在)HIV感染者8,091人、エイズ患者3,949人、凝固因子製剤による感染者1,438人 合計13,458人 抗HIV薬は多数開発されてきたが、進行を遅らせるにとどまっている。1986年には作用機序の異なる抗HIV-1薬を併用する多剤併用療法(HAART;Highly Active Anti-retroviral Therapy)の有効性が報告され, 一時は治癒可能ではないかとまで期待された。 しかし, 長期にわたり残存する感染細胞が証明され, HAARTを中断すると必ずウイルスの再増殖が見られることから, 現在では生涯治療が必要であると考えられている。 このようにHAARTは「長期継続」が必要な治療法であるが, 長期継続に伴うさまざまな問題点が明らかとなってきた。 1つは薬剤耐性変異株の出現であり, もう1つは慢性毒性の蓄積である。
新たなプロテアーゼ阻害剤には、(1)高い経口吸収性 (2)長い血中半減期 (3)低い蛋白結合率 (4)交叉耐性のない薬剤耐性 プロフィルが求められている。
今回採りあげたプロテアーゼ阻害剤ダルナビルは、イリノイ大学ゴーシュ教授が合成し、熊本大学満屋裕明教授が生体内での効果を確認、共同開発したもので野生株および多剤耐性のウイルス株にも高い活性を示した。
プロテアーゼはＨＩＶに含まれる酵素で、ＨＩＶの増殖に必要なタンパク質を正しく切断する「はさみ」の役割を果たす。 ＰＩは酵素に付着してはさみを切れなくし、ＨＩＶの増殖を止める。 既存のＰＩは、酵素の成分であるアミノ酸の端に結合する性質があり、ＨＩＶの遺伝子が変異してアミノ酸が変わると効かなくなってしまう弱点があった。
これに対しダルナビルは、アミノ酸が変わっても影響ない場所に結合するため耐性ができにくい。 ＰＩなどに耐性が検出された患者への臨床試験では約７０％に治療効果がみられ、別の薬の3倍以上高かった。→詳細は参考資料●リソース：エイズ治療剤に纏めた。＜日本語版コメント要約＞
・新規プロテアーゼ阻害薬ダルナビが、前治療歴のあるヒト免疫不全ウイルス（HIV）感染症患者の併用療法に用いる薬剤として承認された。
・本剤は、in vitroで他のプロテアーゼ阻害薬耐性のHIV株に活性を示す。
・本剤は低用量のリトナビルと食事とともに服用する。
・脳出血や致命的な肝毒性を引き起こすチプラナビルに比べ、本剤は忍容性が良いように思われる。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =PREZISTA FDA Application No. =NDA # 021976 Active Ingredient(s)= DARUNAVIR ETHANOLATE Company =TIBOTEC Dosage Form/Route =TABLET; ORAL EQ 300MG BASE Strength = - Approval Date=06/23/2006[000]:Label[添付文書]|Letter[承認書]|Review
●Electronic Orange Book Application Number: 021976 Active Ingredient : DARUNAVIR ETHANOLATE Proprietary Name : PREZISTA [TIBOTEC] TABLET; ORAL EQ 300MG BASE Approval Date : Jun 23, 2006 Exclusivity Data : NCE JUN 23,2011 Patent Data : 843946 DEC 01,2015 Y U-744 6248775 AUG 25,2012 Y 6335460 AUG 25,2012 Y Y U-744
●FDA Advisory Committees 該当なし 参考●ML資料：FDA諮問委員会～議題 FDA Advisory Committees FDAAdvisorycommittee.com
●Tibotec, Inc. -http://www.tibotec.com/ Division of Ortho Biotech Products, LP 1994 設立。 HIV/AIDSやunmet medical needの感染症分野の創薬企業として設立。 1995 VircoがSpin-off 2002.4 両社ともJohnson & Johnsonに買収。 ●開発中の新薬 * TMC114, a protease inhibitor (PI), PREZISTA[TM] (darunavir)。FDA承認されTibotec Therapeutics, a division of Ortho Biotech Products, L.P. により販売。 EUではTibotec, a division of Janssen-Cilagが承認後販売する予定。 * TMC125, a non-nucleoside reverse transcriptase inhibitor (NNRTI), * TMC278, a non-nucleoside reverse transcriptase inhibitor (NNRTI). * TMC120, Tibotec's first NNRTI in clinical development。as a vaginal microbicide 2004.3 International Partnership for Microbicides にライセンス。 * TMC207, a novel anti-TB compound was transferred from Johnson & Johnson PRD to Tibotec for clinical development. * VX-950 C型肝炎 P2 Vertexからライセンス。. an investigational oral inhibitor of hepatitis C virus protease in Phase II development ●News 16 August 2006★48 Week Data On Investigational Antiretroviral TMC125 From Tibotec★TMC125 a next-generation NNRTI
14 August 2006★Analysis provides additional data for PREZISTA (TM) as part of HIV Combination Therapy★Presented Tuesday, 14 August, at the 16th International AIDS Conference (AIDS 2006) in Toronto, Canada
30 June 2006★Tibotec reinforces its commitment in the field of hepatitis★Separate announcements today from both Vertex and Medivir further reinforce Tibotec's commitment to finding innovative treatments for global viral diseases
28 June 2006★PREZISTA (TM) Receives FDA Approval in USA as part of HIV Combination Therapy★PREZISTA is the first compound in the company's research pipeline to receive regulatory approval.
23 June 2006★FDA Approves New HIV Treatment for Patients Who Do Not Respond to Existing drugs★The Food and Drug Administration (FDA) today approved PREZISTA (darunavir), a new drug for adults whose infection with HIV has not responded to treatment with other antiretroviral drugs.
06 March 2006★Tibotec Announces FDA Acceptance for Review of NDA for TMC114★The Prescription Drug User Fee Act (PDUFA) user fee goal date for the NDA will be June 23, 2006
16 February 2006★New Data on Tibotec HIV/AIDS Investigational Product Portfolio★Following the 13th Conference on Retroviruses and Opportunistic Infections (CROI)
11 January 2006★Tibotec Submits Marketing Authorisation Application for Investigational HIV Protease Inhibitor TMC114 in Europe★Follows Recent Submission of New Drug Application to the US FDA★本日EMEA申請を行ったことを発表。 POWER 2研究によると、TMC114 600mg/ ritonavir 100mgの比較試験を行い、TMC114は患者の64%でウイルス濃度が低下(1 log10 以上)しritonavirは14%、一方もっとも一般的な副作用は頭痛・吐き気で両剤とも17%に発生。 一つ以上の副作用発生率はTMC114が15%、Ritonavirが8%。
27 December 2005★New Drug Application for Investigational HIV Protease Inhibitor TMC114 Submitted to U.S. Food & Drug Administration★HIV/AIDS compound marks first regulatory submission by Tibotec Pharmaceuticals Ltd.
19 December 2005★Tibotec Presents Phase 2b Data on 2 Investigational HIV Compounds at ICAAC★TMC114 and TMC125 demonstrate activity against drug resistant HIV
●Tibotec Therapeutics - http://www.tibotectherapeutics.com/ Division of Ortho Biotech Products, LP ●Our Products ●Procrit(R) ●Press Room
●Johnson & Johnson ■Products ●Products - Diseases & Conditions ■J&J Investors Relations ●J&J - Annual reports Annual Report 2006 [html] [pdf](84p) Annual Report 2005 [html] [pdf](78p) Annual Report 2004 [html] [pdf](78p) ●J&J Financial Reports - Pharmaceutical pipeline ●Financial nformation - 四半期報 Sales of Key Products/Franchises 4Q 2007[pdf,2008.1.24] - 個別製品売上高 Sales of Key Products/Franchises 4Q 2006[pdf,2007.1.24] - 個別製品売上高 Sales of Key Products/Franchises 4Q 2005[pdf,2006.1.24] - 個別製品売上高 ●SEC Filings ★10K and 10Q 10-K Annual Report[2008.2.26] - [pdf,128p] 10-K Annual Report[2007.2.21] - [pdf,128p] 10-K Annual Report[2006.3.14] - [pdf,104p] 10-K Annual Report[2005.3.15] - [pdf](126p) ●J&J Investors Relations- News release -http://www.investor.jnj.com/releases.cfm Johnson & Johnson Reports Full-Year and Fourth-Quarter 2005 Results[2006.1.24] ■News -http://www.jnj.com/news/index.htm - Press Releases & Statements[10件毎] -http://www.jnj.com/news/jnj_news/index.htm - News Archives -http://www.jnj.com/news/archive/index.htm
●系列 J&J Company WEBsite --- ５７か国、200社以上、従業員数11.5万人以上の傘下の企業へのリンク Centocor －October 6, 1999 J&J傘下に | Janssen, McNeil, Ortho Ethicon他 Ortho-McNeil[米国医療用医薬品] - 消化器潰瘍薬、感染症(抗菌薬)、疼痛管理 Alza Corporation Janssen-Cilag McNeil Consumer & Specialty Pharmaceuticals - a division of McNeil-PPC Inc. Johnson & Johnson Pharmaceutical Research & Development, L.L.C[JJPRD:米国] Johnson & Johnson Pharmaceutical Research & Development, L.L.C[JJPRD:米国] - 旧R.W. Johnson Pharmaceutical Research Institute(2001-2002頃に社名変更) (Robert Wood Johnson氏はJ&Jの創業者) LifeScan, Inc.[米国]～医療機器
●ヤンセン ファーマ株式会社 ●医療従事者 - 医薬品情報 - CNSネット～精神神経分野★要ID 医療関係者限定 - Pain Relief★要ID 医療関係者限定 ●病気に関する情報 メンタル・ナビwww.mental-navi.net ～一般用・医療関係用(要ID) 水虫ちゃんねる フケ・脂漏性皮膚炎 こころのこと あしのこと フケのこと ●プレスリリース
●参考資料 ●平成１８年４月～６月に欧米４カ国のいずれかの国で 新たに承認された医薬品（類型Ⅰ）[pdf,4p;p3] 未承認薬使用問題検討会議 第９回資料 資料 ３ ６．成分名： ダルナビル（darunavir） 販売名： Prezista 承認国： 米国（2006年6月23日承認） 会社名： Tibotec, Inc. 剤形・規格：経口剤・300mg１錠 効能・効果：HIV感染症（抗レトロウイルス薬による既治療患者） 用法・用量：600mgを１日２回経口投与（リトナビル100mg１日２回との併用） 作用機序等：HIV-1プロテアーゼ阻害 ○適応疾病の重篤性について： 重篤な疾病である。 ○医療上の有用性について： 既存療法の中での本剤の治療上の位置づけについて要検討 ○学会・患者団体からの要望： － ○国内状況： 承認申請準備中 ●「耐性」に効く新エイズ薬 満屋教授ら日米チーム開発 患者への効果３倍以上 記事：共同通信社 【2006年8月15日】 【ワシントン１４日共同＝吉本明美】 既存の薬が効かない多剤耐性エイズウイルス（ＨＩＶ）にも 高い効果を示す抗ＨＩＶ薬を、熊本大の満屋裕明（みつや・ひろあき）教授 や米パデュー大（インディアナ州）のアラン・ゴーシュ教授ら 日米共同チームが開発し、14日までに米食品医薬品局（ＦＤＡ）が 治療薬として承認した。 先進国、発展途上国ともに深刻な脅威となっている耐性ＨＩＶへの 幅広い効果が確認された薬は、世界で初めて。 別の薬の3倍以上の効果があるなど患者には大きな朗報で、 専門家らはこの薬が今後、エイズ治療の主役になる可能性があると みている。臨床試験の成績などは、カナダで13日から始まった 国際エイズ会議で発表される。 ダルナビルと呼ばれるこの薬は、エイズ治療に広く使われている プロテアーゼ阻害剤（ＰＩ）の一種。 ゴーシュ教授が合成し、満屋教授が生体内での効果を確認、 臨床試験へと進めた。 プロテアーゼはＨＩＶに含まれる酵素で、ＨＩＶの増殖に必要な タンパク質を正しく切断する「はさみ」の役割を果たす。 ＰＩは酵素に付着してはさみを切れなくし、ＨＩＶの増殖を止める。 既存のＰＩは、酵素の成分であるアミノ酸の端に結合する性質があり、 ＨＩＶの遺伝子が変異してアミノ酸が変わると効かなくなってしまう 弱点があった。 これに対しダルナビルは、アミノ酸が変わっても影響ない場所に 結合するため耐性ができにくい。 ＰＩなどに耐性が検出された患者への臨床試験では約７０％に 治療効果がみられ、別の薬の3倍以上高かった。 ＦＤＡは患者への恩恵が大きいとして、約半年でスピード承認した。 薬はベルギーのティボテック社が製品化した。 満屋教授は世界初の抗ＨＩＶ薬「ＡＺＴ」の開発者。 その後2剤を世に送り出しており、これが4剤目となる。 この薬剤の作用は、HIVが持っているプロテアーゼという酵素を 使い物にならなくさせるってことなんですが、 これだけだと、いままでのものと何がちがうの？ってなりますよね。 でも、HIVに変異がおきた時、今までのプロテアーゼ阻害薬では 防ぎきれなかったHIVの増殖を、この薬では７０％という高い確率で、 抑えることができるという、まさにミラクルな薬剤なのです。 人類は、当分、この薬剤に未来を託すことになりそうです。 そして、この薬が我々の母国の日本の研究者によって 創り出されたという事に私たちはもっともっと胸を張っても いいのではないでしょうか。
[1219]●製品 Tipranavir Disodium (Aptivus [Boehringer Ing])チプラナビル(アプチバス)
日本語版註）Tipranavir Disodium (Aptivus [Boehringer Ing])チプラナビル(アプチバス)
【別名】PNU-140690E 【開発元】Pfizerが創製し、Boehringer-Ingにライセンス(2000) [DBR_ID]
【化学名】3'-[(1R)-1-[(6R)-5,6-Dihydro-4-hydroxy-2-oxo-6-phenethyl-6-propyl-2H-pyran-3-yl]propyl]-5-(trifluoromethyl)-2-pyridinesulfonanilide, disodium salt. CAS-174484-41-4(Tipranavir).;CAS-191150-83-1(Tipranavir Disodium)
【承認】FDA申請=December 21, 2004,、FDA承認=Jun 22, 2005 ; 【製剤】カプセル中250mg 【適応】(高度な治療経験があり又は多数のプロテアーゼ阻害剤に耐性のHIV-1 ウイルスを有し、ウイルス複製の証拠のあるHIV-1 感染症患者におけるリトナビルとの併用)for the use of Aptivus (tipranavir) capsules, 250 mg, coadministered with 200 mg of ritonavir, for combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. 【用法用量】500mg（２カプセル）を１日２回経口投与 【作用】非ペプチド系プロテアーゼ阻害剤（NPPI）；チプラナビルは非ペプチド系化学構造を持つことで、よりフレキシブルにHIVプロテアーゼ活性部位に結合。 ペプチド系プロテアーゼ阻害剤（PI）と異なり、チプラナビルが薬剤耐性を獲得したHIVに有効で、かつチプラナビルに対しHIVの感受性が低下することが非常にまれという薬剤耐性特性はこのためだと考えられる。 【特徴】 【製品情報】Aptivus(R) (tipranavir) Capsules 【添付文書】Aptivus(R) Capsules 250mg (tipranavir) 【EU】Aptivus[Boehringer Ingelheim]EU申請=2004.10.25,CHMP承認勧告=2005.7.28,EU承認=2005.10.25 【日本】日本ベーリンガーインゲルハイムで開発検討中 【その他】
US Pharmacopeial Commission - 2000 USP DICTIONARY SUPPLEMENT 2[Pharmacopeial Forum Vol.27,No.1 Jan.-Feb 2001] Tipranavir. C31H33F3N2O5S. 602.67. 3'-[(1R)-1-[(6R)-5,6-Dih- ydro-4-hydroxy-2-oxo-6-phenethyl-6-propyl-2H-pyran-3- yl]propyl]-5-(trifluoromethyl)-2-pyridinesulfonanilide. CAS- 174484-41-4. INN. - Revisions of United States Adopted Names (USAN)[Pharmacopeial Forum Vol.25,No.6 Nov.-Dec.1999] Tipranavir Disodium [1998] (tip ra' na veer). C31H31F3N2Na2O5S. 646.64. (1) [R-(R*,R*)]-N-[3-[1-[5,6-Dihy- dro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3- yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide di- sodium salt; (2) 3'-[(1R)-1-[(6R)-5,6-Di- hydro-4-hydroxy-2-oxo-6-phenethyl-6-propyl-2H-pyran-3- yl]propyl]-5-(trifluoromethyl)-2-pyridinesulfonanilide, disodium salt. CAS-191150-83-1. Antiviral (protease inhibitor). (Pharma- cia & Upjohn) PNU-140690E AMA: United States Adopted Names BIAM --- BIAM -ABC順|BIAM -会社順 NLM: MeSH HOme ---MeSH Online search
【日本語版コメント】
現在の抗ＨＩＶ薬の最大の問題点は薬剤耐性ウイルス。 複数の抗ＨＩＶ薬に対しすでに耐性を獲得したウィルスに対する、新薬の緊急の必要性が生まれている。 感染患者の１４％までが、薬の効き目が突然変異をおこしたり、ある特定の薬に対し、効き目が落ちていくという問題点が報告されている。
今回採りあげたチプラナビルは、複数のHIV薬に対し耐性を獲得したウィルスに対し効果を示している。→詳細は参考資料●リソース：エイズ治療剤に纏めた。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =APTIVUS FDA Application No. =NDA # 021814 Active Ingredient(s)=TIPRANAVIR Company =BOEHRINGER INGELHEIM Dosage Form/Route =CAPSULE; ORAL 250MG Strength = - Approval Date=06/22/2005[000] :Label[添付文書]|Letter[承認書]|Review
●Electronic Orange Book Application Number: 021814 Active Ingredient : TIPRANAVIR Proprietary Name : APTIVUS [BOEHRINGER INGELHEIM] CAPSULE; ORAL 250MG Approval Date : Jun 22, 2005 Exclusivity Data : NCE JUN 22,2010 Patent Data : 5852195 DEC 22,2015 Y 6147095 OCT 29,2019 U-670 6169181 MAY 06,2014 Y 6231887 JUL 27,2018 Y
●FDA Advisory Committees 参考●ML_ADD資料：FDA諮問委員会～議題 FDA Advisory Committees FDAAdvisorycommittee.com CDER■Antiviral Drugs - http://www.fda.gov/ohrms/dockets/ac/cder05.html#AntiviralDrugs FDAAdvisorycommittee.com: Antiviral Drugs
ML 開催日 議題 備考 1219 2005.5.19 Boehringer Ingelheim Aptivus (Tipranavir) For HIV
※【審議結果】11-3で承認勧告。しかし本剤の適正使用のための追加研究データが要求された。 pivotal trialsで患者の6%に肝ALT/ALS酵素の上昇を認めており、肝毒性の長期研究もそれに含まれる。
※Brief InformationAptivus (Tipranavir)
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Aptivus INN:Tipranavir - Published 04/11/05 [Boehringer Ingelheim International GmbH, Germany] Date of issue of Marketing Authorisation=25 October 2005 [Therapeutic Indication] APTIVUS, co-administered with low dose ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infection in highly pre-treated adult patients with virus resistant to multiple protease inhibitors.
This indication is based on the results of two phase III studies, performed in highly pre-treated patients (median number of 12 prior antiretroviral agents) with virus resistant to protease inhibitors (see details of resistance profile of patients’ HIV at baseline in section 5.1 of the Summary of Product Characteristics).
In deciding to initiate treatment with APTIVUS, coadministered with low dose ritonavir, careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different agents. Genotypic or phenotypic testing (when available) and treatment history should guide the use of APTIVUS.
1. Abstract 3. Scientific Discussion Product Information 「概要」によると、本剤は２つの大規模多施設臨床試験（RESIST-1,2;各600,800人の患者）
●Boehringer Ingelheim ■Products ★HIV 添付文書 米国 Aptivus(R) Capsules 250mg (tipranavir) ■News Centre ●Press Kit Annual Press Conference 2005 - Business Development2004 /Business Perspectives Slides of Dr Alessandro Banchi[pdf,22p;2005.4.6] Annual Report 2004[pdf,120p,2005.4] ●Publication Download Annual Report 2004[pdf,120p,2005.4] Making your product a success[2005;pdf,16p] ●News Release 28 November 2005★World AIDS Day 2005 � Boehringer Ingelheim is committed to its fight against AIDS
21 November 2005★Aptivus(R) sustains convincing anti-HIV effect through 48 weeks
21 November 2005★Aptivus(R) sustains convincing anti-HIV effect over 48 weeks of treatment
21 November 2005★New data demonstrate efficacy of two leading anti-HIV treatments
26 October 2005★EU commission approves Aptivus(R) for the treatment of HIV
01 August 2005★Boehringer Ingelheim shows continued growth－Net sales and income well ahead of previous year/ new AIDS drug launched
28 July 2005★Positive opinion in Europe for tipranavir -New data support its use as powerful treatment against HIV drug resistance
23 June 2005★U.S. FDA approves new anti-HIV drug Aptivus(R) for use in combination therapy
25 October 2004★Boehringer Ingelheim submits Marketing Authorisation Application to European Union and to the FDA for investigational Anti-HIV agent Tipranavir
●日本ベーリンガーインゲルハイム ●プレスリリース ベーリンガーインゲルハイム、2005年上半期の実績を発表－持続的な力強い成長を示す－[2005.8.1] 近ごろ同社から革新的な新薬が発売されました。同社にとって2番目のHIV/エイズ治療剤 APTIVUS(R)（一般名：チプラナビル）は、特に薬剤耐性ウイルス感染者に対する治療に有 効な、非ペプチド系プロテアーゼ阻害剤（NPPI）です。 ベーリンガーインゲルハイムが開発中のチプラナビル 新規作用機序を持つ抗HIV剤が
耐性ウイルス感染患者に高い効果－後期フェーズII試験で確認－[2003.2.19] 開発中の抗レトロウイルス剤チプラナビル、既存プロテアーゼ阻害剤に耐性を示すHIVウイルスを抑制[2002.7.12] －最大で20種の耐性変異ウイルスを持つHIV陽性患者で投与48週目にも感受性を維持 ●日本ベーリンガーインゲルハイム[製品情報]医療用医薬品
●関連資料 第５回未承認薬使用問題検討会議速記録[2005.7.27] -[川原課長] 資料１について簡単に御説明申し上げます。このリストは、今年の４月から６月まで の３カ月間に欧米４カ国のいずれかの国で新たに承認された医薬品ということでござい ます。全部で４剤ございました。簡単に御紹介します。--- ４つ目、チプラナビルという薬でございます。こちらもアメリカで６月22日に承認さ れました抗エイズ薬でございまして、プロテアーゼ阻害剤の部類に属するものでござい ます。 以上４剤でございますけれども、いずれの薬も今のところ学会とか患者団体からの要 望というのは出てきておりませんけれども、既存の治療法がない重篤な疾病に用いられ る薬も中にはございまして、本日御意見等いただければと思います。 なお、チプラナビルについてはHIV関係の薬でございまして、HIV感染症治療薬につい ては私どもの方で別途、迅速審査というスキームをつくって審査しておりますので、そ ちらの方のスキームで対応させていただきたいと考えております。以上でございます
[1203]●製品 emtricitabine/tenofovir(Truvada[Gilead]) エムトリシタビンとフマル酸テノホビル ジソプロキシル配合剤(ツルバダ(TM)錠)
日本語版註）emtricitabine/tenofovir(Truvada[Gilead])(tru-VAH-dah) エムトリシタビンとフマル酸テノホビル ジソプロキシル配合剤(ツルバダ(TM)錠)
【別名】 【開発元】Gilead Science [DBR_ID]
【化学名】
【承認】FDA申請=March 11, 2004、FDA承認=Aug.02/2004 ; 【製剤】1錠中emtricitabine 200mg and tenofovir disoproxil fumarate 300mg 【適応】TRUVADA is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults. 【用法用量】１錠を１日１回 【作用】逆転写酵素阻害剤。 nucleoside reverse transcriptase inhibitors(NRTI) 【特徴】他の抗HIV剤と併用した場合、複製プロセスを妨害することによりHIV量や人体の負担を低減、免疫システム細胞T cells / CD4 cellsを増加させる。 【製品情報】http://www.truvada.com/ 【添付文書】http://www.truvada.com/fpi.pdf 【提携】ギリアド・サイエンシズ社 【EU】諮問委CHMPは2004.11.18に承認勧告、2005.2.23EU25カ国承認。 Gilead's Access Programにより、68の低資源国ヘ非営利価格で提供。 【日本】ツルバダ(TM)錠(製造販売元／日本たばこ産業株式会社 販売元／鳥居薬品株式会社 提携／GILEAD)承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19(鳥居薬品)。：「ツルバダ(TM)錠」製品概要 【製剤～日本】1錠中エムトリシタビン200mg及びフマル酸テノホビル ジソプロキシル300mg（テノホビル ジソプロキシルとして245mg） 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人には1回1錠（エムトリシタビンとして200mg及びフマル酸テノホビル ジソプロキシルとして300mgを含有）を1日1回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること 【添付文書～日本】ツルバダ錠添付文書 | ツルバダ錠インタビューフォーム 【その他】日本語版註）tenofovir disoproxil fumarate(Viread Tabs[Gilead])フマル酸テノホビル ジソプロキシル(ビリアード)
【別名】GS-4331-05 【開発元】Gilead Science [DBR_ID]
【化学名】9-[(R)-2-[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1); C19H30N5O10P.C4H4O4; m.w.635.52.; CAS-202138-50-9
【承認】FDA申請=April 30, 2001、FDA承認=10/26/2001 ; 【製剤】錠剤－300mg of tenofovir disoproxil fumarate(eq. to 245 mg of tenofovir disoproxil) 【適応】VIREAD is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 【用法用量】1日1回１錠(300mg)を食事と共に服用。 【作用】HIV reverse transcriptase inhibitor 【特徴】 【製品情報】http://www.viread.com/ 【添付文書】http://www.gilead.com/pdf/viread_pi.pdf 【提携】 【EU】Viread[Gilead Sciences]承認2002.2.5; 【日本】ビリアード錠300mg(製造販売元／日本たばこ産業株式会社 販売元／鳥居薬品株式会社 提携／GILEAD)承認申請2004.1.19、輸入承認2004.3.25、薬価収載2004.4.2、発売2004.4.12(鳥居薬品)；抗HIV薬「ビリアード(R)錠300mg」製品概要 【製剤～日本】錠-フマル酸テノホビル ジソプロキシル300mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはフマル酸テノホビル ジソプロキシルとして1回300mg（テノホビル ジソプロキシルとして245mg）を1日1回経口投与する。なお、投与に際しては必ず他の抗ＨＩＶ薬と併用すること。 【添付文書～日本】ビリアード錠300mg 添付文書[html]|[pdf] - インタビューフォーム[pdf] 【その他】a prodrug of tenofovir; an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5’-monophosphate
抗HIV薬「エムトリバ(R)カプセル200mg」、「ツルバダ(TM)錠」の新発売について[2005.4.8] - 「エムトリバ(R)カプセル200mg」(エムトリシタビン) - 「ツルバダ(TM)錠」(エムトリシタビンとフマル酸テノホビル ジソプロキシルの配合剤) 共に承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19。 抗HIV薬「ビリアード(R)錠300mg」の新発売について[2004.4.5] - (一般名：フマル酸テノホビル ジソプロキシル) 承認申請2004.1.19、輸入承認2004.3.25、薬価収載2004.4.2、発売2004.4.12(鳥居薬品) ●USP Dictionary of USAN and International Drug Names: Tenofovir Disoproxil Fumarate[Vol.26,No.2 Mar.-Apr. 2000] Tenofovir [1999] (te noe' fo veer). C9H14N5O4P.H2O. 305.23. (1) (R)-[[2-(6-Amino-9H-purin-9-yl)-1-methyl- ethoxy]methyl]phosphonic acid monohydrate; (2) [[(R)-2- (6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]- phosphonic acid, monohydrate; (3) 9-[(R)-2-(Phosphono- methoxy)propyl]adenine monohydrate. CAS-206184-49-8. Antiviral (reverse transcriptase inhibitor). (Gilead Sci- ences) GS-1278; PMPA Tenofovir Disoproxil Fumarate [1999] (te noe' fo veer dye soe prox' il). C19H30N5O10P.C4H4O4. 635.52. (1) (R)-5-[[2- (6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]-2,4,6,8- tetraoxa-5-phosphanonanedioic acid, bis(1-methylethyl) es- ter, 5-oxide, (E)-2-butenedioate (1:1); (2) Bis(hydroxymethyl) [[(R)-2-(6-amino-9H-purin-9-yl)-1- methylethoxy]methyl]phosphonate, bis(isopropyl carbon- ate) (ester), fumarate (1:1); (3) 9-[(R)-2- [[Bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl] methoxy]propyl]adenine fumarate (1:1). CAS-202138-50-9. Antiviral (reverse transcriptase inhibitor). (Gilead Sci- ences) GS-4331-05; PMPA Prodrug
【日本語版コメント】
エイズ動向委員会報告によると、(2005.4.3現在)HIV感染者6,734人、エイズ患者3,336人、凝固因子製剤による感染者1,434人 累計11,504人。 日本での感染は依然抑止されており、抗エイズ薬市場としての日本は小規模。
国際新薬は、優先的に迅速審査され日本にも導入され、1996-2000年の５年間に１５新薬が日本で承認された。 その後３年間の空白があり硫酸アタザナビル(レイアタッツ[BMS],2003.12承認)、フマル酸テノホビル ジソプロキシル(ビリアード[日本たばこ－鳥居],2004.3.25承認,2004.4.12発売)、エムトリシタビン(エムトリバ([日本たばこ－鳥居],2005.3.22承認,2005.4.19発売)、そして今回採りあげるツルバダ(TM)錠([日本たばこ-鳥居]2005.3.22承認,2005.4.19発売,エムトリシタビン・フマル酸テノホビル ジソプロキシル配合剤)と立て続けに承認販売され、国際導入新薬は一通り日本でも揃った。→詳細は参考資料●リソース：エイズ治療剤に纏めた。＜日本語版コメント要約＞
・2つの新規NRTI配合剤エムトリシタビン／テノフォビル（Truvada）とアバカビル／ラミブジン（Epzicom）が、1日1回投与のHIV感染症治療薬としてFDAに承認された。
・従来のNRTI配合剤は1日2回投与だったため、今回の承認によりHIV感染症の治療が簡便化される。
・これら配合剤の臨床成績は発表されていないが、Epzicomは各成分を個別に服用した場合と同等の効果があると思われ、Truvadaはジドブジン／ラミブジンと同等の有効性を示している。
・いずれも重度の肝障害または腎障害のある患者には禁忌。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =TRUVADA FDA Application No. =NDA # 021752 Active Ingredient(s)=EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE Company =GILEAD Dosage Form/Route =TABLET; ORAL 200MG; 300MG Strength = - Approval Date=Aug.02/2004 :Label[添付文書]|Letter[承認書]| Drug Name(s) =Viread FDA Application No. =NDA # 021356 Active Ingredient(s)=TENOFOVIR DISOPROXIL FUMARATE Company =GILEAD Dosage Form/Route =TABLET; ORAL 300MG Strength = - Approval Date=10/26/2001 :Label[添付文書]|Letter[承認書]|Review
●Electronic Orange Book Application Number: 021752 Active Ingredient : EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE Proprietary Name : TRUVADA [GILEAD] TABLET; ORAL 200MG;300MG Approval Date : Aug 2, 2004 Exclusivity Data : - Patent Data : 5210085 MAY 11,2010 U-541 5814639 SEP 29,2015 Y Y 5914331 SEP 29,2015 Y Y 5922695 JUL 25,2017 Y U-541 5935946 JUL 25,2017 U-541 5977089 JUL 25,2017 Y Y U-541 6043230 JUL 25,2017 Y U-541 6642245 NOV 04,2020 U-541 6703396 MAR 09,2021 Y Y Application Number: 021356 Active Ingredient : TENOFOVIR DISOPROXIL FUMARATE Proprietary Name : VIREAD [GILEAD] TABLET; ORAL 300MG Approval Date : Oct 26, 2001 Exclusivity Data : NCE OCT 26,2006 NPP AUG 15,2006 Patent Data : 4808716 APR 25,2006 U-248 5922695 JUL 25,2017 U-248 5935946 JUL 25,2017 U-248 5977089 JUL 25,2017 U-248 6043230 JUL 25,2017 U-248 6057305 MAY 02,2017 U-248
●Gilead Science ●News
April 25, 2005★Gilead Sciences and Aspen Pharmacare Sign Letter of Intent to Establish Non-Exclusive Licensing and Distribution Agreement for Antiretrovirals Truvada and Viread in Developing World Countries
- 南アAspen Pharmacare社とライセンス契約February 23, 2005★European Commission Approves Truvada, a Once-a-Day Tablet Containing Gilead Sciences' Anti-HIV Drugs Emtriva and Viread
- TruvadaがEU25カ国承認。諮問委CHMPは2004.11.18に承認勧告。February 3, 2005★Gilead Announces Preliminary 48-Week Data From Study 934 Comparing Viread and Emtriva to Combivir Both in Combination With Sustiva in Patients With HIV
-December 20, 2004★Bristol-Myers Squibb and Gilead Sciences Establish U.S. Joint Venture to Develop and Commercialize Fixed-Dose Combination of Three HIV Medicines
-November 18, 2004★European CHMP Gives Positive Opinion on Gilead's Truvada as Part of Combination HIV Therapy
-August 26, 2004★Gilead Announces Preliminary 24-Week Data from Study 934 Comparing Viread and Emtriva to Combivir Both in Combination With Efavirenz In Patients With HIV
-August 18, 2004★Gilead Expands Initiatives Providing Access to New HIV Therapy Truvada in United States and Abroad
-August 2, 2004★U.S. FDA Approves Gilead's Truvada, a One-Tablet, Once-a-Day Fixed-Dose Co-Formulation of Viread and Emtriva as Part of HIV Combination Therapy
-
●Investors - Annual Reports等 ★Annual Report ★SEC Filings Form 10-K Annual report[2005.3.14] - [pdf,331p] ●Advancing Therapeitics Truvada - http://www.truvada.com/ Viread - http://www.viread.com/
●日本たばこ産業株式会社 --- 鳥居薬品 53.5% ●ニュースリリース 抗HIV薬「エムトリバ(R)カプセル200mg」、「ツルバダ(TM)錠」の新発売について[2005.4.8] - 「エムトリバ(R)カプセル200mg」(エムトリシタビン) - 「ツルバダ(TM)錠」(エムトリシタビンとフマル酸テノホビル ジソプロキシルの配合剤) 共に承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19。 抗HIV薬「ビリアード(R)錠300mg」の新発売について[2004.4.5] - (一般名：フマル酸テノホビル ジソプロキシル) 承認申請2004.1.19、輸入承認2004.3.25、薬価収載2004.4.2、発売2004.4.12(鳥居薬品) ●医療用医薬品一覧 ●IR情報 ファクトブック[28p] - 医薬事業関連データ2003 25-26p (発売製品、概況) 医療用医薬品臨床開発品目 - 医療用医薬品臨床開発品目（2005年4月27日現在） - 各旧リストもある
●鳥居薬品株式会社 ●プレスリリース ●財務情報 --- 決算短信等に個別製品売上の記載なし ●医療関係者向け情報 [新発売のご案内]エムトリバカプセル、ツルバダ錠[pdf,2005.4] ビリアード錠300mg 添付文書[html]|[pdf] - インタビューフォーム[pdf]
[1203]●製品 abacavir/lamivudine(Epzicom[GSK])
日本語版註）abacavir sulfate/lamivudine(Epzicom[GSK])
【別名】 【開発元】GSK [DBR_ID]
【化学名】
【承認】FDA申請=2003.10.7、FDA承認=Aug.02/2004 ; 【製剤】Each orange, film-coated tablet contains the active ingredients 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine and the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. 【適応】indicated for the treatment of HIV-1 infection 【用法用量】成人で１日１回１錠を他のantiretroviral agentsと併用して用いる。 【作用】 【特徴】 【製品情報】 【添付文書】Epzicom Tablet -PI 【EU】Kivexa INN:Abacavir/Lamivudine[GSK] - CHMP=2004.9.7承認勧告,MA=2004.12.17 【日本】エプジコム錠[グラクソ・スミスクライン株式会社]薬価基準収載年月=2005年1月;販売開始年月=2005年1月7日 【製剤～日本】1錠中にラミブジン300mg、硫酸アバカビル702mg（アバカビルとして600mg） 【適応～日本】HIV感染症 【用法用量～日本】通常、成人には1回1錠（ラミブジンとして300mg及びアバカビルとして600mg）を1日1回経口投与する。 【添付文書～日本】エプジコム錠 添付文書 - インタビューフォーム【その他】日本語版註）lamivudine(Epivir[GSK])ラミブジン(エピビル錠)
【別名】3TC 【開発元】GSK [DBR_ID]
【化学名】(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one.; C8H11N3O3S ; m.w.229.3 daltons.
