MLリソース：注意欠損多動性障害（ADHD:attention deficit/hyperactivity disorder）治療薬

MLリソース：注意欠損多動性障害（ADHD:attention deficit/hyperactivity disorder）治療薬
■個別収録製品
[1149]Atomoxetine HCl(Strattera - Lilly)
　【日本】LY139603[日本イーライリリー]第Ⅱ相(2004.9現在)
[1130]Dexmethylphenydate(Focalin [Novartis])　【日本】未開発
[1086]Concerta (methylphenidate HCl) Extended-release Tablets, 18 mg & 36 mg, Rx[Alza Corp]
　【日本】コンサータ[ヤンセンファーマ]薬食審医薬品第一部会審議品目2007.8.29通過
[1114]methylphenidate extended-release ( Metadate CD [Celltech])　【日本】未開発
[]methylphenidate HCl 塩酸メチルフェニデート[リタリン]
●[1237]methylphenidate patch (Daytrana [Shire/Noven])(day-TRON-ah)デイトローナ
　日本語版註）methylphenidate transdermal system (Daytrana (methylphenidate) Transdermal System[Noven/Shire])(day-TRON-ah)デイトローナ
　【別名】　【開発元】Noven Pharmaceuticals, Inc　 [DBR_ID]
　【化学名】an adhesive-based matrix(DOT Matrix[TM]) transdermal system (patch) that is applied to intact skin.
　【承認】FDA申請=27-Jun-2000/Jun-2002、FDA承認=6-Apr-2006、米国発売=2006.6.29[販売：Shire社(製造Noven Pharmaceuticals, Inc.)] ;　【製剤】FILM, EXTENDED RELEASE; TRANSDERMAL: Methylphenidate 10MG/9HR (1.1MG/HR); 15MG/9HR (1.6MG/HR); 20MG/9HR (2.2MG/HR); 30MG/9HR (3.3MG/HR)　【適応】for attention deficit hyperactivity disorder (ADHD) in pediatric patients aged 6-12 years old.　【用法用量】必要時の２時間前に臀部に貼り、９時間後に除去する　【作用】血漿濃度が経口投与の1.9倍　【特徴】初の経皮製剤　【製品情報】www.daytrana.com　【添付文書】http://www.daytrana.com/PrescribingInformation.aspx　【EU】　【日本】未開発　【その他】

●[1265]リスデクスアンフェタミン・ジメシラートlisdexamfetamine dimesylate（Vyvanse － Shire）
　日本語版註）リスデクスアンフェタミン・ジメシラートlisdexamfetamine dimesylate（Vyvanse － Shire）
　【別名】NRP104　【開発元】New River Pharmaceuticals Inc.[米]2007.4.18　→Shire Pharmaceuticals Group plcに吸収。　 [DBR_ID]
　【化学名】(2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl]hexanamide dimethanesulfonate
　【承認】FDA申請=Dec 6, 2005、FDA承認=Feb 23,2007(New River Pharmaceuticals Inc)、米国発売=2007.7.27(製造New River Pharmaceuticals Inc、販売Shire US Inc) ;　【製剤】Vyvanse capsules contain 30 mg, 50 mg and 70 mg of lisdexamfetamine dimesylate　【適応】Vyvanse is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) 6-12才児.　【用法用量】１日１回；6-12才児童に朝、初回30mgから開始。増量時は週間隔で20mg/日単位で増量。　６才未満と12才超についての試験データはない。　【作用】a pro-drug of dextroamphetamine. After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug's activity. The mode of therapeutic action in ADHD is not known.　【特徴】１２ヵ月の服用で95%に奏功。　注意力分散、落ち着きのなさ、衝動性を抑制　【製品情報】www.vyvanse.com　【添付文書】Vyvanse-PI　【EU】未開発　【日本】未開発　【その他】VyvanseはShire LLCの商標。2007.6.29 FDAに成人ADHD追加適応を申請
【日本語版コメント1291～小児ADHDの中枢刺激剤投与前の心電図検査】
　American Heart Association（AHA）は、このほど注意欠陥多動性障害（ADHD）児において中枢刺激剤[訳注：アンフェタミン、メチルフェニデート等；以下刺激剤]の投与を行う場合には、事前に心電図（ECG）検査を行うことが妥当であるとの声明を発表した1。　American Academy of Pediatricsは、その後発表されたプレスリリースで、そのような小児においてECGの実施を考慮することは妥当であるとの見解を述べている。
＜日本語版コメント要約＞
・AHA）は、このほど注意欠陥多動性障害（ADHD）児において中枢刺激剤の投与を行う場合には、事前に心電図検査を行うことが妥当との声明を発表。これに対し、American Academy of Pediatricsは、そのような心電図検査の実施を考慮することは妥当との見解を述べた。
・刺激薬と突然死の増加、刺激薬伸しよう制限による突然死の予防効果等を示したデータはない。
・本誌コンサルタントは、目立った既往歴や身体所見の異常のない患者には、刺激薬投与前のルーチンの心電図検査や心エコー検査は不要との見解で一致している。

【日本語版コメント1265】
日本のADHD患者数は約33万人と推定されるが、未だ病気との認識は極めて薄く日本で医療機関で治療する患者は５千人前後(2005年度「患者調査」多動性障害(F90))と少ない。
それでも自閉症、アスペルガー症候群、ADHD、学習障害などの発達障害を持つ者に対し、援助教育や医療現場での適切な支援を行っていくことを目的に、「発達障害者支援法」が2004年12月に制定、2005年4月1日より施行。　同法により発達障害者に対する、国・地方自治体の支援の責務が明らかとなり、具体的な取り組みとして都道府県ごとに発達支援センターの設置、早期発見や発達支援、専門的な医療機関の確保などが行われている。　文部科学省調査でも小・中学校については約8割以上で対応整備が整いつつある(2007.3)。
ADHD治療薬の世界市場規模は2006年で約3400億円($28億ドル)と推定されるが、上位３製品で2900億円。　Concertaコンサータ[J&J;塩酸メチルフェニデート徐放錠;日本は薬食審2007.8通過]1,134億円($930m)、Adderal XR[Shire;複合アンフェタミン]1,053億円($863.6m)、Strattera[Lilly;atomoxetine;日本で2007.6申請]706億円(($579.0m)。　日本の場合、これまで治療薬が承認されていなかったが、漸くコンサータが年内承認見込み。
　一方ADHD治療薬による心血管や精神疾患のリスク(海外の死亡例５１例)も問題視されており安全な薬剤開発が望まれる。
　今回評価したデキストロアンフェタミンのプロドラッグVYVANSE (lisdexamfetamine dimesylate)は開発元のADHD薬大手Shire社がAdderall XRの後継薬として年間売上げ10億ドルを超えるブロックバスターに成長すると期待するをADHD治療薬のFlagshipと位置づけ。

【日本語版コメント1237】
　ADHDは米国では学童の7.8%(440万人)が罹患という統計があるが、日本では内山有子(国立保健医療科学院生涯保健部)の研究(2005)によると、小学校の養護教諭がADHDと考えている児童は1,000人当たり3.7人で，その内医療機関で確定診断されているものは1.2人と極端に少ない[全国小学校563校(児童数約17万4300人)から回答を得、さらに全国531の病院と80の医学部精神科を対象とした厚労省研究班の全国調査として2002年2月に発表]。　それでも「発達障害」の一つとして問題視され、全国公立小中学校41,579人を対象とした初の全国実態調査で、担当教師の判定によるADHDは2.5%,LD(学習障害)を含めると6.5%[文部科学省,2002]で、昨2005年4月から「発達障害者支援法」が実施されるにいたった。　ちなみに日本で実際に治療を受けている患者数は6000人(2002年)が急増中と思われる。
　ADHD治療薬の世界市場規模は2005年で約3000億円と推定されるが、上位４製品で2500億円。　Concerta[J&J;メチルフェニデート;日本P3]913億円($774m)、Adderall XR[Shire;複合アンフェタミン]862億円($730.8m)、Strattera[Lilly;atomoxetine;日本P2/3]651億円(($552.1m)。　これらが治療薬の世界標準。しかし日本にはホパテとメレリルしかのは問題で早期承認すべきだ。
　昨2005年2月アデロールによる突然死の報告、カナダでの販売中止(９月復帰)、その後死者は５１人に。　その後調査がはじまりFDA諮問委(2006.2.9)で患者向け治療ガイド作成とラベル黒枠警告で決着。
　更にその後Adam Cohen博士(CDC)のNEJM(25-May-2006)での研究発表が大きな衝撃を与えた。ADHD治療薬服用後に救急搬送された小児が2004年には2,500人に上ったというのだ。
　さて今回採りあげたのは世界初経皮ADHD治療薬メチルフェニデート・パッチ。　血漿濃度が経口剤の約２倍と強力なせいか、副作用問題でFDA諮問委でクレームがつき、二次使用の制限がつけられた。

【日本語版コメント1189】
　ADHDの治療手段が覚醒剤系メチルフェニデートが唯一であったものが、アトモキセチンが2003年1月に発売されて以来、世代交代しつつあるのは確かだ。　金額面で、メチルフェニデート製剤年間売上高が全世界で2.5億ドル程度だったのが、アトモキセチン製剤ストラテラ[米リリー社]は2003年度$370million(400億円)、2004年度前半$320millionとなっている。
　日本の場合、ADHDは一時マスコミに採りあげられ注目されたものの、現実問題として、治療を受けている患者は公式統計上6000人だけ(患者調査2002)。　治療薬については、メチルフェニデートはリタリン[ノバルティス]として販売されているものの、ADHDの適応は認可されていない(ナルコレプシーとうつ病のみ)。　但しホパテ[田辺]とメレリル[ノバルティス]が「多動」への適応が認められている。

【日本語版コメント1149】
　ADHDは、日本でも小児の3-5%が潜在患者とされるのに、病気との認識は極めて薄く日本で医療機関で治療する患者は１千人前後。　第一選択剤は国内外ともメチルフェニデート。治療手段は限られ問題も多かった。
　従来のADHD治療薬が覚醒剤系統であったのに対し、今回採りあげた塩酸アトモキセチンは、初の非中枢刺激剤のADHD治療剤ということ。　睡眠障害等の副作用も軽微という。　選択的ノルアドレナリン再取り込み阻害薬。
【日本語版コメント to 1086,1114,1130】
　メチルフェニデートは、日本での適応症は「1.ナルコレプシー、2.難治性うつ病、遅延性うつ病での抗うつ薬との併用」。
　ADHDは、米国では1999年に診療所で診療を受けた患者が860万人になる。　学童の3-5%が罹患するとのこと。
　一方、●最近の動きから-麻薬統制委員会,1998年次報告書を発表によると、ADHD治療用の覚醒剤、メチルフェニデートの使用は、50ｶ国以上で倍増し、INCBは各国に対し、ADHDの過剰診断の可能性を洗い出し、メチルフェニデートの過度の使用を抑制するよう申し入れる、などの問題も発生している。
　治療薬は米国では、Concerta [Alza]が2000年8月、Metadate CD[Celltech]が2001年4月にFDA承認を受け販売している。　いずれも１日１回投与の持続性製剤。
【市場】
ADHD治療薬の世界市場規模は2006年で約3400億円($28億ドル)と推定されるが、上位３製品で2900億円。
　Concerta[J&J;メチルフェニデート]1,134億円($930m)、Adderal XR[Shire;複合アンフェタミン]1,053億円($863.6m)、Strattera[Lilly;atomoxetine]706億円(($579.0m)。


($ milllion) 円貨換算 単位 2006 2005 2004 2003 2002 2001 2000 1999 1998 備考
Strattera [Lilly] 706億円 $ M 579.0(+5) 552.1(-17) 666.7(+80) 370.3 2.6(-) - - - - (atomoxetine)ストラテラ/ADHD治療薬(米国発売2003.1)
　　米国 $ M 509.2 498.7 656.4 369.9
　　国外 $ M 69.8 53.4 10.3 0.4
Ritalin [Novartis] - $ M - - - ? ? ? 147(-5) 145(-1) [methylphenidate]ADHD治療薬
Focalin/Ritalin[Elan Corporation, plc[IR]] 27 $ M 22.5(+26) 17.8 Focalin,XR[dexmethylphenidate HCl]/Ritalin,LA[methylphenidate]ADHD治療薬;from Novartis;SODAS technology(spheroidal oral drug absorption system)
Ritalin[Elan Corporation, plc[IR]] - $ M 13.8(+17) 11.8 [methylphenidate]ADHD治療薬※Novartis
Metadate CD/
Equasym XL [UCB] 108億円 Euro M 68(+35) 51 11
*46 - - - - - [Methylphenidate-SR]ADHD治療薬
Metadate CD (US) [Celltech→2004.7 UCBに合併] ￡ M - - - 20.2(+22) 16.6 **20.4 **26.3 **39.4 (methylphenidate HCl徐放)ADHD;**Methylphenidate製剤計
Generic methylphenidate(US/欧) [Celltech→2004.7 UCBに合併] ￡ M - - - 9.8(-16) 11.7 (methylphenidate HCl)ADHD

Concerta　[J&J] 1,134億円 $ M 930(+20) 774(+11) 695(+38) 504 - - - - methylphenidate HCl/ADHD治療薬[特許/NDA]-/ALZA/McNeil-PPC
　US $ M 756(+19) 638(+6) 600(+29) 464
　Intl $ M 174(+28) 136(+43) 95(+137) 40
Concerta(TM) [Alza→2002.6J&J傘下に] $ M - - - - - [Q1]65 67.9 - - [methylphenidate HCl]ADHD治療薬;発売2000.8;
ADDERALL XR [Shire] 1,053億円 $ M 863.6(+18) 730.8(+20) 606.7(+28) 474.5(+49) 317.9 [mixed amphetamine salts] ADHD
　[ADHD市場] $ M 26% 26% 25% 23% 18% 米国各12月シェア
ADDERALL [Shire] 29 $ M 23.6(-45) 43.1 - 61.1 109.8 [mixed amphetamine salts] ADHD;2006.9権利をDuramedに$63.0 millionで売却
Dytrana[Shire] 31 $ M 25.1(-) - [methylphenidate transdermal system]ADHD;発売2006.6
 [ADHD市場] $ M 2% 米国各12月シェア
合計 3,088


[07.02.01]$[USD]=\121.96, Euro[EUR]=\158.99, ￡[GBP]=\241.55, SFr[CHF]=\98.060,豪$=95.76,カナダ$=104.48,NZ$=?
[06.02.01]$[USD]=\118.00, Euro[EUR]=\142.40, ￡[GBP]=\209.40, SFr[CHF]=\91.51 , 豪$=88.85,カナダ$=103.37,NZ$=80.65

市場調査報告書：注意欠陥多動性障害（ADHD）治療薬[2006.11]
 - The value of the ADHD market was US$2.6 billion in 2005 and it is now the 9th largest segment of the
 CNS market by sales with growth of 8% year-on-year. Global sales of ADHD drugs are forecast to reach
 US$4.3 billion by 2012. 

----------------------------------
【開発中の新薬】
●「治験」ホームページ[厚生労働省]
  - 開発中の新薬[＜情報提供：日本製薬工業協会＞]	/2007.8.7

治験薬記号(一般名)
 および剤型 会社名 予定される効能又は効果、
対象疾患名および症状名 開発段階 その他
国内 海外 (地域) 
LY139603（atomoxetine HCl）カプセル剤 日本イーライリリー 注意欠陥/多動性障害 申請2007.6.27 米欧発売 自社開発、自社品
塩酸メチルフェニデート徐放錠(CONCERTA) ヤンセンファーマ 注意欠陥・多動性障害 申請2006.11 発売（欧米） 新効能・新剤型
【日本】コンサータ[ヤンセンファーマ]薬食審医薬品第一部会審議品目2007.8.29通過　【適応～日】小児期における注意欠陥/多動性障害　【その他】１日１回；「コンサータ錠」は、「小児期における注意欠陥/多動性障害（AD/HD）」の効能効果を追加する新効能・新用量医薬品。AD/HD治療薬としては国内初。既に、同成分としては、中枢神経興奮剤のノバルティスファーマ「リタリン」が存在する。「コンサータ錠」は、学会などの要望もあり、今回迅速審査が適用された。再審査期間は４年。承認条件として、本剤の投与に関しては、AD/HDの診断・治療に精通し、本剤のリスク等についても十分に理解している医師のもとのみで使用するよう指示が出た。また、承認条件ではないが、企業に対して、医師および患者やその両親に対して、AD/HDに対する教育資材を作成し、配布するよう指導する方針。
●New Medicines in Development[PhRMA 米製薬協]	/2007.9.6

薬品名 会社名 適応症 段階
ABT 089 Abbott Attention-deficit hyperactivity disorder 米II
ABT 894 Abbott Attention-deficit hyperactivity disorder 米II
Amfetamine transdermal Shire Pharmaceuticals Group Attention-deficit hyperactivity disorder 米I
Aripiprazole Otsuka Attention-deficit hyperactivity disorder 米III
CX 717 Cortex Pharmaceuticals Attention-deficit hyperactivity disorder 米II
Guanfacine extended release
(INTUNIV(TM)/CONNEXYN(TM)/旧SPD503) Shire Pharmaceuticals Attention-deficit hyperactivity disorder 米申請
Lisdexamfetamine Dimesylate (Vyvanse/NRP104) Shire Attention-deficit hyperactivity disorder 米発売
LY 2216684 Lilly Attention-deficit hyperactivity disorder 米I
(Methylphenidate transdermal)
MethyPatch(R) Noven Pharmaceuticals Attention-deficit hyperactivity disorder 米申請準備
(Methylphenidate transdermal)
DAYTRANA Shire Pharmaceuticals Group Attention-deficit hyperactivity disorder 米承認
(Modafinil)
Sparlon(TM) Cephalon/J&J Attention-deficit hyperactivity disorder 米承認
NS 2359
(GSK-372475) GSK/NeuroSearch Attention-deficit hyperactivity disorder
(a monoamine (MAO) reuptake inhibitor) 米II
PF 3654746 Pfizer Attention-deficit hyperactivity disorder 米I
PRX 00023 EPIX Pharmaceuticals
(Predix Pharmaceuticals社が創製、2006.5合併) Attention-deficit hyperactivity disorder 米III
R-sibutramine metabolite Sepracor Attention-deficit hyperactivity disorder 米I
Selegiline transdermal Somerset Attention-deficit hyperactivity disorder 米I
SGS 742 Saegis/ Novartis Attention-deficit hyperactivity disorder 米II
SPD 465
(longer acting Adderall XR) Shire Pharmaceuticals Attention-deficit hyperactivity disorder 米申請2006.7
TC-5231 Targacept, Inc Attention-deficit hyperactivity disorder
(we discontinued development of two of our product candidates, TC-5231 and TC-2403, because they failed to meet defined clinical endpoints in Phase II clinical trials that we completed in 2004. We had been developing TC-5231 as a treatment for attention deficit hyperactivity disorder and TC-2403 as a treatment for ulcerative colitis.) 米II中止

Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD
【解説資料】
　日本で適応を取得している薬剤は、★ホパテ[田辺製薬](ホパンテン酸カルシウム )が適応「下記疾患に伴う多動、注意力低下、言語障害、意欲低下の緩解：　軽度精神発育遅滞、脳炎後遺症、脳性麻痺」　メレリル錠とメレリル散[ノバルティス](塩酸チオリダジン)が「1)精神分裂病 2)神経症における不安・緊張・抑うつ及び興奮 3)下記における不安・焦燥・興奮・多動 - うつ病、精神薄弱、老年精神病」のみ。
●NIMH -Attention Deficit Hyperactivity Disorder[NIH Publication No.96-3572]　米国立精神保健研の一般向け公式解説。日本語翻訳が●ＡＤＨＤ注意欠陥多動性障害 (9p)
●ADHD（注意欠陥/多動性障害）について[4p] by 東京学芸大学太田昌孝：ADHD の歴史、疾病分類からはじまる、わかりやすい総説。
●[CDC]ADHD Home～
●～
【疫学資料】
日本では「患者調査」によると、多動性障害(F90)は5千人(2005年；2002年６千人、1999年１千人前後)。
小中学校児童1078.9万人中2.5%の27万人がADHDと推定。
●AD/HD Fact Sheets
CHADD Attention-Deficit/Hyperactivity Disorder Information
●Concerta -Facts About ADHD (3p)
　Of the estimated 8.6 million visits to office-based physicians for treatment of ADHD in 1999, it was estimated that 16% were adults (age >19 years)(Scott-Levin,Inc. Physician Drug and Diagnosis Audit (PDDA),1999[ C] ).
●ＡＤＨＤの実態と診療体制について
　- 内山有子(国立保健医療科学院生涯保健部);J. Natl. Inst. Public Health, 54 (2) : 2005
小学校，小児科，精神科に対しＡＤＨＤの実態と医療現場での対応について調査を行った
結果，小学校の養護教諭がＡＤＨＤと考えている児童は1,000人当たり3.7人で，その内
医療機関で確定診断されているものは1.2人であった．学年別では1～2年生が4.7人(
確定診断1.4人)，3～4年生が4.1人(1.1人)，5～6年生が2.4人(1.1人)で，学校1校当たり
では1.31人(確定診断0.42人)であった。
回答の得られた小学校563校の総児童数は174,304名。
小児科に対する調査は小児診療の一般的な基幹病院と考えられる全国531の日本小児科学
会研修指定病院とし，回答は責任者または専門外来の担当者に依頼し，305施設より回答
が得られた（回収率57.4％）。精神科に対する調査は，全国80の医学部の精神医学講座と
し，回答は教授または医局長とし51講座より回答が得られた（回収率63.8％）。平成13年2月～3月にかけてアンケートを実施。
※厚労省研究班の成果として2002年２月に発表されたということだが．．．

