MLリソース：ナルコレプシー治療剤
■個別収録製品 [1145]gamma hydroxybutyrate (Xyrem [Orphan Medical]) 【別名】oxybate sodium; GHB 【開発元】Orphan Medical [DBR_ID]02864 【承認】FDA申請=2-Oct-2000、FDA承認=17-Jul-2002、発売=7-Oct-2002 ;【製剤】oral solution 【適応】For the reduction of cataplexy attacks in patients with narcolepsy. 【日本】未開発[1049]モダフィニル［プロビジル］ modafinil [Provigil] :Cephalon, Inc.
日本語版註）モダフィニル［プロビジル］ modafinil [Provigil] :Cephalon, Inc.
【別名】Modiodal,CRL-40476 【開発元】創製開発Lafon[仏]→セファロン社Cephalon Incの子会社に(2001.12) [DBR_ID]24568
【化学名】2-[(diphenylmethyl)sulfinyl]acetamide; CAS : 68693-11-8
【承認】FDA申請=1996-12-27、FDA承認=1998-12-24 発売1999-2-16; [*追加適応]FDA申請=2002.12.20、FDA承認=2004.1.23 【製剤】Tabletes -100mg, 200mg(朝１回400mg) 【適応】ナルコレプシー、*OSAHS[閉塞型睡眠時無呼吸低呼吸症候群]および *SWSD[交代勤務睡眠障害]に伴う過眠症 (PROVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder.) 【製品情報】http://www.cephalon.com -http://www.provigil.com/ 【添付文書】http://www.fda.gov/cder/foi/label/1998/20717lbl.pdf|Provigil(modafinil) Prescribing Information
【EU】現在30か国以上で承認。英国PROVIGIL、仏・スペインMODIODAL(R)[Cepa Schwarz Pharma]、独VIGIL(R)[Merckle GmbH]、オーストリア・スイスMODASOMIL(R)[Merckle GmbH]。→2002.12セファロン社に移管
【日本】モディオダール錠１００ｍｇ[製造販売元／アルフレッサファーマ株式会社 提携／Ｃｅｐｈａｌｏｎ ]ＭＯＤＩＯＤＡＬ 申請2005.4.15-承認2007.1.26-発売2007.3.28 | モディオダール錠１００ｍｇ[製造販売元／アルフレッサファーマ株式会社 提携／Ｃｅｐｈａｌｏｎ 販売元／田辺三菱製薬株式会社]ＭＯＤＩＯＤＡＬ 発売2007.3.28 ；06.3.27田辺と共同販売契約 【製剤～日本】１錠中モダフィニル１００ｍｇ 【適応～日本】ナルコレプシーに伴う日中の過度の眠気 【用法用量～日本】通常、成人にはモダフィニルとして１日１回２００ｍｇを朝に経口投与する。なお、年齢、症状により適宜増減するが、１日最大投与量は３００ｍｇまでとする。 【添付文書～日本】アルフレッサ添付文書情報 田辺三菱添付文書 【その他】U.S. Patent Nos. 4,927,855 / RE37,516
[]methylphenidate HCl (Ritalin [Novartis]) 塩酸メチルフェニデート
【別名】 【開発元】Novartis [DBR_ID]02928 【承認】FDA申請=、FDA承認= ;【製剤】 【適応】Attention Deficit Disorders, Narcolepsy 【適応～日本】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、遷延性うつ病 【日本】リタリン錠「チバ」／1％リタリン散「チバ」[ノバルティスファーマ]薬価基準収載年月1961年11月/販売開始年月1958年11月 []pemoline (Cylert[Abbott]) ペモリン 【別名】phenyl-5-isohydantoin; LA 956 【開発元】Abbott [DBR_ID]02588 【承認】FDA申請=、FDA承認= ,Oct-1998[ADHD追加]; 【適応】Attention Deficit Hyperactivity Disorder (ADHD). 【適応～日本】(1) 軽症うつ病、抑うつ神経症 (2) 次の疾患に伴う睡眠発作、傾眠傾 向、精神的弛緩の改善：ナルコレプシー、ナルコレプシーの近縁傾眠疾患 【日本】ベタナミン錠[三和化学研究所]薬価基準収載年月=1969年1月[錠]、1981年9月[錠25mg,錠50mg] 販売開始年月=1969年1月[錠]、1981年9月[錠25mg,錠50mg] ●メモ 「メチルフェニデート」の関連製剤は、ADHD治療薬として注目されているため、他に →●リソース：ADHD治療剤に含む。 ●追加 Pharmacological management of narcolepsy - Expert Opinion on Pharmacotherapy 4(10)1739-1746(2003) Gert Jan Lammers; Sebastiaan Overeem 最近の発見は、narcolepsy is caused by deficient hypocretin (orexin) transmiss ion opens a perspective on causal therapy
【日本語版コメント1181】
睡眠障害は、大きくわけると、不眠症[Insomnia](患者21万人)、過眠症[Hypersomnia;ナルコレプシーを含む](1000-2000人)、睡眠時無呼吸症候群[Sleep Apnea](2.3万人)、レストレス・レッグ症候群[RLS: Restless Leg Syndrome]。 過眠症やRLS(就寝時脚が火照ったり、ムズムズする)は、患者調査にはあらわれなくとも潜在的に軽度の症状を持つ者は日本人も多いはず。 米国ではナルコレプシー25万人、RLS 1200万人と多い。
睡眠医学・医療は最近独立した専門領域として定着しつつあり、睡眠医療センターやクリニックができ日本睡眠学会会員数も1300名、2002年から導入された認定制度で認定医32名、認定検査技師22名、認定医療機関32施設。 因みに米国睡眠医学会[AASM]は参加施設536、個人会員数4,856(正会員2,556)睡眠医学を主とする専門医が1,546人。不眠症以外は、治療手段がなかったり、著しく制限されてきた。 最近ナルコレプシーによる過眠症治療薬の世界標準となっているモダフィニルが追加適応症「睡眠時無呼吸症候群(SAS)」を認可されたので、本号ではこれをテーマとして採択した。
SASはTV番組でも放映され話題になり、国土交通省が「睡眠時無呼吸症候群に注意しましょう」とのパンフレットをSAS対応可能な500施設に配布(2003.3)。 従来SAS治療には、主に鼻腔からのCPAP(経鼻持続陽圧呼吸療法)が用いられてきた。 薬物療法としてはこれまで認可されたものはなかった。【日本語版コメント1049】
【日本語版コメント1145】
ナルコレプシー（Narcolepsy）の第１の特徴：昼間の睡眠発作では、試験中・商談中のような緊張場面でも眠り込み、これが毎日続く。 第２の特徴：情動脱力発作(cataplexy)では、強い興奮状態（怒り、笑い）が引き金として筋肉脱力がおこり、意識清明のまま数分間にわたり床に崩折れる等、通常の社会生活を困難にする病気。 米国では１４万人もの患者がいるが、日本では少なく2000人程度。
日本で適応症として「ナルコレプシー」を承認されているのは３成分のみ。 塩酸メチルフェニデート（リタリン[ノバルティス]）、塩酸メタンフェタミン、ペモリン（ベタナミン[三和化学研]）。 pemolineの肝障害が問題になって以来現在はリタリンが標準。
国際的には、これ以外に、メチルフェニデート関連製剤と世界標準となった感のあるmodafinil、そして今回評価するGHB(Xyrem)。
このGHBは、筋肉増強薬として、デート・レープ薬として、クラブで踊り狂う"Happy drug"として流行し、58人の死亡者をだした薬剤だ。
日本で適応症として「ナルコレプシー」を承認されているのは３成分のみ。 塩酸メチルフェニデート（リタリン[ノバルティス]）、塩酸メタンフェタミン、ペモリン（ベタナミン[三和化学研]）。
モダナフィルに関して、American Sleep Disorders Assn(ASDA;米国睡眠障害学会)前会長 Dr. Wolfgang Schmidt-Nowara,M.D.によると"ナルコレプシーに伴う昼間過眠症状excessive daytime sleepiness(EDS)の治療に大きな進歩"。 副作用は"mild to moderate"。 主な副作用としては、頭痛、眩暈、下痢。 米国では1993年にオーファンドラッグ指定。 英国でCephalon社はProvigil (modafinil)を発売(March 4, 1998)。 カナダでもMARCH 3, 1999にAlertec (modafinil)が承認。
【市場】 売上 ($Million) 2004 2003 2002 2001 2000 1999 Provigil[Cephalon] 439.7(+51) 290.5(+40) 207.2(+31) 150.3(+108.5) 72.1(+184) (modafinil)[C-IV] Xyrem[Orphan Med] 10.6 3.9 0.25 (発売2002.10) (sodium oxybate)ナルコレプシー Ritalin [Novartis] - ? ? ? 147(-5) 145(-1) [methylphenidate]ADHD【開発中の新薬】 ●「治験」ホームページ[厚生労働省] - 開発中の新薬[＜情報提供：日本製薬工業協会＞] /2006.8.28
($ milllion) 2005 2004 2003 2002 2001 2000 備考 PROVIGIL Tabs 512.8(+17) 439.7(+51) 290.5(+40) 207.2(+31) 150.3(+108.5) 72.1(+184) (modafinil)[C-IV] 米国 475.6(+17) 406.2 欧州 37.2(+11) 33.4 ●New Medicines in Development[PhRMA 米製薬協] /2006.8.28
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) CN-801（モダフィニル） 田辺製薬 精神神経用剤（ナルコレプシー） 申請中 発売（米） オリジン：米 セファロン社
開発：アルフレッサ ファーマ
薬品名 会社名 適応症 国 段階 (Armodafinil)
NUVIGIL(TM)Cephalon Narcolepsy USA 申請準備 【解説資料】
解説としては、●睡眠異常、過眠症 hypersomnia：北里大学電子教科書。 英文ではNarcolepsy -症状・疫学・原因・診断・治療・情報入手...について解説、modafinil.com［modafinil専門サイト］- ナルコレプシーの情報、他のナルコレプシー治療薬についての情報。 NHLBI公式ファクトシートNHLBI, Facts About Narcolepsy【疫学資料】
日本の患者数は、睡眠障害[G47]全体で237(153)千人、うち不眠症210(144)、睡眠時無呼吸23(5)、ナルコレプシーおよびカタプレキシー 1(2) [患者調査2002(1999)]。
・米国では、ナルコレプシー患者数は125,000。 英国でのナルコレプシー患者数は"数千人"（セファロン社推計）。 National Center on Sleep Disorders Pamphlet[Feb. 1994]［NHLBI睡眠障害情報センター］]に拠ると、米国では睡眠障害の患者数は7000万人、60%が慢性疾患、睡眠障害関連医療費は159億＄。 睡眠障害[sleep disorders]のうち最大の研究課題は1)睡眠時無呼吸症[Sleep apnea]で、昼間過眠症状excessive daytime sleepiness(EDS)の主因でもある。 推定患者数2000万人。 年間医療費（病院分）42百万＄で、2000年までに年間医療費は600億＄に達するという。 患者数としては2)不眠症[Insomnia]が最大。 3)ナルコレプシー[Narcolepsy]は25万人、他に4)過眠症[hypersomnia]、5)Jet-lag syndrome等。
【臨床ガイドライン】 日本睡眠学会第30回定期学術集会[2005.6.30-7.1]で 日本で最近誕生した睡眠時無呼吸症候群（SAS）ガイドラインのシンポジウム S2-1成人のSAS･診断と治療のためのガイドライン（睡眠呼吸障害研究会編） S2-2 睡眠呼吸障害（いびきと睡眠時無呼吸症候群）の診療ガイドライン： 日本口腔咽頭科学会 睡眠呼吸障害ガイドライン作成委員会 EFNS guideline on management of narcolepsy - Guideline #47 M. Billiard, C. Bassetti, Y. Dauilliers, L. Dolenc-Groselj, G.J. Lammers, G. Mayer, T. Pollmacher, P. Reading, K. Sonka(2006): European Journal of Neurology, 13: 1035-1048 by The European Federation of Neurological Societies [EFNS]Practice parameters for the treatment of narcolepsy: an update for 2000 American Academy of Sleep Medicine. 1994 (updated 2001 Jun). 16 pages. - [pdf,18p]
- modafinilのみ"standard"として推奨。 methylphenidate, amphetamine等は次ランクの"guideline"。 pemolineはoption。
Xyrem(oxybate)は以降の発売なので、これには含まれない。
Use of Gamma Hydroxybutyrate (GHB) in the Treatment of Narcolepsy[1999,pdf,2p]
【ニュース・トピックス】
「塩酸メチルフェニデート（リタリン）その他向精神薬の適正使用、処方せんに係る疑義照会の徹底等について」
（各都道府県知事宛て厚生労働省医薬食品局長通知）の発出について[2007.9.21] - 塩酸メチルフェニデート（リタリン）その他向精神薬の不適正な使用、偽造処方せん等による不正入手等が報告されている。 本剤の適応症は「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、遷延性うつ病」【リソース】
［リンク集］Google: Narcolepsy
［オンライン雑誌］なるこ会会誌 |MedWebPlus: Sleep Disorders★オンライン雑誌リソース［睡眠障害］
【主要サイト】 NPO日本ナルコレプシー協会[なるこ会] Narcolepsy Network Center for Narcolepsy Research Stanford University - Center for Narcolepsy Narcolepsy Internet ●睡眠関連 日本睡眠学会 -http://jssr.jp/ [Jap Soc Sleep Research]
解説
■睡眠異常
http://jssr.jp/syogai/syogai01.html;[日本睡眠学会] Next:ＩＩ．概日リズム睡眠障害 （Circadian rhythm sleep disorders） Ｉ．睡眠異常 １．精神生理性不眠症 （Psychophysiological insomnia） ２．原発性過眠症 (Primary hypersomnia) ３．ナルコレプシー （Narcolepsy） ４．睡眠時無呼吸症 （Sleep apnea syndrome） ５．反復性過眠症 （Recurrent hypersomnia） ６．特発性過眠症 （Idiopathic hypersomnia） ７．環境条件に起因する睡眠障害Ａ．不眠症の定義：
夜間中々入眠出来ず寝つくのに普段より２時間以上かかる入眠障害、一旦寝ついても夜中に目が醒め易く２回以上目が醒める中間覚醒、朝起きたときにぐっすり眠った感じの得られない熟眠障害、朝普段よりも２時間以上早く目が醒めてしまう早朝覚醒などの訴えのどれかがあること。
そしてこの様な不眠の訴えがしばしば見られ（週２回以上）、かつ少なくとも１ヵ月間は持続すること。不眠のため自らが苦痛を感じるか、社会生活または職業的機能が妨げられること。などの全てを満たすことが必要です。
なお精神的なストレスや身体的苦痛のため一時的に夜間良く眠れない状態は、生理学的反応としての不眠ではありますが不眠症とは言いません。
Ｂ．過眠症の定義：
日中に過剰な眠気または実際に眠り込むことが毎日の様に繰り返して見られる状態で、少なくとも１ケ月間は持続し、そのため社会生活または職業的機能が妨げられ、あるいは自らが苦痛であると感じるものです。 ただし一回の持続期間が１ヵ月より短くても繰り返して過眠期がみられるものも含みます。
●１．精神生理性不眠症 （Psychophysiological insomnia）
何らかのきっかけにより、夜眠ろうとしても寝つけず、それ以来また眠れないのではないかという不安感と緊張が著しく強まり、眠ろうと焦り過ぎるため、かえって興奮して寝つきが悪くなることが繰り返される場合です。 筋肉の緊張、血管収縮増加など身体化された緊張も増大します。 さらに寝室に入るとか、歯磨き、消灯など睡眠に関連する行動に対しても条件づけられた覚醒が形成されます。 寝室では寝つけないが、就寝時のきまりから離れた場面、例えば居間のソファに座ってテレビをみたり、読書したりしているときには容易に眠り込んだり、睡眠検査室の中などではかえって良く眠れることがあります。 このような条件化された外的要因は主観的には体験されないため、患者は不眠の理由を理解出来ないことが多いものです。 夜良く眠りたいと患者が強く意識すればするほど、逆にこの意識自体が睡眠を妨げます。 患者は自らの睡眠問題だけに囚われて頭が一杯であり、不眠の直接のきっかけとなった外因がなくなっても不眠は徐々に発展し、"自己増殖"します。
治療は不眠に対する不安・緊張感を取り除くため、精神療法、睡眠習慣の見直しを指導します。薬物療法としては夕方から抗不安剤を投与し、さらに就寝前に睡眠誘導剤を追加投与します。
●２．原発性過眠症 Primary hypersomnia
過眠症の診断基準を満たすが情動脱力発作は認められないものです。真性過眠症候群（essential
hypersomnia
syndrome)もほぼ同じ概念です。 既知の睡眠障害、器質的原因によるものは除外されます。睡眠時無呼吸症の臨床的所見（夜間の呼吸停止、典型的な間欠的大いびきなど）が認められる場合には、睡眠時無呼吸症との合併である可能性もあります。治療としては夜間睡眠の異常があれば規則正しい睡眠習慣に戻し、日中残る過眠に対しては覚醒効果をもつ精神賦活剤を朝と昼に投与します。必要以上に大量を飲みすぎると精神不安定になることがあるので必ず医師の指導を守る必要があります。
●３．ナルコレプシー （Narcolepsy）
★症状
ナルコレプシーのもっとも基本的な症状は日中反復する居眠り(daytime sleep
episodes)がほとんど毎日、何年間にもわたって続くことです。 通常10～20分位眠ると目が覚めてさっぱりしますが、2～3時間もすると再び眠気が襲ってきます。 このとき意識的に体を動かしたりすることによりある程度眠気を抑える事は可能ですが、毎日続く眠気に打ち克つことは困難です。このほか普通の人であれば緊張してまず居眠りなどしない場面、例えば試験中とか商談中等でも急に強い眠気が起り数分間程度眠り込んでしまうことがあり、これを睡眠発作(sleep attacks)と言います。
次に大切な基本症状は情動脱力発作(cataplexy)です。 大笑いしたり、得意になったり、興奮して怒ったりするなど、主に強い陽性感情の動きをきっかけにして、全身あるいは膝、腰、頚、顎、頬、眼瞼などの姿勢筋の力が両側性に突然脱けてしまう発作です。通常脱力は瞬間的ですが、数分間にわたり床に崩折れることもあります。 この間意識は清明に保たれ、周囲の状況はよく記憶されて、呼吸困難は起りません。てんかんの発作とは全く別のものです。 時には数分から30分間位も脱力状態が持続することがあり、脱力重積状態(status cataplecticus)と呼ばれています。
また入眠時幻覚と睡眠麻痺もしばしば見られますが必発症状ではありません。
入眠時幻覚(hypnagogic hallucinations)は、就床後間もなく、自覚的には半分目が覚めているにもかかわらず、生々しい現実感を伴った鮮明な夢をみることで、睡眠開始時レム睡眠期に一致して起こります。怪しい人間や動物、得体の知れない怪物などが部屋の中に入り込んできて、襲いかかってきたりする幻視、幻触、身体運動感覚などを主とする体験で、強い現実感と恐怖感を伴います。稀には入眠時幻覚が発展して日中にも侵入し、夢幻様体験から幻覚妄想状態を呈することがあります。
睡眠麻痺(sleep paralysis)は入眠時、通常入眠時幻覚による不安・幻覚体験に一致して、全身の脱力状態が起ることをいいます。 患者は恐怖から助けを求めて起上がろうとしますが、全身が金縛り状態となって身動き出来ず、声もほとんど出すことが出来ません。
さらにナルコレプシーにしばしば見られる症状としては、夜間熟眠困難（disrupted nocturnal sleep）、行動の記憶が短時間失われる自動症(automatic behaviors)、精神面の弛緩(decreased psychic tension)などがあります。また肥満、頭痛、多汗、糖尿病などが合併することがしばしばあります。
★診断基準
Ａ．日中反復する居眠りがほとんど毎日、３ヵ月以上持続する。