【承認】FDA申請=、FDA承認=Nov 17, 1995; 【製剤】錠150mg,300mg、経口液10mg/mL 【適応】indicated for the treatment of HIV infection 【用法用量】成人は１日300mgを１回または２分服、３ヵ月～１６才は１日4mg/Kgを２回 【作用】核酸系逆転写酵素阻害剤 【特徴】 【製品情報】 【添付文書】Epivir 【EU】Epivir[Glaxo]MA=1996.8.8 【日本】エピビル錠150,300(GSK): [150mg]薬価収載1997.2、販売開始1997.2 [300mg]薬価収載2003.9、販売開始2003.10.8 【製剤～日本】１錠中ラミブジン150mg,300mg 【適応～日本】下記疾患における他の抗HIV 薬との併用療法：HIV 感染症 【用法用量～日本】通常、成人には他の抗HIV 薬と併用して、ラミブジンとして1日量300mgを1日1回又は2回（150mg×2）に分けて経口投与する。 【添付文書～日本】エピビル錠150,300 -インタビューフォーム 【その他】
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =EPZICOM FDA Application No. =NDA # 021652 Active Ingredient(s)=ABACAVIR SULFATE; LAMIVUDINE Company =SMITHKLINE BEECHAM Dosage Form/Route =TABLET; ORAL:EQ 600MG BASE; 300MG Strength = - Approval Date=Aug.02/2004 :Label[添付文書]|Letter[承認書]| Drug Name(s) =TRIZIVIR FDA Application No. =NDA # 021205 Active Ingredient(s)=ABACAVIR SULFATE; LAMIVUDINE; ZIDOVUDINE Company =GLAXOSMITHKLINE Dosage Form/Route =TABLET; ORAL EQ 300MG BASE; 150MG; 300MG Strength = - Approval Date=11/14/2000 :Label[添付文書]|Letter[承認書]|Review Drug Name(s) =ZIAGEN FDA Application No. =NDA # 020977 Active Ingredient(s)=ABACAVIR SULFATE Company =GLAXOSMITHKLINE Dosage Form/Route =TABLET; ORAL EQ 300MG BASE Strength = - Approval Date=12/17/1998 :Label[添付文書]|Letter[承認書]|Review - Approval Date=12/15/2000[002] :Review -Efficacy Supplement with Clinical Data to Support - Approval Date=04/15/2004[011] :Label[添付文書]|Letter[承認書]| -Accelerated Approval - Approval Date=08/02/2004[012] :Label[添付文書]|Letter[承認書]|-New Dosage Regimen FDA Application No. =NDA # 020978 Active Ingredient(s)=ABACAVIR SULFATE Company =GLAXOSMITHKLINE Dosage Form/Route =SOLUTION; ORAL EQ 20MG BASE/ML Strength = - Approval Date=12/17/1998 :Label[添付文書]|Letter[承認書]|Review - Approval Date=12/15/2000[002] :Review -Efficacy Supplement with Clinical Data to Support - Approval Date=04/15/2004[013] :Label[添付文書]|Letter[承認書]| -Accelerated Approval - Approval Date=08/02/2004[014] :Label[添付文書]|Letter[承認書]| -New Dosage Regimen Drug Name(s) =Combivir FDA Application No. =NDA # 020857 Active Ingredient(s)=LAMIVUDINE; ZIDOVUDINE Company =GLAXOSMITHKLINE Dosage Form/Route =TABLET; ORAL:150MG; 300MG Strength = - Approval Date=09/26/1997 :Label[添付文書,2004.9.29]|Letter[承認書,2004.9.29]|Review[2000.9.26] Drug Name(s) =EPIVIR FDA Application No. =NDA # 020564 Active Ingredient(s)=LAMIVUDINE Company =GLAXOSMITHKLINE Dosage Form/Route =TABLET; ORAL:150MG ;300MG Strength = - Approval Date=11/17/1995 - Approval Date=04/11/1997[002] 適応追加・修正 - Approval Date=06/24/2002[015] 新用量 :Label[添付文書]|Letter[承認書]|Review[2001.3.6] - Approval Date=11/22/2004[020] 承認 :Label[添付文書]|Letter[承認書]| Drug Name(s) =EPIVIR FDA Application No. =NDA # 020596 Active Ingredient(s)=LAMIVUDINE Company =GLAXOSMITHKLINE Dosage Form/Route =SOLUTION; ORAL:10MG/ML Strength = - Approval Date=11/17/1995 - Approval Date=04/11/1997[002] 適応追加・修正 - Approval Date=06/24/2002[015] 新用量 :Label[添付文書]|Letter[承認書]|Review[2001.3.6] - Approval Date=11/22/2004[020] 承認 :Label[添付文書]|Letter[承認書]|
●Electronic Orange Book Application Number: 021652 Active Ingredient : ABACAVIR SULFATE; LAMIVUDINE Proprietary Name : EPZICOM [SMITHKLINE BEECHAM] TABLET; ORAL EQ 600MG BASE;300MG Approval Date : Aug 2, 2004 Exclusivity Data : - Patent Data : 5034394 DEC 18,2011 Y Y 5047407 NOV 17,2009 Y Y U-257 5089500 JUN 26,2009 U-257 5905082 MAY 18,2016 Y Y 6180639 JAN 30,2018 Y U-257 6294540 MAY 14,2018 Y Y U-257 6417191 MAR 28,2016 Y U-257 Application Number: 021205 Active Ingredient : ABACAVIR SULFATE; LAMIVUDINE; ZIDOVUDINE Proprietary Name : TRIZIVIR [GLAXOSMITHKLINE] TABLET; ORAL EQ 300MG BASE;150MG;300MG Approval Date : Nov 14, 2000 Exclusivity Data : - Patent Data : 4724232 SEP 17,2005 4818538 SEP 17,2005 4828838 SEP 17,2005 4833130 SEP 17,2005 4837208 SEP 17,2005 5034394 JUN 26,2009 5034394*PED DEC 26,2009 5047407 NOV 17,2009 5047407*PED MAY 17,2010 5089500 JUN 26,2009 U-248 5089500*PED DEC 26,2009 U-248 5905082 MAY 18,2016 5905082*PED NOV 18,2016 6180639 JAN 30,2018 U-248 6180639*PED JUL 30,2018 U-248 6294540 MAY 14,2018 U-65 6294540*PED NOV 14,2018 U-65 6417191 MAR 28,2016 U-248 Application Number: 020596 Active Ingredient : LAMIVUDINE Proprietary Name : EPIVIR [GLAXOSMITHKLINE] SOLUTION; ORAL 10MG/ML Approval Date : Nov 17, 1995 Exclusivity Data : D-2 JUN 24,2005 Patent Data : 5047407 NOV 17,2009 5047407*PED MAY 17,2010 6004968 MAR 20,2018 6004968*PED SEP 20,2018 6180639 JAN 30,2018 U-248 6180639*PED JUL 30,2018 U-248 Application Number: 021004 Active Ingredient : LAMIVUDINE Proprietary Name : EPIVIR-HBV [GLAXOSMITHKLINE] SOLUTION; ORAL 5MG/ML Approval Date : Dec 8, 1998 Exclusivity Data : PED FEB 16,2005 I-339 AUG 16,2004 Patent Data : 5047407 NOV 17,2009 5047407*PED MAY 17,2010 5532246 JUL 02,2013 U-250 5532246*PED JAN 02,2014 U-250 6004968 MAR 20,2018 6004968*PED SEP 20,2018 Application Number: 021003 Active Ingredient : LAMIVUDINE Proprietary Name : EPIVIR-HBV [GLAXOSMITHKLINE] TABLET; ORAL 100MG Approval Date : Dec 8, 1998 Exclusivity Data : PED FEB 16,2005 I-339 AUG 16,2004 Patent Data : 5047407 NOV 17,2009 5047407*PED MAY 17,2010 5532246 JUL 02,2013 U-250 5532246*PED JAN 02,2014 U-250 5905082 MAY 18,2016 5905082*PED NOV 18,2016 Application Number: 020564 Active Ingredient : LAMIVUDINE Proprietary Name : EPIVIR [GLAXOSMITHKLINE] TABLET; ORAL 150MG,300MG Approval Date : Nov 17, 1995(Tabs-150mg)/Jun 24, 2002(Tabs-300mg) Exclusivity Data : D-2 JUN 24,2005 Patent Data : 5047407 NOV 17,2009 5047407*PED MAY 17,2010 5905082 MAY 18,2016 5905082*PED NOV 18,2016 6180639 JAN 30,2018 U-248 6180639*PED JUL 30,2018 U-248 Application Number: 020857 Active Ingredient : LAMIVUDINE; ZIDOVUDINE Proprietary Name : COMBIVIR [GLAXOSMITHKLINE] TABLET; ORAL 150MG;300MG Approval Date : Sep 26, 1997 Exclusivity Data : - Patent Data : SEP 17,2005 4818538 SEP 17,2005 4828838 SEP 17,2005 4833130 SEP 17,2005 4837208 SEP 17,2005 5047407 NOV 17,2009 5047407*PED MAY 17,2010 5859021 MAY 15,2012 U-248 5905082 MAY 18,2016 U-248 5905082*PED NOV 18,2016 U-248 6113920 OCT 23,2017 U-257 6180639 JAN 30,2018 U-248 6180639*PED JUL 30,2018 U-248
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] Kivexa INN:Abacavir/Lamivudine - Published 14/01/08 CHMP=2004.9.7承認勧告,MA=2004.12.17 [Therapeutic Indication] Kivexa is a fixed-dose combination of two nucleoside analogues (abacavir and lamivudine). It is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection in adults and adolescents from 12 years of age. The demonstration of the benefit of the combination abacavir/lamivudine as a once daily regimen in antiretroviral therapy, is mainly based on results of one study performed in primarily asymptomatic treatment-naive adult patients
●Glaxo SmithKleine ●GlaxoSmithKline - 製品サイト Prescription Medicines Epzicom Epzicom Tablet -PI ●GlaxoSmithKline - Media Press Releases GlaxoSmithKline receives European approval for KIVEXA, new once-daily HIV medication combining two antiretrovirals in one tablet[2004.12.15] - 本日KinevaをEU承認。 EPIVIR (lamivudine, 3TC) and ZIAGEN(abacavir sulfate, ABC) の配合剤。 [適応]treatment of HIV infection in combination with other antiretroviral medications in adults and adolescents from 12 years of age. GlaxoSmithKline receives European CHMP positive opinion for new once-daily HIV medication combining two antiretrovirals in one tablet[2004.9.17] - KIVEXAに関してCHMPの承認勧告を受けた。 FDA approves Epzicom - a new HIV medication combining two antiretrovirals in one tablet dosed once a day[2004.8.2,PDF] - 本日FDA承認。 ●Investors ★GlaxoSmithKline - PRODUCT PIPELINE ★Financial Reports～Annual Reports Annual Report /Annual Review / 20-F 2004[pdf,213p;2005.3.8] ★Financial Results～季刊報告
●グラクソ・スミスクライン - http://www.glaxosmithkline.co.jp/ ●プレスリリース HIV感染症治療薬に新たな選択肢-グラクソ・スミスクライン、HIV感染症治療薬、
「エプジコム(R)錠」および「レクシヴァ(R)錠700」新発売[2005.1.7] - グラクソ・スミスクライン株式会社は、本日2005年1月7日付で、HIV感染症治療薬、「エプジコム(R)錠」(一般名:ラミブジン/硫酸アバカビル)及び「レクシヴァ(R)錠700」 (一般名:ホスアンプレナビルカルシウム水和物)の発売を開始。 グラクソ・スミスクライン、新しい1日1回投与のHIV感染症治療薬、「エピビル錠300」新発売[2003.10.8] ●医療関係者 エプジコム錠 添付文書 - インタビューフォーム エピビル錠150,300 添付文書 - インタビューフォーム レクシヴァ錠700 添付文書 - インタビューフォーム レトロビルカプセル 添付文書 ザイアジェン錠 添付文書 - インタビューフォーム コンビビル錠 添付文書
[1169]●製品 emtricitabine (Emtriva [Gilead])エムトリバ(R)カプセル
日本語版註）emtricitabine エムトリシタビン(Emtriva [Gileadギリアド社])エムトリバ(R)カプセル
【別名】(－)-FTC; 524W91; BW-524W91; FTC-(－) 【開発元】Gilead Science [DBR_ID]43322 [625A]
【化学名】5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.m
【承認】FDA申請=2002.9.3、FDA承認=02-Jul-2003、発売=2003.7 ;【製剤】Capsule; Oral 200MG 【適応】indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults. 【用法用量】18才以上、１日１回200mg 【作用】HIVの増殖に関わる逆転写酵素の働きを阻害する核酸系逆転写酵素阻害剤 【特徴】1日1回1カプセル（200mg）の投与で有効性を示すため、患者の服薬負担が少なく、長期的な服薬遵守の促進につながる 【製品情報】www.emtriva.com 【添付文書】http://www.gilead.com/pdf/emtriva_pi.pdf 【EU】Emtriva[Gilead Sciences]; 諮問委CPMP勧告=2003.7.24; 承認ECMA=2003.10.28 【日本】エムトリバカプセル200mg(製造販売元／日本たばこ産業株式会社 販売元／鳥居薬品株式会社 提携／GILEAD)契約2003.7.31、承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19。 【製剤～日本】1カプセル中エムトリシタビンとして200mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常，成人にはエムトリシタビンとして1回200mgを1日1回経口投与する。なお，投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】エムトリバ添付文書 | エムトリバインタビューフォーム 【その他】nucleoside reverse transcriptase inhibitor (NRTI)抗HIV（逆転写酵素阻害）
抗HIV薬「エムトリバ(R)カプセル200mg」、「ツルバダ(TM)錠」の新発売について[2005.4.8] - 「エムトリバ(R)カプセル200mg」(エムトリシタビン) ●2000 USP DICTIONARY SUPPLEMENT 2[27(1)-Jan/Feb,2001] Emtricitabine [1998] (em trye sye' ta been). C8H103O3S. 247.24. (1) (2R-cis)-4-Amino-5-fluoro-1-[2-(hydroxy- methyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone; (2) 5- Fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5- yl]cytosine. CAS-143491-57-0. INN. Antiviral (treatment of HIV-1 and hepatitis B infections). (Triangle) [Note?Emtricitabine has appeared in the literature with the trivial names, (-)-FTC and FTC-(-).] (-)-FTC; 524W91; BW-524W91; FTC-(-) ●Revisions of United States Adopted Names (USAN)[25(6),Nov./Dec.- 1999] Emtricitabine [1998] (em trye sye' ta been). C8H10FN3O3S. 247.24. (1) (2R-cis)-4-Amino-5-fluoro-1-[2-(hydroxymethyl)- 1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone; (2) 5-Fluoro-1- [(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. CAS- 143491-57-0. Antiviral (treatment of HIV-1 and hepatitis B infections). (Triangle) [Note?Emtricitabine has appeared in the literature with the trivial names, (－)-FTC and FTC-(－).] (－)-FTC; 524W91; BW-524W91; FTC-(－) ●INN: Emtricitabine[WHO] RINN List 42:9p; WHO Drug Information 13(3),1999●日本語版註）収録文献
[ATAZANAVIR (REYATAZ) AND EMTRICITABINE (EMTRIVA) FOR HIV INFECTION]
★RG Gish et al, Antimicrob Agents Chemother 2002; 46(6):1734-1740, Jun 2002
Dose Range Study of Pharmacokinetics, Safety, and Preliminary Antiviral Activity of Emtricitabine in Adults with Hepatitis B Virus Infection
★X Saez-Llorens et al, Conf Retroviruses Opportunistic Infect 2003, February 10-14; 10:abstract 872
★L Nieto-Cisneros et al and R Badaro et al, Antivir Ther 2003; 8 suppl 1:S212, abstracts 117 and 118 x
★I Sanne et al, Int Conf AIDS 2002; July 7-12; 14:abstract Tu PeB4432
★T Schnell et al, AIDS 2003; 17(8):1258-1262,May 23, 2003
Distinct cross-resistance profiles of the new protease inhibitors amprenavir, lopinavir, and atazanavir in a panel of clinical samples[要ID]
【日本語版コメント】
エイズ治療はこの10 年間ほどで急速な進歩をとげた。 HIV遺伝子の働きを抑えて、未感染の細胞に感染しにくくする逆転写酵素阻害剤（reverse transcriptase inhibitor,RTI ）２種とHIV感染細胞からのHIV産生を抑える優れた蛋白分解酵素（プロテアーゼ）阻害剤（protease inhibitor, PI）（あるいは非ヌクレオシド系逆転写酵素阻害剤）1 種との組み合わせによる多剤（3 剤）併用療法（highly active antiretroviral therapy, HAART ）が奏効し、米国では死亡数が半減した。
しかし耐性の問題などから死亡数減少も頭打ちになりつつあり、副作用の問題も依然残されている。（HIV感染症の臨床症状、予防法などについて[2003.12.11 by 愛知県衛生研究所]が最新の優れたレビュー）→詳細は参考資料●リソース：エイズ治療剤に纏めた。＜日本語版コメント用要約＞
・1日1回投与の新規HIV治療薬2剤が承認された。
・アタザナビルは従来のプロテアーゼ阻害薬（PI）とは異なる構造を持つアザペプチドPI。
・エムトリシタビンは、化学的にラミブジンに類似したヌクレオシド系逆転写酵素阻害薬（NRTI）。
・いずれも他剤を上回る有効性を示してはいないものの、HIV治療が簡易化され、遵守性が増加する可能性がある。
・アタザナビルは他のPIよりも脂質代謝異常を引き起こしにくいと思われる。
●承認データ：FDA
情報ソース●CDER New and Generic Drug Approvals: 1998-2003 Emtriva (emtricitabine) Capsules, 200 mg Gilead Sciences, Inc. Application #=NDA 21-500 Approval Date=7/2/03 Letter Posted=7/8/03 Label Posted =7/82/03 Review Posted=9/9/03 情報ソース●NDA APPROVALS FOR CALENDAR YEAR 2003 NDA NUMBER =21500 DRUG NAME =Emtriva GENERIC NAME =Emtricitabine APPLICANT/SPONSOR=Gilead CHEMICAL TYPE =1 THERAPEUTIC CLASS=S APPROVAL DATE =02-Jul-03 情報ソース●NME Approved in Calendar Year 2003 NDA Number =21500 Generic Name =Emtricitabine Trade Name =Emtriva Dosage Form =Capsule Applicant =Gilead Classification =1S Approval Date =02-Jul-03
●Electronic Orange Book Application Number: 021500 Active Ingredient : EMTRICITABINE Proprietary Name : EMTRIVA (Capsule; Oral 200MG) [Gilead] Approval Date : JUL 02, 2003 Exclusivity Data : NCE JUL 02,2008 Patent Data : #5210085 MAY 11,2010 #5814639 SEP 29,2015 #5914331 SEP 29,2015
●Emtriva Consumer Information Brand Name: Emtriva(R) Active Ingredient: emtricitabine Strength(s): 200 mg Dosage Form(s): Capsule Company Name: Gilead Sciences Availability: Prescription only *Date Approved by the FDA: July 2, 2003
What is Emtriva used for? Emtriva is a type of medicine called an HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitor (NRTI). Emtriva helps to block HIV reverse transcriptase, a chemical in your body (enzyme) that is needed for HIV to multiply. Emtriva is always used with other anti-HIV medicines to treat people with HIV infection. Emtriva is for adults age 18 and older. Emtriva has not been studied fully in children under age 18 or adults over age 65.
Emtriva does not cure HIV infection or AIDS. The long-term effects of Emtriva are not known at this time. Emtriva may lower the amount of HIV in the blood (viral load). Emtriva may also help to increase the number of T cells called CD4 cells. Lowering the amount of HIV in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections). People taking Emtriva may still get opportunistic infections or other conditions that happen with HIV infection.
Emtriva does not lower your chances of passing HIV to other people through sexual contact, sharing needles, or being exposed to blood. For your health and the health of others, it is important to always practice safe sex and never use or share dirty needles.
It is very important that you see your healthcare provider regularly while taking Emtriva.
Who should not take Emtriva?
Do not take Emtriva if you are allergic to Emtriva or any of its ingredients.
Special Warnings:
- Some people who have taken medicines like Emtriva (a nucleoside analog) have developed a serious condition called lactic acidosis (buildup of an acid in the blood). Lactic acidosis can be a medical emergency and may need to be treated in the hospital.
- Some people who have taken medicines like Emtriva have developed serious liver problems called hepatotoxicity, with liver enlargement and fat in the liver called steatosis.
- You may be more likely to get lactic acidosis or liver problems if you are female, very overweight (obese), or have been taking nucleoside analog medicines, like Emtriva, for a long time.
General Precautions with Emtriva:
- Do not breast-feed.
- Avoid doing things that can spread HIV infection since Emtriva does not stop you from passing HIV infection to others.
- Do not share needles or other injection equipment.
- Do not share personal items that can have blood or body fluids on them, like toothbrushes or razor blades.
- Do not have sex of any kind without protection. Always practice safer sex by using a latex or polyurethane condom or other barrier to reduce the chance of sexual contact with semen, vaginal secretions, or blood.
What should I tell my health care provider?
Tell your health care provider:
- if you are pregnant or planning to become pregnant.
- if you are breast-feeding.
- if you have kidney problems.
- if you have any liver problems including Hepatitis B Virus infection.
- about all your medical conditions.
- about all the medicines you take, such as prescription and non-prescription medicines and dietary supplements.
What are some possible side effects of Emtriva? (This is NOT a complete list of side effects reported with Emtriva. Your health care provider or pharmacist can discuss with you a more complete list of side effects.)
Serious side effects with Emtriva include:
- lactic acidosis
- serious liver problems
- "flare-ups" of hepatitis B virus infection. Patients with hepatitis B virus infection, who take Emtriva and then stop it, may get "flare-ups" of their hepatitis. A "flare-ups" is when the disease suddenly returns in a worse way than before. Emtriva is not for the treatment of Hepatitis B Virus (HBV) infection.
Some common side effects with Emtriva include:
- changes in body fat distribution
- headache
- diarrhea
- nausea
- rash
- skin discoloration
The long-term effects of Emtriva are not known at this time.
For more detailed information about Emtriva, ask your health care provider or pharmacist.Posted 8/27/03
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] Emtriva[Gilead Sciences]; - CPMP 2003.7.24承認勧告；2003.10.24承認 [Therapeutic indication]
Emtriva is indicated for the treatment of HIV 1 infected adults and children in combination with other antiretroviral agents.This indication is based on studies in treatment naive patients and treatment experienced patients with stable virological control. There is no experience of the use of Emtriva in patients who are failing their current regimen or who have failed multiple regimens.
When deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the patterns of mutations associated with different medicinal products and the treatment history of the individual patient. Where available, resistance testing may be appropriate.