●平成18年度幼稚園、小学校、中学校、高等学校等におけるLD、ADHD、高機能自閉症等のある
幼児児童生徒への教育支援体制整備状況調査結果について[文部科学省,2007.3.2]
 - 小・中学校については，「校内委員会の設置」「特別支援教育コーディネーターの指名」は，9割以上で，
「実態把握」は，約8割の学校で実施されている。「巡回相談員の活用」は，約5～6割，「個別の指導計画の作成」
は約3～4割，「個別の教育支援計画の作成」は，約2割で実施されている。

●今後の特別支援教育の在り方について（中間まとめ）[文部科学省,2002]
 - 参考資料２．「通常の学級に在籍する特別な教育的支援を必要とする児童生徒に関する全国実態調査」調査結果
 　全国公立小中学校41,579人を対象とした調査で、担当教師の判定によるADHDは2.5%。
「学校等における児童虐待防止に向けた取組について」（ 報告書）[文部科学省,2006.5]

[文部科学省]平成18年度学校基本調査速報
 - 生徒数は小学校718.7万人、中学校360.2万人、高校349.4万人、幼稚園172.7万人

欧米など世界10カ国における家族調査“WITHOUT BOUNDARIES”より日本のADHD児を取り巻く環境、更なる改善が必要[2007.5.9]
日本イーライリリー株式会社は、この度、ADHDが、ADHDをもつ子ども達と、その家族に及ぼす影響に関する調査
（WITHOUT BOUNDARIES）を、米国本社などと協力し日本を含む、欧米など世界10カ国で実施しました。
(2)診断に要する期間は43％が1年以上、3年以上かかったケースが22％ 
(3)医療機関から受けてきた治療、薬物療法と非薬物療法がほぼ同数 
「医療機関から受けてきた治療」について、日本では薬物療法（81％）と非薬物療法（79％）がほぼ同じ割合で行
われており、他国と比べると薬物療法の割合は日本が最も低く、非薬物療法の割合は日本が最も高いことがわかりました






【臨床ガイドライン】
Guiding Principles for the Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder[ADDA,pdf,12p;Jan 2006]
 - Stimulants及びAtomoxetineが標準治療薬

米国小児科学会ADHDガイドラインAMERICAN ACADEMY OF PEDIATRICS - Current Clinical Practice Guidelines
 - Diagnosis and Evaluation of the Child With Attention-Deficit/Hyperactivity Disorder[May 2000; 13p] - [pdf]
 - [AAP Health Topics] ADHD
Treatment of the School-Aged Child With Attention-Deficit/Hyperactivity Disorder[October 2001,12p]
 ---薬物療法として、メチルフェニデート、混合アンフェタミン、ペモリン、三環系抗うつ剤、クロニジン等

【総説・文献】
ADHD Drugs and Cardiovascular Risk[NEJM 354(14)1445-1448,6-Apr-2006]
ADHD Drugs and Cardiovascular Risk[NEJM 354(21)2296-2298,25-May-2006]

Stimulant Medications and Attention Deficit--Hyperactivity Disorder[NEJM 354(21)2294-2295,25-May-2006]
 by Adam Cohen, CDC
 - DHD治療薬による救急搬送が多発[Yahoo!ヘルスケア 2006.5.25]
　　注意欠陥・多動障害（ADHD）治療薬の服用後に救急搬送された小児が、2004年には
　　2,500人に上り、その多くの原因が誤った過剰服用によるもの、とする米疾病予防対
　　策センター（CDC）の研究が発表された。
 - ADHD Drugs Tied to ER Visits[WebMed,2006.5.25]

Assessment and management of attention-deficit hyperactivity disorder in adults
Margaret Weiss and Candice Murray   CMAJ 168(6)715-722(18 Mar 2003)

DGReview: Stimulant Therapy In Attention Deficit Children Does Not Contribute To Later Drug Use
 Pediatrics Electronic Pages 01/09/2003 By Elda Hauschildt
Stimulant therapy in children with attention deficit/hyperactivity disorder (AD/
HD) does not lead to increased risk of substance experimentation, use, dependenc
e or abuse by adulthood, research in the United States confirms.



【ニュース・トピックス】
●死亡例多発問題
多動性障害の薬　米で５１人死亡[2006.2.9読売新聞]
 - 英シャイア・ファーマシューティカルズ社の「アデロール」の服用者に２４人、日本
では向精神薬としても使用されているスイス・ノバルティス社の「リタリン」と同タイプ
の薬の服用者に１６人の死亡例
医薬品安全性情報 Vol.3 No.4(2005/02/24)[pdf,12p;国立医薬品食品衛生研究所 安全情報部]
 - p4 & p9 にAdderall XR(amphetamine)による米国の突然死、カナダでの販売中止

Health Canada allows Adderall XR(R) back on the Canadian market[2005.8.24] - カナダで市場復帰
[FDA] Adderall and Adderall XR (amphetamines) Information
 - Public Health Advisory for Adderall and Adderall XR


★ 厚生労働省：注意欠陥多動性障害の治療薬に係る米国の医薬品安全・リスクマネジメント諮問委員会の開催について[2006.2.9]～結果非公開
（１）ADHDの治療に米国で用いられる医薬品服用後の有害事象（1999年～2003年報告分）
　メチルフェニデート（商品名：リタリン等）及びアンフェタミン（商品名：アデロー
ル）等の服用後に報告された心臓血管系の主な有害事象は次のとおり。
(1)メチルフェニデート
・ 突然死8例（ただし、症状発現から24時間以内に死亡というWHOの定義に合致しないものが他に8例あり）。
・ 心臓血管系疾患等19例。
(2)アンフェタミン等
・ 突然死17例（ただし、症状発現から24時間以内に死亡というWHOの定義に合致しないも
のが他に11例あり）。なお、アデロールについては計24例との記載あり。
・ 心臓血管系疾患等35例。
　　（ 	参考）
　（１）我が国におけるメチルフェニデート等の取り扱い
(1) メチルフェニデート（商品名：リタリン）
　昭和32年に承認。その効能・効果は、ナルコレプシー、うつ病。ADHDは承認されていない。
(2) アンフェタミンは、我が国では未承認。覚せい剤に該当。
　（２）メチルフェニデートについて、平成14年4月以降、現在までに我が国において、
因果関係の否定できないと考えられる死亡事例は報告されていない。　（参考）因果関係
が評価できない死亡事例は３例報告あり。

FDA-CDER■Drug Safety and Risk Mgmt
FDAAdvisorycommittee.com: Drug Safety and Risk Mgmt

ML 開催日 議題 備考
　 2006.02.09 Attention Deficit/Hyperactivity Disorder Drug Cardiovascular Adverse Events
※興奮剤系ADHD治療薬のアンフェタミン剤による突然死等を契機に調査がはじまりその結果を踏まえて対応を決める。(Shire’s Adderall, Adderall XR, and Dextrostat; GlaxoSmithKline’s Dexedrine and Dexedrine Spansules), methylphenidate (J&J’s Concerta, Novartis’ Ritalin, Ritalin SR, and Ritalin LA; Alliant’s Methylin and Methylin ER; UCB/Celltech’s Metadate ER and Metadate CD), methamphetamine (Ovation’s Desoxyn) and dexmethylphenidate (Novartis’ Focalin)
※非致命的な重篤に心血管系副作用発生率は処方箋100万件当たりで小児でmethylphenidate 0.18とamphetamine 0.53、成人で各0.74 and 1.79、　突然死発生率=小児0.16 for methylphenidate versus 0.36 for those taking amphetamine. 成人では0.07 for methylphenidate and 0.53 for amphetamine.　※[Brief Information]
※[審議結果] 1)患者及び親用medication guideの作成に賛否15:0棄権1　2)ラベルに黒枠警告追加に賛否8:7棄権1 　


●学校教育制度関連
★小・中学校におけるＬＤ（学習障害），ＡＤＨＤ（注意欠陥／多動性障害），高機能自閉症の児童生徒へ
の教育支援体制の整備のためのガイドライン（試案）の公表について[文部科学省2004.1.30 報道発表]
★中央教育審議会総会（第53回）[2005.12.8]
 - [資料3－2]特別支援教育を推進するための制度の在り方について（答申）（案）
 - [第4章小・中学校における制度的見直しについて]2.LD・ADHD・高機能自閉症等の児童生徒に対する指導及び支援の必要性
 - [参考資料]学習障害(LD)、注意欠陥/多動性障害(ADHD)及び高機能自閉症について

●厚労省検討会
●発達障害者支援に係る検討会[厚生労働省社会・援護局]
掲載案件名開催日
第３回議事録05/03/15
第３回資料について05/03/15
第２回議事録05/01/24
第２回資料について05/01/24
第１回議事録05/01/18
第１回資料について05/01/18

「発達障害」とは、自閉症、アスペルガー症候群その他の広汎性発達障害、学習障害、注
意欠陥多動性障害その他これに類する脳機能の障害であってその症状が通常低年齢におい
て発現するものとして政令で定めるものをいう。

●発達障害者支援法
超党派の議員立法により2004年12月に成立した「発達障害者支援法」は、2005年4月から施行された。
[厚生労働省]発達障害者支援施策について[2005.4.25]
 - 早期発見(学校健診)、都道府県等は「発達障害者支援センター」設置
 　病院や診療所など専門的な医療機関の確保など。
[文部科学省]発達障害者支援法の施行について[2005.4.1]
[文部科学省]通級による指導の対象とすることが適当な自閉症者、情緒障害者、学習障害者又は注意欠陥多動性障害者に該当する児童生徒について（通知）[2006.3.31]
★発達障害白書2007年版
日本発達障害福祉連盟　編　B5判226頁　CD-ROM付　定価2,940円（本体2,800円＋税） ISBN4-8210-7907-0


【リソース・リンク】
●MEDLINEplus: Attention Deficit Disorder with Hyperactivity
●Links[CHADD]
●進化研究と社会：注意欠陥多動性障害／ADHD／リタリン - ニュース、医療施設リストなど

【主要サイト】
●日本小児精神神経学会～
●日本LD学会(学習障害)
●NPO法人　大人のADD・ADHDの会
●NPO法人えじそんくらぶ～ADHDサポート
●日本発達障害ネットワーク～JDD Network
●ADHD Life.Net～当事者である母子の奮闘期。掲示板や参考図書の紹介。
●www.adhd.co.jp～治験参加者募集サイト by 日本イーライリリー

●Attention Deficit Disorder Association[ADDA]
 - 解説、文献、学会などに関する資料が豊富。
●CHADD -Children and Adults with Attention-Deficit/Hyperactivity Disorder
●Concerta by J&J(旧Alza)
●Metadate CD by UCB(旧Celltech)
●http://www.strattera.com/ by Lilly
●www.adhd.com～ by Lilly
●～
●～
●解説

●NIMH -Attention Deficit Hyperactivity Disorder[NIH Publication No.96-3572]
　米国立精神保健研の一般向け公式解説です。
 これを日本語翻訳して公開している人がいます。
●ＡＤＨＤ 注意欠陥多動性障害 (9p)
●ADHD（注意欠陥/多動性障害）について[4p]

by 東京学芸大学太田昌孝
ADHD の歴史、疾病分類からはじまる、わかりやすい総説。

●データ

●Concerta -Facts About ADHD (3p)

[略]
　Of the estimated 8.6 million visits to office-based physicians for treatment of ADHD in 1999, it was estimated that 16%were adults (age >19 years)(Scott-Levin,Inc. Physician Drug and Diagnosis Audit (PDDA),1999[ C] ).

●AD/HD Fact Sheets

CHADD Attention-Deficit/Hyperactivity Disorder Information

These online fact sheets are abbreviated versions of the full series which is provided to all new members. All renewing members will receive a Resource Manual, containing the new set of Fact Sheets, in the Fall. The fact sheets are developed by the CHADD Board of Directors and the CHADD Advisory Board. Fact sheets can also be ordered individually or as a set from the CHADD Store.

Fact Sheet 1 -"Disability Named ADD"
Fact Sheet 2 -"Parenting a Child with Attention-Deficit/Hyperactivity Disorder"
Fact Sheet 3 -"Medical Management of Children and ADults with Attention-Deficit/Hyperactivity Disorder "
Fact Sheet 4 -"Educational Rights for Children with AD/HD "
Fact Sheet 5 -"AD/HD and Co-Existing Disorders "
Fact Sheet 6 -"Unproven Treatments"
Fact Sheet 7 -"Attention-Deficit/Hyperactivity Disorder in Adults"

●臨床ガイドラインなど

●Guiding Principles for the Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder[NADDA]

by The National Attention Deficit Disorder Association ,2000
●米国小児科学会ADHDガイドライン

Diagnosis and Evaluation of the Child With Attention-Deficit/Hyperactivity Disorder[May 2000; 13p] Treatment of the School-Aged Child With Attention-Deficit/Hyperactivity Disorder[October 2001,12p] ---薬物療法として、メチルフェニデート、混合アンフェタミン、ペモリン、三環系抗うつ剤、クロニジン等 in AMERICAN ACADEMY OF PEDIATRICS - Current Clinical Practice Guidelines

●総説記事・文献

●Non-Stimulant Medication for CHildren and Adolescents with AD/HD (2p)

　従来の薬物療法のレビユー。　以下の薬剤について記述。
The tricyclic antidepressants, such as desipramine (Norpramine) imipramine (Tofranil) and nortryptiline (Pamelor) have been shown to effectively treat AD/HD.
Bupropion: There are good studies showing that the antidepressant bupropion (Wellbutrin) is an effective treatment for AD/HD.
Clonidine, Guanfacine: One class of blood pressure medications, the ±-adrengeric agonists, has been shown to be useful for some individuals.
valproate (Depakote) carbamazepine (Tegretol) and others. There is debate among child psychiatrists about the percentage of AD/HD youth who have Bipolar Disorder at the same time.
The Selective Serotonin Reuptake Inhibitors (SSRIs) include paroxetine (Paxil) sertraline (Zoloft) fluvoxamine (Luvox) and others. They probably do not treat the core symptoms of AD/HD but may be helpful for irritability, anxiety or depression accompanying the AD/HD.

●ニュース・トピックス

●最近の動きから-麻薬統制委員会,1998年次報告書を発表

INCB報告（１９９８年）
　国際麻薬統制委員会（INCB）は２月２３日、ウィーンおよび全世界のその他30都市で１９９８年次報告書を発表。過去1年間の全世界における規制対象薬物の乱用と密売の動向を明らかにした。
[略]
　多動症（ADHD）治療用の覚醒剤、メチルフェニデートの使用は、50ｶ国以上で倍増した。オーストラリア、ベルギー、カナダ、ドイツ、アイスランド、アイルランド、オランダ、ニュージーランド、ノルウェー、スペイン、英国などの国々におけるこの薬物の乱用は、現在全世界の消費量の85％以上を占める米国のレベルに到達する可能性がある。

　INCBは各国に対し、ADHDの過剰診断の可能性を洗い出し、メチルフェニデートの過度の使用を抑制するよう申し入れている。この薬物による治療を受ける患者は、1990年代初頭には主として男子小学生であったが、最近ではその層がさらに広がり、ますます多くの子ども、青少年および成人がこの治療を受けるようになっている。米国では、1歳の幼児がADHDと診断されたケースもある。
[略]

●一般ニュース

Adderall XR (SLI 381), for Attention Deficit Hyperactivity Disorder, Receives Approvable Letter From FDA
Shire Pharmaceuticals Group pl社は、注意欠陥多動性障害（ＡＤＨＤ）に対する１日１回の治療薬、「Adderall ＸＲ（ＴＭ）」（ＳＬＩ３８１）に、ＦＤＡ（米国食品医薬品局）からapprovable letterを受けたと発表した。approvable letterはＦＤＡの公式な伝達であり、最終承認に向けて準備中であること示す。２０００年１０月３日にＦＤＡに提出された新薬承認申請（ＮＤＡ）は、６００人以上の患者を対象とした、ＡＤＨＤの薬物に関する過去最大の研究のひとつに基づく。
 FROM MedicalWave薬剤ニュース
●リンク＆リソース

■MEDLINEplus: Attention Deficit Disorder with Hyperactivity

Contents of this page:
News
From the NIH
General/Overviews
Alternative Therapy
Clinical Trials
Coping
Diagnosis/Symptoms
Research
Specific Conditions/Aspects
Treatment
Law and Policy
Organizations
Children
Teenagers
Women
Search MEDLINE for recent research articles on
・ Attention Deficit Disorder with Hyperactivity
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・ Child Behavior Disorders
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・ Brain and Nervous System
・ Child and Teen Health
・ Mental Health and Behavior
●Latest News
Snoring Kids May Become Hyperactive (07/08/2003, Reuters Health)
●From the National Institutes of Health
Attention Deficit Hyperactivity Disorder (National Institute of Mental Health)
Also available in: Spanish
Attention Deficit-Hyperactivity Disorder (National Institute of Neurological Disorders and Stroke)
●General/Overviews
Attention Deficit/Hyperactivity Disorder (American Psychiatric Association)
Attention-Deficit/Hyperactivity Disorder (AD/HD) (National Information Center for Children and Youth with Disabilities)
Also available in: Spanish
Frequently Asked Questions about AD/HD (Children and Adults with Attention-Deficit/Hyperactivity Disorder)
What is Attention-Deficit Hyperactivity Disorder (ADHD)? (National Center on Birth Defects and Developmental Disabilities)
●Alternative Therapy
Assessing Complementary and / or Controversial Interventions (Children and Adults with Attention-Deficit/Hyperactivity Disorder)
●Clinical Trials
ClinicalTrials.gov: Attention Deficit Disorder with Hyperactivity (National Institutes of Health)
●Coping
ADHD: Info and Advice for Parents (American Academy of Family Physicians)
Individualized Education Plans (IEPs) (Nemours Foundation)
Parenting a Child with Attention-Deficit/Hyperactivity Disorder (Children and Adults with Attention-Deficit/Hyperactivity Disorder)
Peer Relationships and ADHD (National Center on Birth Defects and Developmental Disabilities)
●Diagnosis/Symptoms
ADHD -- Common Behaviors and Symptoms (American Academy of Pediatrics)
ADHD -- Making the Diagnosis (American Academy of Pediatrics)
ADHD: Does My Child Have It? (American Academy of Family Physicians)
Attention-Deficit/Hyperactivity Disorder - Symptoms of ADHD (National Center on Birth Defects and Developmental Disabilities)
●Research
Attention-Deficit/Hyperactivity Disorder in School-Aged Children: Association with Maternal Mental Health and Use of Health Care Resources (National Center on Birth Defects and Developmental Disabilities)
Brain Shrinkage in ADHD Not Caused by Medications (National Institute of Mental Health)
Impact of Attention-Deficit Hyperactivity May Be Underestimated (National Institute of Environmental Health Sciences)
Testing of a New Medication to Treat AD/HD (Nemours Foundation)
●Specific Conditions/Aspects
ADHD -- Coexisting Conditions (American Academy of Pediatrics)
ADHD and Risk of Injuries (National Center on Birth Defects and Developmental Disabilities)
Attention-Deficit / Hyperactivity Disorder in Adults (Children and Adults with Attention-Deficit/Hyperactivity Disorder)
Couples and ADD (National Attention Deficit Disorder Association)
●Treatment
ADHD -- Establishing a Treatment Plan (American Academy of Pediatrics)
ADHD -- Evaluating the Treatment Plan (American Academy of Pediatrics)
ADHD -- Treatment Through Behavior Therapy (American Academy of Pediatrics)
ADHD -- Unproven Treatments (American Academy of Pediatrics)
ADHD Medicines (American Academy of Family Physicians)
Also available in: Spanish
Medical Management of Children and Adults with Attention-Deficit/Hyperactivity Disorder (Children and Adults with Attention-Deficit/Hyperactivity Disorder)
Medications (National Institute of Mental Health)
Methylphenidate and Clonidine Help Children with ADHD and Tics (National Institute of Neurological Disorders and Stroke)
●Law and Policy
Educational Rights for Children with AD/HD (Children and Adults with Attention-Deficit/Hyperactivity Disorder)
●Organizations
American Academy of Child and Adolescent Psychiatry
Children and Adults with Attention-Deficit/Hyperactivity Disorder
National Attention Deficit Disorder Association
National Institute of Mental Health
●Children
ADHD in Children (American Academy of Family Physicians)
Also available in: Spanish
Friends and Me and ADD (National Attention Deficit Disorder Association)
What is AD/HD? (Nemours Foundation)
●Teenagers
ADHD and Teens (American Academy of Pediatrics)
Attention Deficit Disorder in College (National Attention Deficit Disorder Association)
Understanding AD/HD (Nemours Foundation)
What is Ritalin? (Nemours Foundation)
●Women
Feeling Overwhelmed, Disorganized, Scattered? (National Attention Deficit Disorder Association)
Page last updated: 09 July 2003 /Topic last reviewed: 20 April 2003
●ADHD(注意欠陥・多動性障害) Link