Ｂ．強い感情の動き（大笑い、得意、驚き、怒りなど）により誘発される姿勢筋の両側性の突然の緊張喪失発作（情動脱力発作）の存在（Ａと共存するものであれば、既往にあったことが臨床的に確認されるだけでよい）。
の両方を満たすことが必要です。単に眠気だけではナルコレプシーとは確定診断出来ません。
★検査所見
日中の普通の脳波検査所見は持続的な浅い眠りが特徴的で、開眼によりびまん性のα波活動がおこることがあり、逆説的アルファ抑制反応と呼ばれています。 睡眠ポリグラフィーでは睡眠潜時の短縮と睡眠開始時レム睡眠期（Sleep-onset
REM period, SOREMP）が出現することが特徴的です。 一日４～６回にわたり入眠潜時を測定する睡眠潜時反復検査（Multiple Sleep Latency Test，MSLT)では睡眠潜時の平均が１０分以下で、レム潜時が１０分以下の場合が２回以上認められることがしばしば見られます。 神経内分泌学的所見として正常者では夜間入眠後にみられる著しい成長ホルモンの分泌がナルコレプシー患者ではほとんど認められません。
★神経薬理学的所見
日中の居眠りに対しては覚醒効果をもつ精神賦活剤が著効を示します。抗てんかん剤は無効です。 情動脱力発作、入眠時幻覚、睡眠麻痺に対しては三環系抗うつ剤が著効を示します。
★疫学
ナルコレプシーの居眠りの発症は１０歳台に多く、とくに１４～１６歳に著しいピークを示します。情動脱力発作が居眠りより早く起こることは稀です。
発症頻度の性差はありませんが、受診頻度は男の方が多くみられます。 一般人口中のナルコレプシーの有病率は正確には分っていませんが、日本では0.16%から0.18%という推定値があります。 ナルコレプシーは低い浸透率をもつ多因子型の遺伝様式を示します。
)経過と予後
ナルコレプシーの諸症状は長期経過する中に少しずつ改善する傾向があります。
情動脱力発作、入眠時幻覚、睡眠麻痺の順に消失する頻度が高くなります。 日中の眠気は時の経過とともにやや改善する傾向はあるものの、長年月持続します。
★ＨＬＡ（ヒト主要組織適合抗原Human Leukocyte Antigen)との相関
日本人ナルコレプシー患者においては白血球の血清学的型判定でHLA-DR2とDＱ1がほぼ全例陽性です。これをＤＮＡレベルで解析すると第６染色体短腕にあるDRB1*1501とDQB1*0602という対立遺伝子がほぼ全症例で陽性であることが分かりました。 このＨＬＡ遺伝子は発症に必要な素因であるものの、十分条件とは言えません。ナルコレプシーの一卵性双生児１３組のうち１１組までが不一致で相手はナルコレプシーを発症していません。またHLA-DRB1*1501とDQB1*0602自体は正常者の約14%でも陽性です。 なおナルコレプシー患者の子供でもHLA-DR2/DRB1*1501,DQ1/DQB1*0602が陰性の場合には、将来ナルコレプシーを発症する可能性はほとんどないと考えることが出来ましょう。
欧米諸国においては、稀ながらDR2陰性のナルコレプシー患者が報告され、とくに黒人についてDR2陰性の患者の報告例が多いようです。このことはナルコレプシーの罹病性遺伝子がＨＬＡ領域ではなくてそのごく近傍にあるという可能性や、ＨＬＡ遺伝子は他の領域にある罹病性遺伝子を活性化する働きをもっているという可能性も考えられましょう。
★治療
規則正しい生活により夜間の睡眠を十分にとることがまず大切です。日中残る眠気に対しては覚醒効果をもつ精神賦活剤を朝と昼に投与します。夜間の睡眠が不十分なまま精神賦活剤を必要以上に服用すると精神不安定を起こすことがありますので、必ず専門の医師の指示に従って服用して下さい。 社会生活上の問題としては眠気のための失敗が繰り返し起り、青年期には勉学上の困難が通常起こります。 車の運転や危険な作業に際しての事故も起こりやすいので、危険を伴う職業は避け、なるべく体を動かし、自分の判断で仕事の時間配分の出来る職業が適応しやすいでしょう。 患者は挫折を繰り返し、はりのない、消極的で諦めやすい性格変化を来すことが多く、治療からも脱落しやすいことが問題です。早期発見と早期治療および治療の長期継続が大切なのですが、眠りやすいことは怠け者であると決め込んだり、近所の手前が悪いからと病院へ行くのをためらう場合も大変多いのが残念な実状です。ナルコレプシー患者により１９５７年以来自主的に運営され、お互いの親睦と助け合い、治療環境の促進を目指すなるこ会（http://www2s.biglobe.ne.jp/~narukohp/）があります。
●４．睡眠時無呼吸症 （Sleep apnea syndrome）
夜間睡眠中に反復して呼吸停止、あるいは呼吸低下の起るもので、夜間睡眠が慢性的に妨げられるため、朝起床時に爽快感が乏しく、日中強い眠気や全身倦怠感が毎日のように起こり、社会生活が妨げられる病気です。 睡眠ポリグラフィーでは、(1)睡眠潜時が短縮し、 (2)睡眠時に１０秒以上（通常20～50秒）持続する呼吸停止または浅い呼吸のエピソードが一時間当り５回以上反復し、無呼吸に伴って覚醒反応が頻回に起こります。(3)無呼吸に伴い動脈血酸素飽和度の低下が反復して生じます。 このため頭痛、口渇、右心不全、高血圧などが合併しやすくなります。 中年の肥満男性に多く、年齢が進むにつれて増加します。亜型分類として肥満や扁桃腺肥大などによる上気道狭窄により胸郭の呼吸運動はあるものの鼻腔からの換気が停止し、覚醒反応により苦悶性の激しいいびきが繰り返す閉塞型と、胸郭の呼吸運動も起らないで呼吸停止が反復する中枢型と、両者の混合した混合型が一応区別されていますが、相互の移行もあります。また完全な呼吸停止には至らず、換気が低下するため頻回の覚醒反応が起こる上気道閉塞症候群もあり、食道内圧の測定が有用である場合もあります。
治療は薬物療法のほか、ＣＰＡＰ（Continuous positive air pressure）という陽圧呼吸器具や、歯の噛み合わせを調節して顎を前に引き出す装具が開発されています。
●５．反復性過眠症 （Recurrent hypersomnia）
従来我が国では周期性傾眠症（Periodic somnolence，Periodische Schlafsucht)と呼ばれていた疾患です。 多くは青年期に発症し、数日間から２週間程度傾眠状態が続き、この間通常毎日１５時間以上昼も夜も眠り続けます。 この間は周囲の人が強く刺激すると一応は目を覚ますのですが、表情は茫乎として簡単な応答はするものの口数が少なく、注意の集中と持続が困難で、周囲への関心が乏しく、記銘力も低下しています。不機嫌で強い眠気を訴え、放置するとすぐに眠り込んでしまいます。自覚的にはぼんやりして周囲に対する現実感が薄れます。 脳波ではびまん性の遅いα波やθ波がしばしば連続して見られます。 この病気の本態としては軽い意識障害が考えられていますが昏睡ほど深いものではなく、食事や排便は自ら行い、失禁することもありません。病相発現の直前に発熱や心身の過労が見られることがしばしばありますが、誘因が必ずしも明確でない場合もあります。傾眠病相の発現頻度は、初めの中は２週間ないし２か月に一度位のことが多いのですが、必ずしも周期的ではなく、経過とともに間隔は延長し、一回の病相の持続が延長する半面、一日の睡眠時間はやや短縮し眠気の強さも軽くなることが多いようです。また経過するうちに特に病相期の後半にかけて無遠慮、易刺激性、衝動的行為、色情的言動、ときに食欲高進、依存性または攻撃性の増加、錯覚、多動・軽躁状態など精神面の抑制力低下が見られることがあります。病相間歇期には全く平常に戻ります。
亜型として傾眠期に食欲の著しい高進と過食の見られる一群をクライネ・レビン症候群（Kleine-Levin syndrome）と呼んでいます。
病相期が始まると治療は困難なことが多く、むしろ病相を予防するための薬物療法が工夫されています。
●６．特発性過眠症 （Idiopathic hypersomnia）
ＩＣＳＤの特発性過眠症の診断基準は以下のA+B+C+Dが最少限基準とされています。
A.長時間にわたる睡眠エピソード、過度の眠気、あるいは過度に深い睡眠の訴。
B.夜間睡眠が長時間に及ぶこと、あるいは頻繁な日中の睡眠エピソードの存在。
C.発症は徐々で、多くの場合25歳未満で発症する。
D.訴えの持続が少なくとも６カ月以上。
しかしこれでは不明確なので、私は以下のような診断基準を提案しています。
a.夜間睡眠時間は十分なのに昼間1時間以上の睡眠エピソードがしばしば見られる。
b.一日の総睡眠時間が10時間以上。
c.睡眠エピソード後の目覚めがすっきりしない。
d.情動脱力発作がない。
特発性過眠症は頻度が少なく、治療法も十分に研究されていません。
しばしば頭痛、起立性低血圧、レイノー現象、頻脈などの自律神経症状を伴います。通常の精神賦活剤では効果がみられないことが多く、methamphetamineやmodafinilが効果のある場合があります。
●７．環境条件に起因する睡眠障害
環境因性睡眠障害、不適切な睡眠衛生、高地不眠症、睡眠不足症候群、しつけ不足睡眠障害、食物アレルギー性不眠、夜間摂食症候群などさまざまなものが記載されています。
■過眠症 hypersomnia：北里大学電子教科書
Kitasato Univ. Electronic Textbook: psy00264.html http://bme.ahs.kitasato-u.ac.jp/qrs/psy/psy00264.html (Size 6.8K) 更新日: 1997.09.17
夜間の睡眠不足によっては説明できないような、過剰な日中のねむ気や睡眠発作をもたらすもので、そのために日常の生活が障害される。不眠症の場合と同様な原因による分類があるが、病態としてはナルコレプシー、周期性傾眠症、ピックウィック症候群が重要である。
● a.ナルコルプシー narcolepsy●
間脳から中脳にかけて存在する覚醒維持機構の障害によって大脳活動水準の維持とレム睡眠の抑制がともに障害されて生ずる。大部分は15～20歳に発病する本態性のもので、ほかに頭部外傷、脳炎後遺症、脳腫瘍、中毒などによる残遺性ないしは症状性のものがある。
ナルコルプシーの4徴に次のようなものがある。
★ 1) 睡眠発作 sleep attack：日中生じる短時間の耐えがたいねむ気の発作で、10分でも20分でも眠ると、すっきりする。ねむ気を我慢して無理に行動すると、後でなにをどうしたか思い出せず、ただ単に自動的に動き続けることになる（ナルコレプシーの自動症）。
★ 2) 情動性脱力発作 cataplexy：笑い・驚き・怒りなどの急激な情動が生じた際、全身の脱力が起こる。たとえば、急に大声で笑ったとたん、ガクンと全身の力が抜けてしまう。10秒前後のものが多いが、ときに1～2分続くうちにレム睡眠に移行する。この現象はレム睡眠の際の筋緊張低下が分離し、先行して現われたものと考えられる。
★ 3) 睡眠麻痺 sleep paralysis：入眠期や夜間の睡眠中のレム睡眠期に現われる情動的色彩の強い入眠時幻覚や夢によって覚醒した際、レム睡眠期での全身の筋緊張低下が続いているため、金縛りにあったかのように身動きもできず、口もきけない状態となる。これを睡眠麻痺とよぶ。
★ 4) 入眠時幻覚 hypnagogic hallucination：ナルコレプシーでは入眠直後にレム睡眠が現われるのが特徴で、入眠時レム段階 sleep onset REM（SOREM）とよばれる。この段階では入眠直後ということもあって、普段のレム睡眠期よりも意識水準が高く、ここでみる夢は普通の夢より鮮明で、現実感が強く、夢というより幻覚の形で体験される。たとえば、なにか真黒い怪物がベッドに近づいてくる、といった強い情動を伴う入眠時幻覚を体験した際、不安・恐怖で叫び声をあげて逃げようとしても、同時に存在する睡眠麻痺のために金縛りにあったかのように身動きができず、助けをよぼうとしても声も出ないといった現象がまま見受けられる。
これを 幻覚脱力不安症候群 halluzinatorischkataplektisches Angstsyndrom (Rosenthal) という。
このように、ナルコレプシーは日中の強いねむ気と睡眠発作を主症状とし、脱力発作、睡眠麻痺、入眠時幻覚といったレム睡眠関連症状を呈するが、4主徴がすべての症例にそろって現われるわけではない。睡眠発作を必須症状とし、4主徴をあわせもつ症例は50～60％とされる。ほかに、昼間の睡眠発作がある反面、夜間の不眠を訴えることが多いのもナルコレプシーの特徴の1つである。
治療には、昼間の覚醒水準をあげるためにmethylphenidateやpemolineを、レム睡眠を抑えるためにimipramineなどの3環系抗うつ薬を用いる。夜間の不眠には短時間作用型のbenzodiazepine系睡眠薬や少量の鎮静作用の強い抗精神病薬levomepromazineが有効である。
★ 5) 周期性傾眠症 periodic somnolence, periodische Schlafsucht ：男子に圧倒的に多く、大部分が10歳台に発病し、20歳を過ぎると自然治癒する予後良好な疾患で、間脳の潜在性機能障害あるいは機能的脆弱性によると想定されている。
心身の過労、熱性疾患、感冒などを契機に傾眠状態に移行する。放置すると、終日就床して眠りこむが、起こすと覚醒し、食事をとり、便所へも行ける。この間、思考力、判断力が低下するのが普通で、なかには不機嫌や抑うつ気分を呈するものがある。5～10日間こうした状態が経過するうちに、かなり急速に回復してもとへもどる。こうした傾眠期が数カ月～数年の間隔で周期的に繰り返す。
傾眠のなかに軽いもうろう状態などの意識障害を呈して、後に健忘を残すものや、精神的抑制力が低下して、性的逸脱行為を呈するものがある。なお、傾眠期に病的空腹感とともに強迫的に摂食する症例があり、 クライネ・レヴィン Kleine-Levin 症候群 とよばれている。
★ 6) ピクウィック症候群 Pickwickian syndrome：極度の肥満・傾眠・周期性呼吸を中心症状とする睡眠時無呼吸過眠症候群の1つである。主として過食による肥満が原因で、ほかに下顎の発育不全、扁桃アデノイドの肥大など上部気道を閉塞させやすい状況のもとに生じてくる。この名称はCharles Dickensの小説、The Posthumous Papers of the Pickwick Clubに出てくる赤ら顔の太った少年が居眠りと過食を呈するのが本症候群に類似していることに由来している。
本症候群の病態生理は、次のように考えられている。肥満のため上部気道が狭くなるうえに、睡眠中の筋緊張低下が加わって上部気道が閉塞されて呼吸が一時止まる。換気が行われないため血中CO2分圧が上昇し、これが呼吸筋の活動を促し、次第に胸腔内圧を高めていき、20～50秒の無呼吸の後に上部気道の閉塞を押しわけ、大きい鼾とともに開通させて呼吸が再開される。何回かの呼吸運動のうちに再び呼吸筋の活動性が低下し、上部気道が閉塞されて、また呼吸が止まる。こうした周期性呼吸が一晩中続いて慢性的な睡眠不足の状態となる。これを代償しようとして、日中座るとすぐ眠りこむ傾眠状態を呈する。他方、肺胞低換気や肺動脈圧亢進を介して2次的に心肺機能の障害が生じ、筋攣縮、チアノーセ゛、2次的赤血球増多、右心室肥大、右心室不全などが生じてくる。
治療は減食による体重調節が中心で、ときには気管切開が必要となることがある。
●Kitasato Univ. Electronic Textbook: psy00145.html
http://bme.ahs.kitasato-u.ac.jp/qrs/psy/psy00145.html Kitasato Univ. Electronic Textbook: psy00145.htmlのミラーサイト 精神刺激薬/psychostimulants
精神刺激薬とは、覚醒度を高め意志欲動を刺激して精神活動を増進させる薬物をいう。 d-amphetamine,methamphetamine（ヒロポン）がその代表であり、他にpiperadol（メラトラン）、methylphenidate（リタリン）、caffeine等も含まれる。
amphetamine類の覚醒作用は上行性網様体賦活系へに刺激効果とされ、生化学的にはシナプスにおいてノルアドレナリンの遊離を増加させる。
適応症は先ずナルコレプシーがあり、その他小児の多動性症候群 hyperkinetic syndromeにも用いられる。
長期服用例では、しばしば抑うつ状態、疲労、活動性の低下などが出現する。
amphetamine類のような精神刺激薬には視床下部の食欲抑制中枢を刺激する作用があり、食欲不振が出現しやすい（やせ薬として濫用される危険がある）。
耐性が起こりやすく薬物依存の危険も大きい。慢性中毒症状としては、外因性反応型よりむしろ精神分裂病に類似した精神異常をきたすことが知られている（246頁参照）。
なお、d-amphetamineやmethamphentamineは覚醒剤取締法の規制を受けている。
データ
●National Center on Sleep Disorders Pamphlet[Feb. 1994]
[[ Sleep Disorders Information ]［NHLBI睡眠障害情報センター］] 米国では睡眠障害の患者数は7000万人、60%が慢性疾患、睡眠障害関連医療費は159億＄。 睡眠障害[sleep disorders]のうち最大の研究課題は1)睡眠時無呼吸症[Sleep apnea]で、昼間過眠症状excessive daytime sleepiness(EDS)の主因でもある。 推定患者数2000万人。 年間医療費（病院分）42百万＄で、2000年までに年間医療費は600億＄に達するという。 患者数としては2)不眠症[Insomnia]が最大。 3)ナルコレプシー[Narcolepsy]は25万人、他に4)過眠症[hypersomnia]、5)Jet-lag syndrome等。
●NHLBI, Facts About Narcolepsy★NHLBIナルコレプシー・ファクトシート
[[ Sleep Disorders Information ]［NHLBI睡眠障害情報センター］] Narcolepsy is a chronic sleep disorder with no known cause. The main characteristic of narcolepsy is excessive and overwhelming daytime sleepiness, even after adequate nighttime sleep. A person with narcolepsy is likely to become drowsy or to fall asleep, often at inappropriate times and places. Daytime sleep attacks may occur with or without warning and may be irresistible. These attacks can occur repeatedly in a single day. Drowsiness may persist for prolonged periods of time. In addition, nighttime sleep may be fragmented with frequent wakenings. Information about Document Formats [ASCII document, 20 K] [PDF document, 176 K] National Institutes of Health National Heart, Lung, and Blood Institute Facts About Narcolepsy ★What Is Narcolepsy? Narcolepsy is a chronic sleep disorder with no known cause. The main characteristic of narcolepsy is excessive and overwhelming daytime sleepiness, even after adequate nighttime sleep. A person with narcolepsy is likely to become drowsy or to fall asleep, often at inappropriate times and places. Daytime sleep attacks may occur with or without warning and may be irresistible. These attacks can occur repeatedly in a single day. Drowsiness may persist for prolonged periods of time. In addition, nighttime sleep may be fragmented with frequent wakenings. Three other classic symptoms of narcolepsy, which may not occur in all patients, are: * Cataplexy: sudden episodes of loss of muscle function, ranging from slight weakness (such as limpness at the neck or knees, sagging facial muscles, or inability to speak clearly) to complete body collapse. Attacks may be triggered by sudden emotional reactions such as laughter, anger, or fear and may last from a few seconds to several minutes. The person remains conscious throughout the episode. * Sleep paralysis: temporary inability to talk or move when falling asleep or waking up. It may last a few seconds to minutes. * Hypnagogic hallucinations: vivid, often