●Gilead Science
【製品情報】 www.emtriva.com 【添付文書】 http://www.gilead.com/pdf/emtriva_pi.pdf ●NewsOctober 28, 2003★Gilead Sciences� HIV Drug Emtriva� Approved for Marketing in European Union
August 11, 2003★Gilead Initiates Study 934, a 48-week Clinical Trial Evaluating Viread(R) and Emtriva versus Combivir(R)
July 31, 2003★Gilead and Japan Tobacco Sign Licensing Agreement for Commercialization of Gilead's HIV Products in Japan★Viread(R) (tenofovir disoproxil fumarate), EmtrivaTM (emtricitabine)
July 24, 2003★European CPMP Gives Positive Opinion on Emtriva�, Gilead's New Once-Daily Treatment for HIV
July 14, 2003★Phase III Trial of Emtriva�, New Once-Daily Capsule for HIV, Shows Continued Response through 60 Weeks
July 2, 2003★U.S. FDA Approves Gilead Sciences� Emtriva�, a One-Capsule, Once-Daily Medication for the Treatment of HIV February 11, 2003★Phase III Data Show Emtricitabine Maintains Viral Load Suppression as Part of Once-Daily, Protease-Sparing Anti-HIV Regimen
●日本たばこ
●ニュースリリース 抗HIV薬「エムトリバ(R)カプセル200mg」、「ツルバダ(TM)錠」の新発売について[2005.4.8] - 「エムトリバ(R)カプセル200mg」(エムトリシタビン) - 「ツルバダ(TM)錠」(エムトリシタビンとフマル酸テノホビル ジソプロキシルの配合剤) 共に承認申請2005.1.25、輸入承認2005.3.22、薬価収載2005.4.6、発売2005.4.19。2003年7月31日★米国ギリアド・サイエンシズ社との抗HIV剤の日本におけるライセンス契約の締結について
-フマル酸テノフォビル・ジソプロキシル（経口） 抗HIV（逆転写酵素阻害） 申請準備中 米国ギリアド・サイエンシズ社から導入
- エムトリシタビン（経口） 抗HIV（逆転写酵素阻害） 申請準備中 米国ギリアド・サイエンシズ社から導入
●鳥居薬品株式会社 ●プレスリリース ●財務情報 --- 決算短信等に個別製品売上の記載なし ●医療関係者向け情報 [新発売のご案内]エムトリバカプセル、ツルバダ錠[pdf,2005.4] ビリアード錠300mg 添付文書[html]|[pdf] - インタビューフォーム[pdf]
[1169]●製品 硫酸アタザナビルatazanavir(レイアタッツREYATAZ[BMS])
日本語版註）硫酸アタザナビルatazanavir sulfate(レイアタッツREYATAZ[BMS])
【別名】BMS-232632-05 【開発元】Novartisが創製しBMSにライセンス [DBR_ID]x
【化学名】dimethyl(3S,8S,9S,12S)-9-benzyl-3,12,di-tert-butyl-8-hydroxy-4,11-dioxo-6-(p-2-pyridylbenzyl)-2,5,6,10,13-pentaazatetradecanedioate, sulfate (1:1)(salt); CAS-229975-97-7
【承認】FDA申請=2002.12.20、FDA承認=20-Jun-2003、米国発売=2003.7 ;【製剤】Capsules - 100 mg, 150 mg, or 200 mg 【適応】indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 【用法用量】 【作用】HIVプロテアーゼ阻害剤 【特徴】レイアタッツカプセルは他の抗ＨＩＶ薬との併用療法で用いられるプロテアーゼ阻害剤で、この系統の薬剤としては日本で初めて１日１回投与を実現。 1回２カプセル（1カプセル200mg x 2）と服用量が少ない上、脂質への影響も少ないことが大きな特徴。 また、耐性変異出現率は低く、未治療患者に対する使用において耐性が出現した場合には、独自の耐性変異（Ｉ５０Ｌ）が現れることにより、他のプロテアーゼ阻害剤に対するウイルス感受性を向上させ、将来の治療に柔軟性をもたらす可能性がある。 既存のプロテアーゼ阻害剤と同等の効果があるが、①投与法が１日１回②脂質代謝異常の出現頻度が少ない③他のプロテアーゼ阻害剤の耐性ウイルスにも効果がある――などの特徴を持つ。
【製品情報】www.reyataz.com 【添付文書】Reyataz Full Prescribing Information
【EU】Reyataz[BMS]; 申請2002.5.29; CPMP承認勧告 21/Nov/03、承認2004.3.2 【日本】レイアタッツカプセル150mg,200mg[発売元／ブリストル・マイヤーズ株式会社 製造販売元／ブリストル製薬有限会社 ]申請2003.10、薬事・食品衛生審議会医薬品第二部会承認了承2003.11.21 薬価収載2003.12.25,販売開始年月=2004年１月6日 【製剤～日本】１カプセル中，硫酸アタザナビル170.84mg(アタザナビルとして150mgに相当)または227.79mg(アタザナビルとして200mgに相当)を含有する。【適応～日本】HIV-1感染症 【用法用量～日本】通常成人には，アタザナビルとして400mgを１日１回食事中又は食直後に経口投与する。 投与に際しては必ず他の抗HIV薬と併用すること。 なお，中等度の肝障害患者には300mgを１日１回に減量して投与することが推奨される。 【添付文書～日本】レイアタッツカプセル150mg,200mg 【その他】
●2001 USP DICTIONARY SUPPLEMENT 5[28(2)-Mar/Apr,2002] Atazanavir Sulfate [2002] (at a za na' veer). C38H52N6O7・H2 SO4. 801.94. (1) 2,5,6,10,13-Pentaazatetradecanedioic acid, 3-12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phe- nylmethyl)-6-[[-4-(2-pyridinyl)phenyl]methyl]-, dimethyl es- ter, (3S,8S,9S,12S)-, sulfate (1:1) (salt); (2) Dimethyl (3S,8S,9S,12S)-9-benzyl-3,12,di-tert-butyl-8-hydroxy-4,11- dioxo-6-(p-2-pyridylbenzyl)-2,5,6,10,13-pentaazatetradeca- nedioate, sulfate (1:1) (salt). CAS-229975-97-7. Treatment of acute and chronic HIV infection (HIV protease inhibitor). (Bristol-Myers Squibb) BMS-232632-05 ●USAN:atazanavir sulfate[AMA]2001-2002
●承認データ：FDA
情報ソース●CDER New and Generic Drug Approvals: 1998-2003 REYATAZ (atazanavir) capsules, 100mg, 150mg and 200mg Bristol-Myers Squibb Application #=NDA 21-567 Approval Date=6/20/03 Letter Posted=8/6/03 Label Posted =7/8/03 Review Posted=9/9/03 情報ソース●NDA APPROVALS FOR CALENDAR YEAR 2003 NDA NUMBER =21567 DRUG NAME =Reyataz GENERIC NAME =Atazanavir Sulfate APPLICANT/SPONSOR=Bristol Myers Squibb CHEMICAL TYPE =1 THERAPEUTIC CLASS=P APPROVAL DATE =20-Jun-03 情報ソース●NME Approved in Calendar Year 2003 NDA Number =21567 Generic Name =Atazanavir Sulfate Trade Name =Reyataz Dosage Form =Capsule Applicant =Bristol Myers Squibb Classification =1P Approval Date =20-Jun-03
●Electronic Orange Book Application Number: 021567 Active Ingredient : ATAZANAVIR SULFATE Proprietary Name : REYATAZ (Capsule; Oral EQ 100MG,150mg,200mg BASE ) Approval Date : JUN 20, 2003 Exclusivity Data : NCE JUN 20,2008 Patent Data : 5849911 APR 09,2017 6087383 DEC 21,2018
●Reyataz Consumer Information - http://www.fda.gov/cder/consumerinfo/druginfo/reyataz.HTM
●FDA Advisory Committees 参考●ML_ADD資料：FDA諮問委員会～議題 FDA Advisory Committees FDAAdvisorycommittee.com CDER■Antiviral Drugs - http://www.fda.gov/ohrms/dockets/ac/cder03.html#AntiviralDrugs FDAAdvisorycommittee.com: Antiviral Drugs
ML 開催日 議題 備考 1169 2003.05.13 Bristol's Reyataz For HIV Treatment
※プロテアーゼ阻害剤2002.12.20申請。他のプロテアーゼ阻害剤と併用。特徴は、1)１日１回投与、2)他のPIではしばしば見られる高脂血症が、本剤では脂質プロファイルが良好
※結果は、全員一致で承認勧告(atazanavir capsules and powder)
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Reyataz from Meeting of the Committee for Proprietary Medicinal Products (CPMP)[Press Release -EMEA 21 November 2003] Atazanavir Reyataz Hard capsules, oral powder 100, 150 and 200 mg, 50 mg/1.5g CPMP承認勧告 21/Nov/03 Reyataz (atazanavir sulphate), from Bristol-Myers Squibb Pharma EEIG, intended for the treatment of HIV-1infected, antiretroviral treatment experienced adults, in combination with other antiretroviral medicinal products EMEA review began on 20 May 2002 and the opinion was adopted on 20 November 2003, with an active review time of 200 days.
●BMS
【製品情報】 www.reyataz.com 【添付文書】 Reyataz Full Prescribing Information ●プレス Presse release07.15.2003★Regimen Containing Ritonavir-Boosted Reyataz� (Atazanavir Sulfate) Demonstrates Comparable Viral Load Reduction Through Week 24 To A Regimen Containing Kaletra(R) (Lopinavir/Ritonavir) In Highly-Treatment Experienced HIV/AIDS Patients
06.20.2003★First Once-Daily Protease Inhibitor -- Reyataz� (atazanavir sulfate) -- Approved By U.S. Food and Drug Administration As Part Of Combination Therapy For The Treatment Of HIV/AIDS
05.13.2003★FDA Antiviral Advisory Committee Recommends Approval For Bristol-Myers Squibb's Investigational Protease Inhibitor Reyataz(TM) (Atazanavir)
02.11.2003★Resistance Data Presented Show Early Use Of Atazanavir May Lead To Increased Viral Susceptibility To Other Protease Inhibitors
12.20.2002★Bristol-Myers Squibb Submits New Drug Application for Investigational Protease Inhibitior Atazanavir For Treatment Of HIV Infection
09.28.2002★Data Show Bristol-Myers Squibb's Investigational Protease Inhibitor Atazanavir Provided Antiviral Effect Comparable To Sustiva(R)In Treatment-Na�ve HIV/AIDS Patients
09.27.2002★Bristol-Myers Squibb Early Access Program Can Provide Investigational Protease Inhibitor Atazanavir For Eligible Patients With HIV
05.29.2002★Bristol-Myers Squibb Announces Marketing Authorization Application Submitted In Europe For Atazanavir, An Investigational Protease Inhibitor
http://www.bms.com/news/press/data/fg_press_release_3353.html
●ブリストル・マイヤーズ株式会社
●最新情報 抗ＨＩＶ薬レイアタッツカプセルを新発売[2003.12.19]2003-6-23★米国食品医薬品局（ＦＤＡ） 初の１日１回投与のプロテアーゼ阻害薬レイアタッツ（硫酸アタザナビル）を承認★FDAからHIV-1感染の治療において他の抗レトロウイルス剤との併用療法で用いられる治療薬として販売承認を取得。 FDAが承認した初の1日1回投与のプロテアーゼ阻害薬。 FDAはレイアタッツを6カ月の優先承認審査品目に指定。 第Ⅱ相第Ⅲ相臨床試験の中核的データにより、レイアタッツは、持続的なウイルス抑制作用に加え、その特異性は独特の脂質データであり、他のプロテアーゼ阻害薬との併用においても、コレステロール及びトリグリセライド値の上昇が見られず、治療レジメンを拡大させる。
2003-2-14★米国ＢＭＳ アタザナビルの耐性データを報告 初期使用により他のプロテアーゼ阻害薬のウイルス感受性を増大する可能性を示唆
2002-12-24★米国ブリストル・マイヤーズ スクイブ社 ＨＩＶ感染治療用のプロテアーゼ阻害薬アタザナビルのＮＤＡを提出
●薬事・食品衛生審議会医薬品第二部会で承認了承：「レイアタッツカプセル」
http://yakunet.yakuji.co.jp/yakunet/yakujinippo/y_y_right_view.asp?y_y_id=36584 薬事日報 2003.11.26シスプラチン動注製剤など新薬３成分の承認了承 薬事・食品衛生審議会医薬品第二部会薬事・食品衛生審議会医薬品第二部会は２１日、ＨＩＶ治療薬「レイアタッツカプセル」、肝細胞癌治療薬「動注用アイエーコール」「動注用コナプリ」など、新薬３成分について審議を行い、いずれも承認して差し支えないとした。また、希少疾病用医薬品２品目の指定も了承された。
▽レイアタッツカプセル１５０、同２００（ブリストル製薬が輸入）：有効成分は硫酸アタザナビル。プロテアーゼ阻害剤でＨＩＶ‐１感染症を効能・効果とする新有効成分医薬品。希少疾病用医薬品に指定されていた。再審査期間は１０年、原体・製剤とも劇薬に指定される。
米国では６月に承認されている。既存のプロテアーゼ阻害剤と同等の効果があるが、①投与法が１日１回②脂質代謝異常の出現頻度が少ない③他のプロテアーゼ阻害剤の耐性ウイルスにも効果がある――などの特徴を持つ。
また、「国内の薬物動態試験については、試験が終了次第、可及的速やかに試験成績、結果を提出すること」「臨床試験については、定期的に試験成績を報告し、終了次第、可及的速やかに試験成績、結果を提出すること」などが承認条件となった。
[1160]●HIV検査薬
日本語版註）OraQuick Rapid HIV-1 Antibody Test[OraSure Technologies, Inc.]
【別名】 【開発元】OraSure Technologies, Inc [DBR_ID]x
【化学名】A kit contsains 1)Test device 2)Absorbent packet 3)Developer solution vial など
【承認】FDA申請=、FDA承認=7-Nov-2002、CLIA (Clinical Laboratory Improvements Amendments of 1988) waiver for the test受取=2003.1.31 ;【製剤】方法 Rapid EIA 検体 全血(指先穿刺) 【適応】a rapid, point-of-care test designed to detect antibodies to HIV-1 within 20 minutes 【製品情報】http://www.orasure.com/products/default.asp?sec=2&subx=2&cid=2&prd=134 【添付文書】http://www.orasure.com/uploaded/331.pdf?134&sec=2&subsec=2 【EU】 【日本】未開発 【その他】
●FDA-CBER Premarket Approval Information: OraQuick Rapid HIV-1 Antibody Test Applicant: OraSure Technologies, Inc, Bethlehem, PA Product: OraQuick Rapid HIV-1 Antibody Test PMA number: BP010047 Indication for Use: Detection of HIV-1 antibodies in fingerstick whole blood specimens Approval Date: 11/7/2002 -------------------------------------------------- Letter (Text) Label (PDF) Summary (PDF) Talkpaper Frequently Asked Questions (FAQs)
●ニュース ●Wider Use of Rapid HIV Test[FDA Updates--January-February 2003 FDA Consumer] 20分で99.6%の精度でHIVを検出するというので、HHS Secretary Tommy G. Thompsonは 迅速HIV検査が現在の38,000ラボから10万拠点にまで拡大できると期待。 現在米国では毎年約8000人がHIV検査を受けにpublic clinicsにやってくるが、１週間 後でないと結果が判明しない。
●OraSure Technologies, Inc - http://www.orasure.com/ ●Press Release OraSure Technologies Announces Record 2003 Second Quarter Results[2003.7.29] CDC Commits $2 Million for Purchase Of OraQuick Rapid HIV-1 Antibody Tests [2003.6.26] - CDCは、2003.12末迄に25万テスト$2 million相当の OraQuick Rapid HIV-1 Antibody Test is Highlighted in New CDC HIV Prevention Initiative [2003.4.28] - CDCがRapid Testingを推奨。CDC's Morbidity and Mortality Weekly Report ("MMWR ") (April 18, 2003 / Vol. 52 / No. 15), の中で、新しいHIV testing initiative で 迅速検査がkey componentであり、OraQuick (R)Rapid HIV-1 Antibody Test がFDAで承認 された唯一のCLIA (Clinical Laboratory Improvements Amendments of 1988) waived rapid HIV-1 test であるとしている。 新しいCDC initiativeは、"Advancing HIV Prevention: New Strategies for a Changi ng Epidemic," というタイトルで妊婦と、20万人とされるHIVウイルス保菌者に対してHIV 検査をルーチン化する事を目的とする。 CDCは新しいHIV検査戦略に$35 million を予算計上、 OraSure Receives CLIA Waiver for OraQuick Rapid HIV-1 Antibody Test [2003.1.31] - これによりoutreach clinics, community-based organizations and physicians' officesを含む多数のSitesでの使用が認められた。 OraSure Begins Shipment of OraQuick Rapid HIV-1 Antibody Test; OraSure Fills Initial Stocking Order to Abbott Laboratories[2003.1.7] - 共同販売提携先Abbott社(2002.6.17契約)に本日5万テスト分初出荷。 米国内の年間HIV検査件数は1700万件と推定、OraSure→Abbottの2003年売上は $4 millionを予定。 OraSure Technologies Announces First International Order for OraQuick Rapid HIV Test[2000.10.23] -- 南アEdison Africa (S.A.) から初の国際注文(10万単位)
日本語版註）Reveal Rapid HIV-1 Antibody Test[MedMira Laboratories, Inc.]
【別名】 【開発元】MedMira Inc. [DBR_ID]x
【化学名】次のものを含むキット。 1)Test cartridge(免疫反応性膜を含む) 2)Disposable pipette 3)Desiccant packet 4)MedMira Colorimetric Detection Agent比色定量検出剤 (a proprietary protein A-colloidal gold conjugate) 5)MedMira HIV-1 Human Test Control 6)MedMira Universal Buffer
【承認】FDA申請=、FDA承認=16-Apr-2003、発売=2003.5.15 ;【製剤】方法 Rapid Immunoassay 検体 血清/血漿 【適応】 【製品情報】http://www.reveal-hiv.com/ 【添付文書】http://www.reveal-hiv.com/pdf/Reveal_Pa.pdf 【EU】 【日本】未開発 【その他】FDA承認を受けた最初で唯一のrapid, point-of-care test designed to detect HIV-1 antibodies。３分で検査終了
●MedMira Inc. - http://www.medmira.com/ ●http://www.reveal-hiv.com/ ●News MedMira announces Third Quarter 2003 Results[2003.6.30,pdf,3p] - We began shipping the Reveal. Rapid HIV Test to our US distributor in May and to date we have shipped some 100,000 kits. In July we expect to further expand production and shipments as we start shipping the MiraWell. Rapid HIV Test to China.” MedMira Announces Initial Shipment and Launch of RevealTM Rapid HIV-1 Antibody test in the United States[2003.5.15] - 米国総販売代理店Cardinal Health向け。数量は50万. RevealTM Rapid HIV-1 Antibody Test Indicates 100% sensitivty in Independent Clinical Study[2003.5.5] MedMira Received Additional China Order for 150,000 Rapid HIV Tests[2003.4.23] MedMira Received FDA Approval[2003.4.17]
【日本語版コメント】
日本の場合、都道府県各行政単位の窓口や保健所でエイズ相談・HIV抗体検査態勢は整っている。 無料化されているところが大半で、夜間対応、匿名にも応じるところもある。 通常HIV抗体検査には一週間程度要するわけだが、今回採り上げた最近のFDA承認検査薬は、OraQuickが20分、Revealが３分と迅速かつ簡便。 日本でも既に個人輸入代行の対象品目として登場している[OraQuick]。
→詳細は参考資料●リソース：HIV検査薬に纏めた。
＜日本語版コメント用要約＞
・2種類のHIV感染の迅速検査法が使用できるようになった。
・これまでの検査法は患者が結果を聞くために再受診する必要があったため、陽性患者の1/3は結果を聞きに来なかった。
・迅速検査法を使用すれば初回受診時に予備結果がわかり、カウンセリングも行うことができるため、確認検査の結果を聞きに来る患者が増えると思われる。
・メーカーによると、いずれの検査法も99%以上の高感度、高特異性である。
●参考資料 エイズ治療拠点病院におけるＨＩＶ抗体検査の実施について[2002.3.27健疾発] 「サーベイランスのためのＨＩＶ感染症／診断基準」によるＨＩＶ感染症の診断による抗体スクリーニング検査法が実施される。 「HIV-1/2感染症診断法(日本エイズ学会推奨法)」[日本エイズ学会] ＨＩＶ検査・相談マップ http://www.hivkensa.com/ 厚生労働省科学研究費エイズ対策研究事業「HIVの検査法と検査体制を確立するための研究班」（班長：神奈川県衛生研究所 今井光信）が提供。 FDA承認HIV検査薬一覧 Licensed / Approved HIV, HTLV and Hepatitis Tests CDC -National HIV Testing Resources
■FDA - CBER : Devices
- http://www.fda.gov/cber/devices.htm; FDAのCBER[Center for Biologics Evaluation and Research]は、生物製剤の審査部門 この中でDevices[用具]部がHIV検査薬の担当。 Licensed / Approved HIV, HTLV and Hepatitis Tests Frequently Asked Questions About the OraQuick Rapid HIV-1 Antibody Test
●FDA承認HIV検査薬一覧 from Licensed / Approved HIV, HTLV and Hepatitis Tests 2003.6.9更新 ●Antibody to Hepatitis B Surface Antigen (HBsAg Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Auszyme Monoclonal EIA Serum / Plasma Donor Screen & Conf. Kit Abbott Laboratories
Abbott Park, IL
US License 00434/1/1985 Genetic Systems HBsAg EIA 3.0 EIA Serum / Plasma / Cadaveric Serum Donor Screen & Conf. Kit Bio-Rad Laboratories
Redmond, WA 98052
US License 11091/23/2003 ORTHO Antibody to HBsAg ELISA Test System 3 EIA Serum / Plasma Donor Screen / Diagnosis & Conf. Kit Ortho-Clinical Diagnostics, Inc.
Raritan, NJ 08869
US License 12364/24/2003 AUK-3 RIA Serum / Plasma Donor Screen & Conf. Kit DiaSorin s.r.l.
Saluggia, Italy
US License 12575/9/1986 ETI-MAK-2 EIA Serum / Plasma Donor Screen & Conf. Kit DiaSorin s.r.l. 4/18/1995 ●Antibody to Human Immunodeficiency Virus (HIV-1 Antigen Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Abbott HIVAG-1 Monoclonal EIA Serum / Plasma Donor Screen / Prognosis & Neut. Kit Abbott Laboratories
Abbott Park, IL
US License 00434/23/1996 Coulter HIV-1 p24 Ag Assay;
HIV-1 p24 Antigen ELISA Test SystemEIA Serum / Plasma Donor Screen / Prognosis & Neut. Kit Coulter Corporation
Miami, FL
US License 11853/14/1996 Abbott HIVAG-1 EIA Serum / Plasma Prognosis & Neut. Kit Abbott Laboratories 8/3/1989 Coulter HIV-1 p24 Ag Assay EIA Viral Culture Supernatant Prognosis (Quantitative) & Neut. Kit Coulter Corporation 3/14/1996 ●Anti-HIV-1 Oral Specimen Collection Device
Tradename(s) Format Sample Use Manufacturer Approval Date Epitope OraSure HIV-1 Oral Specimen Collection Device Oral Specimen Collection Device Oral Fluid For Use in Designated Non-Donor Screen and Non-Donor Supplemental Assays Epitope, Inc.
Beaverton, OR12/23/1994 ●Anti-HIV-1 Testing Service
Tradename(s) Format Sample Use Manufacturer Approval Date Home Access HIV-1 Test System Dried Blood Spot Collection Device Dried Blood Spot Non-Donor Screen Home Access Health Corp.
Hoffman Estates, IL7/22/1996 ●Hepatitis B Surface Antigen (Anti-HBs Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Ausab RIA Serum / Plasma Anti-HBs Abbott Laboratories
Abbott Park, IL
US License 00432/5/1975 Ausab EIA EIA Serum / Plasma Anti-HBs Abbott Laboratories 11/18/1982 AB-AUK-3 RIA Serum / Plasma Anti-HBs DiaSorin s.r.l.
Saluggia, Italy
US License 12576/27/1989 ETI-AB-AUK EIA Serum / Plasma Anti-HBs DiaSorin s.r.l. 4/18/1995 ●Hepatitis B Virus Core Antigen (Anti-HBc Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Corzyme EIA Serum / Plasma Donor Screen Abbott Laboratories
Abbott Park, IL
US License 00433/19/1991 Ortho HBc ELISA Test System EIA Serum / Plasma Donor Screen Ortho-Clinical Diagnostics, Inc.
Raritan, NJ
US License 12364/18/1991 AB-COREK RIA Serum / Plasma Donor Screen DiaSorin s.r.l.
Saluggia, Italy
US License 12573/19/1991 ETI-AB-COREK EIA Serum / Plasma Donor Screen DiaSorin s.r.l. 3/19/1991 ●Hepatitis C Virus Encoded Antigen (Anti-HCV Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Abbott HCV EIA 2.0 EIA Serum / Plasma Donor Screen Abbott Laboratories
Abbott Park, IL
US License 00435/6/1992 Ortho HCV Version 3.0 ELISA Test System EIA Serum / Plasma Donor Screen Ortho-Clinical Diagnostics, Inc.
Raritan, NJ
US License 12365/20/1996 Chiron RIBA HCV 3.0 Strip Immunoblot Assay SIA Serum / Plasma Donor Supplemental Chiron Corporation
Emeryville, CA
US License 11062/11/1999 ●HIV-1 /HCV Nucleic Acid Testing
Tradename(s) Format Sample Use Manufacturer Approval Date Roche Amplicor HIV-1 Monitor Test PCR Plasma Prognosis / Patient Management
HIV-1 Viral Load AssayRoche Molecular Systems, Inc.
Branchburg Township, NJ3/2/1999 NucliSens HIV-1 QT NASBA Plasma Prognosis / Patient Management
HIV-1 Viral Load AssaybioMerieux, Inc.
100 Rodolphe Street
Durham, NC 2771211/19/2001 COBAS Ampliscreen HIV-1 Test PCR Plasma Donor Screen Roche Molecular Systems, Inc
4300 Hacienda Drive
Pleasanton, CA 94566-099012/20/2002 Procleix HIV-1/HCV Nucleic Acid Test (TMA) Plasma Donor Screen Gen-Probe
10210 Genetic Center Drive
San Diego, CA 921212/8/2002 Trugene HIV-1 Genotyping Kit and Open Gene DNA Sequencing System HIV-1 Genotyping Plasma Patient Monitoring Visible Genetics, Inc.
700 Bay Street , Suite 1000
Toronto, CA4/24/2002 UltraQual HIV-1 RT-PCR Assay PCR Plasma Donor Screen National Genetics Institute
Los Angeles, CA 921219/18/2001 UltraQual HCV RT-PCR Assay PCR Plasma Donor Screen National Genetics Institute
Los Angeles, CA 921219/18/2001 ViroSeq HIV-1 Genotyping System HIV-1 Genotyping Plasma Patient Monitoring Applied Biosystems
Foster City, CA 9440412/10/2002 Versant HIV-1 RNA 3.0 (bDNA) Signal amplification nucleic acid probe Plasma Patient Monitoring Bayer Corporation
Berkeley, CA 947029/11/2002 COBAS AmpliScreen HCV Test PCR Plasma Donor Screen Roche Molecular Systems, Inc
4300 Hacienda Drive
Pleasanton, California 94566-099012/3/2002 ●Human Immunodeficiency Virus Type 1 (Anti-HIV-1 Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date HIVAB HIV-1 EIA EIA Serum / Plasma Donor Screen Abbott Laboratories
Abbott Park, IL
US License 00433/1/1985 Genetic Systems rLAV EIA EIA Serum / Plasma Donor Screen Bio-Rad Laboratories Blood Virus Division
Redmond, WA
US License 11096/29/1998 Murex SUDS HIV-1 Test Rapid EIA Serum / Plasma Donor Screen Murex Diagnostics, Inc.
Norcross, GA
US License 11525/22/1992 Vironostika HIV-1 Microelisa System EIA Serum / Plasma Donor Screen bioMerieux, Inc.
100 Rodolphe Street
Durham, NC 27712
US License 162412/18/1987 Vironostika HIV-1 Plus O Microelisa System EIA Plasma / Serum / Dried Blood Spots Diagnostic, Non-Donor Screen bioMerieux, Inc.
100 Rodolphe Street
Durham, NC 27712
US License 16246/6/2003 Cambridge Biotech HIV-1 Western Blot Kit WB Serum / Plasma Donor Supplemental Calypte Biomedical Corp.
Berkeley, CA
US License 12071/3/1991 Genetic Systems HIV-1 Western Blot WB Serum / Plasma Donor Supplemental Bio-Rad Laboratories Blood Virus Division 11/13/1998 Fluorognost HIV-1 IFA IFA Serum / Plasma Donor Supplemental Waldheim Pharmazeutika G.m.b.H.
Vienna, Austria
US License 11502/5/1992 HIVAB HIV-1 EIA EIA Dried Blood Spot Non-Donor Screen Abbott Laboratories 4/22/1992 HIV-1 Urine EIA EIA Urine Screen Non-Donor Screen Calypte Biomedical Corp. 8/6/1996 Genetic Systems rLAV EIA EIA Dried Blood Spot Non-Donor Screen Bio-Rad Laboratories Blood Virus Division 6/29/1998 Vironostika HIV-1 Microelisa System EIA Dried Blood Spot Non-Donor Screen bioMerieux, Inc.
100 Rodolphe Street
Durham, NC 277124/11/1990 Oral Fluid Vironostika HIV-1 Microelisa System EIA Oral Fluid Non-Donor Screen bioMerieux, Inc.
100 Rodolphe Street
Durham, NC 2771212/23/1994 Cambridge Biotech HIV-1 Western Blot Kit WB Urine Non-Donor Supplemental Calypte Biomedical Corp. 5/28/1998 Genetic Systems HIV-1 Western Blot WB Dried Blood Spot Non-Donor Supplemental Bio-Rad Laboratories Blood Virus Division 11/13/1998 OraSure HIV-1 Western Blot Kit WB Oral Fluid Non-Donor Supplemental Epitope, Inc. 6/3/1996 Fluorognost HIV-1 IFA IFA Dried Blood Spot Non-Donor Supplemental Waldheim Pharmazeutika G.m.b.H. 5/14/1996 OraQuick Rapid HIV-1 Antibody Test Rapid EIA Fingerstick Non-Donor Screen OraSure Technologies, Inc.
150 Webster Street
Bethlehem, PA 18015-138911/7/2002 Reveal Rapid HIV-1 Antibody Test Rapid Immunoassay Serum / Plasma Non-Donor Screen MedMira Laboratories, Inc.
Halifax, Nova Scotia
Canada B3S 1B34/16/2003 ●Human Immunodeficiency Virus Types 1 & 2 (Anti-HIV-1/2 Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Abbott HIVAB HIV-1/HIV-2 (rDNA) EIA EIA Serum / Plasma Donor Screen Abbott Laboratories
Abbott Park, IL
US License 00432/14/1992 Genetic Systems HIV-1/HIV-2 Peptide EIA EIA Serum / Plasma / Cadaveric Serum Donor Screen Bio-Rad Laboratories Blood Virus Division
Redmond, WA
US License 110912/9/2000 ●Human Immunodeficiency Virus Type 2 (Anti-HIV-2 Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Genetic Systems HIV-2 EIA EIA Serum / Plasma Donor Screen Bio-Rad Laboratories Blood Virus Division
Redmond, WA
US License 11094/25/1990 ●Human T-Lymphotropic Virus Types I & II (Anti-HTLV-I/II Assay)
Tradename(s) Format Sample Use Manufacturer Approval Date Abbott HTLV-I/HTLV-II EIA EIA Serum / Plasma Donor Screen Abbott Laboratories
Abbott Park, IL
US License 00438/15/1997 Vironostika HTLV-I/II Microelisa System EIA Serum / Plasma Donor Screen bioMerieux, Inc.