●Russell A..Barkley著「集中できない子供たち ――注意欠陥多動性障害」の書評（日経サイエンス1999 年１月号）

●主要サイト

●Concerta
●Free video and information about ADHD
●Product information
	・Information for Patients or Caregivers(PDF; 58K)
 by Alza Corporation and McNeil Consumer Healthcare. Fort Washington PA, USA.
●Information for consumers
	・Facts about ADHD
	・How ADHD is Diagnosed
	・What Makes Concerta Unique?
	・What is the Total Treatment Plan?
	・Concerta Dosing & Safety Info
	・Helpful Questions to ask Your Doctor
	・Patient's Success with Concerta
	・Center of Attention Program
	・Common Questions & Answers
	・Patient Prescribing Information
●Information for Healthcare Professionals
	・Prescribing Information
	・About ADHD
	・About Concerta
	・About OROS® Technology"
	・12 Hour Efficacy
	・Dosing
	・Publications
	・ADHD Info Links
●ADHD(注意欠陥多動性障害)研究会のページ

患者の親が中心となる会。　冊子・ビデオ販売、他交流。

●National Attention Deficit Disorder Association

解説、文献、学会などに関する資料が豊富。
Guiding Principles for the Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder[NADDA]

●CHADD -Children and Adults with Attention-Deficit/Hyperactivity Disorder
About CHADD
Membership
FAQ
AD/HD Fact Sheets

Legislative Info.
●Attention! Magazine[隔月刊;オンライン閲覧可]
Annual Conference
News Releases
School Discipline
Chapter Locator
CHADD Shoppe
Research Studies
CHADD Chat
Donations
●Links
[1149]●製品Atomoxetine HCl(Strattera - Lilly)

　日本語版註）Atomoxetine HCl(Strattera - Lilly)ストラテラ
　【別名】(旧tomoxetine), LY139603　【開発元】Lilly　 [DBR_ID]20927
　【化学名】(-)-N-Methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride.
　【承認】FDA申請=11-Oct-2001、FDA承認=26-Nov-2002、発売=2003.1.22 ;　【製剤】Capsule contains atomoxetine HCl equivalent to 10, 18, 25, 40, or 60 mg of atomoxetine　【適応】indicated for the treatment of Attention-Deficit/Hyperactivity Disorder(ADHD).　【用法用量】1)体重70Kg以下の小児：初回１日量0.5mg/Kg。　最低３日経過後に１日最大1.2mg/Kg迄増量可能で、朝１回または朝夕２回投与。　2)体重70Kg超の小児および成人：初回１日量40mg。　最低３日経過後に１日最大80mg迄増量可能で、朝１回または朝夕２回投与。更に２－３週経過後、１日量100mg迄増量可能。　【作用】選択的ノルアドレナリン再取り込み阻害薬(NRI)　【特徴】世界初の非中枢刺激性AD/HD治療薬　【製品情報】http://www.strattera.com/　【添付文書】http://pi.lilly.com/us/strattera-pi.pdf　【EU】(英)Strattera(Lilly)承認2004.6.3,発売2004.7(欧州初)。他に米国、オーストラリア、メキシコ、アルゼンチンなどで販売。　【日本】LY139603[日本イーライリリー]第Ⅱ相(2004.9現在)　【その他】
●20927-1170
by Lilly
LY 139603;TOMOXETINE

【日本語版コメント1189】
　ADHDの治療手段が覚醒剤系メチルフェニデートが唯一であったものが、アトモキセチンが2003年1月に発売されて以来、世代交代しつつあるのは確かだ。　金額面で、メチルフェニデート製剤年間売上高が全世界で2.5億ドル程度だったのが、アトモキセチン製剤ストラテラ[米リリー社]は2003年度$370million(400億円)、2004年度前半$320millionとなっている。
　日本の場合、ADHDは一時マスコミに採りあげられ注目されたものの、現実問題として、治療を受けている患者は公式統計上6000人だけ(患者調査2002)。　治療薬については、メチルフェニデートはリタリン[ノバルティス]として販売されているものの、ADHDの適応は認可されていない(ナルコレプシーとうつ病のみ)。　但しホパテ[田辺]とメレリル[ノバルティス]が「多動」への適応が認められている。
　→詳細は参考資料●リソース：ADHD治療薬に纏めた。
＜日本語版コメント用要約＞
・注意欠陥多動性障害（ADHD）の治療薬として2003年始めに承認されたアトモキセチンを、再度取り上げた。
・アトモキセチンは、それまでのADHD治療薬とは異なり、非中枢刺激性で指定管理物質ではない。
・発売当時、本誌ではアトモキセチンが従来の刺激薬と同等の有効性を持つかどうかは不明と判断した。
・その後も、アトモキセチンが刺激薬と同等の有効性、同等の忍容性を持つという確実な証拠は得られていない。
【日本語版コメント1149】
　ADHDは、日本でも小児の3-5%が潜在患者とされるのに、病気との認識は極めて薄く日本で医療機関で治療する患者は１千人前後。　第一選択剤は国内外ともメチルフェニデート。治療手段は限られ問題も多かった。
　従来のADHD治療薬が覚醒剤系統であったのに対し、今回採りあげた塩酸アトモキセチンは、初の非中枢刺激剤のADHD治療剤ということ。　睡眠障害等の副作用も軽微という。　選択的ノルアドレナリン再取り込み阻害薬。
　→詳細は参考資料●リソース：ADHD治療薬に纏めた。

＜日本語版コメント用要約＞
・注意欠陥／多動性障害(ADHD)治療薬としては初めての非刺激性薬剤アトモキセチンが承認された。
・既存の刺激薬とは異なり、本剤は指定管理物質でなく、成人への投与も認められた。
・本剤は1日量を朝1回または朝夕2回に分けて投与するカプセル製剤。
・腹痛、食欲減退、悪心、嘔吐などの副作用の他、小児の成長への影響も見られている。
・刺激薬との比較試験は不足しており、成長への影響なども明らかではないため、現時点
では刺激薬を使用できない患者に投与すべきだろう。
●承認データ：FDA

	
情報ソース●CDER New and Generic Drug Approvals: 1998-2003: S
Strattera (Atomoxetine Hydrochloride) Capsules, Rx Eli Lilly 
Application #=NDA 21-411
Approval Date=11/26/02
Letter Posted=12/9/02
Label Posted =12/3/02
Review Posted=

Strattera (Atomoxetine Hydrochloride) Capsules, Rx Eli Lilly 
Application #=NDA 21-411/S1
Approval Date=1/17/03
Letter Posted=1/23/03
Label Posted =1/23/03
Review Posted=


	
情報ソース●NDA APPROVALS FOR CALENDAR YEAR 2002
NDA NUMBER       =21411
DRUG NAME        =Strattera
GENERIC NAME     =Atomoxetine Hydrochloride
APPLICANT/SPONSOR=Lilly
CHEMICAL TYPE    =1
THERAPEUTIC CLASS=S
APPROVAL DATE    =26-Nov-02


	
情報ソース●NME Approved in Calendar Year 2002
NDA Number       =21411
Generic Name     =Atomoxetine Hydrochloride
Trade Name       =Strattera
Dosage Form      =
Applicant        =Lilly
Classification   =1S
Approval Date    =26-Nov-02
■Lilly
 - http://www.lilly.com/

●Strattera　－http://www.strattera.com/



●ニュースから

Jun 8, 2004★Survey Shows Parents Likely to Modify ADHD Medication Over Summer, Despite Results
 Showing Treatment Helps Kids Beyond School★ADHD治療薬Strattera(Atomoxetine)
Jun 3, 2004★First Non-Stimulant ADHD Medication Available in the United Kingdom★ADHD治療薬Strattera(Atomoxetine)
May 4, 2004★Strattera Improved ADHD Impairment, Improved Family Interactions
Apr 27, 2004★Guidelines Include Strattera as a First-line ADHD Therapy Option




●日本イーライリリー



●最新情報 ---ニュース、年次報告
２００４年８月２６日★家族全体に影響を与えるＡＤ/ＨＤ、親はより早い診断を熱望－小児期における代表的な障害の１つであるＡＤ/ＨＤの診断までに平均2年－
２００４年７月２９日★米国イーライリリー社、6四半期連続の2桁売上増を達成－新製品が総額3億5000万ドルの売上を創出－★Strattera売上高は、2004Q2=$178.6m,2004Q1=$141.1m
２００４年６月１６日★「塩酸アトモキセチン」が初の非中枢刺激性AD/HD治療薬として英国で発売－欧州連合（EU）で初めての承認－
２００３年１月２２日★米国イーライリリー社、非中枢刺激性AD/HD治療薬を発売特別な規制対象とならない初の新規AD/HD治療薬

●米国イーライリリー社、長期的戦略を発表長期的な成長を支える有望なパイプラインの
上市時期を示す [2002.11.15]

●注意欠陥／多動性障害（AD/HD）治療薬　塩酸アトモキセチン
ノルエピネフリン再取り込み阻害剤の塩酸アトモキセチンは、幼児から成人までの注意欠陥／多動性障害（AD/HD）治療薬としてFDAに承認申請中です。AD/HDは米国の3%から5%の学齢児童が罹患していると予想され、その60％の児童が成人までAD/HDの症状を抱えると言われています。承認されれば、塩酸アトモキセチンは初めての非刺激性AD/HD治療薬となります。小児の1日1回投与の臨床試験では、不眠の副作用もなく、1日の持続効果が明らかになっています。2002年8月にFDAから承認見込み通知書を受領しており、米国での承認は添付文書記載事項に関する協議や追加分析を終了することを前提に許可されます。リリー社は2003年の春には塩酸アトモキセチンが販売承認されると予測しています。
●米国イーライリリー社、非中枢刺激性AD/HD治療薬を発売:特別な規制対象とならない初の新規AD/HD治療薬[2003.1.22]

イーライリリー・アンド・カンパニー（本社：米国インディアナ州インディアナポリス、シドニー・トーレル会長・社長兼CEO）は米国時間1月14日、小児及び成人の注意欠陥／多動性障害（ＡＤ/ＨＤ）治療薬「塩酸アトモキセチン（一般名）」を米国で発売したことを発表しました。「塩酸アトモキセチン」は、米国食品医薬品局（ＦＤＡ）より小児及び成人AD/HD治療薬として2002年11月26日に承認されました。
この発表に伴い、医薬品・企業開発部門担当執行副社長ジョン・Ｃ・レクライター博士は次のように述べています。「『塩酸アトモキセチン』は新しいタイプのAD/HD治療薬で、ＦＤＡが承認した唯一の非中枢刺激性ＡＤ/ＨＤ治療薬であり、臨床試験の結果に基づき、初めて小児及び成人への使用が認められた薬剤です。このことから、なぜ多くの医師やご家族の方が、『塩酸アトモキセチン』の発売時期について強い関心を持ってくださったかを理解していただけると思います。『塩酸アトモキセチン』の発売により、ＦＤＡが承認した初めての非中枢刺激性AD/HD治療薬が、治療の新たな選択肢として医師や患者さんに提供されることとなります。」
「塩酸アトモキセチン」は選択的ノルアドレナリン再取り込み阻害薬で、FDAが承認した既存のAD/HD治療薬とは異なる作用機序を有しています。FDAが承認した既存のAD/HD治療薬は、全て中枢刺激性の薬剤です。「塩酸アトモキセチン」は１日１回、もしくは２回服用のカプセル製剤で、臨床試験の結果に基づき、米国で初めて成人AD/HDにも適応が承認された薬剤です。臨床試験に参加したほとんどの小児／青少年の患者さんに睡眠障害の副作用は見られず、１日を通して学校や家庭においてAD/HDの症状が軽減しました。
米国でAD/HDに罹患している学齢児童は3％から7％と言われており、AD/HD児は同年齢の児童に比べて、注意力、集中力に欠け、活動や感情および衝動をうまくコントロールできません。専門家によると、AD/HD児の60％が成人までAD/HDの症状が持続すると言われており、米国での成人AD/HD罹患率は4％で、800万人を越えると言われています。しかし、多くの潜在患者さんは適切な診断を受けていません。
●「塩酸アトモキセチン」について
「塩酸アトモキセチン」は選択的ノルアドレナリン再取り込み阻害薬で、FDAが承認した既存のAD/HD治療薬とは異なる作用機序を有しています。「塩酸アトモキセチン」がどのようにAD/HDの症状を抑えるのかについては、完全には解明されていません。しかし研究者たちは、「塩酸アトモキセチン」が注意力や感情をコントロールする力、及び活動レベルの調整に関与していると見られているノルアドレナリンの神経終末への再取り込みを阻害する、もしくは再取り込みの速度を低下させることによって、AD/HDの症状を抑えると考えています。この作用が、脳内シナプス間隙におけるノルアドレナリンの量を増加させます。
「塩酸アトモキセチン」をモノアミン酸化酵素阻害薬（MAOI）と同時に服用する、もしくはMAOI服用後２週間以内に服用することはできません。また狭隅角緑内障の患者さんが服用することもできません。高血圧、低血圧、また心拍数亢進または心血管系の病歴がある患者さんは「塩酸アトモキセチン」の服用に関して医師に相談することが必要です。「塩酸アトモキセチン」の臨床試験には、６才未満の小児は参加していません。小児が「塩酸アトモキセチン」の服用を開始すると、体重が減少することもあります。他のAD/HD治療薬の服用と同様、治療期間中は、成長過程（身長・体重）の経過観察が必要です。
「塩酸アトモキセチン」の臨床試験で副作用を経験したほとんどの患者さんが、服用を中止することはありませんでした。小児／青少年の患者さんにおける一般的な副作用は、食欲不振、吐き気、嘔吐、疲労感、胸やけ、めまい、気分のむらでした。また成人の患者さんにおける一般的な副作用は、睡眠障害、口渇、食欲不振、便秘、胸やけ、吐き気、めまい、排尿障害、生理痛、性機能障害でした。
●Lilly: pipeline
Atomoxetine--attention-deficit hyperactivity disorder Attention-deficit hyperactivity disorder (ADHD) is one of the most common mental disorders among children, affecting between 3 and 5 percent of school-aged children. It's primarily characterized by symptoms of inattentiveness, hyperactivity, and impulsive behavior. ADHD often continues into adolescence and adulthood. The most widely prescribed drugs for ADHD are psychostimulants. But these products can have undesirable side effects, such as insomnia, and often carry a stigma because of their classification as scheduled substances (narcotics).
Atomoxetine (formerly tomoxetine), our investigational drug for ADHD, is not a stimulant; it belongs to a different class of medications. It works by blocking a neurotransmitter that plays an important role in modulating brain systems that control attention and activity. Atomoxetine would be the first such agent approved for the treatment of ADHD.
●Annual Report 2001 - atomoxetine
New class of drugs
ADHD is one of the most common chronic childhood conditions, affecting 3 to 7 percent of school-age children. In clinical studies so far, atomoxetine has significantly reduced symptoms such as severe attention problems and hyperactivity in children and adolescents.
Importantly, atomoxetine is not a stimulant. In fact, it is the first of a new class of drugs and the first new treatment for this disorder in 30 years. It works by acting on norephinephrine, a neurotransmitter that helps modulate brain activity controlling attention and behavior. Many ADHD children go untreated because parents want to avoid stimulants.
Atomoxetine also appears, in clinical trials, to be long-acting. So, if the U.S. Food and Drug Administration agrees, children may be able to take a pill in the morning and avoid the stigma of going to the school nurse at lunchtime for a second dose.
"We are proud of this compound," says Frank Bymaster, (at right) a senior research scientist who played a critical role in developing atomoxetine and also Prozac. "This has the potential to help a lot of children."
Potential help for grownups
Many adults suffer, too. Atomoxetine is the first medication extensively researched for adults with ADHD. These men and women can have trouble holding jobs and sustaining relationships. Up to 60 percent of school-age children who suffer from this disorder struggle with symptoms into adulthood.
That possibility is a long way off for Michael. But his mother says that, as long as he needs help, he'll get it. She adds, "His well-being will always be important to us."
※Strattera -- Atomoxetine
  ・Lilly Newsroom to search press releases for Atomoxetine
  ・For institutional investors and analysts
●【米国薬事情報】注意欠陥多動障害に非中枢刺激薬を承認　ＦＤＡ
 - http://yakunet.yakuji.co.jp/yakunet/yakujinippo/y_y_right_view.asp?y_y_id=31567
 薬事日報　海外通信 ：03/01/08
　ＦＤＡは十一月二十六日に、不注意、多動、衝動性など注意欠陥多動障害（ＡＤＨＤ）の症状に、過去三十年間で初の新治療薬「ストラテラ」（アトモキセチン）を承認した。ストラテラはＡＤＨＤの治療に用いる従来の中枢刺激薬とは作用機序が異なる。ストラテラは処方せん薬ではあるが、依存性は少ないため向精神薬の規制は受けない。
　米国精神医学会（ＡＰＡ）によれば、小児の約三～七％がＡＤＨＤに罹っている。また成人の約四％はＡＤＨＤの経験があると推測している。ＡＤＨＤの人は不注意な過ちを犯す、落ち着きがない、他人の行動に割り込む、おしゃべりが多いなど問題が多い。ＡＰＡ発行の精神障害の診断及び統計マニュアル「ＤＳＭ‐Ⅳ」によれば、症状は永続的で少なくとも六カ月以上示し、また診断が確定する前の比較できる段階の発症は個人に一般に見られるより重症である。成人のＡＤＨＤにつき十分明確な定義はないが、症状として組織活動の欠如、空想にふける、刺激過敏性、動機づけの不足などがある。
　ストラテラは小児、青年及び成人で治験が行われた。同剤の安全性及び有効性はＤＳＭ‐Ⅳの特定診断基準に適合する患者に対する六件の二重盲検プラセボ対照試験で確かめられた。治験でストラテラはプラセボと比べ患者の症状を有意に改善することを示した。
　同剤の副作用は食欲低下、胃の不調、悪心嘔吐、疲労などである。これらの副作用に加え、成人に最も普通な副作用には睡眠、口の渇き、眩暈及び性的副作用問題がある。
　同品はインディアナ州のイーライ・リリー社が販売する。

[1130]●製品Dexmethylphenydate(Focalin [Novartis])

DEXMETHYLPHENIDATE (FOCALIN) FOR ADHD
Dexmethylphenidate (Focalin － Novartis), a new formulation of methylphenidate (Ritalin, and others) is now available for treatment of attention deficit/hyperactivity disorder (ADHD).
Dexmethylphenidate is the d-threo-enantiomer of racemic methylphenidate. "Now the right half may be all your patients need," said a recent ad. Focalin is the third new methylphenidate formulation to be marketed in the last two years (Medical Letter 2001; 43:83; 2000; 42:80).
PHARMACOKINETICS ━Commercially available methylphenidate hydrochloride is a racemic mixture of d- and l-threo-methylphenidate. The d-enantiomer appears to be not only the more active of the two, but also better absorbed; plasma concentrations of d-methylphenidate are 10 to 40 times higher than those of the l-enantiomer (NB Modi et al, J Clin
ADHD治療薬デキサメチルフェニデート（FOCALIN）
　メチルフェニデート（Ritalin他）の新しい製剤デキサメチルフェニデート（Focalin － Novartis）が、注意欠陥／多動性障害（attention deficit/hyperactivity disorder ;ADHD）の治療薬として使用できるようになった。　デキサメチルフェニデートはメチルフェニデートのラセミ体のd-スレオ-エナンチオマーである。　最近の広告では「今や患者さんに必要なのはまさにこの半分だけでしょう」とうたっている。　Focalinはこの2年間に発売された3番目の新規メチルフェニデート製剤（Medical Letter 2001; 43:83; 2000; 42:80）。

　日本語版註）Dexmethylphenydate(Focalin [Novartis])
　【別名】　【開発元】Novartis　 [DBR_ID]x
【化学名】methyl α-phenyl-2-piperidineacetate hydrochloride, (R,R’)-(+)-
【承認】FDA申請=2000.10.25、FDA承認=2001.11.13 ;【製剤】tablets - dexmethylphenidate hydrochloride 2.5, 5, or 10 mg　【適応】indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)　【製品情報】　【添付文書】http://www.pharma.us.novartis.com/product/pi/pdf/focalin.pdf　【日本】未開発　【その他】Focalin. (dexmethylphenidate hydrochloride) is the d-threo-enantiomer of racemic methylphenidate hydrochloride, which is a 50/50 mixture of the d-threo and l-threoenantiomers. Focalin is a central nervous system (CNS) stimulant, available in three tablet strengths.