frightening, dream-like experiences that occur while dozing or falling asleep. Daytime sleepiness, sleep paralysis, and hypnagogic hallucinations can also occur in people who do not have narcolepsy. In most cases, the first symptom of narcolepsy to appear is excessive and overwhelming daytime sleepiness. The other symptoms may begin alone or in combination months or years after the onset of the daytime sleep attacks. There are wide variations in the development, severity, and order of appearance of cataplexy, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience all four symptoms. The excessive daytime sleepiness generally persists throughout life, but sleep paralysis and hypnagogic hallucinations may not. The symptoms of narcolepsy, especially the excessive daytime sleepiness and cataplexy, often become severe enough to cause serious disruptions in a person's social, personal, and professional lives and severely limit activities. ★When Should You Suspect Narcolepsy? You should be checked for narcolepsy if: * you often feel excessively and overwhelmingly sleepy during the day, even after having had a full night's sleep; * you fall asleep when you do not intend to, such as while having dinner, talking, driving, or working; * you collapse suddenly or your neck muscles feel too weak to hold up your head when you laugh or become angry, surprised, or shocked; * you find yourself briefly unable to talk or move while falling asleep or waking up. ★How Common Is Narcolepsy? Although it is estimated that narcolepsy afflicts as many as 200,000 Americans, fewer than 50,000 are diagnosed. It is as widespread as Parkinson's disease or multiple sclerosis and more prevalent than cystic fibrosis, but it is less well known. Narcolepsy is often mistaken for depression, epilepsy, or the side effects of medications. ★Who Gets Narcolepsy? Narcolepsy can occur in both men and women at any age, although its symptoms are usually first noticed in teenagers or young adults. There is strong evidence that narcolepsy may run in families; 8 to 12 percent of people with narcolepsy have a close relative with the disease. ★What Happens in Narcolepsy? Normally, when an individual is awake, brain waves show a regular rhythm. When a person first falls asleep, the brain waves become slower and less regular. This sleep state is called non-rapid eye movement (NREM) sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again, even though the person is in deep sleep. This sleep state, called rapid eye movement (REM) sleep, is when dreaming occurs. In narcolepsy, the order and length of NREM and REM sleep periods are disturbed, with REM sleep occurring at sleep onset instead of after a period of NREM sleep. Thus, narcolepsy is a disorder in which REM sleep appears at an abnormal time. Also, some of the aspects of REM sleep that normally occur only during sleep--lack of muscle tone, sleep paralysis, and vivid dreams--occur at other times in people with narcolepsy. For example, the lack of muscle tone can occur during wakefulness in a cataplexy episode. Sleep paralysis and vivid dreams can occur while falling asleep or waking up. ★How Is Narcolepsy Diagnosed? Diagnosis is relatively easy when all the symptoms of narcolepsy are present. But if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. Two tests that are commonly used in diagnosing narcolepsy are the polysomnogram and the multiple sleep latency test. These tests are usually performed by a sleep specialist. The polysomnogram involves continuous recording of sleep brain waves and a number of nerve and muscle functions during nighttime sleep. When tested, people with narcolepsy fall asleep rapidly, enter REM sleep early, and may awaken often during the night. The polysomnogram also helps to detect other possible sleep disorders that could cause daytime sleepiness. For the multiple sleep latency test, a person is given a chance to sleep every 2 hours during normal wake times. Observations are made of the time taken to reach various stages of sleep. This test measures the degree of daytime sleepiness and also detects how soon REM sleep begins. Again, people with narcolepsy fall asleep rapidly and enter REM sleep early. ★How Is Narcolepsy Treated? Although there is no cure for narcolepsy, treatment options are available to help reduce the various symptoms. Treatment is individualized depending on the severity of the symptoms, and it may take weeks or months for an optimal regimen to be worked out. Complete control of sleepiness and cataplexy is rarely possible. Treatment is primarily by medications, but lifestyle changes are also important. The main treatment of excessive daytime sleepiness in narcolepsy is with a group of drugs called central nervous system stimulants. For cataplexy and other REM-sleep symptoms, antidepressant medications and other drugs that suppress REM sleep are prescribed. Caffeine and over-the-counter drugs have not been shown to be effective and are not recommended. In addition to drug therapy, an important part of treatment is scheduling short naps (10 to 15 minutes) two to three times per day to help control excessive daytime sleepiness and help the person stay as alert as possible. Daytime naps are not a replacement for nighttime sleep. Ongoing communication among the physician, the person with narcolepsy, and family members about the response to treatment is necessary to achieve and maintain the best control. ★What Is Being Done To Better Understand Narcolepsy? Studies supported by the National Institutes of Health (NIH) are trying to increase understanding of what causes narcolepsy and improve physicians' ability to detect and treat the disease. Scientists are studying narcolepsy patients and families, looking for clues to the causes, course, and effective treatment of this sleep disorder. Recent discovery of families of dogs that are naturally afflicted with narcolepsy has been of great help in these studies. Some of the specific questions being addressed in NIH-supported studies are the nature of genetic and environmental factors that might combine to cause narcolepsy and the immunological, biochemical, physiological, and neuromuscular disturbances associated with narcolepsy. Scientists are also working to better understand sleep mechanisms and the physical and psychological effects of sleep deprivation and to develop better ways of measuring sleepiness and cataplexy. ★How Can Individuals and Their Families and Friends Cope With Narcolepsy? Learning as much about narcolepsy as possible and finding a support system can help patients and families deal with the practical and emotional effects of the disease, possible occupational limitations, and situations that might cause injury. A variety of educational and other materials are available from sleep medicine or narcolepsy organizations. Support groups exist to help persons with narcolepsy and their families. Individuals with narcolepsy, their families, friends, and potential employers should know that: * Narcolepsy is a life-long condition that requires continuous medication. * Although there is not a cure for narcolepsy at present, several medications can help reduce its symptoms. * People with narcolepsy can lead productive lives if they are provided with proper medical care. * If possible, individuals with narcolepsy should avoid jobs that require driving long distances or handling hazardous equipment or that require alertness for lengthy periods. * Parents, teachers, spouses, and employers should be aware of the symptoms of narcolepsy. This will help them avoid the mistake of confusing the person's behavior with laziness, hostility, rejection, or lack of interest and motivation. It will also help them provide essential support and cooperation. * Employers can promote better working opportunities for individuals with narcolepsy by permitting special work schedules and nap breaks. ★For More Information For additional information on sleep and sleep disorders, contact the following offices of the National Heart, Lung, and Blood Institute of the National Institutes of Health: * National Center on Sleep Disorders Research (NCSDR) The NCSDR supports research, scientist training, dissemination of health information, and other activities on sleep and sleep disorders. The NCSDR also coordinates sleep research activities with other Federal agencies and with public and nonprofit organizations. National Center on Sleep Disorders Research Two Rockledge Centre Suite 7024 6701 Rockledge Drive, MSC 7920 Bethesda, MD 20892-7920 (301) 435-0199 (301) 480-3451 (fax) * National Heart, Lung, and Blood Institute Information Center The Information Center acquires, analyzes, promotes, maintains, and disseminates programmatic and educational information related to sleep and sleep disorders. Write for a list of available publications or to order additional copies of this fact sheet. NHLBI Information Center P.O. Box 30105 Bethesda, MD 20824-0105 (301) 251-1222 (301) 251-1223 (fax) For more information about narcolepsy and patient support groups, contact the Narcolepsy Network at P.O. Box 42460, Cincinnati, OH 45242. U.S. Department of Health and Human Services Public Health Service National Institutes of Health National Heart, Lung, and Blood Institute NIH Publication No. 96-3649 October 1996
●調査レポート
●[英文調査報告書]ナルコレプシー(嗜眠発作)の治療と医薬品の市場 ―目覚める市場：2001年戦略― Strategic Perspectives 2001: Narcolepsy - Specific Drugs are Waking up the Market 出版日: 2001/09 ; US $ 4100 (ハードコピー) Datamonitor insight into the narcolepsy marketProvigil has established itself as the leading drug in the narcolepsy market remarkably rapidly. This is due to its proven efficacy in treating daytime sleepiness and its improved side effect profile and reduced abuse potential compared to the older treatments.Xyrem (sodium oxybate) is expected to achieve similar success to modafinil when it is approved for treating cataplexy related to narcolepsy. Since Xyrem and modafinil will initially be indicated for different symptoms of narcolepsy, they are unlikely to be in direct competition at first.