100 Rodolphe Street
Durham, NC 27712
US License 16241/17/1998
■関連データ
●関連データ
ＨＩＶ検査・相談マップ http://www.hivkensa.com/ 厚生労働省科学研究費エイズ対策研究事業「HIVの検査法と検査体制を確立するための 研究班」（班長：神奈川県衛生研究所 今井光信）が提供しています。 東京都エイズ・結核・感染症のページ http://www.kenkou.metro.tokyo.jp/kansen/ ＨＩＶ感染症についての情報が掲載されています。また、 南新宿検査相談室の案内 のほか、ＨＩＶ検査実施保健所のリストなどが掲載されています。 「HIV-1/2感染症診断法(日本エイズ学会推奨法)」[日本エイズ学会] - http://jaids.umin.ac.jp/; 2002.12 ●保険新規収載検査[日本臨床検査専門医会] ＨＩＶ-1, 2抗体価（準用先区分D012-14）（区分D-2）[1999.6.1] ダイナスクリーン・HIV-1／2[ダイナボット] -測定法：イムノクロマトグラフィー法定性検査 結果が出るまでの時間：約15分 HIV-1核酸増幅定量精密検査（準用先区分D023-5）（区分D-1[1997.4.1] アンプリコアHIV－1モニター[日本ロシュ] -測定方法：PCR法及び核酸ハイブリダイゼーション法 結果が出るまでの時間：6時間30分 ●CDC -MMWR[Morbidity Mortality Weekly Report] - Advancing HIV Prevention: New Strategies for a Changing Epidemic --- United States, 2003 [MMWR Weekly April 18, 2003 / 52(15);329-332] National HIV Testing Day, June 27, 2003[MMWR Weekly June 27, 2003 / 52(25);581] ●Lateral flow法 lateral-flowは"側方流動"を意味するが、lateral-flow法は妊娠診断薬で使われはじめた。 Lateral Flow Assays Pregnancy and fertiliy tests Concurrent engineering for lateral-flow diagnostics ●Flow-Through法 訳註）検出試薬が飼料を捕捉し、膜を通って流れる(flow through)。迅速検査法 Rapid Diagnostic Test Technologies: Flow-Through ・Reveal Rapid HIV-1 Antibody Test (MedMira) is a rapid immunoassay that was approved by the FDA in April 2003. It consists of a flow-through device contain ing an immunoreactive membrane coated with HIV-1 antigens. ・A rapid, flow-through diagnostic immunoassay ・The agent would simply flow through the membrane, leaving a uniform, faint-pin kish background on the test membrane. cf.Flow-Through Platers フロースループレーター
■ニュース
●【米国薬事情報】血漿のＨＩＶ及びＨＣＶ検査に核酸増幅法を許可 ＦＤＡ http://yakunet.yakuji.co.jp/yakunet/yakujinippo/y_y_right_view.asp?y_y_id=24140
薬事日報：01/10/15
ＦＤＡは九月二十一日に血漿提供者の適格審査を意図した初の核酸増幅法検査（ＮＡＴ）システムを許可した。この検査システムは、供血者のヒト免疫不全ウイルス（ＨＩＶ）またはＣ型肝炎ウイルス（ＨＣＶ）感染を早期に検出でき、血漿分画製剤の安全をさらに確保する期待がある。
すべての米国で許可された血漿分画製剤の製造においてウイルス不活化の効果的操作が要求されるが、供血者の適格審査で感染の可能性ある供血を排除することは、製造工程で取り除くべきウイルス汚染量を制限して予防効果を高める。
新承認の検査システムは、凝固因子や免疫グロブリンなどの製造に使う血漿を選別するため、ロスアンゼルスのナショナル・ジェネティクス・インスチチュート社（ＮＧＩ）が開発した。同地のアルファ・セラピューティック社（ＡＴＣ）にも血漿採取施設での新検査システム使用が承認された。
ＮＡＴは最近開発された技術で、遺伝子フラグメントの大量複製（増幅）処理により極めて少量の遺伝物質（ＤＮＡまたはＲＮＡ）の検出を可能にする。この承認検査システムは多数の供血者から得た五一二件の血漿サンプルの検査プールからＨＩＶ‐１（米国で非常に多くのエイズ症例の原因とされるＨＩＶ変異株）及びＨＣＶのＲＮＡを高感度に検出した。
検出用にプール血漿サンプルを使用し、ＮＡＴシステムを使用すれば費用効率はさらに高まる。検査プールでいずれかのウイルスが陽性なら、ウイルスを含むと疑われた個人の供血を確認し、それは製造用に使わない。そして当該供血者には供血不適と通知される。
現在、血液及び血漿の供血者はＨＣＶ抗体、ＨＩＶ抗体及びウイルス自身の蛋白であるＨＩＶ‐１抗原について検査されている。しかし供血者が感染していても、スクリーニング検査が陰性のウインドー期（検出不可能期）がある。ＮＡＴの使用でＨＣＶ検出のウインドー期は平均で八二日から二五日に五七日短縮した。ＨＩＶ‐１は抗体検査の平均ウインドー期が二二日である。抗原検査ではウインドー期が約一六日に縮まり、ＮＡＴはこの期間をさらに一二日に縮めた。
この承認で根拠とした臨床試験は、三三カ所の血漿成分採取センターが約四万八〇〇〇人の供血者から集めた合計四万二七二九件の採血につき行われたＨＩＶ‐１及びＨＣＶの検査である。ＮＡＴシステムは従来の許可検査法では見逃された多くのＨＩＶ‐１及びＨＣＶ感染が見つかり、同システムの有効性が証明された。今後、抗体検査はすべての血漿成分供血に実施されるが、ＨＩＶに対するＮＡＴの採用で今後ＡＴＣは抗原検査を中止する。
九七年以降、ＦＤＡは血漿分画製剤の安全性を改善し、感染の危険がある血液ユニットの輸血をさらに減らすため、治験実施計画によるＮＡＴ技術の研究を助成してきた。
●ＮＡＴのＢＬＡ申請をＦＤＡが１２日受領 米国ジェン・プローブ社、米国カイロン社 http://yakunet.yakuji.co.jp/yakunet/yakujinippo/y_y_right_view.asp?y_y_id=20413
薬事日報：01/03/16
中外製薬の十三日付ニュースリリースによると、同社一〇〇％子会社の米国ジェン・プローブ社と、米国カイロン社は、ヒト免疫不全ウイルス１型（ＨＩＶ‐１）とＣ型肝炎ウイルス（ＨＣＶ）のための核酸増幅法検査（ＮＡＴ）のＢＬＡ（Biologics License Application）申請をＦＤＡが十二日付で受領した。
ＢＬＡ申請の受領とは、販売許可のための審査が行えるだけの情報が提出物の中に十分揃っているとＦＤＡが判断したことを意味するもの。今回開発されたＮＡＴはジェン・プローブ社が開発したＴＭＡ（Transcription Mediated Amplification）技術に基づくもの。
[1159]●製品 enfuvirtide(Fuzeon [Trimeris/Roche]
日本語版註）enfuvirtide(Fuzeon [Trimeris/Roche]
(en fyoo' vir tide)エンフューヴィルタイド「フューゼオン」
【別名】T-20; DP178; Ro 29-9800;pentafuside 【開発元】Trimeris[US]トライメリス社 [DBR_ID]48270(TC=625A)
【化学名】CH3CO-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu-Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn-Trp-Phe-NH2; CAS-159519-65-0
【承認】FDA申請=17-Sept-2002、FDA承認=3-Mar-2003、発売=27-Mar-2003[Roche] ;【製剤】Injectable; Subcutaneous 90MG/VIAL;１日２回 【適応】FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. 【用法用量】 【作用】現在唯一の融合阻害剤。細胞侵入時におきるGp41の構造変化の段階を阻害すると考えられる。36個のアミノ酸からなる合成ペプチドであり、半減期は3.8時間と短いため、冷蔵庫保存が必要であり、1日2回の皮下注射が必要である。 【特徴】初のHIV-細胞融合阻害剤。T-20は多剤耐性HIVに感染している患者においても強い抗HIVを示すが、問題点も多い。例えば、経口投与ができないこと(注射部位反応98%)やその治療費が高いことなどである。そのため、経口投与ができる小分子化合物の開発が期待されている。 【製品情報】http://www.fuzeon.com/ 【添付文書】http://www.rocheusa.com/products/fuzeon/ 【EU】FuzeonINN:Enfuvirtide[Roche]申請=20-Sept-2002; 諮問委CPMP勧告=19-Mar-2003; 承認=27-May-2003 【日本】未開発 【その他】Antiviral(blockade of gp-41 mediated membrane fusion); FUZEON (enfuvirtide) is an inhibitor of the fusion of HIV-1 with CD4+ cells. Enfuvirtide is a linear 36-amino acid synthetic peptide with the N-terminus acetylated and the C-terminus is a carboxamide. It is composed of naturally occurring L-amino acid residues.
Rec INN List 47: enfuvirtide[WHO Drug Information 16(1),2002; 10p/32p] Proposed INN List 85: enfuvirtide[WHO Drug Information 15(2),2001; 11p/41p] 2001 USP DICTIONARY SUPPLEMENT 3 Enfuvirtide [2001] (en fyoo' vir tide). C204H301N51O64. 4492.00. (1) L-Phenylalaninamide, N-acetyl-L-tyrosyl-L-threonyl-L-seryl- L-leucyl-L-isoleucyl-L-histadyl-L-seryl-L-leucyl-L-isoleucyl- L--glutamyl-L--glutamyl-L-seryl-L-glutaminyl-L-asparagi- nyl-L-glutaminyl-L-glutaminyl-L--glutamyl-L-lysyl-L-aspar- aginyl-L--glutamyl-L-glutaminyl-L--glutamyl-L-leucyl-L- leucyl-L--glutamyl-L-leucyl-L--aspartyl-L-lysyl-L-trypto- phyl-L-alanyl-L-seryl-L-leucyl-L-tryptophyl-L-asparaginyl-L- tryptophyl-; (2) N-Acetyl-L-tyrosyl-L-threonyl-L-seryl-L-leu- cyl-L-isoleucyl-L-histadyl-L-seryl-L-leucyl-L-isoleucyl-L-- glutamyl-L--glutamyl-L-seryl-L-glutaminyl-L-asparaginyl- L-glutaminyl-L-glutaminyl-L--glutamyl-L-lysyl-L-asparagi- nyl-L--glutamyl-L-glutaminyl-L--glutamyl-L-leucyl-L-leu- cyl-L--glutamyl-L-leucyl-L--aspartyl-L-lysyl-L-tryptophyl- L-alanyl-L-seryl-L-leucyl-L-tryptophyl-L-asparaginyl-L-tryp- tophyl-L-phenylalaninamide. CAS-159519-65-0. Antiviral (blockade of gp-41 mediated membrane fusion). (Roche Col- orado); (Trimeris) [Note-The trivial name, pentafuside, has appeared in literature.] T20; DP178
【日本語版コメント】
全く新しい融合阻害剤という種類の抗HIV治療薬が米国で発売された。 画期的新薬で副作用の点でも、臨床試験では98%の患者で注射部位反応が観察されたが、投薬中止は3%と少なかった。
どういう点が画期的かというと、他の抗HIV薬が、既にヒト免疫細胞(CD4)に侵入している状態のHIVに対して働くのと違って、Fuzeonは最初の段階で、HIVが免疫細胞に感染する能力をブロックするわけだ。
今年３月末に発売されたが、供給体制の問題もあり、2003年Q2売上はも米国$4.3 million、米国外$870,000。→詳細は参考資料●MLリソース：エイズ治療剤に纏めた。
＜日本語版コメント用要約＞
・融合阻害剤と呼ばれる新しいクラスのHIV治療薬、enfuvirtideがFDAの加速審査により承認された。
・本剤はHIVウィルスエンベロープのgp41に結合し、形態変化を防ぐことによって、ウィルスの細胞内への侵入を阻害する。
・本剤を有効な抗レトロウィルス療法と併用することによって、治療効果が高くなることが認められた。
・皮下注投与による注射部位反応が主な副作用で、臨床試験では98%の患者に認められている。
●承認データ：FDA
情報ソース●CDER New and Generic Drug Approvals: 1998-2003 Fuzeon (enfuvirtide) Injection, 90 mg, Rx Hoffman-La Roche, Inc. Application #=NDA 21-481 Approval Date=3/13/03 Letter Posted=3/20/03 Label Posted =3/18/03 Review Posted=7/23/03 情報ソース●NDA APPROVALS FOR CALENDAR YEAR 2003 NDA NUMBER =21481 DRUG NAME =Fuzeon GENERIC NAME =Enfuvirtide APPLICANT/SPONSOR=Roche CHEMICAL TYPE =1 THERAPEUTIC CLASS=P APPROVAL DATE =13-Mar-03 情報ソース●NME Approved in Calendar Year 2003 NDA Number =21481 Generic Name =Enfuvirtide Trade Name =Fuzeon Dosage Form =Injectable Applicant =Roche Classification =1P Approval Date =13-Mar-03
●Electronic Orange Book Application Number: 021481 Active Ingredient : ENFUVIRTIDE Proprietary Name : FUZEON Approval Date : MAR 13, 2003 Exclusivity Data : MAR 13,2008 Patent Data : 5464933 JUN 07,2013 6133418 JUN 07,2013 6475491 JUN 07,2015 Injectable; Subcutaneous 90MG/VIAL
●NDAs Approved under Subpart H
ML NDA # Trade
NameGeneric
NameClock Date Approval Date AP Time Appr
oval
BasisIndication 1159 21481 Fuzeon Enfuvirtide 19-Sep-02 13-Mar-03 5.9 S Provides for the use of Fuzeon (enfuvirtide) for injection, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in treatment experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy
●Fast Track Designated Products Approved since 1998
ML NDA# NDA Drug Name Sponsor Applicant Approval Date Indication 1159 N21481 Fuzeon (Enfuviritide) Lypholized Powder Hoffmann LaRoche 3/13/03 Treatment of HIV
●FDA -Consumer Drug Information: Fuzeon - http://www.fda.gov/cder/consumerinfo/druginfo/fuzeon.htm Brand Name: Fuzeon(R) Active Ingredient: enfuvirtide Strength(s): 90mg/mL Dosage Form(s): Injection Company Name: Hoffmann-LaRoche, Inc. Availability: Prescription only *Date Approved by FDA: March 13, 2003
What is Fuzeon used for? Fuzeon is used with other anti-HIV medicines to treat adults and children ages 6 years and older with HIV infection. Fuzeon is not used by itself to treat HIV infection. Fuzeon does not cure HIV-infection or AIDS and does not prevent HIV-transmission.
Fuzeon is called an HIV fusion inhibitor. Fuzeon blocks HIV痴 ability to infect healthy CD4 cells. When used with other anti-HIV medicines, Fuzeon can reduce the amount of HIV in the blood and increase the number of CD4 cells. This may keep your immune system healthy so it can help fight infection.
Who should not use Fuzeon?
Do not use Fuzeon if you are allergic to any of the ingredients in Fuzeon.
Special Warning(s) with Fuzeon:
- Almost all people get injection site reactions with Fuzeon. Reactions are usually mild to moderate but occasionally may be severe. Reactions on the skin where Fuzeon is injected include itching, swelling, redness, pain or tenderness, hardened skin, and bumps.
- Patients with HIV get bacterial pneumonia more often than patients without HIV. In clinical trials, patients taking Fuzeon with other HIV medicines got bacterial pneumonia more often than patients not receiving Fuzeon. It is unclear if this was related to the use of Fuzeon. You should contact your healthcare provider right away if you have a cough, fever or trouble breathing.
- Fuzeon can cause serious allergic reactions. Symptoms of a serious allergic reaction with Fuzeon can include trouble breathing, fever with vomiting and a skin rash, blood in your urine, and swelling of your feet. Call your healthcare provider right away if you get any of these symptoms.
General Precautions with Fuzeon:
- Avoid doing anything that can spread HIV infection since Fuzeon does not stop you from passing the HIV infection to others.
- Do not share needles or other injection equipment.
- Do not share personal items that can have blood or body fluids on them, like toothbrushes or razor blades.
- Do not have any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom or other barrier method to reduce the chance of sexual contact with semen, vaginal secretions or blood.
- Do not drive or operate heavy machinery if Fuzeon makes you feel dizzy.
- Do not change your dose or stop taking Fuzeon without first talking with your healthcare provider.
What should I tell my doctor or health care provider?
Tell your health care provider:
- if you are pregnant or plan to become pregnant. We do not know if Fuzeon can harm your unborn child. You and your health care provider will need to decide if Fuzeon is right for you. If you use Fuzeon while you are pregnant, talk to your health care provider about how you can be in the Antiretroviral Pregnancy Registry.
- if you are breast-feeding. You should not breast-feed if you are HIV-positive because of the chance of passing the HIV virus to your baby. Also, it is not known if Fuzeon can pass into your breast milk and if it can harm your baby.
- about all your medical conditions.
Tell your health care provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Fuzeon has not been tested with all medicines.
What are some possible side effects of Fuzeon? (This is NOT a complete list of side effects reported with Fuzeon. Your health care provider or pharmacist can discuss with you a more complete list of side effects.)
Some side effects with Fuzeon include:
- pain and numbness in feet or legs
- loss of sleep
- depression
- decreased appetite
- weakness or loss of strength
- muscle pain
- constipation
- pancreas problems
For more detailed information about Fuzeon, ask your health care provider or pharmacist.
Link to Fuzeon's approved label
Posted: 4/14/03
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★FuzeonINN:Enfuvirtide[Roche] 諮問委CPMP勧告=19-Mar-2003; 承認=27-May-2003 ★Therapeutic indication
Fuzeon is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected patients who have received treatment with and failed on regimens containing at least one medicinal product from each of the following antiretroviral classes, protease inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors, or who have intolerance to previous antiretroviral regimens.
In deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different medicinal products. Where available, resistance testing may be appropriate.
■メーカー
●Trimeris
- http://www.trimeris.com/ ; (Nasdaq: TRMS) 1999.7 RocheにFuzeon(T-20, enfuvirtide)の全世界開発販売権をライセンス。 Trimeris Announces 2008 Strategic Plan[2007.12.10] - Trimeris社は、従業員を減らし、次世代のHIV融合阻害剤TRI-1144のSAD(single ascending dose)第1相試験が2008年前半に完了したら研究開発機能を廃止すると発表したFuzeon はEU発売2003.6、米国発売2003.3 Fuzeonの出荷数量は、72,200キット(2007年), 79,700キット(2006年), 72,000キット(2005年)。(患者１人月１キット)
($ 000) 2007 2006 2005 2004 2003 2002 2001 備考 Milestone 9,435 3,430 1,722 2,152 2,964 1,133 1,304 Fuzeon分Rocheから Royalty 15,727 11,812 8,784 4,556 755 - - Fuzeon分Rocheから米加外分 Collaboration 24,223 21,738 8,553 (16,125) (25,515) - - Fuzeon分Rocheから米加分 (総収入) 49,385 36,980 19,059 (9,417) (21,796) 1,133 1,304 研究開発費 12,883 18,333 18,274 21,313 36,823 51,226 58,440 一般管理費 11,100 12,453 9,436 10,151 8,577 10,985 9,953 (原価経費 計) 23,983 30,786 27,710 31,464 45,400 78,933 72,218 営業利益 25,402 6,194 (8,651) (40,881) (67,196) (77,800) (70,914) 経常利益 27,801 7,407 (8,106) (40,088) (65,703) (75,678) () 当期純利益 27,425 7,384 (8,106) (40,088) (65,703) (75,678) (66,741) 従業員数[連結] 9(技術1) 64(技術39) 90(技術56) 97(技術60) 100(技術70) Fuzeon売上(Roche) 266,796 248,951 208,211 135,216 36,555 うち米加(調整前) 147,454 152,166 132,609 99,908 32,245 Roche うち米加(調整後) 124,3(-7.3) 134,161 112,734 85,693 28,345 Roche うち米加以外 142,450(+24.1) 114,790 95,477 49,523 8,210 Roche ●競合(2007)
We are engaged in a segment of the biopharmaceutical industry, the treatment of HIV, that is intensely competitive and changes rapidly. FUZEON competes, and our developmental stage HIV fusion inhibitor, TRI-1144, will compete, with numerous existing therapies. For example, there are 29 different drugs that are currently approved in the United States for the treatment of HIV. In addition, a number of companies are pursuing the development of novel pharmaceutical products that target HIV. Some companies, including several multi-national pharmaceutical companies, are simultaneously marketing several different drugs and may therefore be able to market their own combination drug therapies. We believe that a significant number of drugs are currently under development and will become available in the future for the treatment of HIV.
FUZEON is delivered via twice daily subcutaneous injections, each delivering 90 mg of FUZEON. The other approved anti-HIV drugs are delivered orally at various dosing intervals. We believe that this delivery method is one factor that may limit its uptake as compared to other competing drugs. In addition, the WAC of FUZEON is approximately $25,700 for one year of therapy. This price is significantly higher than any of the other approved anti-HIV drugs. FUZEON’s price relative to other approved anti-HIV drugs may also limit patient demand.
The standard of care for the treatment of HIV is to administer a regimen that combines drugs from each of the different classes of anti-HIV drugs. In the event drug candidates are approved that are effective against an HIV virus that has become resistant to currently approved drugs, we believe that using these drugs in combination with FUZEON may provide patients with additional treatment options that do not currently exist. These drugs may be either competitive with FUZEON, or synergistic with FUZEON, or in some circumstances, both.
The need for drugs that have a novel mechanism of action has stimulated interest in the inhibition of HIV entry into the cell. Several companies are developing or attempting to develop HIV drug candidates that inhibit entry of the virus by targeting one of the HIV co-receptors (i.e. either CCR5 or CXCR4). In 2007, Pfizer Inc. received U.S. marketing approval from the FDA for a CCR5 inhibitor, Maraviroc. Also in 2007, Schering-Plough Corp announced the initiation of Phase III studies for its CCR5 inhibitor, Vicriviroc. CCR5 inhibitors impede entry of the virus into the cell through a mechanism that is different from FUZEON.
In the latter part of 2007, Merck & Co., Inc. received U.S. FDA marketing approval for their integrase inhibitor, Raltegravir. Integrase inhibitors represent a novel class of antiretroviral drug and, like FUZEON, may be well-suited to therapy for treatment-experienced patients. Gilead Sciences, Inc. is also developing an integrase inhibitor (Elvitegravir) which is currently in clinical testing. Other companies, including Panacos Pharmaceuticals, Inc., are developing new classes of drugs with novel targets (e.g. Panacos’ maturation inhibitor, Beviramat). Tibotec Therapeutics has developed a next generation non-nucleoside reverse transcriptase inhibitor (“NNRTI”) with activity against viruses that are resistant to earlier forms of NNRTIs. Tibotec’s drug, Etravirine, received U.S. FDA marketing approval in early 2008.
We anticipate that we will face intense and increasing competition in the future as these and other new products enter the market and advanced technologies become available. Existing products or new products for the treatment of HIV developed by our competitors may be more effective, less expensive, or gain wider acceptance by patients and physicians than FUZEON or any other products eventually commercialized by us.
Many of our competitors have significantly greater financial, technical and human resources than we have and may be better able to develop, manufacture, sell, market and distribute products. Many of these competitors have products that have been approved or are in late-stage development. These competitors also operate large, well-funded research and development programs. In addition, smaller companies may prove to be significant competitors, particularly through collaborative arrangements with large pharmaceutical and biotechnology companies. Furthermore, academic institutions, governmental agencies and other public and private research organizations are becoming increasingly aware of the commercial value of their inventions for the treatment of HIV and are more actively seeking to commercialize the technology they have developed.
New developments in our areas of research and development are expected to continue at a rapid pace in both industry and academia. Our drug candidate TRI-1144, if successfully developed and approved, would face competition based on:
・ the safety and effectiveness of the products; ・ the convenience of the dosing regimen; ・ the timing and scope of regulatory approvals; ・ availability of manufacturing, sales, marketing and distribution capabilities; ・ reimbursement coverage; ・ price; and ・ patent position.While our experience to date is that new, active HIV drugs and those in clinical development have been used synergistically with FUZEON in order to achieve maximal viral suppression in treatment experienced patients, we cannot guarantee that this will translate into increased patient adoption. Our competitors may develop more effective or more affordable technology or products, or achieve earlier patent protection, product development or product commercialization than we can. Our competitors may succeed in commercializing products more rapidly or effectively than we can, which could have a material adverse effect on our business, financial condition, results of operations and the market price of our stock.★新規参入
In 2007, two new antiretroviral agents received U.S. FDA marketing approval (SELZENTRY(R) and ISENTRESS(R)) with a third (INTELENCE(R)) approved in January 2008. Data from clinical trials with these new agents continued to demonstrate the benefits of combining FUZEON in regimens that contain these new, active agents. Nevertheless, the availability of a variety of new active agents for use in treatment-experienced patients has placed significant pressure on U.S. FUZEON. Sales for the fourth quarter of 2007, in dollars, were down 25% as compared to the fourth quarter of 2006. Each of these new agents are administered orally and have the potential to provide experienced patients with a more convenient treatment regimen.
★Alternative Administration
Since the commercial launch of FUZEON in 2003, we, along with Roche, have been exploring ways to enhance a patient’s ability to initiate and remain on FUZEON containing therapies, including the potential for using the Biojector 2000 (“B2000”) needle-free delivery system.
The B2000 has been used to deliver millions of injections in a wide range of healthcare settings since receiving FDA approval in 1996. The B2000 needle-free injection works by forcing medication rapidly through a tiny orifice held against the skin, creating a fine stream of fluid that penetrates the skin and deposits medication in the subcutaneous tissue. Positive data from the T-20 405 bioequivalence study of the B2000 needle-free device (versus standard needle/syringe) formed the basis for a supplemental NDA application (“sNDA”) to the FDA in May 2005 to include use of the B2000 for administration in the FUZEON label.
In 2005, the FDA issued an approvable letter regarding the B2000 sNDA. In its reply, the FDA indicated that the filing was approvable pending receipt of the final study report from the ongoing FUZEON WAND (With a Needle-Free Device; ENF-404) study, a randomized, open-label, two-way, cross-over study assessing the tolerability of the B2000 device for administration of FUZEON.
In 2006, the Company presented results from the WAND trial, showing that it achieved the primary endpoint of a 50% reduction in the incidence of painful injection site reactions or ISR's with use of the B2000 needle-free device compared to standard needle-syringes (36% for the device vs. 71% for needle-syringe, p<0.01). Following use of both administration systems, 84% of patients preferred the B2000 needle-free device versus 16% favoring standard needle/syringe administration.
Later that same year, the Company and Roche had discussions with the FDA regarding the submission of an amended sNDA for inclusion of the B2000 device as an administration option for FUZEON. The FDA acknowledged that, based on currently available evidence, administration with B2000 achieves similar blood levels of FUZEON compared to standard needle-syringe administration. However, the FDA indicated that a small number of certain adverse events related to administration of FUZEON with the B2000 device (hematomas and nerve pain) warrant review of additional information in order to better characterize the incidence of these events. Some of these events were associated with use of B2000 to deliver FUZEON either in close proximity to bone joints or into scar tissue. In the current product label, FUZEON is recommended for injection in the upper arm, upper leg and stomach. The FUZEON labeling also cautions against injecting into scar tissue.
Based on this information, the FDA requested additional safety information on the nature and occurrence of ISRs, including data from the FUZEON BOSS (Biojector Open Label Safety Study; ENF 407) trial, as well as from other data sources. Initiated in 2006, BOSS has completed enrollment of approximately 330 current or prior FUZEON patients at 43 trial sites in the U.S. and Puerto Rico in an eight-week study to assess the safety and patient acceptance of B2000 compared to standard needle-syringe administration for FUZEON. Data from BOSS were reported at ICAAC in September 2007 and indicated that use of the B2000 device was associated with an improved ISR profile in ENF-experienced patients, including a reduction in the incidence and severity of treatment-limiting ISRs, and was preferred by the patients compared to a needle and syringe (87.2% vs. 12.5%, respectively).
In advance of receiving additional B2000 safety data, the FDA requested and received changes to the current FUZEON labeling (both Package Insert and Patient Injection Instructions) to add precautions regarding hematoma and nerve pain associated with B2000 administration, as well as precautions regarding the use of the B2000 device in patients with bleeding disorders. In October of 2007, Roche and Trimeris announced that they were withdrawing the sNDA for the B2000 based on a comprehensive assessment of the clinical program as well as the significant delay in achieving U.S. regulatory approval due to the time required to generate additional data. Patients currently administering FUZEON with the device were not advised to discontinue use of the B2000 for administration as long as they continued to follow the precautions in the FUZEON label.
★Current and Future FUZEON Clinical Trials
Following the Company’s reduction-in-workforce in 2006 and 2007, Roche has taken the primary role in conducting our current and future FUZEON clinical trials. Roche will be responsible for conducting ongoing clinical trials with FUZEON during 2008. The table below summarizes recently completed, clinical trials.
The T20 BOSS trial involves the use of the currently approved Biojector 2000 needle-free injection device manufactured by Bioject Medical Technologies, Inc., described above.
Name Description T20 BOSS An assessment of the use of the B2000 system in patients at risk of discontinuing FUZEON therapy due to injection-related difficulties. T20 Intense Comparative trial in earlier line patients assessing ongoing FUZEON use compared to an induction/ maintenance approach. T20 SwitchTox An assessment of the substitution of Anti-Retrovirals (“ARV’s”) associated with undesirable side-effects/toxicities in favor of FUZEON. T20 BLQ An assessment of FUZEON in combination with an investigational protease inhibitor.
There are no further clinical trials with FUZEON planned for initiation in 2008.