【日本語版コメント】
　日本のADHD患者はどのくらいかな？　ということで「平成11年度患者調査」閲覧第97表総患者数，傷病基本分類別を調べると、該当するF90 多動性障害 2000人。(実際は、少なすぎると統計誤差があり信頼性に欠ける)
●承認データ：FDA
●2004.5.1 以降　Drugs@FDA
Drug Name(s)        =FOCALIN
FDA Application No. =NDA # 021278
Active Ingredient(s)= DEXMETHYLPHENIDATE HYDROCHLORIDE
Company             =NOVARTIS
Dosage Form/Route   =TABLET; ORAL: 10MG; 2.5MG; 5MG
Strength            =
 - Approval Date=11/13/2001[000]	:Label[添付文書]|Letter[承認書]|Review [承認]



Drug Name(s)        =FOCALIN XR
FDA Application No. =NDA # 021802
Active Ingredient(s)= DEXMETHYLPHENIDATE HYDROCHLORIDE
Company             =NOVARTIS
Dosage Form/Route   =CAPSULE, EXTENDED RELEASE; ORAL: 10MG; 20MG; 5MG
Strength            =
 - Approval Date=05/26/2005[000]:Label[添付文書]|Letter[承認書]| [承認]
 - Approval Date=04/11/2006[001]:Label[添付文書]|Letter[承認書]|[Efficacy Supplement with Clinical Data to Support]



	
情報ソース●Drug Approvals for November 2001
Original Application #: 021278 
Approval Date: 13-NOV-01 
Trade Name: FOCALIN 
Chemical Type: 3 
Therapeutic Potential: S 
Dosage Form: TABLET 
Applicant: COLGENE CORPORATION 
Active Ingredient(s): DEXMETHYLPHENIDATE HYDROCHLORIDE 
OTC/RX Status: RX 
Indication(s): For the treatment of Attention Deficit Hyperactivity Disorder (ADHD) 

	
情報ソース●Drug Approvals for Januaryr 2002
Application #: 021278 Labeling Supplement#: 001 
To Original New Drug Application 
Approval Date: 03-JAN-02 
Trade Name: FOCALIN 
Dosage Form: TABLET 
Applicant: NOVARTIS PHAMACEUTICALS CORPORATION 
Active Ingredient(s): DEXMETHYLPHENIDATE HYDROCHLORIDE 
OTC/RX Status: RX 

●Reference Listed Drug Labeling Supplements Approved in January 2002
Jan 3
 FOCALIN letter label dexmethylphenidate HCl tablet 21-278 S-001

●FDA CDER Drug Approval Package: Focalin
Focalin (Dexmethylphenidate HCI) Tabelts
Company:  Celgene Corporation
Application No.:  21-278
Approval Date: 11/13/01

Approval Letter(s)
Printed Labeling
Medical Review(s) --- Part 1  Part 2
Chemistry Review(s)
Statistical Review(s)
Administrative Document(s)
Correspondence



●Electronic Orange Book

/2006.8.28/

Appl
No TE Code RLD Active
Ingredient Dosage Form;
Route Strength Proprietary
 Name Applicant
021802 No DEXMETHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 10MG FOCALIN XR NOVARTIS

021802 Yes DEXMETHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 20MG FOCALIN XR NOVARTIS

021802 No DEXMETHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 5MG FOCALIN XR NOVARTIS

021278 Yes DEXMETHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 10MG FOCALIN NOVARTIS

021278 No DEXMETHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 2.5MG FOCALIN NOVARTIS

021278 No DEXMETHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 5MG FOCALIN NOVARTIS



Application Number: 021802
Active Ingredient : DEXMETHYLPHENIDATE 
Proprietary Name  : FOCALIN XR [NOVARTIS] CAPSULE, EXTENDED RELEASE; ORAL 5MG,10mg,20mg
Approval Date     : May 26, 2005
Exclusivity Data  : NDF MAY 26,2008
Patent Data       : 837284 DEC 04,2015 Y 
                    5908850 DEC 04,2015 U-678
                    6228398 NOV 01,2019 Y U-676
                    6528530 DEC 04,2015 Y 
                    6635284 DEC 04,2015 Y U-677
                    6730325 NOV 01,2019 Y U-676 



Application Number: 021278
Active Ingredient : DEXMETHYLPHENIDATE HYDROCHLORIDE 
Proprietary Name  : FOCALIN [NOVARTIS]  TABLET; ORAL  2.5MG,5MG,10MG  
Approval Date     : Nov 13, 2001 
Exclusivity Data  : NP   11/13/2004  
Patent Data       : 5908850   DEC 04,2015          U-422  
                    6355656   DEC 04,2015  
■Novartis

●プレスリリース
06/06/2002 .. FDA grants marketing clearance for Ritalin LA, a once-daily formulation of Ritalin for ADHD that lasts through the entire school day
06/04/2002 .. Novartis introduces S.T.A.R.T. (Straight Talk About Responsible Treatment) Now program to educate about appropriate use of ADHD medications

05/22/2002 .. Data presented at APA meeting suggest RitalinR LA (methylphenidate hydrochloride) extended-release capsules are an effective once-daily treatment for ADHD

●05/22/2002 .. Two studies show Focalin (dexmethylphenidate HCl) is an effective treatment for ADHD

03/07/2002 .. Plaintiffs Withdrawal in New Jersey Marks Fifth and Final Dismissal of all Class Actions Filed Against Maker of Ritalin in 2000
10/26/2001 .. STUDY RESULTS SUGGEST DEXMETHYLPHENIDATE HCL IS AN EFFECTIVE TREATMENT FOR ADHD
●06/04/2002 .. Novartis launches new educational ADHD web site
--- http://www.adhdinfo.com/
The Novartis ADHD product portfolio includes RitalinR (methylphenidate), Ritalin SR, and Focalin? (dexmethylphenidate HCl), a refined formulation of Ritalin. Celgene Corporation (Nasdaq: CELG) of Warren, New Jersey, granted Novartis Pharma AG an exclusive worldwide (excluding Canada) license covering its intellectual property rights associated with Focalin as well as Ritalin LA, a once-daily form of Ritalin that is currently under review at the Food and Drug Administration (FDA). Pursuant to an agreement between Novartis Pharma AG and Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals Corporation markets Focalin in the U.S.
In addition, Novartis Pharmaceuticals Corporation received an approvable letter from the FDA for Ritalin LA in October 2001. Ritalin LA was developed by Elan Corporation, plc's drug delivery division and will be supplied to Novartis under an exclusive worldwide royalty and manufacturing agreement between the companies. Novartis Pharmaceuticals Corporation has commercialization rights to Ritalin LA in the U.S.
●Novartis -US
Focalin[TM]
(dexmethylphenidate hydrochloride)
Integral part of total treatment program for for a stabilizing effect in ADHD/ADD
Full Prescribing Information
www.ADHDinfo.com(For Consumers)
●FDA Grants Marketing Approval for Focalin? (dexmethylphenidate HCl), The First Chemically Advanced Form of RitalinR For ADHD -- New Drug for ADHD Contains Only the Effective Isomer of Ritalin
---Prescribing Information - Focalin(TM)
EAST HANOVER, NJ AND WARREN, NJ, November 15, 2001 --- Novartis Pharmaceuticals Corporation and Celgene Corporation announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for Focalin(R) (dexmethylphenidate HCl) for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).
Focalin, a refined formulation of RitalinR (d,l-methylphenidate HCl), contains only the more active isomer, which is responsible for the effective management of the symptoms of ADHD. Focalin is an advance in single-isomer technology and is formulated by isolating the active d-isomer of Ritalin, which contains both the d and l isomers of methylphenidate. Focalin is available in 2.5, 5 and 10 mg tablets for oral administration and may be administered with or without food. The recommended starting dose for new patients is 2.5 mg twice daily. For patients who are switched from Ritalin or other brands of short-acting methylphenidate, the recommended dose of dexmethylphenidate is half the dose of Ritalin.
"Focalin is a unique formulation that is designed specifically to benefit those patients who need the flexibility of a rapid-onset methylphenidate," said Scott West, M.D., CNS Healthcare, Florida and clinical investigator in the Focalin pivotal trials.
Focalin was proven to be efficacious, safe and well-tolerated in six clinical trials that included a total of 684 ADHD patients, aged 6-17 years, and in 12 healthy adult subjects. Efficacy was confirmed with parents, teachers, physicians and patients using validated, qualitative and objective scales. Two double-blind, placebo-controlled studies involving 221 patients, aged 6 to 17, demonstrated Focalin to be effective in improving performance and behavioral symptoms of ADHD. Symptoms of ADHD in both studies were evaluated using the SNAP-ADHD rating scale (a standard behavioral assessment tool used in clinical trials). Focalin was significantly more effective than placebo in lowering scores on the Teacher SNAP-ADHD rating scale (p<0.0001 vs. placebo), signifying an improvement in the clinical status of the children. Parent SNAP-ADHD assessments supported the teacher SNAP findings. In addition, Focalin significantly improved Math Test and Clinical Global Impression of Improvement (CGI-I) scores.
Overall, there was a low incidence of adverse events with the majority being of mild severity. In double-blind, placebo-controlled trials there were no discontinuations due to adverse events. In long-term extension studies, only 7 %, or 50 of 684, of children and adults treated with Focalin experienced an adverse event that resulted in discontinuation. Like most drugs approved for the treatment of ADHD, and like Ritalin, Focalin is contraindicated in patients known to be hypersensitive to the drug or to Ritalin, in patients with glaucoma, and in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome. It is also contraindicated during treatment with monoamine oxidase inhibitors and also within a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (hypertensive crises may result). In addition, like most drugs approved for the treatment of ADHD, Focalin is a schedule II drug.
"We are very pleased that the FDA has approved Focalin and believe it will be a valuable addition to existing medications for ADHD. Now patients with ADHD may receive the efficacy they need with Focalin, which contains only the effective isomer of Ritalin," said Larry Perlow, M.D., Senior Vice President and General Manager, Commercial Operations, Novartis Pharmaceuticals Corporation. "As the manufacturers of Ritalin, a medication which has helped ADHD patients and their families for more than 40 years, Novartis is committed to developing innovative treatments that will afford new options for tailored, flexible care for people with this condition."
Novartis Pharma AG licensed the worldwide (excluding Canada) marketing rights to Focalin and all related intellectual property and patents from Celgene Corporation (Nasdaq: CELG) of Warren, New Jersey. Pursuant to an agreement between Novartis Pharma AG and Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals Corporation will market Focalin in the U.S.
"We are proud to have developed Focalin, as it represents an advance in single-isomer therapy," said Sol J. Barer, Ph.D., President and Chief Operating Officer, Celgene Corporation. "Focalin is a refined form of methylphenidate that affords patients an important new treatment option."
ADHD is a neurobiologic disorder that interferes with an individual’s ability to regulate activity level and behavior and sustain focus on tasks in developmentally appropriate ways. Scientific research indicates that ADHD may be related to disturbances in certain neurotransmitters in the brain. ADHD is the most common childhood psychiatric disorder. It has been well studied for more than 40 years and is supported by a substantial body of scientific evidence.
[1265]●製品リスデクスアンフェタミン・ジメシラートlisdexamfetamine dimesylate（Vyvanse － Shire）

　日本語版註）リスデクスアンフェタミン・ジメシラートlisdexamfetamine dimesylate（Vyvanse － Shire）
　【別名】NRP104　【開発元】New River Pharmaceuticals Inc.[米]2007.4.18　→Shire Pharmaceuticals Group plcに吸収。　 [DBR_ID]
　【化学名】(2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl]hexanamide dimethanesulfonate
　【承認】FDA申請=Dec 6, 2005、FDA承認=Feb 23,2007(New River Pharmaceuticals Inc)、米国発売=2007.7.27(製造New River Pharmaceuticals Inc、販売Shire US Inc) ;　【製剤】Vyvanse capsules contain 30 mg, 50 mg and 70 mg of lisdexamfetamine dimesylate　【適応】Vyvanse is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) 6-12才児.　【用法用量】１日１回；6-12才児童に朝、初回30mgから開始。増量時は週間隔で20mg/日単位で増量。　６才未満と12才超についての試験データはない。　【作用】a pro-drug of dextroamphetamine. After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug's activity. The mode of therapeutic action in ADHD is not known.　【特徴】１２ヵ月の服用で95%に奏功。　注意力分散、落ち着きのなさ、衝動性を抑制　【製品情報】www.vyvanse.com　【添付文書】Vyvanse-PI　【EU】未開発　【日本】未開発　【その他】VyvanseはShire LLCの商標。2007.6.29 FDAに成人ADHD追加適応を申請
US Pharmacopeial Commission
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1265】
日本のADHD患者数は約33万人と推定されるが、未だ病気との認識は極めて薄く日本で医療機関で治療する患者は５千人前後(2005年度「患者調査」多動性障害(F90))と少ない。
それでも自閉症、アスペルガー症候群、ADHD、学習障害などの発達障害を持つ者に対し、援助教育や医療現場での適切な支援を行っていくことを目的に、「発達障害者支援法」が2004年12月に制定、2005年4月1日より施行。　同法により発達障害者に対する、国・地方自治体の支援の責務が明らかとなり、具体的な取り組みとして都道府県ごとに発達支援センターの設置、早期発見や発達支援、専門的な医療機関の確保などが行われている。　文部科学省調査でも小・中学校については約8割以上で対応整備が整いつつある(2007.3)。
ADHD治療薬の世界市場規模は2006年で約3400億円($28億ドル)と推定されるが、上位３製品で2900億円。　Concertaコンサータ[J&J;塩酸メチルフェニデート徐放錠;日本は薬食審2007.8通過]1,134億円($930m)、Adderal XR[Shire;複合アンフェタミン]1,053億円($863.6m)、Strattera[Lilly;atomoxetine;日本で2007.6申請]706億円(($579.0m)。　日本の場合、これまで治療薬が承認されていなかったが、漸くコンサータが年内承認見込み。
　一方ADHD治療薬による心血管や精神疾患のリスク(海外の死亡例５１例)も問題視されており安全な薬剤開発が望まれる。
　今回評価したデキストロアンフェタミンのプロドラッグVYVANSE (lisdexamfetamine dimesylate)は開発元のADHD薬大手Shire社がAdderall XRの後継薬として年間売上げ10億ドルを超えるブロックバスターに成長すると期待するをADHD治療薬のFlagshipと位置づけ。
　→詳細は参考資料●MLリソース：注意欠損多動性障害（ADHD:attention deficit/hyperactivity disorder）治療薬に纏めた。
＜日本語版コメント要約＞
・リスデクスアンフェタミン・ジメシラートが6～12歳児の注意欠陥・多動性障害（ADHD）の治療薬としてFDAに承認された。
・本剤はL-リシンとd-アンフェタミンを共有結合させたプロドラッグで、アンフェタミンそのものよりも乱用や転用、過量投与毒性の可能性が低い。
・他のアンフェタミン製剤との比較データがほとんどない。
・既知の心構造異常や重篤な心疾患のある若年患者には使用すべきでない。
●承認データ：FDA

●2004.5.1 以降　Drugs@FDA

Drug Name(s)        =VYVANSE  (LISDEXAMFETAMINE DIMESYLATE) 
FDA Application No. =(NDA) 021977
Active Ingredient(s)=LISDEXAMFETAMINE DIMESYLATE
Company             =NEW RIVER PHARMS
Dosage Form/Route   =CAPSULE; ORAL  30MG,50MG,70MG
Strength            =
 - Approval Date=02/23/2007[000]	:Label[添付文書]|Letter[承認書]|Review
Original Approval or Tentative Approval Date February 23, 2007 
Chemical Type 1  New molecular entity (NME)
Review Classification S  Standard review drug    



●Electronic Orange Book

Application Number: 021977
Active Ingredient : LISDEXAMFETAMINE DIMESYLATE
Proprietary Name  : VYVANSE [NEW RIVER PHARMS]  CAPSULE; ORAL  30MG,50MG,70MG  
Approval Date     : Feb 23, 2007 
Exclusivity Data  : NCE   FEB 23,2012 
Patent Data       : 7105486   JUN 29,2023          U-727  
                    7223735   JUN 29,2023       Y  



●FDA Advisory Committees



参考●ML資料：FDA諮問委員会～議題
FDA Advisory Committees
FDAAdvisorycommittee.com

CDER■Drug Safety and Risk Mgmt
 - http://www.fda.gov/ohrms/dockets/ac/cder07.htm#DrugSafetyRiskMgmt
Drug Safety and Risk Mgmt 2006 | 2005 | 2004 | 2003 | 2002
FDAAdvisorycommittee.com: Drug Safety and Risk Mgmt

ML 開催日 議題 備考
1205 2006.02.09 Attention Deficit/Hyperactivity Disorder Drug Cardiovascular Adverse Events
※興奮剤系ADHD治療薬のアンフェタミン剤による突然死等を契機に調査がはじまりその結果を踏まえて対応を決める。(Shire’s Adderall, Adderall XR, and Dextrostat; GlaxoSmithKline’s Dexedrine and Dexedrine Spansules), methylphenidate (J&J’s Concerta, Novartis’ Ritalin, Ritalin SR, and Ritalin LA; Alliant’s Methylin and Methylin ER; UCB/Celltech’s Metadate ER and Metadate CD), methamphetamine (Ovation’s Desoxyn) and dexmethylphenidate (Novartis’ Focalin)
※非致命的な重篤に心血管系副作用発生率は処方箋100万件当たりで小児でmethylphenidate 0.18とamphetamine 0.53、成人で各0.74 and 1.79、　突然死発生率=小児0.16 for methylphenidate versus 0.36 for those taking amphetamine. 成人では0.07 for methylphenidate and 0.53 for amphetamine.　※[Brief Information]
※[審議結果] 1)患者及び親用medication guideの作成に賛否15:0棄権1　2)ラベルに黒枠警告追加に賛否8:7棄権1 　




●FDA Asks Attention-Deficit Hyperactivity Disorder (ADHD) Drug Manufacturers to Develop Patient Medication Guides

 - http://www.fda.gov/cder/drug/infopage/ADHD/default.htm

FDAは2007.2.21, ADHD治療薬の全メーカーに対して、ADHD治療薬の心血管疾患リスクおよび精神症状発症リスク
を警告すべく患者ガイド(Patient Medication Guides)を作成するよう指示した。
FDA has directed the manufacturers of all drug products approved for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) to develop patient Medication Guides to alert patients to possible cardiovascular risks and risks of adverse psychiatric symptoms associated with the medicines, and to advise them of precautions that can be taken.

FDA Press Release

Advisory Committee Transcripts

Drug Safety and Risk Management Advisory Committee, February 9, 2006

Pediatric Advisory Committee, March 22, 2006

Drugs

Adderall (mixed salts of a single entity amphetamine product) Tablets Draft Medication Guide Label

Adderall XR (mixed salts of a single entity amphetamine product) Extended-Release Capsules Medication Guide Label

Concerta (methylphenidate hydrochloride) Extended-Release Tablets Medication Guide Label

Daytrana (methylphenidate) Transdermal System Medication Guide Label

Desoxyn (methamphetamine hydrochloride) Tablets Draft Medication Guide Label (will be updated soon)

Dexedrine (dextroamphetamine sulfate) Spansule Capsules and Tablets Medication Guide Label

Focalin (dexmethylphenidate hydrochloride) Tablets Medication Guide Label

Focalin XR (dexmethylphenidate hydrochloride) Extended-Release Capsules Medication Guide Label

Metadate CD (methylphenidate hydrochloride) Extended-Release Capsules Medication Guide Label

Methylin (methylphenidate hydrochloride) Oral Solution Draft Medication Guide Label

Methylin (methylphenidate hydrochloride) Chewable Tablets Draft Medication Guide Label

Ritalin (methylphenidate hydrochloride) Tablets Medication Guide Label

Ritalin SR (methylphenidate hydrochloride) Sustained-Release Tablets Medication Guide Label

Ritalin LA (methylphenidate hydrochloride) Extended-Release Capsules Medication Guide Label

Strattera (atomoxetine hydrochloride) Capsules Medication Guide Label

Date created: February 21, 2007, Updated May 31, 2007
●EU承認

●EMEA - Human Medcines
●List of Authorized Products (EPARs)★[A-Z 承認品目]
該当なし

★Guideline on the Non-Clinical Investigation of the Dependence Potential of Medicinal Products[2006.3.23]

[P8]
5.2 CNS Stimulants
Whether an active substance is a CNS stimulant actually can only be concluded after behavioural studies in animals have been performed or relevant observations in humans have been made. However, dopaminergic properties, particularly in mesolimbic and mesocortical regions, might be considered a signal suggesting the active substance has reinforcing properties. Such properties can be investigated in a self-administration paradigm. A positive response in a self-administration study is a strong signal indicating dependence potential of an active substance. Yet, in humans such an active substance may not necessarily cause dependence. Other pharmacological properties (e.g. emetogenic) may limit the use in humans. Some therapeutic classes (for example appetite suppressants and medicinal products indicated for Attention Deficit Hyperactivity Disorder (ADHD)) may be associated with reinforcing properties. Medicinal products belonging to such classes should be investigated using the drug self-administration model.
●Shire Pharmaceuticals Group plc

●Investors Relations
★Press Releases
Results for the twelve months to December 31, 2006 - On time execution of operating plan delivers strong 2006 performance[2007.2.20,pdf]
Strong 2005 performance supports positive outlook[2006.2.23,pdf]
Strong 2004 performance: Positive outlook for 2005[2005.3.2,pdf,30p]

★Annual Reports
Annual Review and Summary Financial Statement 2006[2007.5.21]
Annual report and accounts for the year ended December 31, 2006 (IFRS)[2007.5.21,pdf]
10K Report Year End 2006[2007.3.1,pdf]
Annual Review and Summary Financial Statement 2004[2005.5.25] -[pdf]
10K Report Year End 2004[2005.3.15,pdf]
Annual Report (UK GAAP) for the Year Ended 31 December 2004[2005.3.15,pdf]