臨床ガイドラインなど
●Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults American Academy of Child and Adolescent Psychiatry. 2001 Jun 4. 96 pages
●Narcolepsy.
The patient suffers from excessive sleepiness with recurrent sleep attacks and cataplexy (brief episodes of bilateral weakness typical of the rapid eye movement phase of sleep, even though the individual is awake)
●Practice parameters for the treatment of narcolepsy: an update for 2000 American Academy of Sleep Medicine. 1994 (updated 2001 Jun). 16 pages.
●Standard
- This is a generally accepted patient-care strategy that reflects a high degree of clinical certainty. The term standard generally implies the use of Level I Evidence, which directly addresses the clinical issue, or overwhelming Level II Evidence.
●Guideline
- This is a patient-care strategy that reflects a moderate degree of clinical certainty. The term guideline implies the use of Level II Evidence or a consensus of Level III Evidence.
●Option
- This is a patient-care strategy that reflects uncertain clinical use. The term option implies either inconclusive or conflicting evidence or conflicting expert opinion.
- An accurate diagnosis of narcolepsy should be established which shall include a thorough evaluation of other possible contributing causes, apart from narcolepsy, to the excessive daytime sleepiness (Standard).
For patients suspected of having narcolepsy, an all-night polysomnogram is done primarily to ascertain the presence of concurrent sleep disorders and is followed immediately by a multiple sleep latency test (MSLT) to help confirm the diagnosis. The multiple sleep latency test also helps determine the severity of daytime sleepiness. The reader is referred for diagnostic criteria (refer to Table 4 in the original guideline document). Other methods to evaluate sleepiness include objective tests such as the maintenance of wakefulness test (MWT), and subjective approaches such as the Epworth Sleepiness Scale. This part of the recommendation is based on committee consensus and is similar to a recommendation made previously.
Chronic daytime sleepiness is a nonspecific symptom and conditions that produce such sleepiness may coexist with narcolepsy. For example, the obstructive sleep apnea syndrome (OSAS) and periodic limb movement disorder (PLMD) may be present as determined by the results of the all-night polysomnogram. Insufficient sleep, idiopathic hypersomnia, inadequate sleep hygiene, and circadian rhythm disorders, among others should be considered as possible contributors to sleepiness independent of narcolepsy. Management of other disorders possibly contributing to sleepiness in a patient with narcolepsy may require approaches apart from stimulants to treat sleepiness either directly or as therapy of the underlying condition. This part of the recommendation is new and is based on committee consensus.
- Individual treatment objectives should be established for each patient with narcolepsy to improve quality of life (Standard).
One level II, grade B, four level III, grade C, and one level V, grade C, studies, and committee consensus, provide evidence that symptoms of narcolepsy may adversely impact quality of life (Refer to Tables 3 and 4 in the original guideline document). In keeping with the previous practice parameters, a major objective of treatment should be to alleviate daytime sleepiness with stimulants. The goal should be to produce the fullest possible return of normal function for patients at work, at school, at home, and socially. A new recommendation is to control cataplexy, hypnagogic hallucinations, and sleep paralysis, when present and troublesome. The health care provider should consider the benefit-to-risk ratio of medication for an individual patient, the cost of medication, convenience of administration, and the cost of ongoing care including possible laboratory tests when selecting a medication for treatment of narcolepsy.
- The following medications are effective treatments for narcolepsy. Comparative safety and efficacy of the stimulant medications are not defined. The rating of the recommendation is based on the grade of evidence for each. Refer to Table 5 in the original guideline document for dosages.
- Modafinil is effective for treatment of daytime sleepiness due to narcolepsy (Standard). [Refer to Table 3 of the original guideline document] This conclusion is based on the favorable benefit-to-risk ratio for modafinil established in three level I, grade A studies with confirmation from additional studies. This is a new recommendation.
- Amphetamine, methamphetamine, dextroamphetamine, and methylphenidate are effective for treatment of daytime sleepiness due to narcolepsy (Guideline). [Refer to Table 3 of the original guideline document] These medications are mainstays of narcolepsy treatment. Based on 3 level II, grade B and 4 level V, grade C studies and long clinical practice, they have a long record of efficacy. However, the benefit-to-risk ratio is not well documented, because the published clinical trials include only small numbers of patients. This recommendation is similar to that made previously.
- Selegiline is an effective treatment for all narcoleptic symptoms (Guideline}. [Refer to Table 3 of the original guideline document] Based on two level II, grade B and one level IV, grade C studies, selegiline is effective, but the cost of the medication is very high, experience with the high doses needed for narcolepsy is limited, and diet-induced hypertension is a danger at effective doses. This is a new recommendation.
- Pemoline is effective for treatment of daytime sleepiness in narcolepsy (Option). [Refer to Table 3 of the original guideline document] Pemoline can produce rare and potentially lethal liver toxicity that may be unpredictable. Because of this toxicity, the use of pemoline in patients with narcolepsy is rarely indicated. Based on one level II, grade B study, pemoline may be less potent than amphetamines, but adherence to pemoline therapy may be better than adherence to amphetamines or methylphenidate. This is a modification of a recommendation made previously. In particular, the warning on liver toxicity is emphasized to a greater degree than previously.
- Tricyclic antidepressants and fluoxetine may be effective treatment for cataplexy, sleep paralysis, and hypnagogic hallucinations (Guideline). [Refer to Table 4 of the original guideline document] The recommendation for tricyclic agents is based on one level V, Grade C study, long clinical experience and committee consensus. This is a new recommendation. The recommendation for fluoxetine is based on one level II, grade B and one level V, grade C study. This is a new recommendation.
- Combinations of long- and short-acting forms of stimulants may be effective for some patients (Option). Some stimulants have a short (3 to 4 hour) effective period (e.g., methylphenidate). Others have longer duration of activity and longer onset of action (e.g., modafinil, sustained release amphetamine). By combining stimulants with different activity characteristics, it may be possible to achieve alertness quickly and for longer periods of time and also not produce insomnia as an unwanted side effect. In addition, combinations of stimulants and antidepressants may be of benefit for treatment of sleepiness and REM-related symptoms such as cataplexy. For example, modafinil appears compatible with antidepressant medications, but published evidence is limited. This recommendation is similar to that made previously and is based on committee consensus.
- Scheduled naps can be beneficial to combat sleepiness but seldom suffice as primary therapy (Guideline).
[Refer to Table 2 of the original guideline document] This recommendation is based on two level II, grade B, one level IV, grade C and one level V, grade C studies and long clinical experience. This recommendation is similar to that made previously.- Regular follow-up of patients with narcolepsy is necessary to monitor response to treatment, to respond to potential side effects of medications, and to enhance the patient's adaptation to the disorder (Standard).
- A patient stabilized on stimulant medication should be seen regularly by a health care provider at least once per year, and preferably once every 6 months, to assess the development of medication side effects, including sleep disturbances, mood changes, and cardiovascular or metabolic abnormalities. This is the same recommendation as made previously and is based on committee consensus.
- Follow-up is necessary to determine adherence and response to treatment; to monitor for the safety of medications in individual patients; and to assist the patient with occupational and social problems. Adherence to stimulant drug treatment in narcolepsy is impeded by inconvenient dosage, but not by age, educational level, gender, or response to therapy. Of note, many patients with narcolepsy cannot be restored to normal levels of daytime alertness, even when adhering to optimum doses of stimulant medications (Refer to Table 5 of the original guideline document). Most often, response to therapy can be determined by interview of the patient and associates as well as by self-report questionnaires, such as the Epworth Sleepiness Scale. Objective measures, such as the maintenance of wakefulness test (MWT) or the multiple sleep latency test (MSLT), may play a role when occupational or public safety concerns are at issue. This is an expansion of a similar recommendation made previously and is based on committee consensus.