●Fuzeon ●Pipeline ■Investors ●Annual Reports 2006 Annual Report[2008.1.30] ●SEC Filings 10-K Annual Filings[2008.3.17] - [pdf] - [word] - [xls] ●Press Release Trimeris Reports Financial Results for the Fourth Quarter and Year End 2007[2008.3.13] - Trimeris Reports 2007 FUZEON(R) Sales Results[2008.1.29] - Trimeris Announces 2008 Strategic Plan[2007.12.10] - Trimeris社は、従業員を減らし、次世代のHIV融合阻害剤TRI-1144のSAD(single ascending dose)第1相試験が2008年前半に完了したら研究開発機能を廃止すると発表した Roche and Trimeris Provide Update on Development of Alternative Administration Options for Delivery of FUZEON(R)[2007.10.3] - 無針注射器Biojector(R) 2000 申請取り下げ。 Fuzeonは注射部位反応(ISR)が98%に発生し問題視されていた。 New Interim Results Demonstrate High Response Rate With FUZEON(R) Plus Darunavir Regardless of Existing Protease Inhibitor Resistance[2007.7.20] - New Trial to Study Investigational Integrase Inhibitor in Combination with FUZEON(R) Once-Daily Dosing Strategy[2007.7.17] - Trimeris Announces Management Changes[2007.3.15] - CEO & CFO退任。 Trimeris and Roche Amend Research Agreement Covering Next-Generation HIV Fusion Inhibitors[2007.3.15] - 次世代融合阻害剤TRI-1144の全権をRocheがTrimerisに返還。 Updated HIV/AIDS Treatment Guidelines Support Use of FUZEON Plus an Active Boosted Protease Inhibitor to Achieve New Treatment Goal[2005.10.13] - U.S. FDA Grants Traditional Approval for FUZEON(R), First and Only Fusion Inhibitor for the Treatment of HIV[2004.10.15] - FUZEON(R) to be Widely Available Through Specialty and Retail Pharmacies in the U.S.[2004.4.14] - Roche and Trimeris Submit 48-Week Data to U.S. FDA for Full Approval of FUZEON(R), First and Only HIV Fusion Inhibitor[2003.12.16] - New Data Confirm Durable Benefit of FUZEON-Based Regimens Among Treatment-Experienced HIV Patients, Including Those With Less Advanced and Late Stage Disease[2003.10.27] - Trimeris Announces Status of FUZEON Sales and Launch Plans[2003.9.25] - New Data Show FUZEON-Based Regimens Continue to Provide Significant Durable Response in Treatment-Experienced HIV Patients Through 48 Weeks[2003.9.15] - New Data Show FUZEON-Based Regimens Deliver Superior, Sustained Response In Treatment-Experienced Patients[2003.7.15] - The New England Journal of Medicine Publishes Results of Pivotal Trials Demonstrating Efficacy and Safety of FUZEON(TM), World's First FDA-Approved HIV Fusion Inhibitor[2003.5.28] - European Commission Approves FUZEON(TM), First HIV Fusion Inhibitor, for Use Against HIV in the European Union[2003.5.27] - Final Topline Results Show Significant Durable Response at 48 Weeks in HIV Patients Treated with FUZEON(TM) in Combination Therapy[2003.4.28] - Preliminary 48-Week Results Show Longer Term Response in HIV Patients Treated With FUZEON(TM) (enfuvirtide), First Fusion Inhibitor[2003.3.20] - U.S. FDA Approves FUZEON(TM); First Drug to Block Entry of HIV into Immune Cells[2003.3.13] - [] -
●Roche USA
FUZEONTM (enfuvirtide) - http://www.rocheusa.com/products/fuzeon/; 製品情報 ★米国Roche プレスリリース200307-15-2003 NEW DATA SHOW FUZEON-BASED REGIMENS DELIVER SUPERIOR, SUSTAINED RESPONSE IN TREATMENT-EXPERIENCED PATIENTS
05-29-2003 THE NEW ENGLAND JOURNAL OF MEDICINE PUBLISHES RESULTS OF PIVOTAL TRIALS DEMONSTRATING EFFICACY AND SAFETY OF FUZEON, WORLD'S FIRST FDA-APPROVED HIV FUSION INHIBITOR
05-28-2003 ROCHE COMMEMORATES THE 40TH ANNIVERSARY OF VALIUM INVENTOR LEO STERNBACH TURNS 95 YEARS OLD
04-28-2003 FINAL TOPLINE RESULTS SHOW SIGNIFICANT DURABLE RESPONSE AT 48 WEEKS IN HIV PATIENTS TREATED WITH FUZEON IN COMBINATION THERAPY
03-20-2003 ROCHE AND TRIMERIS ANNOUNCE U.S. FUZEON (ENFUVIRTIDE) PROGRESSIVE DISTRIBUTION AND SUPPORT PROGRAMS
03-20-2003 PRELIMINARY 48-WEEK RESULTS SHOW LONGER TERM RESPONSE IN HIV PATIENTS TREATED WITH FUZEON (ENFUVIRTIDE), FIRST FUSION INHIBITOR
03-13-2003 U.S. FDA APPROVES FUZEON; FIRST DRUG TO BLOCK ENTRY OF HIV INTO IMMUNE CELLS
02-24-2003 ROCHE ANNOUNCES EUROPEAN SPECIAL LICENSE SALES PROGRAM FOR INVESTIGATIONAL HIV DRUG FUZEON
02-10-2003 LATEST RESEARCH ON FUZEON AND T-1249, HIV FUSION INHIBITORS, TO BE PRESENTED AT UPCOMING SCIENTIFIC MEETING
●ニュース ●T-20についてのもう少し詳しい話[Positive Street]
T-20は、またの名を「エンフューヴィルタイド（enfuvirtide）」、商品名「Fuzeon」と呼ばる、従来の抗HIV薬とは全くことなる、新しいタイプの薬です。
どこが新しいかというと、これまでの抗ＨＩＶ薬（逆転写酵素阻害剤、プロティアーゼ阻害剤）はウイルスが私たちの健康なＴ細胞に入ってしまってからそれがその細胞内部で複製を作るのを邪魔するという薬でした。これに対して、このＴ20はそもそも最初の段階の、Ｔ細胞自体に入り込むことを邪魔してしまう、つまり、入り口でシャットアウトしてしまう、という点です。融合阻害剤（フュージョン阻害剤）
ＨＩＶがまず最初に私たちのＴ細胞の中に入ることを「フュージョン（融合）」と呼んでいます。それを邪魔するので、この薬の性質を「フュージョン阻害剤」と呼びます。またもっと分かりやすく「細胞侵入阻害剤（エントリー・インヒビター）」とも呼びます。
融合、つまり健康なＴ細胞への侵入を邪魔するメカニズムは簡単に言えばこういうことです。Ｔ20はＨＩＶの表面にあるｇｐ41というタンパク質にくっつく性質を持っています。するとＨＩＶの表面の形が変わってしまって、いままではぴたっとはまっていたＴ細胞の表面の形と合わなくなってしまう。それでどうにもＴ細胞にくっつけなくなってしまうのです。
Ｔ細胞にくっつけないと、その次の段階である、中に入り込んで自分のコピーを作って増殖するまでにも至れません。これまでの抗ＨＩＶ薬は、この、中に入り込んでコピーを作るという作業の「逆転写」と「タンパク質分解」に関する酵素の働きを邪魔するものでした。対して今回のＴ20は、酵素を相手にして間接的にＨＩＶの動きを邪魔するのではなく、ＨＩＶそのものにくっついて、その動きの第一段階から邪魔するという画期的な新薬なのです。
米国、欧州、豪州、南米の計１１２の病院で行った治験で、従来のカクテル療法にＴ20を組み込んだ３２６人中１２１人、つまり37％もの患者・感染者が血液中のウイルス数が推薦値まで減るという、予測を上回るものでした。Ｔ20を与えられなかった患者・感染者では従来のカクテル療法だけでしたが、そちらでウイルス量が減ったのは１６５人中27人、16％にとどまりました。
追試験でも28％対14％という同様の結果でした。効果は歴然です。また、Ｔ20を含めたカクテル療法ではＣＤ４の数値も改善されています。
よいことずくめのような報告ですが、問題も残っています。
その第一は、この薬が注射薬であることです。皮下注射で１日に２回打たなくてはなりません。
第二には副作用があります。注射した場所の皮膚が炎症を起こしがちだといわれています。また、日本では医療者以外の人が注射を行うことはできませんから、とても使いにくいということになります。
錠剤型の別のフュージョン阻害剤の開発が待たれます。
さらに、Ｔ20も他の抗ＨＩＶ薬にもありがちな下痢や吐き気、めまい、疲労感、不眠、頭痛を伴うことがあります。実際の臨床での注射量など、さらに詳しい研究と情報の蓄積が必要でしょう。
[1095]●製品Kaletra(lopinavir/ritonavir) Capsules &Oral sol.[Abbott Labs]
日本語版註） Kaletra(lopinavir/ritonavir) Capsules &Oral sol.[Abbott Labs]
【別名】 【開発元】Abbott(創製者Triangle Pharmaceuticals,Incを買収) [DBR_ID]
【承認～カプセル・液】FDA申請=31-May-2000優先審査、FDA承認=15-Sep-2000 【承認～錠】FDA申請=Apr 28,2005優先審査、FDA承認=28-Oct-2005; 【製剤】Capsules -133.3 mg lopinavir and 33.3 mg ritonavir; Oral solution -80 mg lopinavir and 20 mg ritonavir per milliliter; Tablets -200mg lopinavir and 50mg ritonavir or 100mg lopinavir and 25mg iitonavir
【適応】indicated in combination with other antiretroviral agents for the treatment of HIV-1 infections in adults and pediatric patients age six months
【用法用量】成人(未治療)は800/200mg(200/50mg４錠または10mL経口液)を１日１回または分２ 成人(治療経験者)は400/100mg(200/50mg２錠または5mL経口液)を１日２回 ６ヵ月以上の小児は１日２回体重に応じて 【作用】本剤はロピナビルとリトナビルの配合剤である． ロピナビルはHIVプロテアーゼの活性を阻害し，HIVプロテアーゼによるgag-polポリ蛋白質の開裂を抑制することで，感染性を持つ成熟したHIVの産生を抑制する．リトナビルは，CYP3Aによるロピナビルの代謝を競合的に阻害し，ロピナビルの血中濃度の上昇をもたらす．本剤の抗ウイルス活性は，ロピナビルによるものである． 本剤はHIVプロテアーゼに対する選択的親和性を有し，ヒトのアスパルティックプロテアーゼに対してはほとんど阻害作用を示さない． 【特徴】 【製品情報】http://www.kaletra.com 【添付文書】http://www.rxabbott.com/pdf/kaletratabpi.pdf
【EU】Kaletra[Abbott]MA=20 March 2001
【日本】カレトラ・ソフトカプセル／カレトラ・リキッド[アボットジャパン]承認2000.12.12薬価2000.12.15発売2000.12.25 カレトラ・リキッド[アボットジャパン]承認2000.12.12薬価2000.12.15発売2000.12.25 カレトラ錠[アボットジャパン]承認2006.9.1薬価2006.9.4発売2006.9.15 【製剤～日本】1カプセル中 ロピナビル133.3mg・リトナビル33.3mg；内用液－1mL中 ロピナビル80mg・リトナビル20mg；1錠中 ロピナビル200mg・リトナビル50mg 【適応～日本】HIV感染症 【用法用量～日本】通常，成人にはロピナビル・リトナビルとして1回400mg・100mg（5mLまたは3カプセルまたは2錠）を1日2回食後に経口投与する． なお，体重40kg以上の小児には成人と同用量投与できる． 通常，小児には，体重7kg以上15kg未満で1kgあたり12mg・3mg，15kg以上40kg以下で１kgあたり10mg・2.5mgを1日2回食後に経口投与する．最大投与量は 400mg・100mg（5mL）1日2回投与とする． 【製品情報～日本】 【添付文書～日本】カレトラ錠添付文書|カレトラ・ソフトカプセル添付文書|カレトラ・リキッド添付文書 カレトラ錠・カレトラ・リキッドインタビューフォーム|カレトラ・ソフトカプセルインタビューフォーム 【その他】●lopinavir
;【別名】ABT-378/Aluviran(R) 【開発元】Abbott(創製者Triangle Pharmaceuticals,Incを買収) [DBR_ID]
;【化学名】[1S-[1R*,(R*), 3R*, 4R*]]-N-[4-[[(2,6-dimethylphenoxy)acetyl]amino]-3-hydroxy-5-phenyl-1-(phenylmethyl)pentyl]tetrahydro-alpha-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetamide
【承認】FDA申請=、FDA承認= ; 【製剤】 【適応】 【用法用量】 【作用】 【特徴】 【製品情報】 【添付文書】 【提携】 【EU】 【日本】[] 【その他】
●ritonavir (Norvir[Abbott])ノービア
;【別名】Norvir; ABT-538 【開発元】Abbott(創製者Triangle Pharmaceuticals,Incを買収) [DBR_ID]45128
;【化学名】10-Hydroxy-2-methyl-5-(1-methylethyl)-1- [2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, [5S-(5R*,8R*,10R*,11R*)]
【承認】FDA申請=、FDA承認=1-Mar-1996; 【製剤】ソフトカプセル－100mg ritonavir： 内用液－80mg/mL of ritonavir 【適応】 indicated in combination with other antiretroviral agents for the treatment of HIV-infection【用法用量】通常，成人にはリトナビルとして1回600mg（6カプセルまたは7.5mL）を1日2回食後に経口投与する．ただし，投与初日は1回300mg以上を1日2回，2～3日目毎に1回100mg単位で増量する。 【作用】本剤は、HIV-1及びHIV-2のプロテアーゼの活性を競合的に阻害し，HIVプロテアーゼによるgag-pol蛋白質前駆体の産生を抑制することで抗ウイルス作用を示す．Ｘ線結晶解析で，本剤は基質遷移状態アナログとしてHIVアスパルティックプロテアーゼの活性部位Asp-Thr-Gly配列に直接的に結合することが示されている． 本剤は，HIVプロテアーゼに対する選択的親和性を有し，ヒトのアスパルティックプロテアーゼに対してはほとんど阻害作用を示さない． 【特徴】 【製品情報】http://www.norvir.com/ 【添付文書】http://www.rxabbott.com/pdf/norpi2a.pdf#page=1
【提携】 【EU】Norvir[Abbott]MA=26 August 1996
【日本】ノービアカプセル100mg(硬カプセル)申請1996.7.23承認1997.11.20発売1997.12.18→販売中止； ノービア・ソフトカプセル100mg[アボットジャパン]承認1999.8.25薬価1999.9.10発売1999.9.17 ノービア・リキッド[アボットジャパン]承認1998.9.25薬価1998.9.25発売1998.12.14 【製剤～日本】1カプセル中リトナビル・100mg；内用液1mL中リトナビル・80mg 【適応～日本】下記疾患におけるヌクレオシド系HIV逆転写酵素阻害剤との併用療法 1.後天性免疫不全症候群（エイズ） 2.治療前のCD4リンパ球数500/mm3以下の症候性及び無症候性HIV感染症 【用法用量～日本】通常，成人にはリトナビルとして1回600mg（6カプセルまたは7.5mL）を1日2回食後に経口投与する．ただし，投与初日は1回300mgを1日2回，2日目， 3日目は1回400mgを1日2回，4日目は1回500mgを1日2回，5日目以降は1回600mgを1日2回食後に経口投与する． 【製品情報～日本】 【添付文書～日本】ノービア・ソフトカプセル100mg添付文書|ノービア・リキッド添付文書 インタビューフォーム 【その他】
【日本語版コメント】
２種のプロテアーゼ阻害剤配合。 ２年間投与した100例中83例のHIVが検出レベル以下に低下するという成果をあげた。 FDA申請後、優先審査の対象となり６か月で承認。
■→ 抗エイズ薬・HIV感染症についての詳細は本誌1069号(16/1)[00.01.10]★HIV感染症治療薬を参照
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =KALETRA (LOPINAVIR; RITONAVIR) FDA Application No. =NDA # 021226 Active Ingredient(s)=LOPINAVIR; RITONAVIR Company =ABBOTT Dosage Form/Route =CAPSULE; ORAL 133.3MG; 33.3MG Strength = - Approval Date=09/15/2000[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date September 15, 2000 Chemical Type 1 New molecular entity (NME) 4 New combination Review Classification P Priority review drug - Approval Date=03/13/2001[002][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=01/18/2002[003][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]|Review - Approval Date=11/27/2002[006][Accelerated Approval]:Label[添付文書]|Review - Approval Date=10/19/2004[014][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]|Review - Approval Date=03/28/2005[017][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=04/29/2005[016][New Dosage Regimen]:Label[添付文書]|Letter[承認書]| - Approval Date=04/20/2007[018][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]| - Approval Date=09/26/2007[022][Labeling Revision]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 021251 Active Ingredient(s)=LOPINAVIR; RITONAVIR Company =ABBOTT Dosage Form/Route =SOLUTION; ORAL 80MG/ML; 20MG/ML Strength = - Approval Date=09/15/2000[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date September 15, 2000 Chemical Type 3 New formulation 4 New combination Review Classification P Priority review drug - Approval Date=03/13/2001[002][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=01/18/2002[004][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]|Review - Approval Date=11/27/2002[005][Accelerated Approval]:Label[添付文書]||Review - Approval Date=10/19/2004[010][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]|Review - Approval Date=04/20/2007[012][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]| - Approval Date=11/09/2007[018][New Dosage Regimen]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 021906 Active Ingredient(s)=LOPINAVIR; RITONAVIR Company =ABBOTT Dosage Form/Route =TABLET; ORAL: 100MG; 25MG; 200MG; 50MG Strength = - Approval Date=10/28/2005[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date October 28, 2005 Chemical Type 3 New formulation Review Classification P Priority review drug - Approval Date=04/20/2007[002][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]| - Approval Date=11/09/2007[007][New Dosage Regimen]:Label[添付文書]|Letter[承認書]| Drug Name(s) =NORVIR (RITONAVIR) FDA Application No. =NDA # 020659 Active Ingredient(s)=RITONAVIR Company =ABBOTT Dosage Form/Route =SOLUTION; ORAL 80MG/ML Strength = - Approval Date=03/01/1996[000][Approval]: Original Approval or Tentative Approval Date March 1, 1996 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=05/26/1999[013][Accelerated Approval]:Label[添付文書]|Letter[承認書]|Review - Approval Date=10/06/2005[034][Patient Population Altered]:Label[添付文書]|Letter[承認書]|Review - Approval Date=11/09/2005[033][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=07/31/2007[040][Labeling Revision]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 020680 販売中止 Active Ingredient(s)=RITONAVIR Company =ABBOTT Dosage Form/Route =CAPSULE; ORAL 100MG Strength = - Approval Date=03/01/1996[000][Approval]: Original Approval or Tentative Approval Date March 1, 1996 Chemical Type 3 New formulation Review Classification P Priority review drug - Approval Date=05/21/1998[009][Package Change]:||Review - Approval Date=05/26/1999[011][Accelerated Approval]:Label[添付文書]|Letter[承認書]|Review FDA Application No. =NDA # 020945 Active Ingredient(s)=RITONAVIR Company =ABBOTT Dosage Form/Route =CAPSULE; ORAL 100MG Strength = - Approval Date=06/29/1999[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date June 29, 1999 Chemical Type 3 New formulation Review Classification S Standard review drug - Approval Date=10/06/2005[017][Patient Population Altered]:Label[添付文書]|Letter[承認書]|Review - Approval Date=11/09/2005[016][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=07/31/2007[020][Labeling Revision]:Label[添付文書]|Letter[承認書]|
●Electronic Orange Book Application Number: 021226 Active Ingredient : LOPINAVIR; RITONAVIR Proprietary Name : KALETRA [ABBOTT] CAPSULE; ORAL 133.3MG;33.3MG Approval Date : Sep 15, 2000 Exclusivity Data : D-99 APR 29,2008 PED OCT 29,2008 Patent Data : 5541206 JUL 30,2013 U-348 5541206*PED JAN 30,2014 5635523 JUN 30,2014 U-352 5635523*PED DEC 30,2014 5648497 JUL 15,2014 5648497*PED JAN 15,2015 5674882 OCT 07,2014 U-344 5674882*PED APR 07,2015 5846987 DEC 29,2012 U-350 5846987*PED JUN 29,2013 5886036 NOV 19,2013 Y Y 5886036*PED MAY 19,2014 5914332 DEC 13,2015 U-351 5948436 SEP 13,2013 Y 5948436*PED MAR 13,2014 6037157 JUN 26,2016 U-346 6037157*PED DEC 26,2016 6232333 NOV 07,2017 6232333*PED MAY 07,2018 6284767 FEB 14,2016 U-401 6458818 NOV 07,2017 6458818*PED MAY 07,2018 6521651 NOV 01,2017 6521651*PED MAY 01,2018 6703403 JUN 26,2016 U-257 6703403*PED DEC 26,2016 7141593 MAY 22,2020 Y 7141593*PED NOV 22,2020 Application Number: 021251 Active Ingredient : LOPINAVIR; RITONAVIR Proprietary Name : KALETRA [ABBOTT] SOLUTION; ORAL 80MG/ML;20MG/ML Approval Date : Sep 15, 2000 Exclusivity Data : D-99 APR 29,2008 PED OCT 29,2008 Patent Data : 5541206 JUL 30,2013 U-348 5541206*PED JAN 30,2014 5635523 JUN 03,2014 U-352 5635523*PED DEC 03,2014 5648497 JUL 15,2014 5648497*PED JAN 15,2015 5674882 OCT 07,2014 U-344 5674882*PED APR 07,2015 5846987 DEC 29,2012 U-350 5846987*PED JUN 29,2013 5886036 NOV 19,2013 Y Y 5886036*PED MAY 19,2014 5914332 DEC 13,2015 U-351 5948436 SEP 13,2013 Y 5948436*PED MAR 13,2014 6037157 JUN 26,2016 U-346 6037157*PED DEC 26,2016 6284767 FEB 14,2016 U-401 6703403 JUN 26,2016 U-257 6703403*PED DEC 26,2016 6911214 NOV 28,2021 Y 6911214*PED MAY 28,2022 Application Number: 021906 Active Ingredient : LOPINAVIR; RITONAVIR Proprietary Name : KALETRA [ABBOTT] TABLET; ORAL 100MG,200mg;25MG,50mg Approval Date : Oct 28, 2005 [200MG;50MG ] Nov 9, 2007 [100MG;25MG ] Exclusivity Data : - Patent Data : - Application Number: 020945 Active Ingredient : RITONAVIR Proprietary Name : NORVIR [ABBOTT] CAPSULE; ORAL 100MG Approval Date : Jun 29, 1999 Exclusivity Data : - Patent Data : 5541206 JUL 30,2013 U-348 5541206*PED JAN 30,2014 5635523 JUN 03,2014 U-347 5635523*PED DEC 03,2014 5648497 JUL 15,2014 5648497*PED JAN 15,2015 5846987 DEC 29,2012 U-347 5846987*PED JUN 29,2013 5948436 SEP 13,2013 Y 5948436*PED MAR 13,2014 6232333 NOV 07,2017 6232333*PED MAY 07,2018 6703403 JUN 26,2016 U-564 6703403*PED DEC 26,2016 7141593 MAY 22,2020 Y 7141593*PED NOV 22,2020 Application Number: 020659 Active Ingredient : RITONAVIR Proprietary Name : NORVIR [ABBOTT] SOLUTION; ORAL 80MG/ML Approval Date : Mar 1, 1996 Exclusivity Data : - Patent Data : 5484801 JAN 28,2014 5484801*PED JUL 28,2014 5541206 JUL 30,2013 U-140 5541206*PED JAN 30,2014 5635523 JUN 03,2014 U-190 5635523*PED DEC 03,2014 5648497 JUL 15,2014 5648497*PED JAN 15,2015 5674882 OCT 07,2014 5674882*PED APR 07,2015 5846987 DEC 29,2012 U-190 5846987*PED JUN 29,2013 5948436 SEP 13,2013 Y 5948436*PED MAR 13,2014 6037157 JUN 26,2016 6037157*PED DEC 26,2016 6703403 JUN 26,2016 U-564 6703403*PED DEC 26,2016
情報ソース●Drug Approvals Part2(D-K) Kaletra (lopinavir) oral solution , 80mg lopinavir/20mg ritonavir. Patient Package Insert. Abbott Laboratories Application #=NDA 21-251 Approval Date=9/15/00 |承認書9/18/00|添付文書9/18/00 Kaletra Indication: Kaletra is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infections in adults and pediatric patients age six months and older. Kaletra (lopinavir) capsules, 133.3mg lopinavir/33.3mg ritonavir. Patient Package Insert Abbott Laboratories Application #=NDA 21-226 Approval Date=9/15/00 |承認書9/18/00 |添付文書9/18/00 Kaletra Indication: Kaletra is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infections in adults and pediatric patients age six months and older. 情報ソース●FY 2000 USER FEE PRIORITY APPROVALS NDA # =21-226 Trade Name =Kaletra (Generic Name)=(lopinavir/ritonavir) Dosage Form =Capsules Applicant =Abbott Labs Approval Date =15-Sep-00 Class =1,4P Keletra is indicated in combination with other antiretroviral agents for the tr eatment of HIV-1 infections in adults and pediatric patients age six months 情報ソース●APPROVAL OF FAST TRACK DESIGNATED PRODUCTS NDA# NDA Drug Name Sponsor Applicant Approval Date Indication N21251 Kaletra (Lopinavir/Ritonavir) Oral Solution Abbott Labs 9/15/00 Treatment of HIV N21226 Kaletra (Lopinavir/Ritonavir) Capsule 情報ソース●Drug Approvals for September 2000 Original Application #: 021251 Approval Date: 15-SEP-00 Trade Name: KALETRA Chemical Type: Therapeutic Potential: Dosage Form: SOLUTION Applicant: ABBOTT LABORATORIES Active Ingredient(s): LOPINAVIR OTC/RX Status: RX Indication(s): For the treatment of HIV-1 infection in adults and pediatric pati ents age six months and older Original Application #: 021226 Approval Date: 15-SEP-00 Trade Name: KALETRA Chemical Type: Therapeutic Potential: Dosage Form: CAPSULE Applicant: ABBOTT LABORATORIES Active Ingredient(s): LOPINAVIR; RITONAVIR OTC/RX Status: RX Indication(s): For the treatment of HIV-1 infection in adults and pediatric pati ents age six months and older
●Kaletra Information FDA issued an accelerated approval for Kaletra, a protease inhibitor, for adults and children greater than 6 months of age with HIV. Kaletra is a combination of lopinavir and ritonavir, (a previously approved protease inhibitor). Lopinavir's antiviral properties are combined with a low dose of ritonavir that inhibits lopinavir's metabolism. This results in blood levels of lopinavir that enhance its effectiveness against HIV.
The new drug is used in combination with other anti-HIV drugs. It should be taken with food to increase absorption into the blood stream. The usual dose for adults is three capsules or 5.0 mL twice a day. Dosing for children ages 6 months to 12 years, determined by the child's weight, is also given twice daily.
FDA Talk Paper on Kaletra Approval (9/15/2000) Kaletra Approval Letter 9/18/00 (9/18/2000) Kaletra Label (9/18/2000) Kaletra Patient Package Insert (9/18/2000) FDA/Center for Drug Evaluation and Research Last Updated: September 21, 2000
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Kaletra /INN: lopinavir/ritonavir Rev. 11 05/12/07 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation 5. Procedural steps taken and scientific information after authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Product] Kaletra [Marketing Authorisation Holder] Abbott Laboratories Limited Queenborough,Kent ME11 5EL,United Kingdom [Active Substance] Lopinavir (+ ritonavir) [International Nonproprietary Name or Common Name] Lopinavir (+ ritonavir) [Pharmaco-therapeutic Group] Antiviral for systemic use [ATC Code] JO5AE06 [Therapeutic Indication] Kaletra is indicated for the treatment of HIV-1 infected adults and children above the age of 2 years, in combination with other antiretroviral agents. Most experience with Kaletra is derived from the use of the product in antiretro viral therapy nai"ve patients. Data in heavily pretreated protease inhibitor experienced patients are limited. There are limited data on salvage therapy of patients who have failed therapy with Kaletra. The choice of Kaletra to treat protease inhibitor experienced HIV-1 infected patients should be based on individual viral resistance testing and treatment history of patients. [Date of issue of Marketing Authorisation valid throughout the European Union] 20 March 2001 [Orphan medicinal product designation date] Not applicable ★Norvir /INN: ritonavir Rev. 24 07/12/07 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation 5. Procedural steps taken and scientific information after authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product] Norvir [Marketing Authorisation Holder] Abbott Laboratories Limited Queenborough,Kent ME11 5EL,United Kingdom [Active Substance] Ritonavir [International Nonproprietary Name or Common Name] Ritonavir [Pharmaco-therapeutic Group] Antiviral for systemic use [ATC Code] J05AE03 [Therapeutic Indication] Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infected patients (adults and children of 2 years of age and older). [Date of issue of Marketing Authorisation valid throughout the European Union] 26 August 1996 [Orphan medicinal product designation date] Not applicable ●CHMP Press Releases ●Summaries of Opinion - List of Products - CHMP Opinions諮問委員会審議品目一覧 ---Substance/INN Trade Name Pharmaceuticalform Strength OpinionAdoption Date
●FDA Talk Paper on Kaletra Approval (9/15/2000) September 15, 2000
FDA Approves Kaletra for HIV Infection
FDA today issued an accelerated approval for Kaletra, a protease inhibitor, for adults and children greater than 6 months of age with HIV. Kaletra is a combination of lopinavir and ritonavir, (a previously approved protease inhibitor). Lopinavir's antiviral properties are combined with a low dose of ritonavir that inhibits lopinavir's metabolism. This results in blood levels of lopinavir that enhance its effectiveness against HIV.
The new drug is used in combination with other anti-HIV drugs. It should be taken with food to increase absorption into the blood stream. The usual dose for adults is three capsules or 5.0 mL twice a day. Dosing for children ages 6 months to 12 years, determined by the child's weight, is also given twice daily.
Side-effects associated with Kaletra are diarrhea, fatigue, headache, and nausea. Kaletra also produces increases in blood lipid levels (cholesterol and triglycerides) which in some patients may be large enough to require treatment. In addition, infrequent cases of pancreatitis have been observed among patients receiving antiretroviral regimens that included Kaletra. People with high levels of triglycerides in the blood can be at risk for pancreatitis.
As observed with other protease inhibitors, Kaletra may also be associated with other significant or serious adverse events including increases in blood glucose, redistribution of body fat, and potentially serious or life-threatening drug interactions. Healthcare providers and patients are strongly encouraged to find out about drugs that should not be taken with Kaletra and other antiretrovirals to prevent serious drug interactions or potential loss of drug effectiveness.
Kaletra was studied in six controlled and one expanded access clinical trials and is manufactured by Abbott Laboratories, North Chicago, IL.