●Products

●News & Media
★Press Releases -Shire
Shire voluntarily withdraws a limited portion of DAYTRANA(TM) (methylphenidate transdermal system) patches[2007.9.4]
 - 剥がしにくい不良品lot numbers 2563511, 2563611, and 2570411 を回収。
Shire’s New ADHD medication, VYVANSE(TM) (lisdexamfetamine dimesylate) Now Available in U.S. Pharmacies Nationwide [2007.7.27]
 - 本日全国発売。
[ADHD]
CDCによると、4-17才の児童の7.8%がADHD。
[VYVANSE]
RCT P3試験でVYVANSEはプラセボ対比で４週後ADHD Rating Scale (ADHD-RS-IV) scoresの優位性を実証(P<.0001) 。
親によるConnors' Parent Rating Scale (CPRS)でも確認。 

Shire Announces Filing of VYVANSE(TM) (lisdexamfetamine dimesylate) for the Treatment of ADHD in Adults [2007.6.29]
 - 2007.6.29 FDAに成人ADHD追加適応を申請
Shire Receives Approvable Letter from FDA for INTUNIV(TM) (guanfacine) Extended Release, a Nonstimulant
 for the Treatment of ADHD[2007.6.21]
 - 旧SPD503
Daytrana(TM) (methylphenidate transdermal system) Provides Significant Effectiveness in ADHD Symptom 
Relief in Both Boys and Girls[2007.5.23] 
12-Month Study Demonstrated Tolerability and Efficacy of Daytrana(TM) (methylphenidate transdermal system)[2007.5.23]
Shire Announces Positive Results Of Studies With Guanfacine Extended Release, An Investigational 
Nonstimulant Medication Filed For The Treatment Of ADHD In Children And Adolescents[2007.5.23]
Long-term Treatment with VYVANSE(TM) (lisdexamfetamine dimesylate), the First Prodrug Stimulant,
 Demonstrates Significant Efficacy in Children with ADHD[2007.5.23]
 - １２ヵ月の服用で95%に奏功。
Shire to Present New Scientific Data on ADHD Treatment Portfolio at APA Annual Meeting[2007.5.14]
VYVANSE(TM) (lisdexamfetamine dimesylate) Receives Final DEA Schedule Classification, Clearing Way
 for Launch of First Prodrug Stimulant for Treatment of ADHD[2007.5.3]
Shire announces refinancing of bank facilities connected with the recent acquisition of New River
 through the launch of US$1,000 million Convertible Bonds due 2014 to be offered
 outside the United States and to non-US persons only[2007.5.2]
First quarter results - strong start to the year with upgraded guidance now including New River[2007.4.25] 
Shire Completes Acquisition of New River[2007.4.20] 
Shire Successfully Completes Tender Offer for New River Shares[2007.4.18] 
 - New River Pharmaceuticals Incを買収完了。96.4%を買収。
ADDERALL XR(R) - Shire Files Suit against Colony Pharmaceuticals, Inc., Actavis, Inc. and Actavis Group hf[2007.3.21]
LIALDA with MMX Technology for UC now Available [2007.3.19]
FDA Approval of VYVANSE(TM) as a Novel Treatment for ADHD [2007.2.23]
Shire agrees to acquire new river to gain full control of Vyvanse(TM), its future flagship product for ADHD[2007.2.20]
 - $2.6 billionでNew River Pharmaceuticals Incを買収。
  2005.1 VYVANSE(TM) (lisdexamfetamine dimesylate) で提携契約。


★Press Releases -Non-Shire

●R&D Pipeline	/2007.8.23

Shire has a total of 14 projects in full development of which 4 are in phase II or beyond.



Indication Project Preclinical Phase 
I Phase 
II Phase 
III Registration



Specialty Pharma

ADHD SPD503 

ADHD SPD465 




●主要製品[2007.9.10]

Shire Product Marketed in
(オリジン) Product Description
 ADDERALL XR^(R)
 (mixed salts of a single entity amphetamine) USA & Canada
(Shire) ADDERALL XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and is a once-daily formulation of ADDERALL.
DAYTRANA(TM)
(methylphenidate transdermal system) USA
(Shire/Noven Pharmaceuticals, Inc.) The first and only transdermal medication approved to treat the symptoms of Attention Deficit Hyperactivity Disorder (ADHD). 
VYVANSE(TM)
(lisdexamfetamine dimesylate) USA VYVANSE (lisdexamfetamine dimesylate) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).


●[ADHD market]
 FROM Shire 10K Report Year End 2006[2007.3.1,pdf]
Competition in the US ADHD market has continued to increase as several products that do or will compete with the
Company’s products have been launched in recent years. Among the new entrants to the market in 2006 was
DAYTRANA, the Company’s methylphenidate product.
Many of these products contain methylphenidate. In 2000, Johnson & Johnson (in conjunction with ALZA) launched
CONCERTA, a once-daily formulation of methylphenidate. At December 31, 2006, CONCERTA had a 22.2% share
of the US ADHD market. In 2001, UCB Pharma launched METADATE CD, a once-daily formulation of
methylphenidate. At December 31, 2006, METADATE CD had a 3.1% share of the US ADHD market. In 2002,
Novartis (in conjunction with Elan) launched RITALIN LA, an extended release formulation of methylphenidate, and
in 2005 Novartis launched FOCALIN XR in conjunction with Celgene Corporation, a long-acting formulation of
dexmethylphenidate, the active ingredient of traditional methylphenidate preparations. At December 31, 2006
RITALIN LA and FOCALIN XR had a 2.8% and 5.2% share, respectively, of the US ADHD market.
In 2002, Barr launched a generic version of ADDERALL. Subsequently, five additional generic companies have
launched generic versions. Total ADDERALL generic prescriptions accounted for about 12.2% of the market as at
December 31, 2006. In September 2006, Duramed (a subsidiary of Barr) purchased the product rights to the
Company's ADDERALL product for $63 million. For further information see ITEM 7: Management’s Discussion and
Analysis.
In 2003, Eli Lilly launched STRATTERA, a non-stimulant, non-scheduled treatment for ADHD. At December 31,
2006, STRATTERA had a 10.7% share of the US ADHD market. The Company’s non-stimulant product, SPD503 is
in registration in the US.
The Company is also aware of clinical development efforts by GSK, Gliatech Inc., Cortex Pharmaceuticals Inc.,
Boehringer-Ingelheim, Eisai Inc., Bristol-Myers Squibb (in collaboration with Elan) and Abbott to develop additional
indications and new non-stimulant treatment options for ADHD.
Generic and other possible competition to the Company’s ADHD franchise is separately discussed in “Intellectual
Property” above.
[1237]●製品 methylphenidate transdermal system (Daytrana (methylphenidate) Transdermal System[Noven/Shire])(day-TRON-ah)デイトローナ

　日本語版註）methylphenidate transdermal system (Daytrana (methylphenidate) Transdermal System[Noven/Shire])(day-TRON-ah)デイトローナ
　【別名】　【開発元】Noven Pharmaceuticals, Inc　 [DBR_ID]
　【化学名】an adhesive-based matrix(DOT Matrix[TM]) transdermal system (patch) that is applied to intact skin.
　【承認】FDA申請=27-Jun-2000/Jun-2002、FDA承認=6-Apr-2006、米国発売=2006.6.29[販売：Shire社(製造Noven Pharmaceuticals, Inc.)] ;　【製剤】FILM, EXTENDED RELEASE; TRANSDERMAL: Methylphenidate 10MG/9HR (1.1MG/HR); 15MG/9HR (1.6MG/HR); 20MG/9HR (2.2MG/HR); 30MG/9HR (3.3MG/HR)　【適応】for attention deficit hyperactivity disorder (ADHD) in pediatric patients aged 6-12 years old.　【用法用量】必要時の２時間前に臀部に貼り、９時間後に除去する　【作用】血漿濃度が経口投与の1.9倍　【特徴】初の経皮製剤　【製品情報】www.daytrana.com　【添付文書】http://www.daytrana.com/PrescribingInformation.aspx　【EU】　【日本】未開発　【その他】
【日本語版コメント1237】
　ADHDは米国では学童の7.8%(440万人)が罹患という統計があるが、日本では内山有子(国立保健医療科学院生涯保健部)の研究(2005)によると、小学校の養護教諭がADHDと考えている児童は1,000人当たり3.7人で，その内医療機関で確定診断されているものは1.2人と極端に少ない[全国小学校563校(児童数約17万4300人)から回答を得、さらに全国531の病院と80の医学部精神科を対象とした厚労省研究班の全国調査として2002年2月に発表]。　それでも「発達障害」の一つとして問題視され、全国公立小中学校41,579人を対象とした初の全国実態調査で、担当教師の判定によるADHDは2.5%,LD(学習障害)を含めると6.5%[文部科学省,2002]で、昨2005年4月から「発達障害者支援法」が実施されるにいたった。　ちなみに日本で実際に治療を受けている患者数は6000人(2002年)が急増中と思われる。
　ADHD治療薬の世界市場規模は2005年で約3000億円と推定されるが、上位４製品で2500億円。　Concerta[J&J;メチルフェニデート;日本P3]913億円($774m)、Adderall XR[Shire;複合アンフェタミン]862億円($730.8m)、Strattera[Lilly;atomoxetine;日本P2/3]651億円(($552.1m)。　これらが治療薬の世界標準。しかし日本にはホパテとメレリルしかのは問題で早期承認すべきだ。
　昨2005年2月アデロールによる突然死の報告、カナダでの販売中止(９月復帰)、その後死者は５１人に。　その後調査がはじまりFDA諮問委(2006.2.9)で患者向け治療ガイド作成とラベル黒枠警告で決着。
　更にその後Adam Cohen博士(CDC)のNEJM(25-May-2006)での研究発表が大きな衝撃を与えた。ADHD治療薬服用後に救急搬送された小児が2004年には2,500人に上ったというのだ。
　さて今回採りあげたのは世界初経皮ADHD治療薬メチルフェニデート・パッチ。　血漿濃度が経口剤の約２倍と強力なせいか、副作用問題でFDA諮問委でクレームがつき、二次使用の制限がつけられた。
　→詳細は参考資料●MLリソース：注意欠損多動性障害（ADHD:attention deficit/hyperactivity disorder）治療薬に纏めた。
＜日本語版コメント要約＞
・メチルフェニデートの経皮吸収型パッチ剤が、6歳以上の注意欠陥／多動性障害（ADHD）の治療薬としてFDAに承認された。
・本パッチ剤は、1日1回最大9時間まで、臀部に貼付する。
・パッチ剤の有効性は経口剤と同等のようだが、貼付後2時間は目立った効果が現れないことがある。
・副作用は経口剤と同様で、同じくスケジュールⅡ規制管理物質である。
●承認データ：FDA

●2004.5.1 以降　Drugs@FDA

Drug Name(s)        =DAYTRANA
FDA Application No. =NDA # 021514
Active Ingredient(s)=METHYLPHENIDATE
Company             =SHIRE
Dosage Form/Route   =FILM, EXTENDED RELEASE; TRANSDERMAL: 10MG/9HR (1.1MG/HR); 15MG/9HR (1.6MG/HR); 20MG/9HR (2.2MG/HR); 30MG/9HR (3.3MG/HR)
Strength            =
 - Approval Date=04/06/2006[000]:|Label[添付文書]|Letter[承認書]|[承認]



●Electronic Orange Book

Application Number: 021514
Active Ingredient : METHYLPHENIDATE
Proprietary Name  : DAYTRANA [SHIRE] FILM, EXTENDED RELEASE; TRANSDERMAL 10MG/9HR (1.1MG/HR),15MG/9HR (1.6MG/HR),20MG/9HR (2.2MG/HR) ,0MG/9HR (3.3MG/HR)
Approval Date     : Apr 6, 2006
Exclusivity Data  : NDF APR 06,2009
Patent Data       : 5958446 DEC 12,2012 Y
                    6210705 SEP 30,2018 Y U-727
                    6348211 SEP 30,2018 Y U-727 



●FDA Advisory Committees



参考●ML資料：FDA諮問委員会～議題
FDA Advisory Committees
FDAAdvisorycommittee.com
CDER■Psychopharmacologic Drugs
 - http://www.fda.gov/ohrms/dockets/ac/cder06.html#Psychopharmacologic
 Psychopharmacologic Drugs 2005 | 2004 | 2003 | 2002
FDAAdvisorycommittee.com: Psychopharmacologic Drugs

ML 開催日 議題 備考
1237 2005.12.02 Shire/Noven Daytrana Methylphenidate Patch For Attention Deficit Hyperactivity Disorder
※[Brief Information]※FDA審査官Robert Levinは本剤がADHD治療上Johnson & Johnson/Alza社のConcertaよりも副作用が多い(more adverse effects)とした。“Treatment with [the methylphenidate transdermal system] was associated with a high incidence of insomnia, anorexia or decreased appetite, headache, and gastrointestinal symptoms including vomiting, nausea and upper abdominal pain,”　同審査官は不許可を提案。　本パッチは元々Noven社が2002.6.27にMethypatchの商品名で申請し、2003.4.25 "not approvable" letterを受けていた。　Shire and Novenはその後Phase II analog laboratory classroom study and a Phase III seven-week outpatient naturalistic study with shorter nine-hour wear timesを実施し、2005.6.28再申請したもの。
※【審議結果】Daytrana patchは皮膚過敏症のトラブルが懸念されるため経口薬が投与できないケースに二次選択されるべきという意見があり、添付文書で「経口投与が不可能な場合」と投与制限するという案が１１－１で可決。 Daytrana
(Methylphenidate)





●EU承認

記載無し

●EMEA - Human Medcines
●List of Authorized Products (EPARs)★[A-Z 承認品目]
●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 
●Shire Pharmaceuticals Group plc

 - http://www.shire.com/shirepharma/;  本社in Basingstoke, UK.

1986    設立。　当初hormone replacement therapy (HRT) を手がける。
　　　　　　　アルツハイマー薬galantamine (Reminyl)をJanssenと共同開発
1996.2  ロンドン株式市場上場。　６社買収
1997    米国製剤技術会社Pharmavene社を買収。
　　　　米国Richwood社を買収。　Adderal(ADHD薬)を入手

●Investors Relations
★Press Releases
Strong 2005 performance supports positive outlook[2006.2.23,pdf]
Strong 2004 performance: Positive outlook for 2005[2005.3.2,pdf,30p]

★Annual Reports
Annual Review and Summary Financial Statement 2004[2005.5.25] -[pdf]
10K Report Year End 2004[2005.3.15,pdf]
Annual Report (UK GAAP) for the Year Ended 31 December 2004[2005.3.15,pdf]

●Products

●News & Media
★Press Releases -Shire
Shire's DAYTRANA[TM] CII, First Transdermal Medication for Treatment of Attention Deficit
 Hyperactivity Disorder (ADHD) in Children, Now Available in Pharmacies[2006.6.29] - [pdf]
 - ADHDは米国学童の7.8%(440万人)が罹患、
Significant ADHD Symptom Control With Shorter DAYTRANA[TM] (methylphenidate transdermal system) Wear Time[2006.5.25] - [pdf]
Positive Study Results for DAYTRANA[TM](methylphenidate transdermal system) Presented at a Major Medical Meeting[2006.5.24] - [pdf]
Shire's DAYTRANA[TM] Transdermal Patch Approved.[2006.4.7] - [pdf]
Shire announces status of ongoing FDA review of NDA for DAYTRANA^(TM) for the treatment of ADHD[2006.3.10] - [pdf]

★Press Releases -Non-Shire

●R&D Pipeline






●Noven Pharmaceuticals, Inc

●Products

●Research

■Investors Relations
●SEC
10-K Annual Report[2006.3.15]
 - 2003Q2にNovenはDaytranaの全世界独占販売権をShireに$150.0 millionで許諾、製造はNovenが実施。
 [ADHD競合]ジェネリック製品の多い持続性Methylphenidate製剤等のSchedule II管理物
質間の競争が激しくDaytrana以外は経口剤。　Strattera(Lilly)は市場トップで非興奮剤
であるが、治療面でStimulantsに優ると医師や患者に認知されれば、Stimulantsの状況は
悪化する。


●News
NOVEN CONFIRMS AVAILABILITY OF DAYTRANA^(TM) METHYLPHENIDATE TRANSDERMAL SYSTEM[2006.6.29]
NOVEN ANNOUNCES FDA APPROVAL OF DAYTRANA^(TM) METHYLPHENIDATE TRANSDERMAL SYSTEM[2006.4.6]
FDA DECLARES DAYTRANA^(TM) NDA RESUBMISSION TO BE COMPLETE CLASS I RESPONSE[2006.3.10]
FDA ISSUES APPROVABLE LETTER FOR DAYTRANA^(TM) METHYLPHENIDATE TRANSDERMAL SYSTEM[2005.12.23]
NOVEN ANNOUNCES AVAILABILITY OF BRIEFING DOCUMENTS FOR DAYTRANA^(TM) ADVISORY COMMITTEE MEETING[2005.12.1]
[1205]mixed amphetamine salts(Aderall XR [Shire])
[1205]●製品 mixed amphetamine salts(Aderall XR [Shire])

　日本語版註）mixed amphetamine salts(Aderall XR [Shire])
　【別名】　【開発元】Shire Pharmaceuticals Group plc　 [DBR_ID]
　【化学名】
　【承認】FDA申請=2000.10.3、FDA承認=2001.10.11 ;　【製剤】EACH CAPSULE CONTAINS: Dextroamphetamine Saccharate 2.5mg 5.0mg 7.5mg, Amphetamine Aspartate Monohydrate 2.5mg 5.0mg 7.5mg, Dextroamphetamine Sulfate USP 2.5mg 5.0mg 7.5mg, Amphetamine Sulfate USP 2.5mg 5.0mg 7.5mg　【適応】indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).　【用法用量】１日１回朝。６才以上初回10mgから開始し、週単位で最大30mg迄増量可。　【作用】ADDERALL XR combines the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d,l-amphetamine aspartate monohydrate.　【特徴】The ADDERALL XR capsule contains two types of drug-containing beads designed to give a double-pulsed delivery of amphetamines, which prolongs the release of amphetamine from ADDERALL XR compared to the conventional ADDERALL (immediaterelease) tablet formulation.　【製品情報】www.adderallxr.com　【添付文書】ADDERALL XR Full Prescribing Information　【EU】　【日本】未開発　　【その他】

　日本語版註）Adderall [Shire]
　【別名】　【開発元】Shire Pharmaceuticals Group plc　 [DBR_ID]
　【化学名】
　【承認】FDA申請=、FDA承認=1960.1.19 ;　【製剤】EACH Tablet CONTAINS: Dextroamphetamine Saccharate 1.25mg,1.875mg,2.5mg,3.125mg,3.75mg,5mg,7.5mg, Amphetamine Aspartate Monohydrate 1.25mg,1.875mg,2.5mg,3.125mg,3.75mg,5mg,7.5mg, Dextroamphetamine Sulfate USP 1.25mg,1.875mg,2.5mg,3.125mg,3.75mg,5mg,7.5mg, Amphetamine Sulfate USP 1.25mg,1.875mg,2.5mg,3.125mg,3.75mg,5mg,7.5mg　【適応】1)Attention Deficit Disorder with Hyperactivity　2)Narcolepsy　【用法用量】[ADHD 3-5才児]１日2.5mgから開始、週単位で2.5mgずつ増量　[ADHD 6才以上]5mgを１日１回か２回から開始、週単位で5mgずつ増量　[Narcolepsy]１日5mg-60mgを分服　【作用】Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevation of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action.　【特徴】　【添付文書】Adderall-PI　【EU】　【日本】未開発　【その他】
●承認データ：FDA

●2004.5.1 以降　Drugs@FDA

Drug Name(s)        =ADDERALL XR 10  (AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE) 
FDA Application No. =(NDA) 021303
Active Ingredient(s)=AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE
Company             =SHIRE
Dosage Form/Route   =CAPSULE, EXTENDED RELEASE; ORAL
Strength            =1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG;
1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG;
1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG;
1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG
 - Approval Date=10/11/2001[000]	:Label[添付文書]|Letter[承認書]|Review
Original Approval or Tentative Approval Date October 11, 2001 
Chemical Type 3  New dosage form
Review Classification S  Standard review drug    


Drug Name(s)        =ADDERALL 10  (AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE) 
FDA Application No. =(NDA) 011522
Active Ingredient(s)=AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE
Company             =SHIRE
Dosage Form/Route   =TABLET; ORAL 
Strength            =1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG
 - Approval Date=01/19/1960[000]
Original Approval or Tentative Approval Date January 19, 1960 
Chemical Type 2  New active ingredient/4  New combination
Review Classification S  Standard review drug    



●Electronic Orange Book

/2007.9.7

Appl
No TE Code RLD Active
Ingredient Dosage Form;
Route Strength Proprietary
 Name Applicant 承認日
021303 No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE CAPSULE, EXTENDED RELEASE; ORAL 1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG;
1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG;
1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG;
1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG ●ADDERALL XR 5,10,15,20,25,30 SHIRE [10,20,30]2001.10.11
[5,15,25]2002.5.22
　 [先発権]PED   JAN 21,2009
NPP   AUG 11,2007
NPP   JUL 21,2008
[特許]6322819   OCT 21,2018
6322819*PED   APR 21,2019
6605300   OCT 21,2018
6605300*PED   APR 21,2019
040422 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE BARR [1.25,2.5,5,7.5]2002.2.11
[1.875,3.125,3.75]2003.3.19
040444 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE COREPHARMA 2002.6.19
040440 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE MALLINCKRODT 2003.10.7
040480 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE MUTUAL PHARM 2003.9.9
040470 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG;1.25MG;1.25MG;1.25MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE SANDOZ 2002.9.27
040439 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 2.5MG,5MG,7.5MG;2.5MG,5MG,7.5MG;2.5MG,5MG,7.5MG;2.5MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE SANDOZ 2002.6.14
011522 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG;
1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG ●ADDERALL 5,7.5,10,12.5,15,20,30 SHIRE [10,20]1996.2.13
[5,30]1997.5.12
[7.5,12.5,15]2000.8.31
　 [先発権]-
[特許]6384020   JUL 06,2020
6384020*PED   JAN 06,2021
040472 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE TEVA PHARMS 2003.9.30
040456 AB No AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE TABLET; ORAL 1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG;
1.25MG,2.5MG,5MG,7.5MG DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE WATSON LABS 2003.5.6




●FDA

STATEMENT ON ADDERALL[2005.2.9]
 - Health CanadaのAdderall販売中止に対応した、FDA声明。
　 FDAは、本剤に関する添付文書に関する変更は行わない。
　しかし、a Public Health Advisory and information sheets の公開は実施。

●Medwatch 2005 Safety Information Alerts - Adderall[2005.2.10]
Audience: Neuropsychiatric and other healthcare professionals FDA issued a Public Health Advisory to notify healthcare professionals that Health Canada, the Canadian drug regulatory agency, has suspended the sale of Adderall XR in the Canadian market. Adderall XR is a controlled release amphetamine used to treat patients with Attention Deficit Hyperactivity Disorder (ADHD). The Canadian action was based on U.S. post-marketing reports of sudden deaths in pediatric patients. FDA is continuing to evaluate these and other post-marketing reports of serious adverse events in children, adolescents, and adults being treated with Adderall and related products. Adderall XR is approved in the United States for the treatment of adults and pediatric patients 6-12 years old with ADHD, and Adderall, the immediate release formulation of the drug, is approved for pediatric patients with ADHD.
●Adderall and Adderall XR (amphetamines) Information Page


●Public Health Advisory for Adderall and Adderall XR
 - http://www.fda.gov/cder/drug/advisory/adderall.htm







●Health Canada

 - http://www.hc-sc.gc.ca/
Canadian Advisory on Adderall 
　小児に突然死sudden unexplained death (SUD)が発生したことにより、Adderall及び
Adderall XRの販売中止を決定。





●Shire Pharmaceuticals Group plc

 - http://www.shire.com/shirepharma/;  本社in Basingstoke, UK.