- Patients with severe sleepiness should be advised to avoid potentially dangerous activities at home and at work, and should not operate a motor vehicle until sleepiness is appropriately controlled by stimulant medications. This recommendation is the same as that previously and is based on one level II, grade B and one level III, grade B study (Refer to Table 4 of the original guideline document) and committee consensus.
- Of the stimulants used to treat narcolepsy, amphetamines, especially at high doses, are the most likely to result in the development of tolerance. This is the same recommendation as previously. Reiteration of the discussion and literature cited in the previous review paper are beyond the scope of the current review and the reader is referred for further information.
- Patients who fail to respond to adequate doses of stimulant medication should be carefully assessed for other sleep disorders such as insufficient sleep, inadequate sleep, hygiene, circadian rhythm disorders, obstructive sleep apnea syndrome, or periodic limb movement disorder, that may contribute to excessive sleepiness. This is essentially the same recommendation as previously and is based on committee consensus.
- For side effects, dosage ranges, use in pregnancy and by nursing mothers, class of medication and use in narcolepsy, see Table 5 in the original guideline document. The information found in Table 5 on stimulants is similar and, in some cases, an expansion of information provided previously. The information on the other classes of medications is new. Note that any of the stimulant medications can be abused.
- Treatment of narcolepsy with methylphenidate in children between the ages of 6 and 15 appears relatively safe, but caution must be used if other medications are employed. See Table 5 in the original guideline document for dosages. This recommendation is similar to that previously and is based on the considerable experience with use of methylphenidate for treatment of attention deficit disorder.
- Health care providers should assist the patient with occupational and social accommodation for disabilities due to narcolepsy. The Americans with Disabilities Act provides legal guidance. Patients deserve appropriate help from health care providers to insure that the intent of the law is realized. Because sustained alertness often is difficult to achieve even with optimum treatment, some patients should be advised to avoid potentially dangerous activities, such as driving, climbing, or working in the vicinity of dangerous machinery, which could result in injury to the patient or others. This recommendation is similar to that previously and is based on committee consensus.
- Polysomnographic reevaluation of patients should be considered if symptoms of sleepiness increase significantly or if specific symptoms develop that suggest new or increased sleep abnormalities as might occur in disorders such as sleep apnea or periodic limb movement disorder. This is the same recommendation as that previously and is based on committee consensus.
総説記事・文献
ニュース・トピックス
■Sleep Medicine Alert, Volume 3, Number 3
■National Sleep Foundation Home Page This quarterly newsletter is for healthcare professionals. It offers updates on sleep research and its clinical implications, information on diagnosing and treating a variety of sleep disorders. It also offers reports on drowsy driving research and countermeasures, coverage of sleep-related meetings and research funding sources. Click here for the current issue.
VOLUME III Number 3
Click here for past issues.
CONTENTS
1 An Update on Genetic Studies in Narcolepsy
2 Diagnosis of Narcolepsy
2 New Narcolepsy Study Aims to Improve Treatment
●
An Update on Genetic Studies in Narcolepsy by Emmanuel Mignot, MD, PhD
A genetic basis for narcolepsy has been long recognized by researchers and clinicians. One of the most surprising breakthroughs was the discovery by Dr. Honda in Japan that narcolepsy is associated with the HLA antigen DR2. This led researchers to hypothesize that narcolepsy may have an autoimmune basis, like many other known HLA-associated
disorders, such as multiple sclerosis or type I diabetes mellitus. Moreover, Honda's finding provided impetus toward finding the cause of narcolepsy.［略］
●
Diagnosis of Narcolepsy by Michael S. Aldrich, MD
Narcolepsy is a life-long disorder; consequently, accurate diagnosis is essential. As with any medical disorder, diagnosis of narcolepsy depends in part on clinical features and in part on laboratory findings.
The Character of Sleepiness
Sleepiness and a tendency to fall asleep easily, particularly in sedentary boring situations, help to distinguish sleep disorders from disorders that cause fatigue without sleepiness. Narcolepsy is often associated with brief irresistible episodes of daytime sleep - sleep attacks - that occur without warning and provide temporary relief from sleepiness. However, persistent sleepiness, sleep attacks and the refreshing effect of short naps are not specific; they also may occur with obstructive sleep apnea and in those who are chronically sleep-deprived. Furthermore, persons with mild narcolepsy may not have sleep attacks. Sleep attacks are more an indication of the chronicity and severity of sleepiness than of its cause. Their absence does not exclude the presence of narcolepsy.
★Cataplexy
Cataplexy is defined as muscular weakness brought on by emotion, and a history of clear-cut cataplexy in patients with normal neurologic
examination is virtually pathognomonic for narcolepsy. However, about 6% of normal adults have experienced a "sudden and abrupt feeling of weakness in both arms and legs" with emotion1. Thus, a sensation of weakness without actual loss of strength is not specific. In persons with sleepiness, brief bilateral definite weakness - without alteration of consciousness - that is precipitated by emotion, particularly laughter, is almost always due to narcolepsy. However, about one-third of narcoleptics do not have cataplexy; thus, its absence does not exclude the diagnosis.
★Sleep Paralysis and Hypnagogic Hallucinations
Sleep paralysis and hypnagogic hallucinations, common in narcolepsy, also occur in about 15% of normal persons, often precipitated by altered sleep schedules or other factors that disrupt normal sleep patterns2.
★HLA Testing and the Multiple Sleep Latency Test
The presence of HLA antigens has limited diagnostic value. However, the propensity for narcoleptics to enter REM sleep prematurely is useful for diagnosis. On an MSLT, persons are given four or five opportunities to sleep at two hour intervals; the average time to fall asleep (mean sleep latency) is usually less than five minutes compared to ten to 20 minutes in control subjects. While the presence of two or more SOREMPs (sleep onset REM periods) during the MSLT supports a diagnosis of narcolepsy, this finding is not specific3. In 22 patients with two or more SOREMPs on MSLT, only 59% had narcolepsy, while the remainder had other sleep disorders, mainly obstructive sleep apnea4. Furthermore, of 170 narcoleptics, only 80% had two or more SOREMPs on an initial MSLT 4.
★In summary, definite unambiguous cataplexy has the strongest positive predictive value for diagnosis. In the absence of cataplexy, the clinician must weigh the significance of clinical and laboratory findings and assess the likelihood that other sleep disorders are contributing to symptoms. Astute clinical judgment and knowledge of the prevalence and characteristics of narcolepsy and other sleep disorders will help the clinician to arrive at a correct diagnosis.
Michael S. Aldrich, MD, is an associate professor of neurology and director of the Sleep Disorders Center at the University of Michigan Medical Center in Ann Arbor.
REFERENCES
Hublin C, Kaprio J, Partinen M et al. The prevalence of narcolepsy: an epidemiologic study of the Finnish twin cohort. Annals of Neurology 1994;35:709-716.
Aldrich MS. The clinical spectrum of narcolepsy and idiopathic hypersomnia. Neurology 1996;46:393-401.
Moscovitch A, Partinen M, Guilleminault C. The positive diagnosis of narcolepsy and narcolepsy's borderland. Neurology 1993;43:55-60.
Aldrich MS, Chervin RD, Malow BA. Value of the Multiple Sleep Latency Test (MSLT) for the diagnosis of narcolepsy. Sleep 1997;20:620-629.
NSF Narcolepsy REFERENCES
Living with Narcolpsy Brochure
How does narcolepsy affect education, careers, social and family life? This exploration of the medical and psychosocial aspects of living with narcolepsy provides answers and resources.
An Introduction to Narcolepsy Slide Kit
Includes 62 attractive slides, comprehensive notes and bibliography.
For ordering information, call (202) 347-3471, ext. 200, or click here.
●
New Narcolepsy Study Aims to Improve Treatment
by Ann E. Rogers, PhD, RN
Many of the psychological and economic consequences of narcolepsy can be directly attributed to sleep attacks and excessive daytime sleepiness. Uncontrollable episodes of daytime sleep make driving difficult or hazardous, affect an individual's academic performance, career advancement, and interpersonal relationships. Although stimulant medication can provide short-term relief of excessive daytime sleepiness, no drug currently available completely or permanently eliminates this symptom.
★Improved Treatment Needed
While treatment of narcolepsy can improve symptoms dramatically in some patients, up to a third of patients with narcolepsy obtain little or no benefit from current therapies. Moreover, studies have shown widespread dissatisfaction with current pharmacologic treatments. Some patients report that their symptoms are not adequately controlled with stimulant medications; they are not satisfied when treatment requires daytime naps and/or drug holidays. Researchers don't understand the differences - or the basis for them - between those who respond well to treatment and those who do not. In addition, identifying patients who are less likely to respond to stimulant medications will allow clinicians to concentrate more efforts on improving treatment regimens for those patients. An instrument that is reliable, sensitive to treatment effects, and easy to administer would help assess patients' treatment responses for early identification of additional treatment needs.
★Narcolepsy Research Project
The Narcolepsy Research Project, a new five year, NIH-funded study, aims to lay the groundwork for developing better treatment protocols. This multicenter study will:
Develop profiles of those patients who respond to stimulant medications and those who do not.
Evaluate two brief questionnaires (Narcolepsy Symptom Status Questionnaire (NSSQ) and Epworth Sleepiness Scale (ESS)) to see if they can be used to assess treatment efficacy in a clinical setting.
Narcoleptic subjects (135 established patients and 85 newly diagnosed patients) will be recruited from five sleep disorders centers. Researchers will develop profiles from demographic data, symptom severity measures, and 24-hour ambulatory polysomnographic recordings. Compliance with stimulant medications will be evaluated using a MEMS TrackCap. In order to judge whether or not the NSSQ and ESS are sensitive to treatment effects, newly diagnosed subjects will be tested prior to starting stimulant medications, after three months of treatment, and after one year of treatment.
★Subject Recruitment
Recruitment of sleep center patients in Southern California, New York, Michigan, Missouri and Illinois, and from the National Narcolepsy Registry (NNR), is ongoing. The NNR is a confidential database of genetic and other information from persons with narcolepsy and their families.
Questions or patient referrals may be directed to:
Ann E. Rogers PhD, RN, Associate Professor
University of Michigan, School of Nursing, 400 N. Ingalls, Ann Arbor, MI 48109-0482 Tel: (723) 763-0001 E-mail: aerogers@umich.edu
For more information on the NNR, contact the National Sleep Foundation at (202) 347-3471, ext 200, visit the NSF's Web site: www.sleep foundation.org, or use the fax-on-demand system by calling (888) FYI-SLEEP, and requesting document #710.
★Resources
The complete 1998 NSF Omnibus Sleep in America Poll is available for $25 plus $4 shipping and handling. Write to the National Sleep
Foundation, 729 Fifteenth St., NW, 4th Floor, Dep't SA, Washington, DC 20005.
Sleep Medicine Alert is a publication of the National Sleep Foundation.
Comments, suggestions and letters to the editor are welcome. Please write
to:
National Sleep Foundation
729 Fifteenth Street, NW
Fourth Floor, Washington, DC 20005.
Editor: James K. Walsh, Ph.D., Sleep Medicine and Research Center,
St Luke's Hospital, Chesterfield, MO
Managing Editor: Joan Rachel Goldberg
Assistant Editor: Heidi Wunder
RLS FOUNDATION
4410
19TH ST., NW, SUITE 201, ROCHESTER, MN 55901
FOUNDATION OFFICERS
Lorraine L. Wearley, Ph.D., President Carla G. Kidd,
Vice President Michael J. Thorpy, M.D., Secretary Patricia M.
Smith, CPA, Treasurer Thomas Roth, Ph.D., Health & Scientific Advisor
Orville John Hoag, Jr., CPA, Past-President
BOARD OF DIRECTORS
Patricia B. Adduci Mary A. Carskadon,
Ph.D. Norman H. Edelman, M.D. Christopher A. Hart Robert Y.
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Franklin K. Willis, Esq. Peter C. Whybrow, M.D.
リンク
■Yahoo! - :健康と医学:病気、症状:睡眠障害
■Yahoo! - :健康と医学:病気、症状:睡眠障害:ナルコレプシー
なるこ会 - 日中強い眠気に襲われ居眠りを繰り返すナルコレプシーの患者の会。同会会誌の紹介や関連リンク集。 Yahoo! USAの同一カテゴリへ
■Yahoo! Health:Diseases and Conditions
Insomnia (3) Narcolepsy (5) Sleep Apnea (13) Sleep Disorders (23) --------------------------------------------------
■Yahoo! Home : Health : Diseases and Conditions :Narcolepsy
-------------------------------
Institutes (2)
-------------------------------
Narcolepsy Internet [new] - e-mail based support group for people with narcolepsy, their partners and family. Narcolepsy Network - support group for individuals with narcolepsy, their families and friends.
Usenet - alt.support.narcolepsy
--------------------------------------------------
■Yahoo! Home > Health > Diseases and Conditions > Narcolepsy > Institutes
Center for Narcolepsy Research
Stanford University - Center for Narcolepsy
■MedWebPlus: Sleep Disorders★オンライン雑誌リソース［睡眠障害］
Diseases -
★Related terms: - Eating Disorders - Pain - Companies -Discussion groups -Neurophysiology -Patient Education -Professional Practice -Sleep Research -Software -
------------------------------ American Sleep Disorders Association (ASDA) GO JAMA Patient Page Narcolepsy Internet GO Phantom Sleep Page (Sleep apnea, snoring & other sleep problems) GO Sleep Disorders Center in Silicon Valley GO Sleep Medicine Associates of Texas GO Sleeping on the Internet by Jerry Halberstadt (incorporating S.N.O.R.E and the Sleep Apnea FAQ created by Doug Linder) GO Stellate Systems (Montreal, Quebec).