●Abbott Laboratories and Triangle Pharmaceuticals Announce $335 Million Worldwide Alliance to Market Six Antiviral Products Abbott Laboratories Press Releases
June 3,1999 Abbott Laboratories (NYSE: ABT)and Triangle Pharmaceuticals,Inc.(Nasdaq:VIRS) today announced a worldwide strategic alliance for six antiviral products. In the United States, Abbott and Triangle will co-promote the four Triangle products currently in development for HIV and hepatitis B (HBV),and Abbott's two HIV protease inhibitors (PIs). Outside the United States,Abbott will have exclusive sales and marketing rights for the four Triangle antivirals.
The agreement significantly expands Abbott's antiviral pharmaceutical product portfolio which currently includes two HIV PIs:Norvir ｮ (ritonavir),approved in 1996,and ABT-378,currently in Phase III development to include three nucleoside reverse transcriptase inhibitors (NRTIs)and one non-nucleoside reverse transcriptase inhibitor (NNRTI),medications commonly used for the treatment of HIV and HBV. The agreement provides Abbott and Triangle with an unequaled development portfolio of all marketed classes of HIV treatments.
In 1998 in the United States,NRTIs accounted for an estimated $885 million in antiviral sales,PIs accounted for $865 million and NNRTIs accounted for approximately $100 million. Outside the United States,the market for antiviral HIV treatment,which includes these three categories,is estimated at $2 billion.
According to the Centers for Disease Control,HIV affects approximately 33 million people worldwide and approximately 650,000 to 950,000 Americans. Hepatitis B is the ninth leading cause of death worldwide and affects approximately 350 million people. Currently,only two treatments have been approved for the treatment of chronic hepatitis B.
Among the four Triangle products Abbott will co-promote is Coactinon(TM)(emivirine),formerly known as MKC-442,an NNRTI,currently in Phase III clinical trials. Triangle expects to file a New Drug Application (NDA)for Coactinon by the end of this year,while Abbott expects to submit a European application in mid-2000.
Coviracil(TM)(emtricitabine),formerly known as FTC,an NRTI,is also in Phase III clinical trials for the treatment of HIV and in Phase I/II for HBV. An NDA for Coviracil for the treatment of HIV is expected to be filed in 2000 with a European filing expected in 2001. Abbott also expects to file an NDA for its investigational PI,ABT-378,in 2000.
The other two NRTIs included in the agreement are in earlier development stages. DAPD,an NRTI, is in Phase I/II for the treatment of HIV. Triangle plans to begin Phase I/II trials in HBV later this year. Phase I/II trials with L- FMAU,a compound under investigation for the treatment of HBV,are also planned for late 1999.
Under the terms of the agreement,Abbott will purchase approximately 6.57 million shares of Triangle's Common Stock at $18 per share. Additionally,the agreement provides for non-contingent research funding of $31.7 million,up to $185 million of contingent development milestone payments and the sharing of future commercialization costs.
Triangle's website at http://www.tripharm.com.
Abbott Laboratories has been a leader in AIDS research since the early years of the epidemic. In 1985,the company developed the first licensed test to detect HIV in the blood,and remains the leader in HIV diagnostics. Abbott retroviral and hepatitis tests are used to screen more than half of the world's donated blood supply. In addition,Abbott developed the HIV protease inhibitor Norvir,and Advera ｮ,a nutritional supplement to meet the unique dietary needs of people living with HIV.
●Abbott Laboratories
★Latest News First ABT-378-r Data in Multiple PI-Experienced Patients Presented at World AIDS Conference 72-Week Phase II Data on ABT-378-r Presented at World AIDS Conference First ABT-378-r Pediatric Data Presented at World AIDS Conference Abbott Laboratories Submits Application to European Regulatory Authorities Seeking Approval for ABT-378-r for the Treatment of HIV[July 5,2000] ★Patient Resources Additional internet resources ★Partners In 1999, Abbott and Triangle Pharmaceuticals announced a worldwide co-marketing agreement for six anti-viral products. Norvir Protease inhibitor for the treatment of HIV and AIDS. Diagnostic Tests The world's leading tests for screening and diagnosis of HIV. Advera Adult nutritional specially designed for the dietary support of people living with HIV/AIDS. ★疾病サイト Pediatric Health Men's Health Women's Health Diabetes HIV Horizon Respiratory Infections Pain Management Animal Health ●Abbott Lab Online - http://www.rxabbott.com/
●アボット ジャパン - http://www.abbott.co.jp 2003年２月１日、ダイナボット(株)と北陸製薬(株)が合併し、アボット ジャパン(株)設立 アボット ジャパン株式会社（ダイナボット（株）と北陸製薬（株）が合併） アボット ジャパン(株)、4月から医療用医薬品の自社販売を開始[2006.3.31] - 1953年、アボット（米国）の子会社であるアボットジャパン （旧ダイナボット(株 )）と大日本住友製薬株式会社（旧大日本製薬(株)）との間で、アボット製品の国内にお ける総代理店契約が締結され、旧大日本製薬がアボット製品の販売を始めました。 両社 の販売提携契約は、2006年3月31日をもって契約期間満了により終結いたします。 アボット ジャパン(株)と大日本住友製薬(株)販売提携契約を満了[2006.3.27] ●医療関係者の皆様 ★医療用医薬品 ★血糖測定器 ●プレスリリース アボット ジャパン株式会社HIVプロテアーゼ阻害剤ロピナビル・リトナビル（製品名：カレトラ）の新剤形「カレトラ錠」薬価基準に収載[2006.9.4]
●Triangle Pharmaceuticals :HIV and AIDS Information Coactinon lCoviracil lDAPD lDMP-450 |HIV and AIDS Information
Unless otherwise stated, all preclinical tests and clinical trials discussed on this website refer to tests and trials conducted by third parties prior to the time the company obtained rights to the applicable drug candidate. In some cases, in its drug development efforts the Company has access to and will be able to use certain results of these preclinical tests and clinical trials.
The Company will not, however, be able to use or rely on all data from all preclinical tests and clinical trials conducted by third parties, and will have to conduct its own studies for many preclinical tests and virtually all the clinical trials for its drug candidates.
●CDC News - Abbott's AIDS Drug Kaletra Shows Promise
CDC National Center for HIV, STD and TB Prevention Daily News Update: August 22, 2000 Current CDC daily news index Wall Street Journal (www.wsj.com) (08/22/00), P. B6 Abbott Laboratories' experimental AIDS drug, Kaletra, may have advantages over current AIDS treatments. An early report shows that 90% of patients taking Kaletra responded to the drug after 24 weeks, compared to 77% who continued to respond to Pfizer's Viracept. According to Merrill Lynch medical analyst Daniel T. Lemaitre, "At first blush, the data look highly encouraging" for the drug, which was formerly known as ABT-378.
[1041]製品：abacavir (Ziagen [GSK])ザイアジェン[GSK]
日本語版註）abacavir sulfate (Ziagen Tabs & Oral Sol [GSK])
【別名】1592U89;GW592 【開発元】GSK [DBR_ID]
【化学名】(-)-[(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopenta-2- enyl]methanol hemisulfate ;CAS188062.50.2
【承認～錠・内服液】FDA申請=24-Jun-1998、FDA承認=17-Dec-1998 【製剤】錠EQ 300MG BASE ；内服液EQ 20MG BASE/ML 【適応】For the treatment of HIV-1 infection in adults and children (ages 3 months and above). This indication is based on analyses of surrogate markers in controlled studies up to 24 weeks in duration. 【用法用量】成人には他の抗HIV薬と併用して、アバカビルとして1日量600mgを1日2回経口投与。 ３ヵ月～１６才小児は8mg/kg(最大300mg)を1日2回経口投与する。 【作用】ヌクレオシド系逆転写酵素阻害薬（NRTI）；アバカビルは細胞内で細胞性酵素によって活性代謝物のカルボビル三リン酸に変換される。カルボビル三リン酸は天然基質dGTPと競合し、ウイルスDNAに取り込まれることによって、HIV-1逆転写酵素（RT）の活性を阻害する。取り込まれたヌクレオシド誘導体には3'-OH基が存在しないため、DNA鎖の伸長に不可欠な5'-3'ホスホジエステル結合の形成が阻害され、ウイルスのDNA複製が停止する。 【特徴】 【製品情報】US-Product :Ziagen 【添付文書】Ziagen Tablets-PI | Ziagen Oral Solution-PI
【EU】Ziagen[GSK]MA=8 July 1999 ； 2004 年12 月現在、世界70 ヵ国以上で承認されている。
【日本】ザイアジェン錠300mg[GSK]承認1999.9.10、薬価収載1999.9.10、発売1999.9.17 【製剤～日本】1錠中にアバカビル硫酸塩351mg（アバカビルとして300mg）を含有する。 【適応～日本】HIV感染症 【用法用量～日本】通常、成人には他の抗HIV薬と併用して、アバカビルとして1日量600mgを1日1回又は2回に分けて経口投与する。 【添付文書～日本】ザイアジェン錠 添付文書情報 - インタビューフォーム - 製品情報(詳細) 【その他】
●承認データ：FDA
●2004.5.1 以降 Drugs@FDADrug Name(s) =ZIAGEN (ABACAVIR SULFATE) FDA Application No. = NDA # 020977 Active Ingredient(s)=ABACAVIR SULFATE Company =GLAXOSMITHKLINE Dosage Form/Route =TABLET; ORAL: EQ 300MG BASE Strength = - Approval Date=12/17/1998[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date December 17, 1998 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=12/15/2000[002][Efficacy Supplement with Clinical Data to Support]:||Review - Approval Date=04/15/2004[011][Accelerated Approval]:Label[添付文書]|Letter[承認書]| - Approval Date=08/02/2004[012][New Dosage Regimen]:Label[添付文書]|Letter[承認書]|Review - Approval Date=08/11/2006[014][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=05/07/2007[016][Labeling Revision]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 020978 Active Ingredient(s)=ABACAVIR SULFATE Company =GLAXOSMITHKLINE Dosage Form/Route =SOLUTION; ORAL: EQ 20MG BASE/ML Strength = - Approval Date=12/17/1998[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date December 17, 1998 Chemical Type 3 New formulation Review Classification P Priority review drug - Approval Date=12/15/2000[002][Efficacy Supplement with Clinical Data to Support]:||Review - Approval Date=12/24/2002[009][Manufacturing Change or Addition]:||Review - Approval Date=04/15/2004[013][Accelerated Approval]:Label[添付文書]|Letter[承認書]| - Approval Date=08/02/2004[014][New Dosage Regimen]:Label[添付文書]|Letter[承認書]|Review - Approval Date=08/11/2006[016][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=05/07/2007[019][Labeling Revision]:Label[添付文書]|Letter[承認書]|
●Electronic Orange Book
Application Number: 020978 Active Ingredient : ABACAVIR SULFATE Proprietary Name : ZIAGEN [GLAXOSMITHKLINE] SOLUTION; ORAL EQ 20MG BASE/ML Approval Date : Dec 17, 1998 Exclusivity Data : D-40 AUG 02,2007 Patent Data : 5034394 DEC 18,2011 5034394*PED JUN 18,2012 5089500 JUN 26,2009 U-248 5089500*PED DEC 26,2009 6294540 MAY 14,2018 U-65 6294540*PED NOV 14,2018 U-65 6641843 FEB 04,2020 Y Application Number: 020977 Active Ingredient : ABACAVIR SULFATE Proprietary Name : ZIAGEN [GLAXOSMITHKLINE] TABLET; ORAL EQ 300MG BASE Approval Date : Dec 17, 1998 Exclusivity Data : D-40 AUG 02,2007 Patent Data : 5034394 DEC 18,2011 5034394*PED JUN 18,2012 5089500 JUN 26,2009 U-248 5089500*PED DEC 26,2009 6294540 MAY 14,2018 U-65 6294540*PED NOV 14,2018 U-65 Abacavir (Ziagen), Glaxo Wellcome
Appl
NoTE Code RLD Active
IngredientDosage Form;
RouteStrength Proprietary
NameApplicant 承認日 020978 Yes ABACAVIR SULFATE SOLUTION; ORAL EQ 20MG BASE/ML ZIAGEN GLAXOSMITHKLINE Dec 17, 1998 020977 Yes ABACAVIR SULFATE TABLET; ORAL EQ 300MG BASE ZIAGEN GLAXOSMITHKLINE Dec 17, 1998 021652 Yes ABACAVIR SULFATE; LAMIVUDINE TABLET; ORAL EQ 600MG BASE;300MG EPZICOM SMITHKLINE BEECHAM Aug 2, 2004 021205 Yes ABACAVIR SULFATE; LAMIVUDINE; ZIDOVUDINE TABLET; ORAL EQ 300MG BASE;150MG;300MG TRIZIVIR GLAXOSMITHKLINE Nov 14, 2000
情報ソース●Approved December 17, 1998 to treat HIV-1in adults and children.; Accelerated Approval Approval Letter ;Approved Labeling Ziagen (abacavir sulfate) Tablets and Oral Solution Glaxo Wellcome Inc. Application #=NDA 20-977 & NDA 20-978 Approval Date=12/17/98 Letter Posted=1/6/99 Label Posted =1/6/99 Ziagen Indications: For the treatment of HIV-1 infection in adults and children (ages 3 months and above). This indication is based on analyses of surrogate mar kers in controlled studies up to 24 weeks in duration.
●抗ウイルス剤諮問委員会
Ziagen (abacavir sulfate) Antiviral Drug Advisory Committee Meeting announcement, November 2, 1998
[U.S. Food and Drug Administration] Antiviral Drugs Advisory Committee
Agenda: The committee will discuss new drug applications (NDA's)
20-977 (tablets) and 20-978 (oral solution) for abacavir sulfate (Ziagen, Glaxo Wellcome, Inc.) for the treatment of human immunodeficiency virus (HIV) infection.
General Function of the Committee: To provide advice and recommendations to the agency on FDA's regulatory issues.
Date and Time: The meeting will be held on November 2, 1998, 8:30 a.m. to 5 p.m.
Location: Gaithersburg Holiday Inn, Walker/Whetstone Rooms, Two Montgomery Village Ave., Gaithersburg, MD.
Contact Person: Rhonda W. Stover or John B. Schupp, Center for Drug Evaluation and Research (HFD-21), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-7001, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 12531. Please call the Information Line for up-to-date information on this meeting.
Procedure: Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to the contact person by October 26, 1998. Oral presentations from the public will be scheduled between approximately 11 a.m. and 12 m. Time allotted for each presentation may be limited. Those desiring to make formal oral presentations should notify the contact person before October 26, 1998, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation.
Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2).
Dated: October 2, 1998.
Michael A. Friedman, Deputy Commissioner for Operations.
[FR Doc. 98-27082 Filed 10-8-98; 8:45 am] BILLING CODE 4160-01-F
Posted on the Web by: Office of Special Health Issues, Office of External Affairs
October 13, 1998
Published in the Federal Register October 9, 1998
■---------------------------------------------------
Abacavir (ZiagenTM) Advisory Committee Meeting, November 2
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Ziagen /INN: abacavir Rev. 13 15/01/08 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation 5. Procedural steps taken and scientific information after authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product] Ziagen [Marketing Authorisation Holder] Glaxo Group Limited Greenford,Middlesex UB6 0NN,United Kingdom [Active Substance] abacavir sulfate [International Nonproprietary Name or Common Name] abacavir sulfate [Pharmaco-therapeutic Group] Nucleoside reverse transcriptase inhibitors [ATC Code] J05A F06 [Therapeutic Indication] Ziagen is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection. The demonstration of the benefit of Ziagen is mainly based on results of studies performed with a twice daily regimen, in treatment-nai"ve adult patients on combination therapy (see section 5.1). [Date of issue of Marketing Authorisation valid throughout the European Union] 8 July 1999 [Orphan medicinal product designation date] Not applicable ●CHMP Press Releases
●Glaxo SmithKleine ●Our Products - 製品サイト ★Prescription Medicines US-Product :Ziagen /abacavir sulfate UK-Product :Ziagen ●Your Health ●Investors ★Annual Reports～年報、Annual Revew、SEC Filings - Annual Report 2007[pdf,p] - Annual Review 2007[pdf,p] - 20-F 2007[pdf,357p] ●Media Centre ★News ★News Topics ●Ziagen GlaxoSmithKline Alerts Patients, Pharmacists and Physicians to Watch for Third-Party Tampering that Incorrectly Labels Ziagen(R) as Combivir(R)[2002.5.10] Paediatric approval for GlaxoSmithKline's anti-HIV treatment, Ziagen (Abacavir)[2001.10.25] Simple and compact Ziagen/Combivir regimen results in superior efficacy compared to protease inhibitor-based regimen for the treatment of HIV[2001.7.10] Glaxo Wellcome's new anti-HIV medicine, Ziagen (abacavir), approved in the European Union[1999.7.9] European CPMP gives positive opinion on Glaxo Wellcome's anti-HIV treatment, Ziagen (Abacavir)[1999.3.26] Glaxo Wellcome's new anti-HIV medicine, Ziagen, approved for marketing in the US[1998.12.18] Abacavir offers new options for highly potent, compact treatment regimens[1998.6.29] - in P3 - 12th World AIDS Conference Glaxo Wellcome submits marketing applications for abacavir in the USA, European Union & Canada[1998.6.25]
●グラクソ・スミスクライン - http://www.glaxosmithkline.co.jp/ ●プレスリリース グラクソ・スミスクライン、2006年度業績発表[2007.2.15] ●グラクソ・ウエルカム（株）抗HIV薬「ザイアジェン錠」の製造承認を取得[1999.9.13] ★業績情報 ●医療関係者 ●ザイアジェン錠[日本：GSK] 添付文書情報 インタビューフォーム 製品情報(詳細) 承認年月日2006.11.24、薬価収載年月日2007.6.15、発売年月日1999.9.17
■一般サイトから
●Abacavir (ZiagenTM) Approval Recommended
情報ソース●AIDS Treatment News Issue #306, November 6, 1998 他の収録製剤T-20 Results Published| Amprenavir (AgeneraseTM) Submitted for Approval| Alitretinoin Gel (Panretin®) FDA Hearing November 16| Efavirenz (SustivaTM) Available through Patient Assistance Program
by John S. James
On November 2 the FDA Antiviral Drug Products Advisory Committee recommended accelerated approval of abacavir (brand name Ziagen). The vote was 7-2.
The most important trial compared abacavir plus AZT plus 3TC vs. indinavir plus AZT plus 3TC. In preliminary analysis at 16 and 24 weeks, the two groups looked very similar. This study is still blinded, so it is not known which group is receiving which combination.
Extensive information about this drug will be available in a transcript of the meeting, which will be placed on the FDA Web site. For instructions on finding the transcripts there, see "Abacavir (ZiagenTM) Advisory Committee Meeting, November 2," in AIDS Treatment News #304, October 2, 1998.
●グラクソ・ウエルカムが抗ＨＩＶ薬「ザイアジェン錠」製造承認を取得
薬事日報：99/09/20 グラクソ・ウエルカムは十日、抗ＨＩＶ薬「ザイアジェン錠」（一般名：硫酸アバカビル）の製造承認を取得した。今回の承認は、ＨＩＶ感染症治療薬の迅速承認審査の取り扱いに関する通知に則ったもの。
同剤はグラクソ・ウエルカムとしては「エピビル錠」「レトロビルカプセル」「コンビビル錠」に続く四剤目の抗ＨＩＶ薬となり、四剤ともヌクレオシド系逆転写酵素阻害薬に属する。「ザイアジェン錠」は現在、ＥＵ諸国や米国など二三カ国で承認を取得している。
特徴としては、抗ＨＩＶ薬の使用経験の有無を問わず、ＨＩＶ感染症患者の血漿中ウイルスを減少させることが海外臨床試験で明らかになった。成人の用法・用量は、他の抗ＨＩＶ薬と併用して一回一錠（アバカビル三〇〇mg）を一日二回経口投与であり、服薬コンプライアンスの維持向上が期待できる。
重要な副作用として、海外臨床試験において投与した患者の三％に過敏症の発現が報告されている。従って、有効成分のアバカビルによる過敏症の徴候や症状が発現した場合には、ただちに投与を中止する必要がある。また投与中止後に再び同剤を投与すると、さらに重篤な症状や生命を脅かすほどの血圧低下の可能性があるので、再投与は不可能としている。
[1041]●製品：efavirenz [SUSVETA, DMP 266; BMS]ストックリン[万有]
日本語版註）エファビレンズ efavirenz [SUSVETA, Dupont] ストックリン
【別名】DMP 266 【開発元】DuPont Pharm→現BMS [DBR_ID]
【化学名】(-)-(S )- 6-Chloro-4-(cyclopropylethynyl)-1, 4-dihydro-4-(trifluoromethyl)-2H - 3,1-benzoxazin-2-one
【承認～カプセル】FDA申請=11-Jun-1998、FDA承認=17-SEP-1998[DuPont Pharmaceuticals] 【承認～錠】FDA申請=30-Mar-2001、FDA承認=1-Feb-2002[BMS] ;【製剤】カプセル100MG; 200MG; 50MG efavirenz；錠600mg efavirenz 【適応】Treatment of HIV-1 infection 【用法用量】推奨用量は600mg 経口、１日１回である。投与に際しては、プロテアーゼ阻害剤およびまたはヌクレオシド系逆転写酵素阻害剤と併用する。小児は体重40kg 以上の患児に対する本剤の推奨用量は、600mg １日１回である。3 歳以上と体重10～40kgの患児の用量は添付文書参照 【作用】本剤は、ヒト免疫不全ウイルス1型(HIV-1)の選択的非ヌクレオシド系逆転写酵素阻害剤である。本剤は、HIV-1逆転写酵素(RT)のテンプレート (鋳型)、プライマー又はヌクレオシド三リン酸に対する非拮抗的阻害剤であり、混合型非拮抗阻害形式を示し、拮抗的阻害作用をわずかに併せ持つ。本剤は、臨床における血中濃度を十分に上回る濃度においても、HIV-2RT及びヒトDNAポリメラーゼα、β、γ及びδを阻害しない。 【特徴】 【製品情報】http://www.sustiva.com/ 【添付文書】Sustiva-PI
【EU】Stocrin[Merck Sharp & Dohme]MA=28 May 1999 Sustiva[Bristol-Myers Squibb]MA=28 May 1999；2006年現在、世界100の国と地域で承認
【日本】ストックリンカプセル２００[萬有製薬]承認1999.9.10、薬価収載1999.9.10、発売1999.9.14/STOCRIN 【製剤～日本】１カプセル中200mgエファビレンツ 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはエファビレンツとして600mgを1日1回経口投与する。本剤は、食事の有無にかかわらず投与できる。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】ストックリンカプセル200 添付文書 インタビューフォーム 【その他】米国、カナダ、一部の欧州ではBMS社がSustivaの製品名で販売し、それ以外の地域では、Merck & Co., Inc.,によってStocrinの製品名で発売
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =SUSTIVA (EFAVIRENZ) FDA Application No. =NDA # 020972 Active Ingredient(s)=EFAVIRENZ Company =BRISTOL MYERS SQUIBB Dosage Form/Route =CAPSULE; ORAL: 100MG; 200MG; 50MG Strength = - Approval Date=09/17/1998[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date September 17, 1998 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=02/09/2000[001][Accelerated Approval]:Label[添付文書]|Letter[承認書]|Review - Approval Date=02/28/2002[014][Manufacturing Change or Addition]:||Review - Approval Date=08/13/2004[022][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]|Review - Approval Date=03/28/2006[027][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=01/24/2007[029][Labeling Revision]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 021360 Active Ingredient(s)=EFAVIRENZ Company =BRISTOL MYERS SQUIBB Dosage Form/Route =TABLET; ORAL: 600MG Strength = - Approval Date=02/01/2002[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date February 1, 2002 Chemical Type 3 New formulation Review Classification S Standard review drug - Approval Date=08/13/2004[006][Efficacy Supplement with Clinical Data to Support]:Label[添付文書]|Letter[承認書]|Review - Approval Date=03/28/2006[014][Labeling Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=01/24/2007[016][Labeling Revision]:Label[添付文書]|Letter[承認書]|
●Electronic Orange Book Application Number: 020972 Active Ingredient : EFAVIRENZ Proprietary Name : SUSTIVA [BRISTOL MYERS SQUIBB] CAPSULE; ORAL 50MG,100MG,200MG Approval Date : Sep 17, 1998 Exclusivity Data : - Patent Data : 5519021 MAY 21,2013 Y Y 5663169 SEP 02,2014 U-257 5811423 AUG 07,2012 Y Y U-256 6238695 APR 06,2019 Y 6555133 APR 06,2019 U-248 6639071 FEB 14,2018 Y 6939964 JAN 20,2018 Y Application Number: 021360 Active Ingredient : EFAVIRENZ Proprietary Name : SUSTIVA [BRISTOL MYERS SQUIBB] Approval Date : Feb 1, 2002 Exclusivity Data : - Patent Data : 5519021 MAY 21,2013 Y Y 5663169 SEP 02,2014 U-248 5811423 AUG 07,2012 U-256 6639071 FEB 14,2018 Y 6939964 JAN 20,2018 Y Application Number: 021937 Active Ingredient : EFAVIRENZ; EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE Proprietary Name : ATRIPLA [GILEAD] TABLET; ORAL 600MG;200MG;300MG Approval Date : Jul 12, 2006 Exclusivity Data : PED JAN 02,2009 NCE JUL 02,2008 Patent Data : 5210085 MAY 11,2010 U-750 5210085*PED NOV 11,2010 5519021 MAY 21,2013 Y Y 5663169 SEP 02,2014 U-750 5811423 AUG 07,2012 U-750 5814639 SEP 29,2015 Y Y 5814639*PED MAR 29,2016 5914331 SEP 29,2015 Y 5914331*PED MAR 29,2016 5922695 JUL 25,2017 Y U-750 5935946 JUL 25,2017 Y Y U-750 5977089 JUL 25,2017 Y Y U-750 6043230 JUL 25,2017 U-750 6639071 FEB 14,2018 Y 6642245 NOV 04,2020 U-750 6642245*PED MAY 04,2021 6703396 MAR 09,2021 Y Y 6703396*PED SEP 09,2021 6939964 JAN 20,2018 Y
情報ソース● FDA Drug Approvals List September 1998 Original Application #: 020972 Approval Date: 17-SEP-98 Trade Name: SUSTIVA Chemical Type: 1 Therapeutic Potential: P Dosage Form: CAPSULE Applicant: DUPONT MERCK PHARMACEUTICAL CO Active Ingredient(s): EFAVIRENZ OTC/RX Status: RX Indication(s): Treatment of HIV-1 infection 情報ソース● 02-Dec-1998 06:05:03 pm, Approvals Sustiva (efavirenz), 50mg, 100mg, 200mg capsules (Group Leader Memo) (Divison Director Memo) DuPont Pharmaceuticals Company Application #=NDA 20-972 Approval Date=9/17/98 Letter Posted=9/24 承認データ[.pdf] Label Posted =9/17 添付文書[.pdf] Review Posted=12/10
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Stocrin /INN: efavirenz Rev. 18 05/10/07 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product] Stocrin [Marketing Authorisation Holder] Merck Sharp & Dohme Ltd Hertford Road,Hoddesdon, Herts EN11 9BU,United Kingdom [Active Substance] Efavirenz [International Nonproprietary Name or Common Name] Efavirenz [Pharmaco-therapeutic Group] Non-nucleoside reverse transcriptase inhibitors [ATC Code] J05A G03 [Therapeutic Indication] STOCRIN is indicated in antiviral combination treatment of HIV 1 infected adults, adolescents and children 3 years of age and older. STOCRIN has not been adequately studied in patients with advanced HIV disease, namely in patients with CD4 counts < 50 cells/mm3, or after failure of protease inhibitor (PI) containing regimens. Although cross resistance of efavirenz with PIs has not been documented, there are at present insufficient data on the effi cacy of subsequent use of PI based combination therapy after failure of regimens containing STOCRIN. For a summary of clinical and pharmacodynamic information, see section 5.1. [Date of issue of Marketing Authorisation valid throughout the European Union] 28 May 1999 [Orphan medicinal product designation date] Not applicable ★Sustiva /INN: efavirenz Rev. 17 05/10/07 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product] Sustiva [Marketing Authorisation Holder] Bristol-Myers Squibb Pharma EEIG Uxbridge Business Park,Sanderson Road,Uxbridge UB8 1DH,United Kingdom [Active Substance] Efavirenz [International Nonproprietary Name or Common Name] Efavirenz [Pharmaco-therapeutic Group] Non-nucleoside reverse transcriptase inhibitors [ATC Code] JO5A G03 [Therapeutic Indication] SUSTIVA is indicated in antiviral combination treatment of HIV-1 infected adult s, adolescents and children 3 years of age and older. SUSTIVA has not been adequately studied in patients with advanced HIV disease, namely in patients with CD4 counts < 50 cells/mm3, or after failure of protease inhibitor (PI) containing regimens. Although cross-resistance of efavirenz with protease inhibitors has not been documented, there are at present insufficient data on the efficacy of subsequent use of protease inhibitor based combination t herapy after failure of regimens containing SUSTIVA. See 5.1 Pharmacodynamic properties: Pharmacodynamic effects for a summary of cli nical and pharmacodynamic information. [Date of issue of Marketing Authorisation valid throughout the European Union] 28 May 1999 [Orphan medicinal product designation date] Not applicable ●CHMP Press Releases
FDA : FDA Press:Sustiva (efavirenz), DuPont Pharmaceuticals, received approval on September 17, 1998 to treat HIV and AIDS. Approval Letter| Approved Labeling | Sustiva Consumer Information
●FDA APPROVES NEW DRUG TO TREAT HIV, AIDS
Summary: The Food and Drug Administration has approved efavirenz, a new drug, to treat HIV and AIDS in children and adults. Efavirenz, in combination with other antiretroviral agents, was approved to treat HIV-1 infection after 24-week studies showed it to be effe HHS NEWS September 18, 1998 FDA APPROVES NEW DRUG TO TREAT HIV, AIDS The Food and Drug Administration has approved efavirenz, a new drug, to treat HIV and AIDS in children and adults. Efavirenz, in combination with other antiretroviral agents, was approved to treat HIV-1 infection after 24-week studies showed it to be effective in suppressing HIV. The effect of efavirenz on viral suppression beyond 24 weeks has not been demonstrated. "This action significantly boosts the arsenal available in the fight against HIV and AIDS," said HHS Secretary Donna E. Shalala. "It is important that people with HIV and AIDS have as many treatment options as possible." "Drug development for serious and life-threatening diseases, including AIDS, is one of our highest agency priorities," said Dr. Michael A. Friedman, FDA Acting Commissioner. "Each approval of antiretroviral agents offers people with HIV and AIDS more opportunities to maintain meaningful quality of life. This treatment is taken once a day, which can be beneficial to people who generally take several drugs concurrently." Efavirenz is the third non-nucleoside, reverse transcriptase inhibitor FDA has approved. The results of three adequate and well-controlled trials conducted in 928 adults and an uncontrolled open-label study conducted in 57 pediatric patients (some as young as age 3) support the safety and efficacy of efavirenz. Additional supportive information on safety and activity is provided by the results of phase I and phase II trials and the sponsor's expanded access program. Drug labeling recommends that patients take 600 mg of efavirenz once daily in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors. Although the drug may be taken with or without food, as desired, the label suggests that patients avoid high-fat meals. Health care providers should consult the drug labeling for a discussion of drug interactions with efavirenz. Nervous system symptoms, such as dizziness, insomnia, impaired concentration, abnormal dreams, and drowsiness have been reported in more than half of patients treated with efavirenz. These symptoms generally occur in the first or second day of treatment and usually resolve as treatment continues. Additionally, bedtime dosing may make these symptoms more tolerable. Patients should avoid potentially hazardous tasks such as driving or operating machinery, if they experience these symptoms. Reports of delusions and severe acute depression have also occurred, predominantly in patients with a history of mental illness or substance abuse. Efavirenz should be discontinued in patients with these more severe symptoms. During clinical trials, approximately 27 percent of patients treated with efavirenz experienced a skin rash, compared to 17 percent of patients in control groups. Severe rash, requiring stopping efavirenz, was infrequently seen in clinical trials. The labeling also recommends that health care providers monitor patients' liver enzymes, especially in those infected with hepatitis B or C viruses. Cholesterol levels should also be monitored because clinical studies could not distinguish whether this drug contributed to elevated levels or not. Several AIDS drugs have been associated with increased cholesterol and liver enzyme levels. Adverse reactions in pediatric patients have been similar to those seen in adults, with a higher incidence of, and more severe rash than in adults. Information from some preclinical studies showed that efavirenz appears to cause birth defects, so women should be screened for pregnancy before starting treatment and should be encouraged to use effective contraception. The sponsor has established a pregnancy registry to track fetal exposures to the drug. FDA's approval of the efavirenz marketing application was granted as an accelerated approval, a regulatory mechanism that speeds approvals of drugs for people with serious or life-threatening illnesses. The agency bases early approval for a product on laboratory markers such as CD4 cell counts and viral load, rather than on clinical endpoints such as delay in death or reduction in opportunistic infections. FDA may withdraw the approval of products granted accelerated approval if post-marketing studies fail to verify clinical benefits. DuPont Pharmaceuticals of Wilmington, Delaware, manufacturers efavirenz under the trade name Sustiva.