●製品売上高
($ million)   2004         2003         2002 
製品売上高計  1,112.5(+11) 1,029.8(+20)  859.4 
----------------------------------------------------------------
ADDERALL XR     606.7(+28)   474.5(+49)  317.9  [mixed amphetamine salts] ADHD
 [ADHD市場]      25%          23%         18%   米国各12月シェア
ADDERALL            -         61.1       109.8  [mixed amphetamine salts] ADHD
 [ADHD市場]                    2%          5%   米国各12月シェア
 *Adderallは同社のトップ製品。
・Adderall XR Adult - 2004.8 FDA認可、米国販売開始
・Adderall XR - FDAによる市場独占権が６か月延長され2005.4迄。
・Adderall XR - 2005.2のカナダ政府による販売中止。　カナダでのAdderall XR 売上高
は$7.8 million(2004)と少ない。


●Investors Relations
★Press Releases
★Annual Reports

●Products
Adderall XR - Shire -http://www.adderallxr.com/


●News & Media
★Press Releases -Shire
ADDERALL XRR - Paragraph IV notice received[2005.2.23]
Adderall XR(TM) recall has highlighted a critical problem for Health Canada,
 clinicians, patients and their families across the country[2005.2.22]
Important information about Adderall XR(R)[2005.2.11]
Shire announces suspension of ADDERALL XR(R) sales in Canada[2005.2.10]

★Press Releases -Non-Shire
[1086]●製品 Concerta (methylphenidate HCl) Extended-release Tablets, 18 mg & 36 mg, Rx[Alza Corp]

to 1086
　日本語版註)Alza社[http://www.alza.com/] は製剤技術開発の国際的企業で、徐放性製剤OROSは既に数種の薬剤に利用されている。　詳細は●Concerta -OROS Technology

　日本語版註）Concerta (methylphenidate HCl) Extended-release Tablets, 18 mg & 36 mg, Rx[Alza Corp]
　【別名】　【開発元】Alza Corporation　[DBR_ID]02928
　【化学名】d,l(racemic)methyl-phenyl-2-piperidineacetate hydrochloride
　【承認】FDA申請=15-Jul-1999、FDA承認=01-AUG-00 ;米国発売=Aug-00　【承認～Adolescents適応、72mg迄】FDA申請=5-Sept-2003、FDA承認=21-oct-2004　【適応】for once daily treatment of attention deficit disorder　【用法用量】１日１回朝服用。初回18mg。最大量として小児6-12才には54mg迄、Adolescents 13-17才は72mg迄。　　【製品情報】http://www.concerta.net/　【添付文書】Full Prescribing Information ; http://www.fda.gov/cder/foi/label/2000/21121lbl.pdf　【EU】　【日本】コンサータ[ヤンセンファーマ]薬食審医薬品第一部会審議品目2007.8.29通過　【適応～日】小児期における注意欠陥/多動性障害　【その他】１日１回；「コンサータ錠」は、「小児期における注意欠陥/多動性障害（AD/HD）」の効能効果を追加する新効能・新用量医薬品。AD/HD治療薬としては国内初。既に、同成分としては、中枢神経興奮剤のノバルティスファーマ「リタリン」が存在する。「コンサータ錠」は、学会などの要望もあり、今回迅速審査が適用された。再審査期間は４年。承認条件として、本剤の投与に関しては、AD/HDの診断・治療に精通し、本剤のリスク等についても十分に理解している医師のもとのみで使用するよう指示が出た。また、承認条件ではないが、企業に対して、医師および患者やその両親に対して、AD/HDに対する教育資材を作成し、配布するよう指導する方針。
●02928-1170
by Ciba-Geigy
4311-B CIBA;CENTEDRIN;METHYLPHENIDATE;METHYLPHENIDATE[BAN];METHYLPHENIDATE HCL[INN][CSP][DCF][NC*][NFN];PHENIDYLATE;RITALIN;塩酸ﾒﾁﾙﾌｪﾆﾃﾞｰﾄ;ﾒﾁﾙﾌｪﾆﾃﾞｰﾄ;リタリン

●承認データ：FDA
●2004.5.1 以降　Drugs@FDA
Drug Name(s)        =CONCERTA
FDA Application No. =NDA # 021121
Active Ingredient(s)=METHYLPHENIDATE HYDROCHLORIDE
Company             =ALZA
Dosage Form/Route   =TABLET, EXTENDED RELEASE; ORAL: 18MG; 27MG; 36MG; 54MG
Strength            =
 - Approval Date=08/01/2000[000]:Label[添付文書]|Letter[承認書]|Review [承認]
 - Approval Date=10/21/2004[008]:Label[添付文書]|Letter[承認書]|[適応症追加]



	
情報ソース●FDA Drug Approvals Part 1 (A-C)
Concerta (methylphenidate HCI) Extended-release Tablets, 18 mg & 36 mg, Rx[Alza Corp]
NDA 21-121
8/1/00
承認書8/4/00
添付文書8/4/00
Concerta Indications: for once daily treatment of attention deficit disorder.

	
情報ソース●CDER New and Generic Drug Approvals: 1998-2001:m
Concerta (methylphenidate HCI) Extended-release Tablets,18 mg & 36 mg, Rx Alza Corp. 
Application #	=NDA 21-121
Approval Date	=8/1/00
Letter Posted	=8/4/00
Label Posted	=8/4/00
Review Posted	=5/25/01
Concerta Indications:   for once daily treatment of attention deficit disorder


	
情報ソース●FDA Drug Approvals List Aug-2000
Original Application #: 021121
Approval Date: 01-AUG-00
Trade Name: CONCERTA
Chemical Type: 3
Therapeutic Potential: S
Dosage Form: TABLET, EXTENDED RELEASE
Applicant: ALZA CORP
Active Ingredient(s): METHYLPHENIDATE HYDROCHLORIDE
OTC/RX Status: RX
Indication(s): For the treatment of attention deficit disorder




●Electronic Orange Book

/2006.8.28/

Appl
No TE Code RLD Active
Ingredient Dosage Form;
Route Strength Proprietary
 Name Applicant
021121 No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 18MG CONCERTA ALZA

021121 No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 27MG CONCERTA ALZA

021121 No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 36MG CONCERTA ALZA

021121 Yes METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 54MG CONCERTA ALZA



Application Number: 021121
Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE 
Proprietary Name  : CONCERTA [ALZA]  TABLET, EXTENDED RELEASE; ORAL  18MG ,27MG,36MG,54MG 
Approval Date     : Aug 1, 2000[18MG,36MG]/ Dec 8, 2000[54MG]/ Apr 1, 2002[27MG]
Exclusivity Data  : NP   8/1/2003  
Patent Data       : 5082668*PED   MAR 16,2004           
                    4612008   SEP 16,2003           
                    4783337*PED   MAR 16,2004           
                    5082668   SEP 16,2003           
                    4612008*PED   MAR 16,2004           
                    4783337   SEP 16,2003          U-372  



●EU承認

●EMEA - Human Medcines
●List of Authorized Products (EPARs)★[A-Z 承認品目]

★
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

●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 
●ALZA Announces FDA Approval of Once-Daily Concerta(TM) (CII), For Attention Deficit Hyperactivity Disorder[02-Aug-2000]

PR Newswire -August 02, 2000 08:19
-First to Offer Full-Day ADHD Symptom Control That 'Lasts From Home to Homework' -MOUNTAIN
VIEW, Calif., Aug. 2 /PRNewswire/ --ALZA Corporation (NYSE: AZA) announced today that it has received approval from the U.S. Food & Drug Administration (FDA) to market Concerta(TM) (methylphenidate HCl) extended-release tablets (CII) for the treatment of attention deficit hyperactivity disorder (ADHD) in patients age six and older. Developed on behalf of Crescendo Pharmaceuticals Corporation (Nasdaq: CNDO), Concerta(TM) is expected to be available by prescription before the start of the 2000 school year.
Until Concerta(TM), there was no once-daily methylphenidate medication for ADHD that worked effectively throughout the day. Some other forms of medication may require two or three doses per day to achieve the desired improvement in symptoms. Concerta(TM) uses an advanced OROS(R) patterned-release delivery system. The OROS(R) system has been used safely for nearly 20 years in widely accepted prescription and over-the-counter medications, including medications taken by children. 　[以下略]
/Web site: http://www.alza.com/

●Concerta
 - http://www.concerta.net/
●Free video and information about ADHD
●Product information
	・Information for Patients or Caregivers(PDF; 58K)
 by Alza Corporation and McNeil Consumer Healthcare. Fort Washington PA, USA.
●Information for consumers
	・Facts about ADHD
	・How ADHD is Diagnosed
	・What Makes Concerta Unique?
	・What is the Total Treatment Plan?
	・Concerta Dosing & Safety Info
	・Helpful Questions to ask Your Doctor
	・Patient's Success with Concerta
	・Center of Attention Program
	・Common Questions & Answers
	・Patient Prescribing Information
●Information for Healthcare Professionals
	・Prescribing Information
	・About ADHD
	・About Concerta
	・About OROS® Technology"
	・12 Hour Efficacy
	・Dosing
	・Publications
	・ADHD Info Links
●その他
Johnson & Johnson Announces Completion of Merger with ALZA Corporation[22-June-2001]
 ---21-June-2001付けで、Alza社はJ&J社の100%子会社になった。　社名などは従来どおり。


●他の会社の製品

Ritalin[Novartis] 2000年度売上　241 CHF millions(前年比-5%)　Attention-deficit/hyperactivity disorder
 x@73.948=約178億円

●Methylin ER [Mallinckrodt]などのFDA承認データ
Methylin ER Tablets (Methylphenidate Hydrochloride Extended-release Tablets USP), 10 mg and 20 mg.
Mallinckrodt, Inc. 
Application #	=ANDA 75-629
Approval Date	=5/9/00
Letter Posted	=5/22/00

●Methylphenidate Hydrochloriade Extended-release Tablets USP, 10mg, & 20 mg, Rx
 Able Laboratories, Inc. 
Application #	=ANDA 76-032
Approval Date	=5/9/01
Letter Posted	=6/5/01

●Methylphenidate Hydrochloriade Extended-release Tablets USP, 10mg, & 20 mg
Mallinckrodt Inc.
Application #	=ANDA 75-629
Approval Date	=5/9/00

●Methylphenidate Hydrochloride Extended-release Tablets USP,  20 mg, Rx
Danbury Pharmacal, Inc.
Application #	=ANDA 40-410
Approval Date	=2/9/01
Letter Posted	=3/5/01

●Methylphenidate Hydrochloride Tablets USP, 5 mg, 10mg, & 20 mg, Rx
Able Laboratories, Inc.
Application #	=ANDA 40-404
Approval Date	=3/29/01
Letter Posted	=3/30/01

●Methylphenidate Hydrochloride Tablets USP, 5 mg, 10mg, & 20 mg
Mallinckrodt Inc.
Application #	=ANDA 40-300
Approval Date	=11/27/98
Letter Posted	=11/30
[1114]●製品methylphenidate extended-release ( Metadate CD [Celltech])

　日本語版註）methylphenidate extended-release ( Metadate CD [Celltech])
　【別名】　【開発元】Medeva Pharmaceuticals[英国]→2000.1.25 Celltech Group[英国]と合併→2004 UCBに吸収　[DBR_ID]02928
　【化学名】d,l (racemic)-threo-methyl α-phenyl-2-piperidineacetate hydrochloride
　【承認】FDA申請=31-Mar-2000、FDA承認=3-Apr-2001、米国発売mid-2001 ;　【製剤】CAPSULE, EXTENDED RELEASE; ORAL: 10MG; 20MG; 30MG; 40MG; 50MG; 60MG(速放IR分30%、遅放ER分70%) 　【適応】For the treatment of attention deficit disorder　【用法用量】　【作用】　【特徴】１日１回　【製品情報】Metadate CD　【添付文書】Metadate CD Prescribing Information　【EU】Equasym XL[UCB]英申請2003.7承認2005.2.11　　【製剤～EU】modified-release capsules - 10 mg, 20 mg or 30 mg(速放IR分30%、遅放ER分70%) 　【適応～EU】indicated as part of a comprehensive treatment programme for attention-deficit/hyperactivity disorder (ADHD) in children over 6 years of age when remedial measures alone prove insufficient. 　【用法用量～EU】１日１回朝食後。　【製品情報～EU】www.equasym.com　【添付文書～EU】(英)Equasym XL[UCB]　【日本】未開発　【その他】

DESCRIPTION: METADATE CD is a central nervous system (CNS) stimulant. METADATE CD contains 20 mg of methylphenidate hydrochloride for oral administration. The extended-release capsules comprise both immediate-release (IR) and extended-release (ER) beads such that 30% of the dose (6 mg) is provided by the IR component and 70% of the dose (14 mg) is provided by the ER component.
１日１回投与


Metadate CD
http://www.metadate-cd.com/
 ADHD解説ページ
Metadate CD Prescribing Information


Marketed by:
Celltech Pharmaceuticals, Inc.  http://www.celltechgroup.com/
Rochester, NY 14623

Manufactured by:
Eurand America, Inc.
Vandalia, Ohio 45377  USA

(R)Celltech Pharma Limited
●承認データ：FDA
●2004.5.1 以降　Drugs@FDA
Drug Name(s)        =METADATE CD
FDA Application No. =NDA # 021259
Active Ingredient(s)=METHYLPHENIDATE HYDROCHLORIDE
Company             =UCB INC
Dosage Form/Route   =CAPSULE, EXTENDED RELEASE; ORAL: 10MG; 20MG; 30MG; 40MG; 50MG; 60MG
Strength            =
 - Approval Date=04/03/2001[000]:Label[添付文書]|Letter[承認書]|Review



Drug Name(s)        =METADATE ER
FDA Application No. =ANDA # 040306[10MG],ANDA # 089601[20MG]
Active Ingredient(s)=METHYLPHENIDATE HYDROCHLORIDE
Company             =UCB INC
Dosage Form/Route   =TABLET, EXTENDED RELEASE; ORAL: 10MG; 20MG
Strength            =
 - Approval Date=10/20/1999[040306-000]	:Label[添付文書]|Letter[承認書]|Review
   申請10-Apr-1998
 - Approval Date=06/01/1988[089601-000]



	
情報ソース●CDER New and Generic Drug Approvals: 1998-2001:m

Metadate ER tablets (methylphenidate HCl) USP, 10 mg
Medeva Pharmaceuticals
Application #	=ANDA 40-306
Approval Date	=10/20/99
Letter Posted	=12/30/99
Label Posted	=
Review Posted	=
　註) Medeva Pharmaceuticals[英国本社]は、2000.1.25 Celltech Group[英国本社,1980設立]と合併。


●FDA Drug Approvals List April 2001
Original Application #: 021259
Approval Date: 03-APR-01
Trade Name: METADATE CD
Chemical Type: 3
Therapeutic Potential: S
Dosage Form: CAPSULE, EXTENDED RELEASE
Applicant: CELLTECH PHARMACEUTICALS INC
Active Ingredient(s): METHYLPHENIDATE HYDROCHLORIDE
OTC/RX Status: RX
Indication(s): For the treatment of attention deficit disorder




●Electronic Orange Book

/2006.8.28/

Appl
No TE Code RLD Active
Ingredient Dosage Form;
Route Strength Proprietary
 Name Applicant
021259 BX
No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 10MG METADATE CD UCB INC

021259 BX
No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 20MG METADATE CD UCB INC

021259 BX
Yes METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 30MG METADATE CD UCB INC

021259 BX
No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 40MG METADATE CD UCB INC

021259 No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 50MG METADATE CD UCB INC

021259 Yes METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 60MG METADATE CD UCB INC

040306 AB
No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 10MG METADATE ER UCB INC

089601 AB
Yes METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 20MG METADATE ER UCB INC



Application Number: 021259
Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE 
Proprietary Name  : METADATE CD [CELLTECH PHARMS]  CAPSULE, EXTENDED RELEASE; ORAL  10MG,20MG,30MG  
Approval Date     : Apr 3, 2001 [20MG]/ May 27, 2003 [10MG]/Jun 19, 2003 [30MG]
Exclusivity Data  : NDF   4/3/2004  
Patent Data       : 6344215   OCT 27,2020  

Application Number: 040306
Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE 
Proprietary Name  : METADATE ER [CELLTECH PHARMS]  TABLET, EXTENDED RELEASE; ORAL  10MG  
Approval Date     : Oct 20, 1999 
Exclusivity Data  : -
Patent Data       : -

Application Number: 089601
Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE 
Proprietary Name  : METADATE ER [CELLTECH MFG]  TABLET, EXTENDED RELEASE; ORAL  20MG  
Approval Date     : Jun 1, 1988 
Exclusivity Data  : -
Patent Data       : -





●EU承認

●EMEA - Human Medcines
●List of Authorized Products (EPARs)★[A-Z 承認品目]
該当なし

●CHMP Press Releases

CHMP Monthly Report May 2006[2006.6.14]
P24
★Information on applications referred to the CMD(h) in accordance with Article 29(1) of Directive 2001/83/EC, as amended
*CMD(h)(Co-ordination Group for Mutual Recognition and Decentralised procedures-Human)
Please find below information on the Name of the products in the RMS, active substances, pharmaceutical forms, procedure numbers, CMS, legal basis, grounds for referral to CMD(h), Day 60 and outcome of the procedures, for the referrals to the CMD(h) finalised on 2 May 2006.

Name of the product in the RMS Equasym 10, 20 and 30mg Capsules
Active substance Methylphenidate hydrochloride
Pharmaceutical form Capsule
Procedure number UK/H/819/01-03
CMS AT, BE, DK, FR, DE, EL, IS, IE, LU, MT, NO, NL
Legal basis Article 10.1(a)(iii), last paragraph, Directive 2001/83/EC
Grounds for referral to CMD(h) There were concerns that the once daily treatment with Equasym XL would not give sufficient therapeutic cover relative to the immediate release (IR) formulations. There were concerns that treatment with Equasym XL would provide less control of symptoms after the school day than a conventional twice daily regimen of IR methylphenidate and hence that patients using Equasym XL would be more likely to require additional IR methylphenidate to control ADHD, resulting in increased overall exposure to methylphenidate.
There were concerns regarding initiating methylphenidate treatment with Equasym XL in the treatment of naive patients.
Finally the applicant was requested to provide a risk management plan (RMP).
The applicant addressed all the concerns. Some alterations were made to the Summary of Product Characteristics to clarify some of the above issues and a RMP has been agreed.
Day 60 02.05.06
Outcome Agreement reached


CHMP press release July 2007[2007.7.19]
[p3] Referral procedures started.
The CHMP started a referral under Article 31 of the Community code on human medicinal products
for methylphenidate-containing products intended for the treatment of attention deficit
hyperactivity disorder and narcolepsy, because of safety concerns related to cardiovascular events and
cerebrovascular disorders. The procedure was initiated at the request of the European Commission.