■Insomnia - Doctor's Guide to the Internet
●SiteMap - Doctor's Guide to the Internet●Patient Information and Resources The latest medical news and information for patients or friends/parents of patients diagnosed with insomnia and insomnia-related disorders. ●Current Content Medical News and Alerts Insomnia Information Discussion Groups and Newsgroups Other Related Sites Stay abreast of Insomnia developments on the Internet ● Medical News and Alerts Sonata Approved In Europe For Insomnia Cognitive-Behaviour Therapy And Drug Treatments Effective In Treating Late-Life Insomnia Study Shows Zaleplon Helps People Get To Sleep Faster Without Residual Effects Nocturnal Asthma Increases Risk Of Psychological Problems Provigil Approved In Republic Of Ireland For Narcolepsy Asians Have Higher Incidence Of Severe Obstructive Sleep Apnea Than Caucasians Sex And Sleep -- Major Barriers To Canadians' Quality Of Life Most MDs Overprescribe Sleep Medications, Says Expert Elderly On Long-Acting Anxiety, Insomnia Drugs Have More Car Crashes Importance of Proper Diagnosis Of Chronic Insomnia Stressed ● Insomnia Information Facts About Insomnia Insomnia What to Do When You Can't Sleep Insomnia and Other Sleep Problems ● Discussion Groups and Newsgroups alt.support.sleep-disorder ● Other Related Sites The American Sleep Disorders Association Home Page National Sleep Foundation Sleep Disorders Sleep Medicine Home Page The Sleep Site ● Stay abreast of Insomnia developments on the Internet If you would like to receive e-mail notification of additions or changes to the resources listed on this page, simply send us your e-mail address by clicking here. This page was last updated July 23, 1998.
主要サイト
■NPO日本ナルコレプシー協会 旧なるこ会 - 日中強い眠気に襲われ居眠りを繰り返すナルコレプシーの患者の会。同会会誌の紹介や関連リンク集。
お知らせ・更新内容 なるこ会ってどんな会 なるこ会会誌 新聞・雑誌等の記事 睡眠障害 専門病院 関連ホームページ アンケート -------------------------------------------------- ■お知らせ・更新内容
☆平成９年１２月９日総会が開かれました。 詳しくは会誌『なるこ』１５号（１９９７年１２月２５日）をご覧下さい。 ☆平成９年１１月 厚生省に対して下記の要望書を提出しました。 睡眠科（仮称）の設置 睡眠障害センタの設置 アナフラニールの保険適用薬認定 新薬モダフィニールの許可 前回（１９９７年１２月７日）からの更新内容 -------------------------------------------------- ■関連ホームページ 日本睡眠学会 http://jssr.jp/index.html 望洋台病院 http://www.artpia.co.jp/IHJ/SIN-NAI/boyo.htm なごやメンタルクリニック http://www.gld.mmtr.or.jp/~nmc/nmc(1).htm （米）ナルコレプシーネット http://www.websciences.org/narnet/ （米）スリープネット－睡眠障害 http://www.sleepnet.com/ （米）スタンフォード大学ナルコレプシーセンタ http://www-med.stanford.edu/school/Psychiatry/narcolepsy/index.html （米）イリノイ大学ナルコレプシー研究センタ http://www.uic.edu/depts/cnr/ （米）睡眠心理生理学会 WFSRS ニュースレター・オンライン http://bisleep.medsch.ucla.edu/ （米）青年なるこ会 http://www.yawn.org/ 更新日 98/08/08 -------------------------------------------------- ■なるこ会会誌 なるこ会会誌『なるこ』総目次 『なるこ』第１５号 創立三十周年記念号（平成９年１２月） -------------------------------------------------- ■『なるこ』第１５号 創立三十周年記念号（平成９年１２月） ［略］ ------------------------------● 1532 行政への要望陳情
平成９年１２月２０日
厚生大臣
小泉 純一郎 殿
なるこ会 会長 白倉 昌夫
陳 情 書
なるこ会は、ナルコレプシー患者自身の会として昭和４２年に発足し、全国に約４００名の会員が居ります。なるこ会は会員相互の親睦・互助、社会生活面の向上、治療・研究への協力を目的として活動をしております。
ナルコレプシーは、比較的希な疾患であり専門医が少なくかつ精神（神経）科で治療が行われていること、根本的な治療がなく薬の服用が毎日必要であることから下記について要望いたします。
記
１．診療科名として睡眠科（仮称）を設置してください
新聞・雑誌などによると日本では５人に１人が何らかの睡眠障害をもっているといわれています。睡眠障害の治療は、現在は精神（神経）科などの一部として行われていますが、このことを知っている人はごく少数に過ぎません。なるこ会会員を対象としたアンケート調査でも最初に訪れた診療科が精神（神経）科と答えたものは５０％以下であり、またなるこ会の事務局（対外窓口）に対しても「睡眠の悩みはどこで診療してもらえるのか」という問い合わせが数多くきております。眼科や歯科などと同じように誰にでも分かるような名称にする必要があります。［略］
２．睡眠障害センタを設立してください
米国では睡眠障害センタをはじめ、全国に睡眠障害センタが配置され患者の治療、睡眠障害の研究、専門家の育成に大きな成果を上げていると聞きます。さらに最近国立睡眠財団（National Sleep Foundation）も設立され、活発な啓蒙活動を行っております。是非日本においても同様の組織の発足をお願いします。さらに民間において睡眠障害センタが運営可能となる健康保険制度の枠組みを作っていただくことを要望いたします。
３．アナフラニールをナルコレプシーの保険適用薬として認定してください
抗うつ剤として認可されているアナフラニール錠がナルコレプシーの情動発作を抑える上で特効的な効用があることは、国内国外の医学界において広く認められており、昭和３６年の厚生省保険局長通達「精神科の治療方針」の中にも明記されております。
またこの効果は我国で初めて発見されたものでもあり、実際にひろく用いられております。 私たち患者にとっては情動脱力発作や入眠時の幻覚・金縛りを防止するアナフラニールは毎日欠かすことができません。
しかしながら、３０年間におよぶ私たちの再三再四の要請にもかかわらず製薬会社がナルコレプシーの保険適用薬としての効能追加の申請をしていないため現在でも保険薬として認められていません。
一方、保険の財政事情から保険適用薬でない薬品についてはその使用を制限する方向にあり私たちナルコレプシー患者としては大きな危機感を抱かざるをえません。
これまで十分実績のあるアナフラニールを早急に保険薬として認定して頂きたいと要望致します。
４．モダフィニール（Modafinil）を認可してください
インターネットなどの情報によると約１０年ほど前からフランスで開発・使用さ れ米国で治験薬とされているモダフィニールが米国の食品医薬品局（ＦＤＡ）より認可されました。
通常の社会生活を行うために精神賦活剤を毎日服用することが必要な私たちにとってモダフィニールのような効果が高く副作用が少ない薬品の開発を待望しております。 できる限り早急にモダフィニールを医薬品として、さらにナルコレプシーに対する健康保険適用薬剤として認可されることを希望致します。
■日本睡眠学会 http://jssr.jp/index.html
Japanese Society of Sleep Research[JSSR] 日本睡眠学会について 睡眠の基礎知識 (1998/9/14更新) 学会からのお知らせ 日本睡眠学会会則 セミナー等のお知らせ ＰＳＧ共通フォーマットについて 学術集会 １９９７年 第22回学術集会抄録 １９９８年 第23回学術集会抄録 １９９９年 第24回学術集会のご案内 日本睡眠学会ニューズレター 第１７号 （1998/3/1発行） 第１８号 関連学会等へのリンク集 E-mail: WebMaster ------------------------------------------------
■CENTER FOR NARCOLEPSY [www-med.stanford.edu] ■CENTER FOR NARCOLEPSY
Narcolepsy is a serious medical disorder and a key to understanding other sleep disorders
Narcolepsy is a disabling illness affecting
more than 1 in 2,000 Americans. Most individuals with the disorder are not diagnosed and are thus not treated. The disease is principally characterized by a permanent and overwhelming feeling of sleepiness and fatigue. Other symptoms involve abnormalities of dreaming sleep, such as dream-like hallucinations and finding oneself physically weak or paralyzed for a few seconds (see Symptoms).
The Stanford University Sleep Clinic was the first medical clinic
ever established to specialize in sleep disorders. It was founded in the
early 1970s by Dr. William Dement to diagnose and treat narcoleptic patients.
The Stanford Center for Narcolepsy was established in the 1980s and is now directed by Drs. Emmanuel Mignot and Seiji Nishino. The Center for Narcolepsy is part of the Department of Psychiatry and Behavioral Sciences and has published more than 100 articles on narcolepsy. It is the world leader in the search for the cause of narcolepsy. Several hundred patients with the disorder are currently treated at the Center or participate in various research protocols. A colony of Dobermans affected with the disorder is also bred and maintained to study narcolepsy and search for the canine narcolepsy gene (see Research).
We are always looking for volunteers in our narcolepsy research studies. We are presently recruiting narcoleptic patients with cataplexy for genetic studies, drug clinical trials and functional MRI studies. If you are interested in participating, you can contact us either on our site's message page or telephoning Ms. Michele Okun, Research Coordinator at (650) 725-6512 (see Contact)
More on Narcolepsy
■National Heart, Lung, and Blood Institute (NHLBI) Home Page［米国心肺血液研究所］
------------------------------------------------ ■[ Sleep Disorders Information ]［NHLBI睡眠障害情報センター］ -------------------------------------------------- ■Sleep Information for Patients/General Public★患者向け Awake At the Wheel Materials Facts About Problem Sleepiness Facts About Insomnia Facts About Narcolepsy Facts About Restless Leg Syndrome (RLS) Facts About Sleep Apnea Test Your Sleep I.Q. -------------------------------------------------- ■Sleep Information for Health Care/Other Professionals★医療専門家向け ★Sleep Disorders Restless Legs Syndrome: Detection and Management in Primary Care Sleep Apnea: Is Your Patient at Risk? Insomnia: Assessment and Management in Primary Care Problem Sleepiness in Your Patient Working Group Report on Problem Sleepiness National Center on Sleep Disorders Pamphlet ★Sleep in Youth Awake At the Wheel Materials Educating Youth About Sleep and Drowsy Driving Drowsy Driving and Automobile Crashes ★Additional Resources National Center on Sleep Disorders Research Web Site Trans-NIH Sleep Research Coordinating Committee, FY99 Annual Report Sleep Disorders Research Advisory Board (SDRAB) National Sleep Disorders Research Plan List of Publications Information Center Sleep Information for Patients/Public
■National Sleep Foundation 729 Fifteenth Street, NW, Fourth Floor
Washington, DC 20005
202-347-3471
e-mail: natsleep@erols.com
The National Sleep Foundation (NSF) is a nonprofit, charitable organization dedicated to improving the quality of life for the millions of Americans who suffer from sleep disorders and to the prevention of catastrophic accidents caused by sleep deprivation or sleep disorders. The National Sleep Foundation provides free brochures on sleep, drowsy driving and sleep disorders, regional listings of accredited sleep centers, and other public education materials.
--------------------------------------------------
| About NSF| What's New?| Activities|Publications | | Sleep Disorders |Sleep Links| Press Archives | | Opportunities with the NSF| Guestbook |Copyright (c) 1996 UCLA BrainInformation Service -------------------------------------------------- ■NSF: Publications
★Helping Yourself to a Goodnight's Sleep
About half of Americans report sleep difficulty at least occasionally, according to National Sleep Foundation surveys. These woes - called insomnia by doctors - have far-reaching effects.
This brochure details the many things you can do to improve your sleep.
★The NSF Connection
An introduction to the National Sleep Foundation's programs and products, this quarterly newsletter also reports on new sleep research in an easy-to-understand format. The NSF Connection newsletter explores such subjects as drowsy driving, sleep and aging, sleep and travel, insomnia, and sleeplessness associated with pain. Click here for the current issue.
★Sleep Medicine Alert★季刊オンライン誌
This quarterly newsletter is for healthcare professionals. It offers updates on sleep research and its clinical implications, information on diagnosing and treating a variety of sleep disorders. It also offers reports on drowsy driving research and countermeasures, coverage of sleep-related meetings and research funding sources. Click here for the current issue.
★National Sleep Foundation
The mission of the National Sleep Foundation, along wih its programs and goals, are described in this brochure. Statistics about the number of Americans suffering from sleep disorders and the costs and consequences of sleep disorders, sleep deprivation and sleepiness - including drowsy driving accidents - are included.
★Women and Sleep
A brochure dealing with the effects of sleep on women which explores reasons for tiredness, increased accidents, problems concentrating, poor performance on the job and in school, and possibly, increased sickness.
★The Nature of Sleep...and Its Disorders
An exploration of societal and individual sleeplessness and the process and evolution of sleep patterns, with a discussion of shiftwork and napping and a description of the most common sleep disorders. Tips on getting help included.
★When You Can't Sleep
A primer on sleep basics, including getting enough sleep, why sleep is important, and "sleep stealers." Plus a "sleep quotient" quiz.
★WAKE UP! (Drive Alert...Arrive Alive)
A booklet dedicated to the drowsy driving problem, including the risks, the myths, the danger signals and recommendations.
★Sleep & Aging
An overview of how sleep changes with age; explaining common sleep problems and solutions, including insomnia, medical problems affecting sleep, sleep disorders, and the impact of menopause, drugs, nicotine and travel.
★ Sleep Apnea
A brochure about sleep apnea, a breathing disorder characterized by brief interruptions of breathing during sleep. Brochure explains what it is, who gets it, and how it is diagnosed and treated.
★ Sleep and the Traveler
A brochure dedicated to the unique problems of the traveler, including jet lag, sleep anxiety, and the sleep environment.
★ National Narcolepsy Registry
The National Narcolepsy Registry (NNR) is a confidential database of genetic information provided
by individuals with narcolepsy. It will be used for the sole purpose of promoting further research in narcolepsy.