■メーカーサイト
●DuPont Pharmaceuticals Company
●DuPont Pharmaceuticals Company →DuPontは医薬品部門をBMSに売却。
●BMS ●BMS Virology ●SUSTIVA http://www.sustiva.com/
●万有製薬 - http://www.banyu.co.jp/ ●万有について ★Merck & Coパイプライン ●医療用医薬品のページ ストックリンカプセル200 添付文書 インタビューフォーム メルク・マニュアル ●ニュースルーム
●SUSTIVA efavirenz - Index［BMS］ - http://www.sustiva.com/
This site is intended for residents of the U.S.; for residents My interest in SUSTIVA is as a: SUSTIVA in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in ... Healthcare| Consumer SUSTIVA(efavirenz) in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV-RNA with SUSTIVA.
Resistant virus emerges rapidly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are administered as monotherapy. Therefore, SUSTIVAmust not be used as a single agent to treat HIV or added on as a sole agent to a failing regimen. SUSTIVA therapy should always be initiated in combination with at least one other antiretroviral agent to which the patient has not been previously exposed.
添付文書：Full Prescribing Information Available for online viewing/download as Adobe PDF format [96k]
■一般サイト
●Efavirenz (SustivaTM) Available through Patient Assistance Program
情報ソース●AIDS Treatment News Issue #306, November 6, 1998 他の収録製剤T-20 Results Published| Amprenavir (AgeneraseTM) Submitted for Approval| Alitretinoin Gel (Panretin®) FDA Hearing November 16| Abacavir (ZiagenTM) Approval Recommended
Efavirenz (SustivaTM) Available through Patient Assistance Program
Several states, including California, Pennsylvania, and New York, have not yet added efavirenz (Sustiva) to their AIDS Drug Assistance Program (ADAP) formulary, due to concern that a new wave of high drug prices could make it impossible to assure uninterrupted supply of important medications. DuPont Pharmaceuticals has assured the community that people who need the drug will not be denied it. The company, like most large companies in the pharmaceutical industry, has set up a patient assistance program to locate possible sources of reimbursement, and if necessary provide the drug to persons who have no other way to pay for it.
For information about this program, physicians and patients can call 800-334-4486.
●Efavirenz (SUSTIVATM) Approved
情報ソースAIDS Treatment News Issue #304, October 2, 1998 Contents: Efavirenz (SUSTIVATM) Approved Crixivan® (Indinavir): Three Doses Daily, Not Two, in Most Regimens Amprenavir (AgeneraseTM) Now Available in Expanded Access Successful Standard Treatment for Lipid Abnormalities: Experience with 44 Patients San Francisco: Body Shape Changes and Lipodystrophy -- Community Forum October 19 ICAAC Conference: Daily Summaries Available Abacavir (ZiagenTM) Advisory Committee Meeting, November 2 Prison Treatment Programs: Glaxo-Wellcome Awards 19 Grants Iscador Update: Interview with Robert Gorter, M.D. United States Conference on AIDS, Dallas, Oct. 29 - Nov. 1 San Francisco: POZ Life Expo, October 16-17
Efavirenz (SUSTIVATM) Approved
by John S. James
On September 18 DuPont Pharmaceuticals announced that its antiretroviral efavirenz (brand name SUSTIVA) had been approved by the FDA. Efavirenz had already been available through a large expanded-access program (over 14,000 people worldwide), but only for patients who could not be treated effectively with approved drugs. Now that it has been approved "for the treatment of HIV-1 infection" -- meaning that the FDA has not recommended its use be limited to any particular group of patients -- the medical community will need to make the more difficult decisions on how to use this drug with patients who have many treatment options.
Efavirenz has been approved for children as well as for adults.
Efavirenz is a "non-nucleoside reverse transcriptase inhibitor" -- sometimes abbreviated NNRTI; the other approved drugs in this class are nevirapine (Viramune®), and delavirdine (Rescriptor®). These drugs target the reverse transcriptase enzyme of HIV-1; but unlike AZT, ddI, etc., which also target this enzyme, the NNRTIs are not nucleoside analogs, as they do not provide "false building blocks" for the DNA created by the virus. All of the approved NNRTIs are not active against HIV-2, a variant of HIV-1 which is found in some parts of Africa.
Viral resistance to NNRTIs can develop rapidly, so these drugs must be used carefully, in combination with other antiretrovirals to which the person has not been previously exposed, so that HIV replication is kept at very low levels, to give less opportunity for resistant virus to develop. Because of cross-resistance within the NNRTI class, once significant viral resistance has occurred to one of these drugs, the other two are also probably ineffective for that patient.
A major question now is whether or not the medical community will be comfortable using efavirenz plus two nucleoside analogs, without a protease inhibitor, when beginning 3-drug treatment (and for which patients?). Or will physicians and patients stay with the now-standard three-drug regimens (protease inhibitor plus two nucleosides), or start with four drugs (protease inhibitor plus efavirenz plus two nucleoside analogs)? These complex decisions involve not only the long-term antiretroviral activity vs. toxicities of the initial drug combination, but also long-term treatment strategy: what drug combinations will be available for later use if the first treatment fails? At this time it is too early to know what medical consensus will develop.
One example of the complexity concerns the consequences of virological treatment "failure." A major trial compared efavirenz plus AZT plus 3TC (lamivudine, brand name Epivir® -- often combined with AZT in a single pill called Combivir®) vs. a standard-of-care regimen (indinavir -- brand name Crixivan® -- plus AZT plus 3TC), in patients who had already been treated with nucleoside analogs except 3TC but had not taken any protease inhibitors or NNRTIs; the efavirenz-containing regimen did at least as well as the indinavir-containing regimen at 24 and 36 weeks, as measured by the proportion of patients whose viral load remained under the 400-copy limit of the test (the same result was also found with a 50-copy limit). (See the FDA-approved "package insert," which summarizes some of the 24-week data; the recent ICAAC conference included data to 36 weeks with similar results.) But even in the efavirenz arm, at 24 weeks fewer than 80% of those originally assigned to the regimen still had a viral load under 400 copies (by the most rigorous method of counting, which considers anyone who dropped out of the study for any reason, or was missing important data, to be a treatment failure).
What happens to the patients, on either regimen, who fail to keep the virus under control? With protease inhibitors there is experience indicating that those who "fail" treatment virologically (in that the viral load becomes measurable again), but who stay on the drugs, still seem to benefit, in that CD4 counts tend to stay higher, and there are fewer AIDS-related illnesses and deaths, than would have been expected for those patients. No one knows why this seems to be the case; possibly the virus which has become resistant to protease inhibitors has become less damaging in some way. But with efavirenz, there is not enough experience yet to know if there could be any similar benefit even after virologic failure occurs.
A major hope for efavirenz is that it may reduce the need for protease inhibitors and therefore reduce the lipodystrophy problems which have become increasingly serious. But at this time no one knows for sure that protease inhibitors are causing these problems, or that efavirenz will not do so in long-term use.
Considerations on Taking Efavirenz (SUSTIVA)
Efavirenz is taken only once per day, usually at bedtime, with or without food (but not with a high-fat meal, which may increase drug absorption and therefore could cause increased side effects).
Patients need to be warned that about half or more of the people starting efavirenz have problems with CNS (central nervous system) effects, such as dizziness, trouble sleeping, drowsiness, trouble concentrating, or vivid dreams and nightmares. If these problems occur, they can start within hours. Usually they are mild to moderate, and go away after one has taken the drug for two to four weeks.
The drug can also cause rash, which usually goes away without change in treatment, but can be serious in a small number of patients.
Efavirenz must not be taken by pregnant women, because it caused birth defects in an animal test. If a woman does become pregnant while taking the drug, she should notify her physician immediately. The physician can enroll the patient in a voluntary pregnancy registry.
Some drugs must not be taken at all with efavirenz, because the combination could cause serious or life-threatening side effects. Other drugs require dose adjustment if taken with efavirenz. All your doctors and pharmacists need to know that you are taking efavirenz, and they should know all the medications you take, so that harmful interactions can be avoided.
Because resistance can develop rapidly, it is especially important to avoid running out of medicines or otherwise interrupting treatment unnecessarily.
If you are using efavirenz, be sure to get at least the "patient package insert" a one-page fact sheet on this drug, published by DuPont Pharmaceuticals. It should be available from your physician, clinic, or pharmacist. (The current version is not called a patient package insert, but begins, "SUSTIVATM (efavirenz) capsules: Patient Information about SUSTIVA*(sus-TEE-vah)...")
You may also want to get the "package insert," which is several pages of small print written primarily for physicians; despite the name it usually does not come with the package you get from the pharmacy, but may be available from your physician, and will be published in future editions of the Physicians' Desk Reference. More information can also be found on the Web or through electronic mailing lists; the company's Web site is www.sustiva.com, and it includes both the package insert and the patient package insert. For a directory of the treatment Web sites which AIDS Treatment News has found most useful overall, see www.aidsnews.org.
Also, the company has set up a phone line (800-4PHARMA), allowing callers to question an information specialist (in English or in many other languages, using an AT&T translation service). Persons can also request a package insert or patient package insert by fax or by mail. (For mailed information a full name is required, since to maintain confidentiality, the company will not mail a package which may be opened by the wrong person.)
Efavirenz Pricing Controversy
Well over 100 organizations and 200 individuals have signed a consensus statement protesting the price of SUSTIVA, which was set well above the price of the other drugs in the NNRTI class. [Note: This writer is a member of the Fair Price Working Group, which circulated the statement.] A particular concern is that this price will delay acceptance by many state ADAPs (AIDS Drug Assistance Programs), which will have to balance efavirenz against other important drugs which they will no longer be able to provide, due to the additional expense. As we go to press, negotiations are focusing on providing relief to the ADAPs. (Medicaid and the Veterans Administration already have low drug prices; and due to the expense of AIDS drugs, few individuals can pay for them out of pocket.)
We will report on the pricing situation as it develops. You can contact the Fair Price Working Group by email to linda_grinberg@prodigy.com, or by fax at 310-471-4565.
Reimbursement Assistance, and Expanded Access Contacts
DuPont Pharmaceuticals has assured the community that it will not deny access to SUSTIVA if somebody needs the drug. Persons who need help getting the drug paid for can call 1-800-334-4486, for reimbursement counseling to advise patients on public or private programs under which they may be eligible. There is also a patient assistance program to provide drug without charge to patients who meet certain financial qualifications and have no other way to have the drug paid for.
Persons on expanded access when SUSTIVA is approved will be given a one-month supply to allow time to make arrangements to pay for the drug. According to DuPont Pharma, no one on expanded access will be denied the drug, even if they have no way to pay and fail to meet the financial criteria for the patient assistance program. If they are initially turned down for the patient assistance program, they can appeal, and all these appeals will be granted. A letter explaining the transition from the expanded access program will be sent to the investigators for delivery to patients at their next visit.
Approval is pending in Canada and Europe; meanwhile, the expanded access programs there will soon begin to enroll children. For more information, patients in Canada can call 800-998-6854, or in Europe, call +44 (0) 38 842779.
Note: Efavirenz will be marketed as SUSTIVA only in the U.S., Canada, UK, Spain, France, Germany, and Italy. Elsewhere Merck will market efavirenz under the brand name StocrinTM. Apparently the companies could not agree on a price for the rights elsewhere.
●万有製薬がエイズ治療薬「ストックリン・カプセル２００」
薬事日報：99/09/22
万有製薬は十四日、エイズ治療薬「ストックリン・カプセル２００」（一般名・エファビレンツ）を発売した。
同薬剤は非ヌクレオシド系逆転写酵素阻害剤。プロテアーゼ阻害剤などこれまでのＨＩＶ感染症の治療薬は服用回数も剤数も多かったが、同薬剤は一日一回六〇〇mgを服用する。
ＨＩＶ感染症の薬物療法ではプロテアーゼ阻害剤を含む三剤以上の併用療法が主流になっている。 それぞれの薬剤の服用方法が異なるため、一層服薬は煩雑となり、副作用、高額になる治療費などと並んでＨＩＶ感染治療の問題点となっている。
専門家もこれからは一日一～二回の服用でよいのみやすさがＨＩＶ感染症の治療にも求められてくるとしている。
同薬剤もヌクレオシド系逆転写酵素阻害剤やプロテアーゼ阻害剤との併用で優れた効果を示すことが確認されているが、専門家は同剤など新しい薬剤の登場により、プロテアーゼ阻害剤を含まない併用療法への期待もあるとしている。 同薬剤は米国のメルク社により開発された。これまでに欧米など三〇以上の国で承認されている。薬価基準は一カプセル（二〇〇mg）七五五円。 万有製薬としては一九九七年四月に発売したプロテアーゼ阻害剤クリキシバン（一般名・サキナビル）に次いで二つ目のＨＩＶ感染症治療薬である。
[1057]●製品：amprenavir (Agenerase: Glaxo Wellcome)プローゼProzei［キッセイ］
日本語版註）amprenavir (Agenerase [GSK]) アムプレナビル（アジェネラーゼ［GSK社］
【別名】KVX-478, VX-478, 141W94 【開発元】Vertex Pharm [DBR_ID]46082
【化学名】4-Amino-N-[2(R)-Hydroxy-4-phenyl-3(S) -{tetrahydrofuran-3 (S)-yloxycarbonamylamino}butyl} -N-isobutylbenzenesulfonamide [CAS Registry Number] 161814-49-9
【承認】FDA申請=15-Oct-1998(カプセル)7-Dec-1998(内服液)、FDA承認=15-Apr-1999、発売=99.6.23[GSK] ;【製剤】カプセル50mg,150mg amprenavir、内服液15mg/mL amprenavir 【適応】for the treatment of HIV-1 infection 【用法用量】通常他の抗HIV 薬と併用し，成人にはアンプレナビルとして1回1200mgを1日2回経口投与する。 リトナビルと併用時、本剤1200mg+R 200mgを１日１回または本剤600mg+R 100mgを１日２回。 体重50Kg以上の１３～１６才は成人と同じ。 体重50Kg未満の１３～１６才児童および4-12才児は20mg/Kgを１日２回または15mg/Kgを１日３回。 【作用】HIV‐1 プロテアーゼの阻害剤。アンプレナビルは，HIV‐1 プロテアーゼの活性部位に結合し，ウイルスのgag及びgag‐pol 前駆体ポリ蛋白質の切断を阻害し，その結果，感染性をもたない未成熟なウイルスにする。 【特徴】 【製品情報】 【添付文書】Agenerase Capsules-PI | Agenerase Oral Solution-PI
【EU】Agenerase[GSK]承認=2000.10.20
【日本】プローゼProzei[キッセイ]99.7.2申請; 承認=1999/9/10、薬価収載=1999/9/10、発売=1999/10/1、プローゼカプセル販売中止～最終出荷2005.9末、経過措置期間 2006年3月末迄、提携：ヴァーテックス・ファーマスーティカルズ・インコーポレイティッド 【製剤～日本】1 カプセル中 アンプレナビル150mg 含有 【適応～日本】HIV-1 感染症 【用法用量～日本】通常，成人にはアンプレナビルとして1回1200mgを1日2回経口投与する。投与に際しては，必ず他の抗HIV 薬と併用すること。なお，肝機能低下の程度により減量を考慮する。 【製品情報～日本】プローゼカプセル 【添付文書～日本】プローゼカプセル添付文書[pdf] - インタビューフォーム 【その他】[US Pat] 5,585,397: HIVプロテアーゼ阻害剤
（参考）日本語による紹介：amprenavir.pdf(145KB)＜中四国エイズセンター 部内学習資料：翻訳＞Adkins JC and Faulds D.:｢AMPRENAVIR｣ Drugs 1998; 55: 837-842.
日本語版註）Fosamprenavir calcium(Lexiva[GSK])ホスアンプレナビルカルシウム水和物(レクシヴァ錠700)
【別名】VX-175;旧称GW433908 【開発元】Vertex Pharm [DBR_ID]
【化学名】(3S)-tetrahydrofuran-3-yl (1S,2R)-3-[[(4-aminophenyl) sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy) propylcarbamate monocalcium salt
【承認～錠】FDA申請=19-Dec-2002、FDA承認=20-Ot-2003[GSK] ; 【承認～内服液】FDA申請=13-Dec-2006、FDA承認=14-Jun-2007[GSK] ; 【製剤】700 mg tablets and 50 mg/mL oral suspension 【適応】indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 【用法用量】(未治療成人)1,400mg１日２回または本剤1400mg+リトナビル100mg/200mgを１日１回または本剤700mg+リトナビル100mgを１日２回 (プロテアーゼ阻害剤経験者)本剤700mg+リトナビル100mgを１日２回 (小児2-18才)体重Kg別投与 【作用】an HIV protease inhibitor; アンプレナビル（APV）のプロドラッグであり、１日の服薬剤数を４錠または２錠（リトナビル２カプセル併用時）に低減した。。 【特徴】本剤はDHHS（Department of Health and Human Services）のHIV感染症治療ガイドライン（2005.4.7改訂版）や、HIV感染症「治療の手引き」＜第８版＞２）にも初回治療に推奨される多剤併用療法の１薬剤として掲載。 【製品情報】http://www.lexiva.com/ 【添付文書】Lexiva -PI 【提携】 【EU】Telzir[GSK]承認12 July 2004 ；2005年7月現在米国、EU加盟国を含む30カ国以上で承認 【日本】レクシヴァ錠700[GSK]承認2004.12.24薬価2005.1.7発売2005.1.7 【製剤～日本】1錠中にホスアンプレナビルカルシウム水和物をホスアンプレナビルとして700mg含有する。 【適応～日本】HIV感染症 【用法用量～日本】通常、成人には以下の用法・用量に従い経口投与する。投与に際しては、必ず他の抗HIV薬と併用すること。
[(1) 抗HIV薬の治療経験がない患者]・ホスアンプレナビルとして1回700mgとリトナビル1回100mgをそれぞれ1日2回併用投与 ・ホスアンプレナビルとして1回1400mgとリトナビル1回200mgをそれぞれ1日1回併用投与 ・ホスアンプレナビルとして1回1400mgを1日2回投与
[(2) HIVプロテアーゼ阻害剤の投与経験がある患者] ・ホスアンプレナビルとして1回700mgとリトナビル1回100mgをそれぞれ1日2回併用投与 【添付文書～日本】レクシヴァ錠700添付文書 | インタビューフォーム 【その他】
アムプレナビル: 新しいHIVプロテアーゼ阻害剤
Amprenavir: A New HIV Protease Inhibitor
アムプレナビル（アジェネラーゼ［グラクソ・ウエルカム社］；日本ではプローゼProzei［キッセイ］が99.7.2申請；別名KVX-478, VX-478, 141W94） Amprenavir(Agenerase - Glaxo Wellcome)は、HIV感染症の治療薬としては第5番目のプロテアーゼ阻害剤。 本剤は、HIVに感染した成人及び少なくとも4歳の小児の治療における、他剤との併用薬としてFDAにより承認された。 プロテアーゼ阻害剤は、HIV成熟に必須な蛋白質前駆体の分解を阻害し、一般に少なくとも2種の核酸系逆転写酵素阻害剤と併用する。
日本語版註）本剤は他のプロテアーゼ阻害剤と耐性様式が異なり、交差耐性が殆どない。 副作用が10%以上に見られるものの軽微、などの特徴がある。
エイズ治療薬に「KVX‐478」－FDAから承認 【グラクソ・ウエルカム社】
薬事日報：99/04/23 グラクソ・ウエルカム社は１６日、ＦＤＡ（米国食品医薬品局）から「ＫＶＸ‐４７８」をエイズ治療薬として承認を受けた。同薬剤は、北米・欧州についてグラクソ・ウエルカム社、日本はキッセイ薬品によって共同研究・開発が行われている。日本での承認は順調にいけば夏ごろになりそうである。
「ＫＶＸ‐４７８」は米国のヴァーテックス社が創製した化合物。経口の新規ＨＩＶプロテアーゼ阻害剤である。 エイズ治療では、逆転写酵素阻害剤とＨＩＶプロテアーゼ阻害剤を用いた多剤併用療法が基本的な治療法となっている。 同化合物は、既存のＨＩＶプロテアーゼ阻害剤が無効な症例に対しても効果が期待される。
グラクソ・ウエルカム社は昨年１０月、米国・カナダで、１１月にはＥＵで承認申請を行っている。 日本では厚生省により事前評価が行われている。キッセイ薬品は、早ければ今年５月から６月ごろに承認申請を行い、夏ごろまでには承認を得られるのではないかと期待している。 事前評価に使われているのはすべて米国でとられた臨床試験データに基づいている。日本における臨床試験は承認がおりる前後から開始されることになっている。
●承認データ：FDA
●2004.5.1 以降 Drugs@FDADrug Name(s) =AGENERASE (AMPRENAVIR) FDA Application No. =NDA # 021007 Active Ingredient(s)=AMPRENAVIR Company =GLAXOSMITHKLINE Dosage Form/Route =CAPSULE; ORAL: 50MG Strength = - Approval Date=04/15/1999[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date April 15, 1999 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=05/11/2001[006][Accelerated Approval]:Label[添付文書]|Letter[承認書]|Review - Approval Date=02/05/2002[010][Efficacy Supplement with Clinical Data to Support]:|Letter[承認書]| - Approval Date=11/04/2005[017][Labeling Revision]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 021039 Active Ingredient(s)=AMPRENAVIR Company =GLAXOSMITHKLINE Dosage Form/Route =SOLUTION; ORAL: 15MG/ML Strength = - Approval Date=04/15/1999[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date April 15, 1999 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=05/11/2001[006][Accelerated Approval]:Label[添付文書]|Letter[承認書]|Review - Approval Date=02/05/2002[010][Efficacy Supplement with Clinical Data to Support]:|Letter[承認書]| - Approval Date=11/04/2005[017][Labeling Revision]:Label[添付文書]|Letter[承認書]| Drug Name(s) =LEXIVA (FOSAMPRENAVIR CALCIUM) FDA Application No. =NDA # 021548 Active Ingredient(s)=FOSAMPRENAVIR CALCIUM Company =GLAXOSMITHKLINE Dosage Form/Route =TABLET; ORAL: EQ 700MG BASE Strength = - Approval Date=10/20/2003[000][Approval]:Label[添付文書]|Letter[承認書]|Review Original Approval or Tentative Approval Date October 20, 2003 Chemical Type 2 New ester, new salt, or other noncovalent derivative Review Classification S Standard review drug - Approval Date=10/12/2007[013][New Dosage Regimen]:Label[添付文書]|Letter[承認書]| - Approval Date=03/05/2008[017][Labeling Revision]:Label[添付文書]|Letter[承認書]| FDA Application No. =NDA # 022116 Active Ingredient(s)=FOSAMPRENAVIR CALCIUM Company =GLAXOSMITHKLINE Dosage Form/Route =SUSPENSION; ORAL: EQ 50MG BASE/ML Strength = - Approval Date=06/14/2007[000][Approval]:Label[添付文書]|Letter[承認書]| Original Approval or Tentative Approval Date June 14, 2007 Chemical Type 3 New formulation Review Classification P Priority review drug - Approval Date=03/05/2008[001][Labeling Revision]:Label[添付文書]|Letter[承認書]|
●Electronic Orange Book Application Number: 021007 Active Ingredient : AMPRENAVIR Proprietary Name : AGENERASE [GLAXOSMITHKLINE] CAPSULE; ORAL 50MG Approval Date : Apr 15, 1999 Exclusivity Data : - Patent Data : 5585397 DEC 17,2013 5646180 JUL 08,2014 U-257 5723490 MAR 03,2015 U-257 6730679 NOV 11,2017 Y Application Number: 021039 Active Ingredient : AMPRENAVIR Proprietary Name : AGENERASE [GLAXOSMITHKLINE] SOLUTION; ORAL 15MG/ML Approval Date : Apr 15, 1999 Exclusivity Data : - Patent Data : 5585397 DEC 17,2013 5646180 JUL 08,2014 U-257 5723490 MAR 03,2015 U-257 Application Number: 022116 Active Ingredient : FOSAMPRENAVIR CALCIUM Proprietary Name : LEXIVA [GLAXOSMITHKLINE] SUSPENSION; ORAL EQ 50MG BASE/ML Approval Date : Jun 14, 2007 Exclusivity Data : NDF JUN 14,2010 Patent Data : 6436989 DEC 24,2017 Y Y U-257 Application Number: 021548 Active Ingredient : FOSAMPRENAVIR CALCIUM Proprietary Name : LEXIVA [GLAXOSMITHKLINE] TABLET; ORAL EQ 700MG BASE Approval Date : Oct 20, 2003 Exclusivity Data : - Patent Data : 6436989 DEC 24,2017 Y Y U-257 6514953 JUL 15,2019 Y Y U-257
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Agenerase INN: amprenavir Rev. 13 13/02/08 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product] Agenerase [Marketing Authorisation Holder] Glaxo Group Limited Greenford Road ,Greenford,Middlesex UB6 0NN,United Kingdom [Active Substance] Amprenavir [International Nonproprietary Name or Common Name] Amprenavir [Pharmaco-therapeutic Group] Protease inhibitor [ATC Code] JO5A E05 [Therapeutic Indication] Agenerase, in combination with other antiretroviral agents, is indicated for the treatment of protease inhibitor (PI) experienced HIV-1 infected adults and children above the age of 4 years. Agenerase capsules should normally be administered with low dose ritonavir as a pharmacokinetic enhancer of amprenavir (see sections 4.2 and 4.5). The choice of amprenavir should be based on individual viral resistance testing and treatment history of patients (see section 5.1). The benefit of Agenerase boosted with ritonavir has not been demonstrated in PI naive patients (see section 5.1). [Date of issue of Marketing Authorisation valid throughout the European Union] 20 October 2000 [Orphan medicinal product designation date] Not applicable ★Telzir INN: fosamprenavir Rev. 13 05/03/08 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name of the Medicinal Product ] Telzir [Marketing Authorisation Holder] Glaxo Group Limited Greenford Road ,Greenford, Middlesex ,UB6 0NN,United Kingdom [Active Substance] Fosamprenavir calcium [International Nonproprietary Name or Common Name] Fosamprenavir [Pharmaco-therapeutic Group] Protease inhibitor [ATC Code] J05AE07 [Therapeutic Indication] Telzir in combination with low dose ritonavir is indicated for the treatment of Human Immunodeficiency Virus Type 1 (HIV-1) infected adults, adolescents and children of 6 years and above in combination with other antiretroviral medicinal products. In moderately antiretroviral experienced adults, Telzir in combination with low dose ritonavir has not been shown to be as effective as lopinavir / ritonavir. No comparative studies have been undertaken in children or adolescents. In heavily pretreated patients the use of Telzir in combination with low dose ritonavir has not been sufficiently studied. In protease inhibitor (PI) experienced patients the choice of Telzir should be based on individual viral resistance testing and treatment history (see section 5.1). [Date of issue of Marketing Authorisation valid throughout the European Union] 12 July 2004 [Orphan medicinal product designation date] Not applicable ●CHMP Press Releases
情報ソース●Drug Approvals Part 1 Agenerase (amprenavir) Capsules and Oral Solution, 50mg, 150mg
Glaxo Wellcome
Application #=NDA 21-007, NDA 21-039
Approval Date=4/15/99
Label Posted =5/25/99★添付文書
Agenerase Indication: for the treatment of HIV-1 infection.