ASSESSMENT OF THE PAEDIATRIC NEEDS PSYCHIATRY[2007.7.27]
 - The Paediatric Working Party (PEG)は小児用医薬品の各領域別の必要性を調査している。
ここで掲載したのはリストの一部

CNS STIMULANTS AND OTHER DRUGS FOR ADHD
ATOMOXETINE
Authorised indication ADHD
Authorised age group > 6 years
Authorised dose < 70 kg: usual maintenance dose 1.2 mg/kg
> 70 kg: usual maintenance dose 80 mg daily
Authorised formulation Capsules 10 mg, 18 mg, 40 mg, 60 mg
Needs Long-term safety data
Availability in all Member States
METHYLPHENIDATE HYDROCHLORIDE
Authorised indication ADHD
Authorised age group Child > 6 years
Authorised dose Child 4-6 years: 2.5 mg twice daily (max. 1.4 mg/kg daily)
Child > 6 years: 5-10 mg 1-2 times daily (max. 60 mg daily in divided doses)
Authorised formulation Tablets 5 mg, 10 mg
Modified release tablets: 18 mg, 36 mg, and capsules: 10 mg, 20 mg, 30 mg
Needs Long-term safety data



[EU Referrals] human medicinal products[医薬品のReferralリスト]Refferal=紹介の意だが、国別審査方式による製品リスト
 -[List of Referred products ]
該当なし
[総合索引～成分別]General index on active ingredient
[総合索引～銘柄別]General index on brand name
該当なし
●ニュース

●FDAの認可新薬
04/04/2001 FDA Approves Metadate (Methylphenidate) Extended Release For Attention Deficit Hyperactivity Disorder
注意欠陥多動性障害（ADHD）の６歳以上の患者の治療のため、「Metadate CD」（塩酸メチルフェニデート、USP）徐放カプセルの、1日1回、20mg、メチルフェニデートのbiphasicタイプの市場販売が、FDAより承認されたと発表
●Celltech Announces FDA Approval of MetadateR CD Capsules (CII)[3-Apr-2001]
Celltech Announces FDA Approval of MetadateR CD Capsules (CII),

A New Once-Daily Treatment for Attention Deficit Hyperactivity Disorder
Offers Active Control During a Child’s Active Hours
Celltech Pharmaceuticals, Inc. (formerly Medeva Pharmaceuticals, Inc.), a member of the Celltech Group ((LSE: CCH, NYSE: CLL)) announces today that it has received approval from the U.S. Food and Drug Administration (FDA) to market MetadateR CD (methylphenidate HCl, USP) Extended-Release Capsules., 20 mg, a once-daily biphasic formulation of methylphenidate for the treatment of attention deficit hyperactivity disorder (ADHD) in patients six years of age and older.
The biphasic release profile of MetadateR CD provides an initial rapid release of methylphenidate, followed by a second continuous release phase, resulting in school-day-long control of ADHD symptoms. In clinical trials, MetadateR CD did not interfere with evening appetite or sleep in the majority of patients. MetadateR CD utilizes Eurand’s novel DiffucapsR technology, which provides the biphasic release profile suitable for once-daily dosing.
●Metadate CD  Schedule II, controlled medicine for attention deficit hyperactivity disorder    Sold in USA
Methylphenidate
 Schedule II, controlled medicine for attention deficit hyperactivity disorder
 Made & sold in USA

Metadate CD
●12-Mar-2002 Celltech Group Plc Preliminary Announcement Of Results For Year Ended 31st December 2001

Following its launch in May 2001, MetadateR CD has made steady progress and had achieved a share of over 9% of the once-daily methylphenidate market by end-February 2002. The US ADHD market continues to be highly competitive, particularly in the light of recent and planned competitor launches, and Celltech is undertaking a number of Phase IV studies aimed at highlighting the competitive profile of MetadateR CD
￡million
Sales of Major Products 	 2001      2000  1999*
Tussionex 　　　　　　　	 64.1(+42) 45.3  42.4
Methylphenidate 　　　　	 20.4(-22) 26.3  39.4
Zaroxolyn 　　　　　　　	 30.3(+28) 23.7  26.6
Delsym 　　　　　　　　　	  9.9(-23) 12.8   6.7
Ionamin 　　　　　　　　	  5.5(-37)  8.7   7.1
Pediapred 　　　　　　　	  6.0(-5)   6.3    4.8
Semprex-D 　　　　　　　	  6.7(+24)  5.4    5.1
Coracten 　　　　　　　　	  5.4(+15) 4.7(-16) 5.6
Other 　　　　　　　　　	 84.8(-2)  86.8  87.7
Total Product Sales 　　	241.7(+10)220.0 225.4
●Preliminary Announcement of Results for the year ended 31st December 2000[14-Mar-2001]

Metadate CD
- Receipt of a US FDA approvable letter. Launch is planned in mid-2001 for this once-daily formulation of methylphenidate for attention deficit hyperactivity disorder, subject to final approval
New Product Pipeline
・ Metadate CD - following the receipt of an approvable letter from the US FDA in February 2001, launch of this once-daily controlled release formulation of methylphenidate is planned in mid 2001, subject to final approval by FDA. Celltech has recently significantly increased its US salesforce for the launch and initial marketing, and will undertake a range of Phase IV studies.
Celltech Pharmaceuticals
Celltech Pharmaceuticals, the former Medeva pharmaceutical business, is undergoing significant restructuring to strengthen and reinforce its business.
Overall product sales, excluding royalties, declined to ￡211.6 million (1999: ￡225.4 million at CER), due to the continuing and expected substantial reduction in generic methylphenidate sales. Full year sales excluding methylphenidate were stable at ￡186.7 million (1999: ￡186.0 at CER), and showed growth of 4% in the second half as the effects of intentional first half destocking diminished.
Sales of Major Products 	 2000 	 1999* 	 % change
Tussionex 　　　　　　　	 42.9 	 42.4 	 +1
Methylphenidate 　　　　	 24.9 	 39.4 	 -37
Zaroxolyn 　　　　　　　	 22.5 	 26.6 	 -15
Delsym 　　　　　　　　　	 12.2 	 6.7 	 +82
Ionamin 　　　　　　　　	 8.3 	 7.1 	 +17
Pediapred 　　　　　　　	 6.0 	 4.8 	 +25
Semprex-D 　　　　　　　	 5.1 	 5.1 	 0
Coracten 　　　　　　　　	 4.7 	 5.6 	 -16
Other 　　　　　　　　　	 85.0 	 87.7 	 -3
Total Product Sales 　　	 211.6 	 225.4 	 -6.1
US sales of ￡137.5 million (1999: ￡152.1 million) reflected continuing price and volume pressures on generic methylphenidate, which declined by 37%. This reduction accounted for the entire US sales decline. Overall sales of other products were flat over the full year, due to planned destocking of distribution pipeline inventories from the high levels experienced at the end of 1999, and a shorter than usual cough/cold season at the beginning of 2000. Above market growth from key promoted products was offset by the pipeline destocking and reductions in older products.
Celltech believes that Metadate?CD represents a significant market opportunity for its US business, and following the recent FDA approvable letter, resources are being devoted to its expected forthcoming launch and subsequent marketing. Comprehensive launch plans have been prepared, and an additional 75 US sales representatives have been recruited. Importantly, a range of Phase IV studies have been initiated.
Sales from European operations increased slightly to ￡74.1 million (1999: ￡73.3 million).

●FDA Approves Metadate (Methylphenidate) Extended Release For Attention Deficit Hyperactivity Disorder

ROCHESTER, NY -- April 4, 2001 -- Celltech Pharmaceuticals, Inc. (formerly Medeva Pharmaceuticals, Inc.), a member of the Celltech Group announced that it has received approval from the U.S. Food and Drug Administration (FDA) to market MetadateR CD (methylphenidate HCl, USP) Extended-Release Capsules, 20 mg, a once-daily biphasic formulation of methylphenidate for the treatment of attention deficit hyperactivity disorder (ADHD) in patients six years of age and older.
The biphasic release profile of Metadate CD provides an initial rapid release of methylphenidate, followed by a second continuous release phase, resulting in school-day-long control of ADHD symptoms. In clinical trials, Metadate CD did not interfere with evening appetite or sleep in the majority of patients. Metadate CD utilizes Eurand's novel DiffucapsR technology, which provides the biphasic release profile suitable for once-daily dosing.
"Metadate CD Capsules improve symptoms of ADHD for a full school-day," said Laurence Greenhill, M.D., a psychiatrist at New York State Psychiatric Institute and lead investigator of the Metadate CD multi-center study. "For school-age children, a morning dose of Metadate CD effectively controls inattentiveness, disruptive behavior and other symptoms of ADHD during the school-day, when the need for control is greatest. The once-daily regimen also eliminates the inconvenience and embarrassment of a school-day dose."
"Metadate CD exerts a treatment effect both in the morning and in the afternoon, when it is needed most, and offers the convenience of once-daily dosing in a way that doesn't come at the expense of a child's lifestyle," said Dr Michael Tidd, Vice President of Medical Affairs, Celltech Pharmaceuticals, Inc.
Metadate CD: proven efficacy for control throughout the school-day
Three hundred and fourteen children with ADHD between the ages of six and 15 were evaluated in a randomized, double-blind, parallel-group, placebo-controlled, 32-center study. The study was comprised of a one-week, single-blind, placebo run-in and a three-week, double-blind titration and treatment period. The treatment schedule included Metadate CD capsules given in individually titrated doses of 20, 40 or 60 mg daily or matching placebo. The primary objective of the study was to compare the efficacy, safety and tolerability of once-daily (before school) administration of Metadate CD capsules with placebo, in children with a confirmed diagnosis of ADHD.
The primary efficacy measure was the difference from baseline on the teacher's version of the Conners' Global Index Scale (TCGIS). The TCGIS assesses 10 different aspects of behavior and monitors treatment effectiveness and changes over time. The measurement was completed in the morning and afternoon during each week of treatment. Patients' average scores during the last week of treatment were used in the primary efficacy outcome assessment. The calculated mean improvement from baseline on the TCGIS was significantly greater for Metadate CD capsules compared with placebo (7.9 vs 1.2, respectively). Additionally, comparative analyses showed clinically and statistically significant improvement compared with placebo (p<.001) in both the morning and afternoon. The most common adverse reactions demonstrated in clinical trials were headache (12 percent), loss of appetite (9 percent), abdominal pain (7 percent) and insomnia (5 percent).
In a pharmacokinetic study, Metadate CD demonstrated an initial peak plasma level at about 1.5 hours and a second peak at about 4.5 hours. The biphasic release of medication provided school-day-long control of ADHD symptoms.
Eurand's Diffucaps technology provides customized release profiles for optimal therapeutic results. The technology is a multi-particulate system in which individual beads of the drug are prepared with specific rate-controlling membranes providing a unique release profile. Customized release profiles, designed to provide optimal clinical benefit, can then be achieved by combining different types of beads into each capsule. Metadate CD Capsules contain methylphenidate in both rapid release and continuous release beads such that 30 percent of the dose is rapidly released and 70 percent of the dose is continuously released.
Metadate CD is available in a dose pack of 30 blister-sealed capsules. This distinctive packaging helps parents and other caregivers keep track of remaining doses. In addition, the dose pack contains patient information and space for parents to note when a dose of Metadate CD was given.
Metadate CD should not be used in children under six years of age. Metadate CD Capsules are contraindicated in patients with marked anxiety, tension, and/or agitation since the drug may aggravate these symptoms. Metadate CD Capsules should not be used in patients with glaucoma, motor tics, or a family history or Tourette's Syndrome, and during or within 14 days of treatment with MAO inhibitors.
Metadate CD Capsules should be used with caution in patients with a history of psychosis, drug dependence, or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence. Caution is advised when Metadate CD is prescribed for patients with a history of seizures. Hypertension or cardiovascular disease, and in those who are receiving anticoagulants. Anticonvulsants, some antidepressants (tricyclics, SSRI's), and pressor agents.

●New Medications for ADHD

[IADHD] Prime Medical Net : Concerta(TM)- -
Concerta is a new controlled release form of Ritalin. It utilizes a special coating and matrix that allows the medication to be slowly released for up to 12 hours. The coating layer consists of immediate release Ritalin. The result is that one pill in the morning can last through the day until school is out or even longer, eliminating the need for a noon dose. Also the blood level of medication is smoother so that there is not as much of a rebound or "withdrawal" that can be disturbing to children (particularly if they are already "moody"). It seems to be superior to Ritalin SR (sustained release), seemed to lose its effectiveness in about 6 hours. A potential problem is that an after school dose may be necessary to cover the entire waking day (the 12 hour effectiveness does not apply to everyone), but one cannot give Concerta again because it could interfere with sleep. Therefore a single dose of regular Ritalin may be necessary. Concerta comes in 18 mg and 36 mg tabs only; 18 mg is roughly equivalent in strength to Ritalin 5 mg three times per day, and 36 mg to Ritalin 10 mg three times per day. Overall an improvement over straight Ritalin.
Side effects are similar to that of all stimulants: appetite suppression (somewhat worse for Concerta as one cannot dose around meals as well as the short acting stimulants such as Ritalin and Dexedrine), tics, initial insomnia, anxiety, palpitations, drowsiness, headache, and mild abdominal pain. Almost certainly there will be some degree of appetite suppression but the other side effects occur infrequently in practice. A potentially disturbing element to Concerta, not a side effect, is the fact that the matrix of the tablet will pass through the bowel and appear in the stool. As with all stimulants, there may be a benign pulse and blood pressure increase; this is usually less than 10%.
Metadate ER
The only innovation with Metadate is the sustained release of 10 mg of Ritalin (methylphenidate), a previously unavailable strength. It also comes in a 20 mg strength, roughly the same as Ritalin SR 20 mg. The 10 mg strength does offer more flexibility, but it doesn't increase the effective duration very much (perhaps up to 6 hours in practice). All the side effects mentioned above apply.
Metadate CD
On March 19, 2001, the Food and Drug Administration (FDA) approved Metadate CD, an extended-release methylphenidate capsule. The manufacturer of Metadate CD, Celltech Medeva, states that Metadate CD is intended for the treatment of children with attention deficit hyperactivity disorder (ADHD) and provides a convenient once-daily dosing. This medication uses a very unique method of controlled drug delivery called Diffucaps(tm), the first medication in the United States to use it. Basically there are beads inside a capsule that are released in two main "waves" initially and after about 8 hours. Preliminary results are promising. A disadvantage is that it only comes in a 20 mg tablet ; a 10 mg tablet is in the works.
Methylin ER
The FDA approved the extended release form of Methylin in May, 2000. Again, there is no particular innovation here other than to provide a 10 mg form of methylphenidate, previously only available in 20 mg as Ritalin SR. Methylin , manufactured by Mallinckrodt, is available in immediate release strengths of 5, 10, and 20 mg and is virtually identical to Ritalin (manufactured by Novartis)

●Metadate CD
http://www.metadate-cd.com/
 ADHD解説ページ
Metadate CD Prescribing Information


Marketed by:
Celltech Pharmaceuticals, Inc.
Rochester, NY 14623

Manufactured by:
Eurand America, Inc.
Vandalia, Ohio 45377  USA

(R)Celltech Pharma Limited
●Primary Care Clinical Practice Guidelines
Attention Deficit/Hyperactivity Disorder (ADHD)

NIH Consensus Statement 1998 Nov 16-18 Vol 16, No. 2 - Diagnosis and Treatment of Attention Deficit Disorder

Am Fam Physician 1999 May 1 - Special Medical Reports NIH Issues Consensus Statement on Attention-Deficit/Hyperactivity Disorder

MEDLINEplus: Attention Deficit Disorder with Hyperactivity National Library of Medicine
 1999 Dec 7,13 2000 Feb 10,15,24



●UCB

●Media Centre - Press Release
★CORPORATE PRESS RELEASES [INVESTOR RELATIONS] ～通常型プレスリリース
UCB Completes Mutual Recognition Procedure for Equasym(TM) XL[2006.5.24]
 - Equasym(TM) XL は英国で2005年欧州の最初に発売。
17-Apr-2003★Studies In The Journal Of Applied Research Demonstrate Optimal Dose Ratio For Celltech's Metadate(R) CDCelltech Announces Results From Head-to-Head Trial of Metadate(R) CD And McNeil's Concerta(R)>

★MEDICAL PRESS RELEASES～製品毎

●Products
Equasym XL(TM) / Metadate CD(TM) (ADHD)(methylphenidate) 

●Therapeutic Areas

●R&D
★Pipeline

●Investors Relations
★Press Releases
 - UCB Full-Year 2006 Financial Results[2007.2.28]
 - UCB Group confirms its previously announced 2004 results and provides IFRS reconciliation and product update[2005.3.23]
 - UCB Group preliminary full-year 2004 results[2005.2.7]

★Annual Reports
 - Annual Report 2006[pdf,128p]
 - Annual Report 2005[pdf,140p]
 - Annual Report 2004[pdf,76p]
 - Annual Report 2003[pdf,72p]
 - Annual Report 2002



●UCB Pharma

 - http://www.ucbpharma.com/
●Media Centre - Press Releases
CORPORATE PRESS RELEASES [INVESTOR RELATIONS]～通常型プレスリリース
MEDICAL PRESS RELEASES～製品毎
　UCBは医薬事業のみになったので、UCBと同一。


●About UCB
●Products
Equasym XL(TM) / Metadate CD(TM) (ADHD) (methylphenidate)


●Therapeutic Areas～疾病専門サイト
ADHD
http://www.theucbinstituteofallergy.com/　－アレルギー
http://www.ucbepilepsy.com/　－てんかん
http://www.ucb-bioproducts.com/　－蛋白
http://www.memorycare.net/　－呆け

●R & D



★ADHD
[2003]
In anticipation of the launch of Metadate(R) CD in mid-2001, the US sales force was expanded in order to maximize the market opportunity offered by this product. Following an appraisal of in-market performance of Metadate(R) CD, we significantly reduced the level of detailing for this product, which resulted in the US general sales force being reduced from 350 to 170 representatives during the third quarter of 2002. The restructured sales force will continue to detail our cough/cold range of products (including Tussionex(R) and Codeprex(R) which we intend to launch in the third quarter of 2004), and will support Metadate(R) CD, which is promoted predominantly to pediatricians and child psychiatrists. Since the sales force restructuring, Metadate(R) CD has made a positive financial contribution to the business. In addition, the US gastrointestinal sales force established in January 2003 which consists of 30 representatives will continue to promote Dipentum(R) and establish important relationships in advance of commercialization of CDP 870.
Equasym XL(R) We submitted an application for a marketing authorization in the UK for Equasym XLR, a once daily ADHD product, in July, 2003. We expect to launch the product in the UK during 2004. Following approval in the UK, we anticipate seeking additional approvals in other key European territories for a 2005 launch.
Metadate(R) CD. Following approval by the US FDA in April 2001, we launched this new biphasic once-daily controlled release formulation of methylphenidate. Metadate(R) CD is indicated for the treatment of attention deficit hyperactivity disorder, or ADHD. This controlled release product avoids the need for a midday dose, thus improving convenience and addressing potential concerns with pediatric patients relating to the administration of this treatment during the school day. In 2001 we increased our US sales force for the launch and initial marketing of Metadate(R) CD. Following an appraisal of in-market performance of Metadate(R) CD, however, we significantly reduced the level of detailing for this product, which resulted in the US general sales force being reduced from 350 to 170 representatives during the third quarter of 2002. The restructured sales force supports a more focused marketing campaign for Metadate(R) CD. In 2003, the product was re-packaged (100 count bottles) and two new dosage strengths were added (10 & 30 mg capsules, in addition to the original 20 mg capsules). Since that time, prescriptions have consistently grown. The product is promoted predominantly to pediatricians and child psychiatrists by our primary care sales force. Notwithstanding the increasingly competitive nature of the ADHD market, Metadate(R) CD is expected to continue to make a positive financial contribution to the business in 2004, particularly following the restructured sales force and introduction of the 10 mg and 30 mg dosage strengths. In the UK, this product will be marketed under the trademark Equasym(R) XL. During 2003, Equasym(R) XL was filed for approval in the UK and is expected to be launched in European territories towards the end of 2004/beginning of 2005, with the European organization able to build on experience from this product in the US.
In March 2002 a comparative clinical trial of Metadate(R) CD Extended-Release Capsules and McNeil’s (a Johnson & Johnson Group company) Concerta(R) Extended-Release Tablets, the current market leader in the once-daily methylphenidate market segment, was initiated. The study, published in the March 2004 on-line issue of “Pediatrics,” showed that once-daily Metadate(R) CD Extended-Release Capsules were more effective than Concerta(R) in children with ADHD during the morning hours, and that the two treatments were similar in efficacy during the afternoon. The study also showed that, with near-equal daily doses, the overall behavioral effects of Metadate(R) CD were greater than those for Concerta(R) across time periods corresponding to a typical school day (averaged over 1.5-7.5 hours post dose).
Methylphenidate. Methylphenidate is used in the treatment of ADHD in children and young adults. The DEA classifies methylphenidate as a Schedule II controlled substance.
In addition to 10 mg, 20 mg and 30 mg Metadate(R) CD, our methylphenidate range in the US consists of 5 mg, 10 mg and 20 mg immediate release tablets, and 10 mg and 20 mg extended release tablets. All the immediate release formulations and the 10 mg and 20 mg extended release tablets are generic equivalents of formulations of the branded product Ritalin which is sold in the US by Novartis AG. The 10 mg and 20 mg extended release tablets are marketed in the US under the trademark Metadate(R) ER. In May 2000, we obtained a license in Europe for the immediate release methylphenidate range and launched the product in the UK under the trademark EquasymR.
[2002]
Our attention deficit/hyperactivity disorder franchise achieved modest growth. Our franchise consists of branded Metadate(R) CD and the generic methylphenidate range. Together the franchise achieved sales of ￡30.5 million compared with the ￡29.0 million achieved during 2001. During 2002, Metadate(R) CD continued to maintain a share of approximately 9% of the once daily methylphenidate market and achieved sales for the year of ￡18.0 million (2001: ￡8.6 million). During 2002 we announced positive results from a head-to-head study against the then and still market leader in the once daily methylphenidate segment. The study was designed to confirm that the pharmacokinetic profile of Metadate(R) CD translates into improved clinical control during the school day. The positive results from this study were in a peer review journal during 2003.
●ユーシービージャパン