★ National Narcolepsy Registry Update
The newsletter of the National Narcolepsy Registry (NNR), which continues to grow and provide valuable information to sleep researchers.
★Sleep Medicine Review
A bimonthly newsletter for office-based physicians, published from 1993 - 1995, with articles about sleeplessness and sleep disorders.
★Melatonin: The Facts
If you're curious about melatonin, it's not surprising. There has been a lot of attention paid to the hormone in popular magazines and books, scholarly journals, and advertisements. You may have heard claims that melatonin cures everything from jet lag to insomnia to aging.
★Strategies for Shift Workers
What happens if you work nontraditional hours (hours outside of the typical business hours of 9 a.m. to 5 p.m.)? Do you wear sleepiness like a second skin? Dream about slipping into your empty bed when you should be concentrating on the work at hand? Toss and turn when you finally get to bed, tired but unable to sleep, as the minutes slowly tick by? Or do you drop into sleep like a train speeding into a tunnel, only to awaken suddenly, hours before you'd like to greet a new day?
★Pain and Sleep
When you can't sleep and your headaches, or back hurts, what do you lose? A lot of sleep. In fact, one out of three American adults (56 million people!) lose more than 20 hours of sleep each month. That was the finding of a 1996 National Sleep Foundation (NSF) Gallup Poll. Yet many people don't recognize how large the problem is. Nor do they consider the possible consequences: lack of energy, bad mood, poor general health, and trouble handling stress. Worse, many sufferers don't realize what can be done about the problem.
★Living with Narcolepsy
Narcolepsy is a chronic (long-lasting) neurological (affecting the brain or nerves)
disorder that involves your body's central nervous system. The central nervous system is the "highway" of nerves that carries, messages from your brain to other parts of your body. For people with narcolepsy, the messages about when to sleep and when to be awake sometimes hit roadblocks or detours and arrive in the wrong place at the wrong time. This is why someone with uncontrolled narcolepsy may fall asleep while
eating dinner or driving a car - times when he or she wants to be awake.
★The Pharmacological Management of Insomnia: A White Paper of the National Sleep Foundation
A discussion of insomnia's effects, costs, diagnosis and pharmacological treatment, including a summary of the risks and benefits of treatment with different categories of drugs. Includes chapter on melatonin and L-tryptophan. 56 pages. This report is available for $25
★Doctor, I Can't Sleep Insomnia Training Manual
Comprehensive course manual for primary care physicians and the public. Outlines basic facts about epidemiology, sleep hygiene, relaxation techniques, diagnosis and treatment. 100+ pages. This manual is available for $25
★Gallup Poll on Sleep in America
A report on the 1995 Gallup Poll, commissioned by the National Sleep Foundation, with information on insomnia's prevalence, attitudes and sleeping habits of sufferers, treatment, effect on health and driving, and more. Includes charts. 78 pages. This report is available for $25
★Gallup Poll on Adult Public's Experiences with Nighttime Pain
A report on the 1996 Gallup Poll, commissioned by the National Sleep Foundation, covering the prevalence, impact and treatment of occasional minor nighttime pain and sleeplessness. Includes charts. 87 pages. This report is available for $25
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■★Sleep Medicine Review
A bimonthly newsletter for office-based physicians, published from 1993 - 1995, with articles about sleeplessness and sleep disorders.
VOLUME IV Number 1 January/February 96 VOLUME III Number 4 July/August 95 Number 5 September/October 95 Number 6 November/December 95 INFORMATION ABOUT THIS DOCUMENT This document describes the National Center on Sleep Disorders Research. You may order the published version from: NHLBI Information Center P.O. Box 30105 Bethesda, MD 20892-0105 (301) 251-1222 (voice) (301) 251-1223 (fax) nhlbiic@dgsys.com (Internet) ★Introduction The National Center on Sleep Disorders Research was established by law in June 1993 to combat a serious public health problem. The Center seeks to improve the health of Americans by supporting research, training, and education about sleep disorders. The Center is situated within the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH), in Bethesda, Maryland. ★Scope of the Problem "By any measuring stick, the deaths, illness, and damage due to sleep deprivation and sleep disorders represent a substantial problem for American society." --from Wake Up America: A National Sleep Alert, 1993 Report of the National Commission on Sleep Disorders Research About 70 million Americans suffer from a sleep problem; among them, nearly 60 percent have a chronic disorder. Sleep problems affect men and women of every age, race, and socioeconomic class. Despite this widespread prevalence, most cases remain undiagnosed and untreated. Each year, sleep disorders, sleep deprivation, and sleepiness add an estimated $15.9 billion to the national health care bill. Additional costs to society for such consequences as lost worker productivity and accidents have never been calculated. Moreover, the contribution of sleep disorders to such serious problems as heart disease and stroke, which kill and debilitate thousands each year, has not been quantified. ★A Wide Spectrum Sleep disorders and disturbances of sleep comprise a broad range of problems. Even a partial list adds up to 70 conditions. Some of the major problems are: Sleep apnea Narcolepsy Insomnia Parasomnia Jet-lag syndrome ★Disturbed biological and circadian rhythms Sleep disturbances associated with such diseases as neurological disorders, heart and lung diseases, mental illness, and addictions The magnitude and prevalence of many sleep disorders are difficult to assess. The most studied sleep disorder is sleep apnea, a cessation of breathing during sleep that is a major cause of excessive daytime sleepiness. It is the second most common sleep disorder after insomnia and affects about 20 million Americans. Sleep apnea is associated with high blood pressure, coronary heart disease, heart attack, pulmonary hypertension, congestive heart failure, stroke, neuropsychiatric problems, mental impairment, and injury from accidents. Each year, sleep apnea accounts for about $42 million in hospital bills. The costs for diagnosis and treatment of this one sleep disorder could reach $60 billion by the year 2000. Other startling statistics about sleep disorders include the following: About 25 percent of American children aged 1 to 5 have a sleep disturbance; an estimated 250,000 people suffer from narcolepsy; more than 50 percent of Americans aged 65 and older have a sleep problem; and disturbed sleep is among the reasons most frequently cited by caretakers for institutionalization of older Americans. Because the prevalence of sleep disorders appears to increase with advancing age, the graying of the US population suggests that we will encounter an increasing public health burden in the years to come it is estimated that nearly 80 million Americans will have a sleep problem by the year 2010 and 100 million will have one by the year 2050. ★Milestones Despite their heavy toll, sleep disorders only recently have been recognized as a significant public health problem. To begin attacking this problem, the US Congress in 1987 passed legislation requiring the NIH Director to develop a plan for coordinating sleep research within the Public Health Service, part of the Department of Health and Human Services. That first step led to formation of an NIH coordinating committee on sleep disorders. In 1988, the Congress created a National Commission on Sleep Disorders Research to conduct a comprehensive study of the status of current knowledge and research on sleep disorders, including the resources (such as manpower, health care facilities, and social programs) available for addressing sleep problems. The Commission was also charged with developing a long-range plan to promote sleep disorders research. In January 1993, the Commission delivered its report to the Congress. Wake Up America: A National Sleep Alert identified sleep problems as a public health crisis and recommended a number of countermeasures, the most crucial being creation of a national center for sleep research to lead a Federal initiative against sleep disorders. The Commission stressed that a clear organizational focus was necessary not only to coordinate and manage such an initiative, but also to be accountable for its results and to ensure wide dissemination of research findings to health care professionals, patients, and the public. In June 1993, President William J. Clinton signed Public Law 103-43. Title IV of that law establishes the National Center on Sleep Disorders Research. ★Missions and Goals The National Center on Sleep Disorders Research was established to conduct and support research, scientist training, dissemination of health information, and other activities on sleep disorders and related concerns. The Center also is responsible for coordinating sleep research activities with other Federal agencies, and with public and nonprofit organizations. The Center fulfills its goals by serving four key functions: Research, training, technology transfer, and coordination. ★Research Sleep disorders span many medical fields, requiring multidisciplinary approaches not only to treatment, but also to basic research. The Center is working with neuroscientists, cellular and molecular biologists, geneticists, physiologists, neuropsychiatrists, immunologists, clinicians, pulmonary specialists, cardiologists, epidemiologists, behavioral scientists, and other experts. These scientists and health professionals are conducting basic, epidemiological, clinical, and behavioral research, as well as studies on prevention and health services. Research is supported by the NIH and other Federal agencies. Examples include studies on: ★The genetic component of narcolepsy Neural mechanisms that regulate the body's respiration, circulation, and temperature during sleep The role of the upper airway in sleep abnormalities, including the use of sophisticated imaging devices to assess obstruction The possible role of sleep/wake cycles in triggering heart attacks ★Cholesterol metabolism and diurnal rhythms Sleep quality and the management of insomnia among middle-aged women The prevalence, natural history, and genetic basis of respiratory disturbances in sleep among men and women The impact of sleep and sleep deprivation on immune function Surgical and other treatments for obstructive sleep apnea The cardiovascular complications of sleep disorders Those efforts represent only a beginning in the struggle to understand sleep disorders. Many other areas of sleep research urgently need investigation. These include: the basic functions of sleep; the genetics of sleep; the epidemiology of sleep disorders among minorities, women, and the poor; natural history data on normal and disrupted sleep throughout life; the neurobiology of excessive daytime sleepiness and motor control; sleep deprivation; and the role of sleeping pills in treating insomnia. ★Training Today, questions about sleep are far more numerous than the cadre of scientists available to answer them. In the absence of trained investigators, no new cures or treatments can be found. Training researchers in sleep disorders is rigorous and time- consuming--the skills and knowledge needed span many fields. The Center seeks to support and promote formal training programs on the doctoral and postdoctoral levels. It also plans to expand existing career development paths and create new training programs for scientists in sleep disorders research. These opportunities would include the formation of individual and institutional training awards for young and advanced investigators, particularly established scientists wishing to move into this challenging area. ★Technology Transfer Scientific advances do not improve health unless they become useful medical practices. In this area the Center seeks to develop new ways of ensuring that research results lead to health benefits. The Center expects to: Educate health care professionals about sleep and sleep disorders, with a special emphasis on reaching primary care physicians (who are the first line of treatment for most Americans), nurses, and clinical psychologists Encourage medical schools to add sleep disorders to current curricula Rapidly deliver new findings on prevention, diagnosis, and treatment to clinicians Work with leading experts in sleep and related disorders to develop professional guidelines on prevention, diagnosis, and management of, and referral for, sleep problems Sponsor continuing medical education programs for health professionals Since many sleep problems remain undiagnosed and untreated, the Center also seeks to improve Americans' lives by increasing public awareness of such issues as healthy sleep behaviors, the ramifications of sleep deprivation, the nature of sleep disorders, and the ways to obtain treatment for a sleep problem. Plans are to: Produce patient and public information materials Serve as an information resource on sleep and sleep disorders Educate policy makers, employers, and those in the transportation industry about the hazards of sleep disorders and deprivation Facilitate efforts to incorporate information about healthy and disordered sleep into curricula used in elementary and secondary schools, colleges, and driver education courses ★Coordination The Center coordinates the Federal Government's efforts on sleep disorders and works closely with other public, private, and nonprofit groups. It collaborates with such NIH components as the National Institute on Aging, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Institute of Child Health and Human Development, and other Government agencies and departments, including the Centers for Disease Control and Prevention and the Departments of Transportation, Defense, and Veterans Affairs. The Center is developing plans for sharing information among these groups and for encouraging their cooperation, especially in crosscutting areas. This process eliminates duplication of effort, allows the most efficient use of limited resources, and ensures that important research gaps are identified and effectively addressed. Further, the Center is seeking to improve communication among scientists, policy makers, and health care professionals to accelerate the speed of scientific discovery and the dissemination of findings to health professionals, patients, and the public. ★Center Operations A 12-member Sleep Disorders Research Advisory Board provides guidance for the Center's activities. The Center and its Advisory Board are collaborating with scientists and the public, including voluntary groups, to develop a comprehensive plan for conducting and supporting sleep disorders research and for setting goals for educational programs. Much of this collaboration occurs through various workshops and conferences. Additionally, the Center works with other Federal agencies to collect data, conduct studies, and disseminate public information about sleep disorders and their effects on society. ★Questions and Inquiries Can Be Directed To: National Center on Sleep Disorders Research Write to: The NHLBI Information Center P.O. Box 30105 Bethesda, Maryland 20824-0105 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Heart, Lung, and Blood Institute February 1994 --------------------------------------------------
[1145,1227]●製品gamma hydroxybutyrate (Xyrem [Orphan Medical])ザイレム
日本語版註）gamma hydroxybutyrate (Xyrem [Orphan Medical])ザイレム
【別名】oxybate sodium; sodium oxybate[INN]; GHB 【開発元】Orphan Medical [DBR_ID]02864
【化学名】sodium 4-hydroxybutyrate
【承認～Cataplexy】FDA申請=2-Oct-2000、FDA承認=17-Jul-2002、発売=7-Oct-2002 【承認～EDS】FDA申請=19-Jan-2005、FDA承認=18-Nov-2005 (The sNDA includes two Phase III(b) trials with excessive daytime sleepiness (EDS) as the primary efficacy measure, as well as positive data relating to the treatment of other symptoms of narcolepsy);【製剤】oral solution 【適応】Xyrem (sodium oxybate) oral solution is indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. 【用法用量】就寝時および2.5-4後に服用。推奨用量は夜間4.5gを2.25gずつ２回分服。 【作用】 【特徴】本剤はナルコレプシーの症状であるcataplexy治療薬として初めてで唯一の薬剤。 【製品情報】http://xyrem.info/ 【添付文書】http://xyrem.info/pdf/542599.ap.pdf 【EU】Xyrem[UCB Pharma Ltd.] CHMP承認勧告=2005.6.30; MAA[承認]=2005.10.13; オーファン指定=2003.2.3 [適応]Treatment of cataplexy in adult patients with narcolepsy 欧州はCelltech Pharm(現在UCB傘下)にライセンス[2003.10.30] 【日本】未開発 【その他】Drug Class: Hypnotic, but mechanism of action is unknown;
本剤はthe Controlled Substances ActのSchedule III drugとして指定、本人以外の服用 は禁止。 Xyrem is available only through restricted distribution, the Xyrem Success Program(SM), by calling 1-866-XYREM88SM (1-866-997-3688).