●Agenerase Consumer Information [FDA]
Agenerase(R) Brand Name: Agenerase(R) Active Ingredient: amprenavir Strength(s): 50mg & 150mg capsules and 15mg/ml oral solution Dosage Form(s): Capsules and solution Company Name: Glaxo Wellcome Availability: Prescription only *Date Approved by the FDA: April 15, 1999 ●What is Agenerase used for? Agenerase is used to treat HIV-1 infection in combination with other anti-HIV medications. Agenerase belongs to t he class of anti-HIV medications called protease inhibitors and should only be t aken in combination with other anti-HIV medications. Agenerase is not a cure for HIV infection. You may continue to develop infections and other complications associated with HIV disease. Agenerase has not been shown to reduce the risk of transmitting HIV to others through sexual contact or blood contamination. The long-term effects of Agenerase are not known at this time. Who should not take Agenerase? There are potential drug interactions that can cause serious side effects. You must not take Agenerase with: astemizole (Hismanal(R)) bepridil (Vascor(R)) cisapride (Propulsid(R)) ergot derivatives (Cafergot and others(R)) midazolam (Versed(R)) triazolam (Halcion(R)) In addition, if you take certain other medications with Agenerase, serious or life-threateningside effects can also occur. Because of this, it is very important that you tell your doctor about all the medications you are taking, including those you take without a prescription. ●Special Warnings with Agenerase: Agenerase should not be taken alone to treat HIV. Because resistance to the HIV virus can occur quickly with single drug treatment, Agenerase should always be t aken in combination with other anti-HIV medications. If your current treatment is not working, contact your doctor; Agenerase should not be taken by itself. Talk to your doctor if you are taking Viagra(R) (sildenafil) with Agenerase. You may be at risk for an increase in Viagra-related side effects such as low blood pressure, changes in vision, or penile erection lasting more than 4 hours. Increased blood sugar (hyperglycemia) or diabetes may develop while taking Agenerase. If you take diabetes medication, your dose may need to be adjusted. Agenerase can cause a skin rash that is sometimes potentially severe and life-th reatening. If you develop a skin rash, tell your health care provider immediately. Agenerase may cause hemolytic anemia (a decrease in the number of red blood cell s in your body). Tell your health care provider if you are trying to become pregnant, are already pregnant, or are breast-feeding. You should not become pregnant or breast-feed while taking Agenerase. If you are using hormonal contraceptives (e.g., birth control pills), you should use another form of birth control (e.g., condom, diaphragm) while taking Agenerase. ●General Precautions with Agenerase: If you have a history of liver problems, your health care provider will decide if Agenerase is right for you. Tell your doctor if you have had an allergic reaction to sulfa drugs. If you are taking a blood-thinning medication or you have low vitamin K, your doctor will decide if the amount of vitamin E in Agenerase interferes with your treatment. Do not take vitamin E supplements while being treated with Agenerase, because Agenerase contains vitamin E. Tell your doctor if you have hemophilia, as hemophiliac patients have sometimes experienced spontaneous bleeding while taking Agenerase. Agenerase may increase the amount of fat in your body or you may notice changes in the location of your body fat. Tell your doctor if you experience any changes like these. ●How should I take Agenerase? Before using Agenerase, read the patient information sheet carefully for importa nt precautions and instructions. Your doctor will prescribe Agenerase in combination with other anti-HIV medications. It is important to take Agenerase exactly as prescribed. Do not ski p doses. If you miss a dose by less than 4 hours, take the missed dose at once. Then take the next dose at the regularly scheduled time. If you miss a dose by m ore than 4 hours, wait and take the next dose at the regularly scheduled time. D o not take more or less than your prescribed dose at any time. It is important t o remain under the care of a doctor while taking Agenerase. Agenerase may be taken with or without food; however, you should not take Agenerase with a high fat meal, because this may reduce the effectiveness of Agenerase. Take Agenerase at least 1 hour before or 1 hour after the following medications: antacids didanosine (Videx(R)). ●What should I avoid while taking Agenerase? Do not switch from the capsule to the solution without advice from your doctor. Agenerase capsules and Agenerase oral solution are not the same on a milligram p er milligram basis. Do not take additional vitamin E because the amount of vitamin E contained in Agenerase is more than the Reference Daily Intake of vitamin E. Do not refrigerate Agenerase capsules or oral solution. Store Agenerase at room temperature ●What are some possible side effects of Agenerase? (This is NOT a complete list of side effects reported with Agenerase. Your health care provid er can discuss with you a more complete list of side effects.) Side effects may include: Skin rash (see Special Warnings) Nausea Vomiting Diarrhea Tingling sensation around the mouth Contact your doctor if you have nausea, vomiting, diarrhea, or rash. Your doctor may be able to help you manage these symptoms. Your doctor will advise you whether your symptoms can be managed on therapy or whether Agenerase should be stopped. For more detailed information about Agenerase, ask your health care provider. Link to Agenerase's Labeling Pdf.gif (146 bytes) Posted 6/10/99
●FDA APPROVES AMPRENAVER FOR HIV INFECTION - FDA TALK PAPER
April 16, 1999 FDA APPROVES AMPRENAVIR FOR HIV INFECTION The Food and Drug Administration has granted accelerated approval to amprenavir, a new protease inhibitor. Amprenavir is approved for use in children age four and older and in adults in combination with other antiretrovirals for HIV infection. The following may be used to answer questions: FDA based its approval for amprenavir on 24-week data from two ongoing well-controlled clinical studies involving more than 700 patients. Results from these trials showed a decrease in viral load (or the amount of virus circulating in plasma), and an increase in CD4 cell counts (the measure of immune cells created by the body) in patients taking amprenavir. These results were shown in previously untreated patients and in patients who had previously received reverse transcriptase inhibitors. Amprenavir was studied in 118 pediatric patients over the age of four years and is available as capsules or liquid. The two formulations of amprenavir are not interchangeable on a milligram per milligram basis. For many patients, amprenavir is taken twice a day. For some children, however, the dosing regimen is three times daily. This drug is not approved to be used alone. It must be used in combination with other antiretroviral agents. Amprenavir has shown antiviral activity in clinical trials, but there are no results from studies to show long-term suppression of HIV viral load, or HIV disease progression with this drug. The most frequently reported adverse events among patients in the clinical trial were nausea, diarrhea, vomiting, and rash. Severe and life-threatening skin reactions, including Stevens- Johnson syndrome, have occurred in patients treated with amprenavir. Acute hemolytic anemia, diabetes melitus and hyperglycemia may also be associated with amprenavir. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. Currently, there are five protease inhibitors approved by FDA for the treatment of HIV infection. These medications work at the final stage of viral replication and attempt to prevent HIV from making new copies of itself by interfering with the HIV protease enzyme. As a result, the new copies of HIV are not able to infect new cells. Amprenavir is manufactured by Glaxo Wellcome, Inc. under the trade name Agenerase.
●抗ウイルス剤諮問委員会
Ziagen (abacavir sulfate) Antiviral Drug Advisory Committee Meeting announcement, November 2, 1998
■メーカーサイト
●Vertex Pharmaceuticals Vertex Pharmaceuticals Reports Year End 2001 Financial Results[2002.2.7] Vertex and Glaxo Wellcome's New Anti-HIV Medicine, Agenerase(R) (Amprenavir), Approved in the European Union[2000.10.23] Vertex Receives Positive Opinion from CPMP for Market Approval of Agenerase in European Union[2000.6.30] Kissei Pharmaceutical Files for Approval of HIV Protease Inhibitor in Japan[1999.7.2] Newest HIV Protease Inhibitor Agenerase(R) Now Available in Oral Solution[1999.6.23] U.S. FDA Approves Agenerase? for the Treatment of HIV Infection - Twice-Daily
Protease Inhibitor Offers Potent New Option for Combination Antiretroviral Therapy[1999.4.16]
●Kissei Pharmaceutical Files for Approval of HIV Protease Inhibitor in Japan[1999.7.2]
日本ではキッセイ薬品が商品名Prozeiとして99.7.2に厚生省に申請、special fast-track evaluation processによる審査を受ける。 米国では99.4承認、最近スイスで承認、EU等ではpending。 Kissei Pharmaceutical Files for Approval of HIV Protease Inhibitor in Japan Matsumoto-City, Japan, July 2, 1999 -- Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) announced today that Kissei Pharmaceutical Co., Ltd. (Matsumoto-City, Japan) has filed for approval in Japan of Prozei™ (amprenavir), an orally administered HIV protease inhibitor, as part of a special fast-track evaluation process instituted by the Japanese Ministry of Health and Welfare. Prozei (known outside of Japan by the trade name Agenerase™) was discovered at Vertex and has been developed in Japan by Kissei. In conjunction with the filing, Vertex received a $1 million milestone payment. In the United States, Vertex's partner Glaxo Wellcome received accelerated approval for Agenerase from the FDA in April 1999. Agenerase is being marketed in the United States by Glaxo Wellcome, with co-promotion assistance from Vertex. Agenerase has also received approval in Switzerland. Approval of Agenerase is pending in the European Union, Australia, and other countries. Agenerase was discovered by Vertex Pharmaceuticals and licensed to Glaxo Wellcome for development outside the Far East. Kissei was founded in 1946 and has grown into one of Japan's leading pharmaceutical companies. Kissei's emphasis is on the research and development of original drugs having the potential to be widely accepted in the world market. The company has been successfully developing promising new drugs including those for dysuria, diabetes, and prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Kissei also continues to collaborate with Vertex on the development of VX-745, a p38 MAP kinase inhibitor for the treatment of inflammatory diseases. Vertex Pharmaceuticals Incorporated is engaged in the discovery, development and commercialization of novel, small molecule pharmaceuticals for the treatment of diseases for which there are currently limited or no effective treatments. The Company is a leader in the use of structure-based drug design, an approach to drug discovery that integrates advanced biology, biophysics, chemistry and information technologies. The Company is concentrating on the discovery and development of drugs for the treatment of viral diseases, multidrug resistance in cancer, autoimmune and inflammatory diseases, and neurodegenerative diseases. There can be no assurance that Agenerase will receive approval in Japan, full approval from the U.S. Food and Drug Administration, or approval from any other regulatory authorities, or that Agenerase will be marketed successfully. Investors are also directed to consider other risks and uncertainties discussed in Vertex documents filed with the Securities and Exchange Commission. Prozei is a trademark of Kissei Pharmaceutical Co., Ltd. Agenerase is a trademark of the Glaxo Wellcome group of companies. Additional Vertex Contact: Michele Karpf, Manager, Product Communications -- 617-577-6259 Vertex's press releases are also available by fax-on-demand at (800) 758-5804, Code 938395 ======================================================= ●Newest HIV Protease Inhibitor Agenerase(R) Now Available in Oral Solution[1999.6.23]米国でAgenerase (amprenavir)経口液剤が99.6.23発売。 過去２年以上では最初のプロテアーゼ阻害剤。 Vertexが開発しGlaxo Wellcome社（Combivir (lamivudine/zidovudine), Epivir and Retrovir and Ziagen (abacavir sulfate)を販売）にライセンス。 Newest HIV Protease Inhibitor Agenerase™ Now Available in Oral Solution Cambridge, MA June 23, 1999 - Agenerase™ (amprenavir), the latest protease inhibitor to be approved by the U.S. Food and Drug Administration for use in combination with other antiretrovirals for the treatment of HIV infection, is now available in a flavored oral solution. Agenerase was approved on April 15, 1999 and is the first protease inhibitor to be approved in more than two years. Agenerase has been studied in clinical trials of previously untreated patients, as well as patients who have received prior reverse transcriptase inhibitor therapy. Agenerase was discovered by Vertex Pharmaceuticals (Nasdaq: VRTX) and licensed to Glaxo Wellcome for development. "The oral solution of Agenerase was easily administered, generally well tolerated and children may benefit from this important new medication," said Joseph A. Church, M.D., of Children's Hospital Los Angeles. "Agenerase appears to offer a new treatment option, as part of combination therapy, for children and adolescents with HIV infection." The recommended dose of Agenerase oral solution for patients between 4 and 12 years of age or for patients 13 to 16 years of age with weight <50 kg is 22.5 mg/kg (1.5 mL/kg) twice daily or 17 mg/kg (1.1 mL/kg) three times daily (to a maximum daily dose of 2800 mg) in combination with other antiretroviral agents. Agenerase capsules and oral solution are not interchangeable on a milligram per milligram basis. "We are very pleased Agenerase is now available in a formulation that is easy for children to use," said Mike D. Rogers, Ph.D., International Product Development Team Leader for Agenerase at Glaxo Wellcome. "This underscores Glaxo Wellcome's commitment to improving treatment options for people of all ages with HIV." In vitro and genotypic analysis of isolates from Agenerase-treated patients showed mutations at 46I/L, 47V, 50V, 54L/V and 84V. A single mutation does not result in significant reduction in susceptibility; multiple mutations are needed to cause significant loss of susceptibility. The 50V mutation has not been seen in patients treated with other protease inhibitors or as a natural variant; however, resistance to Agenerase has been observed in patients without the 50V mutation. The clinical relevance of the genotypic and phenotypic changes associated with Agenerase therapy has not been established. Varying degrees of cross-resistance among protease inhibitors have been observed. Agenerase in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV RNA levels and CD4 cell counts in controlled studies up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV RNA or disease progression with Agenerase. The safety of Agenerase was studied in over 1,400 adult patients. In patients receiving protease inhibitors, diabetes mellitus, hyperglycemia, acute hemolytic anemia and redistribution/accumulation of fat have been reported. Severe and life-threatening drug interactions could be associated with therapy with Agenerase (see full prescribing information for specific drug interactions). The majority of adverse events were of mild to moderate intensity, early to onset and transient in nature. The most frequently reported adverse events were nausea, diarrhea, vomiting, rash and perioral paresthesia. Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have been associated with Agenerase. The Glaxo Wellcome price to wholesalers for Agenerase oral solution, available as a grape-bubblegum peppermint-flavored liquid (15 mg/mL), will be $25.20/240 mL bottle. The price to patients could vary depending on where they get the prescription filled. Agenerase was discovered by scientists at Vertex Pharmaceuticals of Cambridge, MA. Glaxo Wellcome has been responsible for product formulation and manufacture of Agenerase, design and implementation of clinical trials, and regulatory submissions to the FDA. Glaxo Wellcome will also lead the commercialization efforts for Agenerase with co-promotion assistance from Vertex Pharmaceuticals. Glaxo Wellcome is the pharmaceutical industry leader in HIV research and therapies. Glaxo Wellcome also manufactures and markets the widely prescribed anti-HIV drugs Combivir® (lamivudine/zidovudine), Epivir® and Retrovir®, and another recent approval, Ziagen (abacavir sulfate). The company is engaged in basic research programs designed to investigate new targets to treat HIV, and is continuing to lead the way in pioneering efforts to study the viability of increasing access to HIV therapies in the developing world. Vertex Pharmaceuticals Incorporated is engaged in the discovery, development and commercialization of novel, small molecule pharmaceuticals for the treatment of diseases for which there are currently limited or no effective treatments. The Company is a leader in the use of structure-based drug design, an approach to drug discovery that integrates advanced biology, biophysics, chemistry and information technologies. The Company is concentrating on the discovery and development of drugs for the treatment of viral diseases, multidrug resistance in cancer, autoimmune and inflammatory diseases, and neurodegenerative diseases. There can be no assurance that clinical trials will continue, that initial clinical trial results will be predictive of any future results, that Agenerase will receive marketing approval from any other regulatory authorities, or that Agenerase will be marketed successfully. Investors are also directed to consider other risks and uncertainties discussed in Vertex documents filed with the Securities and Exchange Commission. Additional Vertex Contact: Michele Karpf, Manager, Product Communications -- 617-577-6259 Vertex's press releases are also available by fax-on-demand at (800) 758-5804, Code 938395
●Glaxo SmithKlein
●Media Centre ★News ●Agenerase (amprenavir)プレスリリース Glaxo Wellcome's New Anti-HIV Medicine, Agenerase (amprenavir), Approved in the European Union[2000.10.23] European CPMP Gives Positive Opinion on Glaxo Wellcome's New Treatment for HIV, Agenerase [2000.6.30] Glaxo Wellcome’s New Anti-HIV medicine, Agenerase (amprenavir), approved in the European Union[2000.10.23] European CPMP Gives Positive Opinion on Glaxo Wellcome’s New Treatment for HIV, Agenerase[2000.6.30] U.S. FDA approves Agenerase for the treatment of HIV infection[1999.4.16] Glaxo Wellcome submits regulatory applications for new anti-HIV medicine, amprenavir, in the USA & Canada[1998.10.16] ●Our Products - 製品サイト ★Prescription Medicines UK-Product :Agenerase -amprenavir ●Investors ★Annual Reports～年報、Annual Revew、SEC Filings - Annual Report 2007[pdf,p] - Annual Review 2007[pdf,p] - 20-F 2007[pdf,357p]
●グラクソ・スミスクライン - http://www.glaxosmithkline.co.jp/ ★Migraine - http://www.miglesson.com/ ★zensoku.jp ●プレスリリース グラクソ・スミスクライン、2006年度業績発表[2007.2.15] ★業績情報 ●医療関係者
●キッセイ薬品 ●プローゼカプセル 添付文書[pdf] インタビューフォーム くすりのしおり[pdf] プローゼカプセル販売中止のお知らせ[2005.7.25]～最終出荷2005.9末、経過措置期間 2006年3月末迄 ●ニュースリリース ・抗エイズ薬（HIV感染症治療薬）「プローゼカプセル」発売のお知らせ[1999.9.30] ・抗エイズ薬（ＨＩＶ感染症治療薬）「プローゼR」の輸入承認を申請[1999.7.2] ・共同開発中の抗エイズ薬が米国で承認取得[1999.4.19]
■一般サイトから
●Simple Facts Sheets: amprenavir (Agenerase) a Simple Facts Sheet from the AIDS Treatment Data Network
amprenavir (Agenerase)
For more information about clinical trials for anti-HIV treatments currently enrolling, see the clinical trials page Drugs for treating HIV.
Warning! Each Agenerase pill contains 109 IU of vitamin E per capsule. This means that if you're taking Agenerase, you're also taking 1,744 IU of vitamin E per day. Because vitamin E can thin the blood, you should not take any other vitamin E supplements in addition to Agenerase. People taking blood-thinning drugs should talk to their doctor about the amount of vitamin E in Agenerase to make sure it isn't dangerous to your health. (6/14/99
Amprenavir (trade name Agenerase) is one of the class of anti-HIV drugs called protease inhibitors. These drugs work by blocking a part of HIV called protease. When protease is blocked, HIV makes copies of itself that can't infect new cells. Agenerase is now approved for prescription. Agenerase is the fifth protease inhibitor to be approved for the treatment of HIV infection.
Taking the drug: The standard dose of Agenerase is 1,200mg (8 pills) taken twice-a-day with or without food.
Trial results: One study compared the triple combination of Agenerase, AZT (Retrovir) and 3TC (Epivir) to the double combination of AZT/3TC. This study started some time ago. The double combination of AZT/3TC is no longer recommended for the treatment of HIV. No-one in this study had taken anti-HIV drugs before. The study only lasted six months. At the end of the study, just over half of the 116 people taking Agenerase/AZT/3TC had viral loads less than 400 copies. In the AZT/3TC group, only 11% ( 1 in 10) of people had viral loads less than 400 copies. The average increase in T-cell counts was about the same in both groups.
Another study compared Agenerase taken with two NRTIs (the approved NRTI drugs are: AZT, ddI, ddC, d4T, 3TC and abacavir) to the combination of Crixivan (indinavir) with two NRTIs. People in this study were allowed to have taken NRTI anti-HIV drugs in the past. This study has only been going on for six months. So far, 109 of the 254 people (43%) in the Agenerase/AZT/3TC group have viral loads less than 400 copies. In the Crixivan/AZT/3TC group 132 of the 250 people (53%) have viral loads less than 400 copies.
Side effects: The major side effects of Agenerase are nausea, vomiting, diarrhea, headache, stomach pains/gas, rash and numbing sensations on the skin, particularly around the mouth. Skin rashes have occurred in about 1 in 4 people taking Agenerase. In some cases the rash is mild and treatment can be continued. About 1% of people taking Agenerase developed a severe, life-threatening allergic reaction called Stevens-Johnson Syndrome. In cases of severe rash, Agenerase must be stopped. In studies, about 1 in 3 (around 30%) of people taking Agenerase chose to drop out and stop taking the drug. About half of these drop-outs were due to side effects.
So far, Agenerase does not seem to be causing increased fat levels in the blood, a known side effect of the approved protease inhibitors. But Agenerase studies may not have been going on long enough for this side effect to show up. People taking Agenerase should still have fat levels called triglycerides and cholesterol monitored regularly. Protease inhibitors have also been associated with high blood sugar and diabetes, and these side effects should be watched for if you're taking Agenerase.
Combining Agenerase with other anti-HIV drugs: There are no serious interactions between amprenavir and nucleoside analog anti-HIV drugs (AZT, ddI, ddC, d4T, 3TC, abacavir).
An early study found that amprenavir can be safely used in double-protease inhibitor combinations. The following combinations have been studied in a small number of people: Agenerase/indinavir (Crixivan), Agenerase/nelfinavir (Viracept) and Agenerase/saquinavir (Fortovase). No changes in doses were needed. The combination of ritonavir (Norvir) and Agenerase has not been studied.
The NNRTI drugs delavirdine (Rescriptor) and nevirapine (Viramune) have not been studied with Agenerase. Based on what is already known about the drugs, it is likely that Rescriptor will increase Agenerase levels. Viramune is likely to reduce Agenerase levels. A study has shown that efavirenz (Sustiva) lowers Agenerase levels in the body. For these reasons, combinations of NNRTIs with Agenerase should be avoided until correct dosing has been worked out.
Drug interactions: The drugs astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion), midazolam (Versed) and drugs called ergot derivatives should not be taken with Agenerase as the interactions can be life-threatening. The TB drug rifampin should not be taken with Agenerase as it lowers the amount of amprenavir in the body. If rifabutin must be taken with Agenerase, the dose of rifabutin should be cut in half.
The manufacturer of Agenerase has set up a patient assistance program for people having trouble accessing or affording the drug. Call (800) 722-9294 for more information.
The Simple Facts Project is a program of The Network. If you need help finding out whether or not a specific drug or therapy is covered by private or public insurance, contact The Network at (800) 734-7104. This information does not intend to promote or endorse any specific treatment for any health related condition.
Last modified: 6/15/99
●「アンプレナビル」
＜中四国エイズセンター 部内学習資料：翻訳＞ ● 著者：Adkins JC and Faulds D. ● 原題：AMPRENAVIR ● 出典：Drugs 1998; 55: 837-842. ● 翻訳：広島大学医学部小児科 加藤 恭博 ★ HIVプロテアーゼ阻害剤であるAmprenavir(アメリカでの商品名はAgenerase) についてのレビュー記事を翻訳しました。 部内学習資料としてご利用下さい。 '98/10/23: amprenavir.pdf(145KB)
製品：Delavirdine mesylate(Rescriptor : Pfizer)レスクリプター[ファイザー、第一三共]
日本語版註）Delavirdine mesylate(Rescriptor [Pfizer])メシル酸デラビルジン(レスクリプター錠[[ファイザー、第一三共]])
【別名】U90152S 【開発元】Agouron社→現在Pfizerの100%子会社 [DBR_ID]
【化学名】1-[3-[(1-methyl-ethyl)amino]-2-pyridinyl]-4-[[5-[(methylsulfonyl)amino]-1H-indol-2-yl]carbonyl]-piperazine,monomethanesulfonate.
【承認】FDA申請=、FDA承認=4-Apr-1997 ;【製剤】１錠中100mg or 200 mg of delavirdine mesylate 【適応】indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. 【用法用量】通常、成人にはデラビルジンメシル酸塩として1回400mgを1日3回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【作用】a synthetic non-nucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1).デラビルジンはHIV-1の非ヌクレオシド系逆転写酵素阻害剤である。デラビルジンは逆転写酵素に直接結合し、RNA依存性及びDNA依存性のDNAポリメラーゼ活性を阻害する。デラビルジンはテンプレートであるプライマー又はデオキシヌクレオシド三リン酸と競合しない。HIV-2逆転写酵素及びヒト細胞DNAポリメラーゼ（α、γ、δ）はデラビルジンによって阻害されない。また、HIV-1グループ0（北米では少ないが、高度の多様性を示す株の一群）もデラビルジンによる阻害を受けないと考えられる。 【特徴】 【製品情報】 【添付文書】http://media.pfizer.com/files/products/uspi_rescriptor.pdf
【EU】
【日本】レスクリプター錠200mg [製造販売元／ファイザー株式会社 販売元／第一三共株式会社]承認=2000.2.25、薬価収載2000.4.3、発売 【製剤～日本】1錠中デラビルジンメシル酸塩 200.00mg 【適応～日本】HIV-1感染症 【用法用量～日本】通常、成人にはデラビルジンメシル酸塩として1回400mgを1日3回経口投与する。なお、投与に際しては必ず他の抗HIV薬と併用すること。 【添付文書～日本】レスクリプター錠200mg 添付文書 【その他】
Agouron Pharmaceuticals, Inc.; RESCRIPTOR is a registered trademark of Pharmacia & Upjohn Company.
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =RESCRIPTOR (DELAVIRDINE MESYLATE) FDA Application No. = Active Ingredient(s)=DELAVIRDINE MESYLATE Company =AGOURON Dosage Form/Route = Strength = - Approval Date=04/04/1997[000][Approval]: Original Approval or Tentative Approval Date April 4, 1997 Chemical Type 1 New molecular entity (NME) Review Classification P Priority review drug - Approval Date=10/23/1998[002][Manufacturing Change or Addition]:|Review - Approval Date=07/14/1999[003][Formulation Revision]:Label[添付文書]|Letter[承認書]|Review - Approval Date=08/16/1999[004][Labeling Revision]:|Review - Approval Date=05/16/2001[008][Accelerated Approval]:Label[添付文書]|Review - Approval Date=03/14/2002[009][Labeling Revision]:|Letter[承認書]|Review
●Electronic Orange Book Application Number: 020705 Active Ingredient : DELAVIRDINE MESYLATE Proprietary Name : RESCRIPTOR [AGOURON] TABLET; ORAL 100MG,200MG Approval Date : Apr 4, 1997[100MG] Jul 14, 1999[200MG] Exclusivity Data : - Patent Data : 5563142 OCT 08,2013
情報ソース●Drug Approvals for April 1997 Original Application #: 020705 Approval Date: 04-APR-97 Trade Name: RESCRIPTOR Chemical Type: 1 Therapeutic Potential: P Dosage Form: TABLET Applicant: PHARMACIA AND UPJOHN CO Active Ingredient(s): DELAVIRDINE MESYLATE OTC/RX Status: RX Indication(s): Treatment of HIV-1 infection in combination with appropriate antiretroviral agents when therapy is warranted 情報ソース●FDA Drug Approvals List August 1999 Application #: 020705 Labeling Supplement#: 004 To Original New Drug Application Approval Date: 16-AUG-99 Trade Name: RESCRIPTOR Dosage Form: TABLET Applicant: PHARMACIA AND UPJOHN CO Active Ingredient(s): DELAVIRDINE MESYLATE OTC/RX Status: RX 情報ソース● Rescriptor (delavirdine mesylate) Tablet, 200mg Pharmacia & Upjohn Company Application #=20-705/S-003 Approval Date=7/14/99 Letter Posted=7/28/99 Label Posted =7/28/99 Rescriptor Indication: For the treatment of HIV-1 infection in combination with appropriate antiretroviral agents.
■メーカーサイト
●Pfizer ■Investors ●SEC Filings 10-K Annual report[2007.3.1; pdf,188p] -[xls] -[doc] ●Financial Report Annual Review 2006 - [pdf] Financial Report 2006 - [pdf] ●News Release ●Products～全製品の添付文書 ●Research & Development～The Pfizer Pipeline Pfizer | What We Do | Medicines & Products | Rescriptor Pfizer | What We Do | Medicines & Products | HIV Infection ViraceptR and RescriptorR are available through the Agouron Pharmaceuticals Pati ent Assistance Program Agouron社は現在、Pfizerの100%子会社 本品は、Pharmacia & Upjohn社により開発され、現在Pfizer社に吸収されたため、当時 のPress releaseは参照不可。
●ファイザー株式会社 - 2003.8.1 ファルマシア社と経営統合、ファィザー製薬→ファイザー（株）に ●プレスリリース ●医療従事者
●第一三共株式会社 - http://www.daiichisankyo.co.jp/ ●ニュースリリース ★年別 2008 | 2007 | 2006 | 2005[2005.09.28～] ★カテゴリ別 統合関連 | IR関連 | その他 ●医療用医薬品の新製品発売のご案内:「レスクリプター錠200mg」[2000.5.31] 抗ウイルス化学療法剤「レスクリプター錠200mg」(一般名=メシル酸デラビルジン)を、 5月29日(月)に発売致しましたので、ご案内申し上げます。本剤は、HIV－1感染症の治療 のために米国ファルマシア・アップジョン社により開発された非ヌクレオシド系逆転写酵 素阻害剤であり、HIV感染症治療薬の迅速承認審査を受け2000年2月25日に承認されました。 輸入元はワーナー・ランバート株式会社で、本邦では3番目の非ヌクレオシド系逆転写酵 素阻害剤となります。 ■投資家向け情報 －IR公表資料 ●中期経営計画 ●決算短信 2007年3月期 決算短信（2007年5月15日発表） 決算短信 |補足資料 2007年3月期 中間決算短信 （2006年11月6日発表） 中間決算短信[pdf,p] | 決算短信補足資料[pdf,p] ●説明会資料 2007年3月期 決算説明会資料 2007年3月期 中間決算説明会 （2006年11月7日開催）説明会資料[pdf,24p]
製品：その他
●承認データ：FDA
情報ソース●Drug Approvals Part 4 (P-Z) ●VIDEX (didanosine) chewable/dispersible tablets, Buffered Powder for Oral Solution, and Pediatric Powder for Oral Solution, Rx Bristol-Myers Squibb Application #=NDA 20-154/S29, S30;20-155/S21 ; 20-156/S22 Approval Date=10/29/99 Letter Posted=12/30/99 Label Posted =12/30/99 ●Vistide (cidofovir injection) 75 mg/mL Application #=NDA 20-638 Approval Date=3/9/99 Vistide Indications: For the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. ●Vitravene Injection (fomivirsen sodium intravitreal injectable), 6.6mg, Rx Isis Pharmaceuticals Application #=NDA 20-961 Approval Date=8/26/98 Letter Posted=8/28 Label Posted =8/28 Vitravene Indications: Vitravene Injection for the local treatment of cytomegalo virus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) who are intolerant of or have a contraindication to other treatment(s) for CMV retinitis or who were insufficiently responsive to previous treatment(s) for CMV retinitis.
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- 作成：2003.8.20、全面改定2008.9.15 最終更新:2008.9.21 小菅博之
The Medical Letter日本語版
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On Drugs and Therapeutics
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