 - http://www.ucb-group.co.jp/
 - 2000年六月に富士レビオから医薬品事業部門を譲受し、自販体制
●プレスリリース
●製品
●製品情報

●鼻アレルギー情報センター - http://www.nasal-allergy.net/
●製品 methylphenidate HCl 塩酸メチルフェニデート[リタリン]
　ノバルティス
●リタリンの上手な使い方
●ドラッグ調査室 ：精神刺激薬(リタリン他) リタリン10mg錠
●リタリンの添付文書改訂について

適応
1.ナルコレプシー
2.抗うつ薬で効果の不十分な下記疾患に対する抗うつ薬との併用
難治性うつ病、遅延性うつ病
●Attention Deficit Disorder(ADD-ADHD)

(1/13)
[Contents]
Decade of the Brain
Ritalin:How Dangerous?/ How Effective?
What Parents Should Know / Diagnostic Checklist
Center for Current Research Report:
株式会社メドレット Medlet Japan KK
〒103-0024 東京都中央区日本橋小舟町１２－１０共同ビル（掘留）５Ｆ　久永&Co気付
tel.03-3664-2020 fax.03-3666-3188　URL:www.medmk.com/mm/ 　E-Mail: support@medmk.com

一覧へ戻る。
---------------------------------
関連●MLリソース：ナルコレプシー
---------------------------------
■2008
★★1291★24/15★08.07.28★060★小児ADHDの中枢刺激剤投与前の心電図検査/2p●MLリソース：ADHD治療薬
---------------------------------
■2007
★★1265★23/15★07.07.16★058★ADHD治療薬リスデクスアンフェタミン・ジメシラート（Vyvanse － Shire）/2p●MLリソース：ADHD治療薬
---------------------------------
■2006
★★1237★22/13★06.06.19★049★ADHD治療薬経皮メチルフェニデート(Daytrana － Noven/Shire)/2p●MLリソース：ADHD治療薬
---------------------------------
■2005
★★1205★21/07★05.03.28★028★[短信]Adderall/1p●MLリソース：ADHD治療薬
---------------------------------
■2004
★★1189★20/17★04.08.16★065★アトモキセチン (STRATTERA) 再掲/2p●リソース：ADHD治療薬
---------------------------------
■2003
★★1149★19/03★03.02.03★011★ADHD治療薬アトモキセチン(Strattera)/2p●リソース：ADHD治療薬
---------------------------------
■2002
★★1130★18/10★02.05.13★045★ADHD治療薬デキサメチルフェニデート（FOCALIN）/2p●リソース：ADHD治療剤[73KB]
--------------------------------------
■2001
★★1114★17/20★01.10.01★083★もう一つの長時間作用型メチルフェニデート（METADATE CD）/2p●リソース：ADHD治療剤[73KB]
--------------------------------------
■2000
★★1086★16/18★00.09.04★080★新しい長時間作用型メチルフェニデート(Concerta)●1086追加メモ:注意欠損多動性障害（ADHD:attention deficit/hyperactivity disorder）治療薬[25KB]
--------------------------------------
■1996
0989★12/25★96.12.06★109★注意欠陥／過剰活動性疾患の治療に対するクロニジン
--------------------------------------
ホームへ戻る。
作成：2000.10.11　最終更新:2008.11.12　小菅博之
The Medical Letter日本語版
●追加メモ to 1086,1114,1130,1149,1189,1265,1291
On Drugs and Therapeutics

このページは［The Medical Letter日本語版］の補足データとして添付しています。　［The Medical Letter］は新薬の厳正な評価誌であり、ここに収録される製品は新しくＦＤＡ承認された新薬に対する評価を中心としています。
　企画意図の第一は、収録製品についての米国内・世界での背景情報です。　例えば、各製品の承認関連データ、競合品との、あるいは市場での位置づけ、疫学データなど。　第二は、日本での該当製品や市場の情報。　市場の主要製品売上、開発中の治験薬等。　調査項目としては、■製品■解説■データ■臨床ガイドラインなど■総説記事・文献■ニュース・トピックス■リンク■主要サイト

($ milllion)	円貨換算	単位	2006	2005	2004	2003	2002	2001	2000	1999	1998	備考
Strattera [Lilly]	706億円	$ M	579.0(+5)	552.1(-17)	666.7(+80)	370.3	2.6(-)	-	-	-	-	(atomoxetine)ストラテラ/ADHD治療薬(米国発売2003.1)
米国		$ M	509.2	498.7	656.4	369.9
国外		$ M	69.8	53.4	10.3	0.4
Ritalin [Novartis]	-	$ M	-	-	-	?	?	?	147(-5)	145(-1)		[methylphenidate]ADHD治療薬
Focalin/Ritalin[Elan Corporation, plc[IR]]	27	$ M	22.5(+26)	17.8								Focalin,XR[dexmethylphenidate HCl]/Ritalin,LA[methylphenidate]ADHD治療薬;from Novartis;SODAS technology(spheroidal oral drug absorption system)
Ritalin[Elan Corporation, plc[IR]]	-	$ M		13.8(+17)	11.8							[methylphenidate]ADHD治療薬※Novartis
Metadate CD/ Equasym XL [UCB]	108億円	Euro M	68(+35)	51	11 *46	-	-	-	-	-		[Methylphenidate-SR]ADHD治療薬
Metadate CD (US) [Celltech→2004.7 UCBに合併]		￡ M	-	-	-	20.2(+22)	16.6	**20.4	**26.3	**39.4		(methylphenidate HCl徐放)ADHD;**Methylphenidate製剤計
Generic methylphenidate(US/欧) [Celltech→2004.7 UCBに合併]		￡ M	-	-	-	9.8(-16)	11.7					(methylphenidate HCl)ADHD
Concerta　[J&J]	1,134億円	$ M	930(+20)	774(+11)	695(+38)	504	-	-	-	-		methylphenidate HCl/ADHD治療薬[特許/NDA]-/ALZA/McNeil-PPC
US		$ M	756(+19)	638(+6)	600(+29)	464
Intl		$ M	174(+28)	136(+43)	95(+137)	40
Concerta(TM) [Alza→2002.6J&J傘下に]		$ M	-	-	-	-	-	[Q1]65	67.9	-	-	[methylphenidate HCl]ADHD治療薬;発売2000.8;
ADDERALL XR [Shire]	1,053億円	$ M	863.6(+18)	730.8(+20)	606.7(+28)	474.5(+49)	317.9					[mixed amphetamine salts] ADHD
[ADHD市場]		$ M	26%	26%	25%	23%	18%					米国各12月シェア
ADDERALL [Shire]	29	$ M	23.6(-45)	43.1	-	61.1	109.8					[mixed amphetamine salts] ADHD;2006.9権利をDuramedに$63.0 millionで売却
Dytrana[Shire]	31	$ M	25.1(-)	-								[methylphenidate transdermal system]ADHD;発売2006.6
[ADHD市場]		$ M	2%									米国各12月シェア
合計	3,088

治験薬記号(一般名) および剤型	会社名	予定される効能又は効果、対象疾患名および症状名	開発段階		その他
治験薬記号(一般名) および剤型	会社名	予定される効能又は効果、対象疾患名および症状名	国内	海外 (地域)	その他
LY139603（atomoxetine HCl）カプセル剤	日本イーライリリー	注意欠陥/多動性障害	申請2007.6.27	米欧発売	自社開発、自社品
塩酸メチルフェニデート徐放錠(CONCERTA)	ヤンセンファーマ	注意欠陥・多動性障害	申請2006.11	発売（欧米）	新効能・新剤型

薬品名	会社名	適応症	段階
ABT 089	Abbott	Attention-deficit hyperactivity disorder	米II
ABT 894	Abbott	Attention-deficit hyperactivity disorder	米II
Amfetamine transdermal	Shire Pharmaceuticals Group	Attention-deficit hyperactivity disorder	米I
Aripiprazole	Otsuka	Attention-deficit hyperactivity disorder	米III
CX 717	Cortex Pharmaceuticals	Attention-deficit hyperactivity disorder	米II
Guanfacine extended release (INTUNIV(TM)/CONNEXYN(TM)/旧SPD503)	Shire Pharmaceuticals	Attention-deficit hyperactivity disorder	米申請
Lisdexamfetamine Dimesylate (Vyvanse/NRP104)	Shire	Attention-deficit hyperactivity disorder	米発売
LY 2216684	Lilly	Attention-deficit hyperactivity disorder	米I
(Methylphenidate transdermal) MethyPatch(R)	Noven Pharmaceuticals	Attention-deficit hyperactivity disorder	米申請準備
(Methylphenidate transdermal) DAYTRANA	Shire Pharmaceuticals Group	Attention-deficit hyperactivity disorder	米承認
(Modafinil) Sparlon(TM)	Cephalon/J&J	Attention-deficit hyperactivity disorder	米承認
NS 2359 (GSK-372475)	GSK/NeuroSearch	Attention-deficit hyperactivity disorder (a monoamine (MAO) reuptake inhibitor)	米II
PF 3654746	Pfizer	Attention-deficit hyperactivity disorder	米I
PRX 00023	EPIX Pharmaceuticals (Predix Pharmaceuticals社が創製、2006.5合併)	Attention-deficit hyperactivity disorder	米III
R-sibutramine metabolite	Sepracor	Attention-deficit hyperactivity disorder	米I
Selegiline transdermal	Somerset	Attention-deficit hyperactivity disorder	米I
SGS 742	Saegis/ Novartis	Attention-deficit hyperactivity disorder	米II
SPD 465 (longer acting Adderall XR)	Shire Pharmaceuticals	Attention-deficit hyperactivity disorder	米申請2006.7
TC-5231	Targacept, Inc	Attention-deficit hyperactivity disorder (we discontinued development of two of our product candidates, TC-5231 and TC-2403, because they failed to meet defined clinical endpoints in Phase II clinical trials that we completed in 2004. We had been developing TC-5231 as a treatment for attention deficit hyperactivity disorder and TC-2403 as a treatment for ulcerative colitis.)	米II中止

ML	開催日	議題	備考
	2006.02.09	Attention Deficit/Hyperactivity Disorder Drug Cardiovascular Adverse Events ※興奮剤系ADHD治療薬のアンフェタミン剤による突然死等を契機に調査がはじまりその結果を踏まえて対応を決める。(Shire’s Adderall, Adderall XR, and Dextrostat; GlaxoSmithKline’s Dexedrine and Dexedrine Spansules), methylphenidate (J&J’s Concerta, Novartis’ Ritalin, Ritalin SR, and Ritalin LA; Alliant’s Methylin and Methylin ER; UCB/Celltech’s Metadate ER and Metadate CD), methamphetamine (Ovation’s Desoxyn) and dexmethylphenidate (Novartis’ Focalin) ※非致命的な重篤に心血管系副作用発生率は処方箋100万件当たりで小児でmethylphenidate 0.18とamphetamine 0.53、成人で各0.74 and 1.79、　突然死発生率=小児0.16 for methylphenidate versus 0.36 for those taking amphetamine. 成人では0.07 for methylphenidate and 0.53 for amphetamine.　※[Brief Information] ※[審議結果] 1)患者及び親用medication guideの作成に賛否15:0棄権1　2)ラベルに黒枠警告追加に賛否8:7棄権1

Appl No	RLD	Active Ingredient	Dosage Form; Route	Strength	Proprietary Name	Applicant
021802	No	DEXMETHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	10MG	FOCALIN XR	NOVARTIS
021802	Yes	DEXMETHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	20MG	FOCALIN XR	NOVARTIS
021802	No	DEXMETHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	5MG	FOCALIN XR	NOVARTIS
021278	Yes	DEXMETHYLPHENIDATE HYDROCHLORIDE	TABLET; ORAL	10MG	FOCALIN	NOVARTIS
021278	No	DEXMETHYLPHENIDATE HYDROCHLORIDE	TABLET; ORAL	2.5MG	FOCALIN	NOVARTIS
021278	No	DEXMETHYLPHENIDATE HYDROCHLORIDE	TABLET; ORAL	5MG	FOCALIN	NOVARTIS

Adderall (mixed salts of a single entity amphetamine product) Tablets	Draft Medication Guide	Label
Adderall XR (mixed salts of a single entity amphetamine product) Extended-Release Capsules	Medication Guide	Label
Concerta (methylphenidate hydrochloride) Extended-Release Tablets	Medication Guide	Label
Daytrana (methylphenidate) Transdermal System	Medication Guide	Label
Desoxyn (methamphetamine hydrochloride) Tablets	Draft Medication Guide	Label (will be updated soon)
Dexedrine (dextroamphetamine sulfate) Spansule Capsules and Tablets	Medication Guide	Label
Focalin (dexmethylphenidate hydrochloride) Tablets	Medication Guide	Label
Focalin XR (dexmethylphenidate hydrochloride) Extended-Release Capsules	Medication Guide	Label
Metadate CD (methylphenidate hydrochloride) Extended-Release Capsules	Medication Guide	Label
Methylin (methylphenidate hydrochloride) Oral Solution	Draft Medication Guide	Label
Methylin (methylphenidate hydrochloride) Chewable Tablets	Draft Medication Guide	Label
Ritalin (methylphenidate hydrochloride) Tablets	Medication Guide	Label
Ritalin SR (methylphenidate hydrochloride) Sustained-Release Tablets	Medication Guide	Label
Ritalin LA (methylphenidate hydrochloride) Extended-Release Capsules	Medication Guide	Label
Strattera (atomoxetine hydrochloride) Capsules	Medication Guide	Label

Shire Product	Marketed in (オリジン)	Product Description
ADDERALL XR^(R) (mixed salts of a single entity amphetamine)	USA & Canada (Shire)	ADDERALL XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and is a once-daily formulation of ADDERALL.
DAYTRANA(TM) (methylphenidate transdermal system)	USA (Shire/Noven Pharmaceuticals, Inc.)	The first and only transdermal medication approved to treat the symptoms of Attention Deficit Hyperactivity Disorder (ADHD).
VYVANSE(TM) (lisdexamfetamine dimesylate)	USA	VYVANSE (lisdexamfetamine dimesylate) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).

Appl No	TE Code	RLD	Active Ingredient	Dosage Form; Route	Strength	Proprietary Name	Applicant	承認日
021303		No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	CAPSULE, EXTENDED RELEASE; ORAL	1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG; 1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG; 1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG; 1.25MG,2.5MG,3.75MG,5MG,6.25MG,7.5MG	●ADDERALL XR 5,10,15,20,25,30	SHIRE	[10,20,30]2001.10.11 [5,15,25]2002.5.22
	[先発権]PED JAN 21,2009 NPP AUG 11,2007 NPP JUL 21,2008 [特許]6322819 OCT 21,2018 6322819PED APR 21,2019 6605300 OCT 21,2018 6605300PED APR 21,2019
040422	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	BARR	[1.25,2.5,5,7.5]2002.2.11 [1.875,3.125,3.75]2003.3.19
040444	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	COREPHARMA	2002.6.19
040440	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	MALLINCKRODT	2003.10.7
040480	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	MUTUAL PHARM	2003.9.9
040470	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG;1.25MG;1.25MG;1.25MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	SANDOZ	2002.9.27
040439	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	2.5MG,5MG,7.5MG;2.5MG,5MG,7.5MG;2.5MG,5MG,7.5MG;2.5MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	SANDOZ	2002.6.14
011522	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG; 1.25MG,1.875MG,2.5MG,3.125MG,3.75MG,5MG,7.5MG	●ADDERALL 5,7.5,10,12.5,15,20,30	SHIRE	[10,20]1996.2.13 [5,30]1997.5.12 [7.5,12.5,15]2000.8.31
	[先発権]- [特許]6384020 JUL 06,2020 6384020*PED JAN 06,2021
040472	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	TEVA PHARMS	2003.9.30
040456	AB	No	AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE	TABLET; ORAL	1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG; 1.25MG,2.5MG,5MG,7.5MG	DEXTROAMP SACCHARATE, AMP ASPARTATE, DEXTROAMP SULFATE AND AMP SULFATE	WATSON LABS	2003.5.6

Appl No	RLD	Active Ingredient	Dosage Form; Route	Strength	Proprietary Name	Applicant
021121	No	METHYLPHENIDATE HYDROCHLORIDE	TABLET, EXTENDED RELEASE; ORAL	18MG	CONCERTA	ALZA
021121	No	METHYLPHENIDATE HYDROCHLORIDE	TABLET, EXTENDED RELEASE; ORAL	27MG	CONCERTA	ALZA
021121	No	METHYLPHENIDATE HYDROCHLORIDE	TABLET, EXTENDED RELEASE; ORAL	36MG	CONCERTA	ALZA
021121	Yes	METHYLPHENIDATE HYDROCHLORIDE	TABLET, EXTENDED RELEASE; ORAL	54MG	CONCERTA	ALZA

Appl No	TE Code	RLD	Active Ingredient	Dosage Form; Route	Strength	Proprietary Name	Applicant
021259	BX	No	METHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	10MG	METADATE CD	UCB INC
021259	BX	No	METHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	20MG	METADATE CD	UCB INC
021259	BX	Yes	METHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	30MG	METADATE CD	UCB INC
021259	BX	No	METHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	40MG	METADATE CD	UCB INC
021259		No	METHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	50MG	METADATE CD	UCB INC
021259		Yes	METHYLPHENIDATE HYDROCHLORIDE	CAPSULE, EXTENDED RELEASE; ORAL	60MG	METADATE CD	UCB INC
040306	AB	No	METHYLPHENIDATE HYDROCHLORIDE	TABLET, EXTENDED RELEASE; ORAL	10MG	METADATE ER	UCB INC
089601	AB	Yes	METHYLPHENIDATE HYDROCHLORIDE	TABLET, EXTENDED RELEASE; ORAL	20MG	METADATE ER	UCB INC

Name of the product in the RMS	Equasym 10, 20 and 30mg Capsules
Active substance	Methylphenidate hydrochloride
Pharmaceutical form	Capsule
Procedure number	UK/H/819/01-03
CMS	AT, BE, DK, FR, DE, EL, IS, IE, LU, MT, NO, NL
Legal basis	Article 10.1(a)(iii), last paragraph, Directive 2001/83/EC
Grounds for referral to CMD(h)	There were concerns that the once daily treatment with Equasym XL would not give sufficient therapeutic cover relative to the immediate release (IR) formulations. There were concerns that treatment with Equasym XL would provide less control of symptoms after the school day than a conventional twice daily regimen of IR methylphenidate and hence that patients using Equasym XL would be more likely to require additional IR methylphenidate to control ADHD, resulting in increased overall exposure to methylphenidate. There were concerns regarding initiating methylphenidate treatment with Equasym XL in the treatment of naive patients. Finally the applicant was requested to provide a risk management plan (RMP). The applicant addressed all the concerns. Some alterations were made to the Summary of Product Characteristics to clarify some of the above issues and a RMP has been agreed.
Day 60	02.05.06
Outcome	Agreement reached

CNS STIMULANTS AND OTHER DRUGS FOR ADHD
ATOMOXETINE
Authorised indication	ADHD
Authorised age group	> 6 years
Authorised dose	< 70 kg: usual maintenance dose 1.2 mg/kg > 70 kg: usual maintenance dose 80 mg daily
Authorised formulation	Capsules 10 mg, 18 mg, 40 mg, 60 mg
Needs	Long-term safety data Availability in all Member States
METHYLPHENIDATE HYDROCHLORIDE
Authorised indication	ADHD
Authorised age group	Child > 6 years
Authorised dose	Child 4-6 years: 2.5 mg twice daily (max. 1.4 mg/kg daily) Child > 6 years: 5-10 mg 1-2 times daily (max. 60 mg daily in divided doses)
Authorised formulation	Tablets 5 mg, 10 mg Modified release tablets: 18 mg, 36 mg, and capsules: 10 mg, 20 mg, 30 mg
Needs	Long-term safety data