【日本語版コメント1227】
→詳細は参考資料●リソース：ナルコレプシーに纏めた。＜日本語版コメント要約＞
・γ-ヒドロキシ酪酸塩（GHB）の適応が、ナルコレプシー患者の日中の過剰な眠気（EDS）に拡大された。
・推奨量を就寝時と夜間の2回に分けて同量ずつ服用することで、EDSを改善する。
・本剤は「デートレイプ」の俗称で知られる乱用薬のため、販売には特別な条件が課せられている。
【日本語版コメント1145】
ナルコレプシー（Narcolepsy）の第１の特徴：昼間の睡眠発作では、試験中・商談中のような緊張場面でも眠り込み、これが毎日続く。 第２の特徴：情動脱力発作(cataplexy)では、強い興奮状態（怒り、笑い）が引き金として筋肉脱力がおこり、意識清明のまま数分間にわたり床に崩折れる等、通常の社会生活を困難にする病気。 米国では１４万人もの患者がいるが、日本では少なく2000人程度。
日本で適応症として「ナルコレプシー」を承認されているのは３成分のみ。 塩酸メチルフェニデート（リタリン[ノバルティス]）、塩酸メタンフェタミン、ペモリン（ベタナミン[三和化学研]）。 pemolineの肝障害が問題になって以来現在はリタリンが標準。
国際的には、これ以外に、メチルフェニデート関連製剤と世界標準となった感のあるmodafinil、そして今回評価するGHB(Xyrem)。
このGHBは、筋肉増強薬として、デート・レープ薬として、クラブで踊り狂う"Happy drug"として流行し、58人の死亡者をだした薬剤だ。→詳細は参考資料●リソース：ナルコレプシーに纏めた。 ＜日本語版コメント用要約＞ ・ナルコレプシー患者のカタプレキシーの治療薬として、半減期が短い速効型の中枢神経抑制剤γ-ヒドロキシブチレート（GHB）が承認された。この種の承認は初めて。 ・カタプレキシーの治療には、就寝前と2.5-4時間後の2回服用する。 ・臨床試験では、GHBの投与によりカタプレキシー発作の回数が減少することが示された。 ・GHBは乱用物質でもあるため、流通には厳しい制限が与えられた。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =Xyrem FDA Application No. =NDA # 021196 Active Ingredient(s)=SODIUM OXYBATE Company =ORPHAN MEDCL Dosage Form/Route =SOLUTION; ORAL 500MG/ML Strength = - Approval Date=07/17/2002[000] :Label[添付文書]|Letter[承認書]|Review[承認] For the reduction of cataplexy attacks in patients with narcolepsy. - Approval Date=11/18/2005[005] :Label[添付文書]|Letter[承認書]|[適応追加] Xyrem (sodium oxybate) oral solution is indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.
情報ソース●CDER New and Generic Drug Approvals: 1998-2002 - X Xyrem (sodium oxybate) oral solution, Rx Orphan Medical Application #=NDA 21-196 Approval Date=7/17/02 Letter Posted=7/24/02 Label Posted =7/18/02 Review Posted=10/23/02 情報ソース●NDA APPROVALS FOR CALENDAR YEAR 2002 NDA NUMBER =21196 DRUG NAME =Xyrem GENERIC NAME =Sodium Oxybate APPLICANT/SPONSOR=Orphan Medical CHEMICAL TYPE =1 THERAPEUTIC CLASS=PV APPROVAL DATE =17-Jul-02 情報ソース●NME Approved in Calendar Year 2002 NDA Number =21196 Generic Name =Sodium Oxybate Trade Name =Xyrem Dosage Form =Solution Applicant =Orphan Medical Classification =1PV Approval Date =17-Jul-02 情報ソース●FY 2002 User Fee Priority Approvals NDA # =21-196 Trade Name =Xyrem (sodium oxybate) (Generic Name)= Dosage Form =Oral Applicant =Orphan Medical Approval Date =17-Jul-02 Class =1PV Indication =Xyrem is indicated for the treatment of cataplexy associated with narcolepsy 情報ソース●FY 2002 User Fee NME Approvals NDA # =21-196 Trade Name =Xyrem (sodium oxybate) (Generic Name)= Dosage Form =Oral Applicant =Orphan Medical Approval Date =17-Jul-02 Class =1PV Indication =Xyrem is indicated for the treatment of cataplexy associated with narcolepsy
●Electronic Orange Book Application Number: 021196 Active Ingredient : SODIUM OXYBATE Proprietary Name : XYREM [ORPHAN MEDCL] SOLUTION; ORAL 500MG/ML Approval Date : Jul 17, 2002 Exclusivity Data : NCE 7/17/2007 ODE 7/17/2009 ODE NOV 18,2012 Patent Data : 6780889 DEC 22,2019 Y
●Drug Information - Xyrem (sodium oxybate) - http://www.fda.gov/cder/drug/infopage/xyrem/default.htm The Food and Drug Administration approved Xyrem (sodium oxybate or gamma hydrox ybutyrate, also known as GHB) for treating a small population of patients with n arcolepsy who experience episodes of cataplexy, a condition characterized by wea k or paralyzed muscles. Because of safety concerns associated with the use of th e drug, the distribution of Xyrem will be tightly restricted. FDA Talk Paper on Xyrem Medication Guide for Xyrem Questions and Answers About Xyrem Last Updated: July 17, 2002
●EU承認 ●EMEA - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE SUMMARY OF OPINION.[2005.6.23] -Committee for Medicinal Products for Human Use (CHMP)は2005.6.23承認勧告。 ★Xyrem INN:Sodium oxybate - Published 22/11/05 [UCB Pharma Ltd.] MAA[承認]=2005.10.13; オーファン指定=2003.2.3 [適応]Treatment of cataplexy in adult patients with narcolepsy 1. Abstract 2. All Authorised Presentations Product Information 3. All Patient Information Leaflets 4. All Summary of Product Characteristics 5. All Labellings 6. Scientific Discussion 7. Procedural steps taken before authorisation ■[Enterprise and Industry DG] Directorate F - Consumer Goods -http://pharmacos.eudra.org/ ★The Community Register[承認製品リスト] - 医薬品は1995.10以降。 各製品データシートにリンク。 [医薬品]Community Register of medicinal products for human use - [年月別] - 取下げ・中断 - 却下 [総合索引～成分別]General index on active ingredient [総合索引～銘柄別]General index on brand name
■Orphan Medical
- http://www.orphan.com/ ; NASDAQ [ORPH] 13911 Ridgedale Drive, Suite 250, Minnetonka, MN 55305 ;888-8ORPHAN Jazz Pharmaceuticalsにより買収された。(mid-2005). [Yahoo!]Orphan Medical, Inc. Company Profile 主力品は、Antizol (fomepizole)注とBusulfex (busulfan; キリンビールが導入契約)注。 従業員数80名。 米国 ●決算 ($ 000) 2004 2003 2002 2001 2000 1999 ----------------------------------------------------------- 収入 23,768 15,526 16,130 11,274 11,185 6,457 うち製品 21,337 15,526 16,130 11,274 11,185 6,457 License 2,431 - - - - - ----------------------------------------------------------- 研究開発費 13,221 10,805 8,713 営業利益 -13,233 -18,828 -11,656 -6,318 -6,880 -5,509 営業外収支 186 30,334 255 321 793 288 純利益 -13,047 10,997 -11,401 -5,997 -6,087 -5,221 ★地域別売上高 米国内 20,618 13,788 12,553 9,566 日本 - 68 800 25 英国 59 529 915 621 その他 660 1,141 1,862 1,062 --------------------------------------------- 合計 21,337 15,526 16,130 11,274 ●製品売上高 ($ 000) 2004 2003 2002 2001 2000 1999 ----------------------------------------------------------- 収入 23,768 15,526 16,130 11,274 11,185 6,457 うち製品 21,337 15,526 16,130 11,274 11,185 6,457 ----------------------------------------------------------- Xyrem 10,570 3,931 250 (発売2002.10) (sodium oxybate)ナルコレプシー Antizol 9,051 6,622 6,103 (fomepizole)注;解毒剤 Antizol-Vet 278 274 288 Cystadane 1,438 1,186 994 (betraine anhydrous)homocystimuria治療薬 Busulfex (1) - 3,321 7,748 (busulfan) Elliotts B (1) - 15 35 Sucraid (1) - 177 712 (sacrosidase)sucraose欠損治療薬 (1) These products were divested during the second quarter of 2003. ★[2003期決算メモ] 【経営】 ・2003.6 Busulfex(busulfan) Inj.をESP Pharma,Inc.に売却($29.5million)。 ・2003.5 Sucraid(sacrosidase)経口液($1.5million)とElliotts B SolutionをQOL Medical社に売却 以上が営業外収益$30millionの内訳。 ・2003.9 Xyremの欧州の開発・販売権をCelltech Pharmaceuticals(Celltech Group plc１部門) にライセンス。→CelltechはUCBに買収された。In October 2003, the Company announced that it had licensed European sales and marketing rights for Xyrem (sodium oxybate) oral solution to UCB Pharma (formerly Celltech Pharmaceuticals). Under the terms of the agreement, UCB Pharma will be responsible for the registration, sales and marketing of Xyrem in Europe. UCB Pharma has made an initial payment of $2.5 million to Orphan Medical. The Company received a $1.0 million milestone payment in 2004 as a result of the submission of the marketing application in Europe. In 2005, the Company has received an additional $1.0 million milestone payment as a result of the submission of the sNDA on January 15, 2005. UCB Pharma will make further payments of up to $5 million tied to product development and registration milestones and up to $6 million tied to sales-related milestones. UCB Pharma will also pay Orphan Medical a royalty on sales of the product which is expected to begin at the earliest in late 2005. The ten-year licensing agreement includes the use of Xyrem in narcolepsy and provides UCB Pharma with rights to negotiate in regard to other potential future indications including fibromyalgia syndrome. The term of this agreement is for 10 years from the date of approval in Europe with automatic extension until UCB Pharma provides 12 month notice to Orphan Medical. The agreement may be terminated under certain conditions including material breach of contract provisions prior to the ten year initial term.【営業】 【開発】 ●SEC Filings - 10-K[2005.3.15,pdf,130p] - 10-K[2004.3.15,pdf,130p]
●Jazz Pharmaceuticals,Inc. - http://www.jazzpharmaceuticals.com/index.php 本社Palo Alto, California; 設立2003.3 私企業なので決算非公開。 ●News 03/27/2006★JAZZ PHARMACEUTICALS SUPPORTS NARCOLEPSY NETWORK INITIATIVE TO LAUNCH ITS FIRST-EVER NATIONAL NARCOLEPSY AWARENESS CAMPAIGN
03/06/2006★XYREM(R) (SODIUM OXYBATE) NOW AVAILABLE FOR THE TREATMENT OF EXCESSIVE DAYTIME SLEEPINESS (EDS) IN PATIENTS WITH NARCOLEPSY
02/23/2006★STUDY FINDS THAT THAT XYREM(R) (SODIUM OXYBATE) RELIEVES PAIN
12/08/2005★JAZZ PHARMACEUTICALS ANNOUNCES EUROPEAN COMMISSION MARKETING APPROVAL OF XYREM(R)★EU承認され(2005.10.13)、ドイツで2005.12.8発売。
11/22/2005★XYREM(R) (SODIUM OXYBATE) RECEIVES FDA APPROVAL FOR THE TREATMENT OF EXCESSIVE DAYTIME SLEEPINESS IN PATIENTS WITH NARCOLEPSY
11/17/2005★STUDY FINDS THAT XYREM(R) (SODIUM OXYBATE) RELIEVES PAIN AND IMPROVES FUNCTIONING IN PATIENTS SUFFERING FROM FIBROMYALGIA
06/27/2005★JAZZ PHARMACEUTICALS COMPLETES ACQUISITION OF ORPHAN MEDICAL
04/19/2005★JAZZ PHARMACEUTICALS TO ACQUIRE ORPHAN MEDICAL
●Our Products Xyrem(R) (sodium oxybate) ---ナルコレプシー Antizol ---ethylene glycol(不凍液等) or methanol 中毒 Cystadane(betaine anhydrous for oral solution)---homocystinuriaの治療
●Press Release ※ORPHAN MEDICAL REITERATES RECORD 2002 REVENUE GUIDANCE AND PROVIDES POSITIVE OUTLOOK[2003.1.6] - 2002年度収入は、$15.5 -$16.0 million見込み。 Xyremの年度末までの処方箋枚数は新規のみで726枚。これを年間換算すると$3.5 million。 ※ORPHAN MEDICAL ANNOUNCES POSITIVE NOTIFICATION FOR EUROPEAN ORPHAN PRODUCT
※ORPHAN MEDICAL ANNOUNCES NEW DATE FOR FDA ADVISORY COMMITTEE MEETING FOR XYREM(R)
DESIGNATION FOR XYREM(R) (SODIUM OXYBATE) ORAL SOLUTION[December 12, 2002] - the Committee for Orphan Medicinal Products (COMP) がオーファン指定を勧告。 これによりEMEAは45日以内に指定の見込み。欧州は提携先を検討中で2003年前半に契約予定 ※ORPHAN MEDICAL PROVIDES UPDATE ON PRESCRIPTION LEVELS FOR XYREM(R) (SODIUM OXYBATE)
ORAL SOLUTION[December 3, 2002] - 本剤はナルコレプシーの症状であるcataplexy治療薬として初めてで唯一の薬剤。 2002.10.7発売以来11.29迄で予想を上回る処方実績。552件。第４四半期で50万ドルの売 上見込み。 筋緊張の突発的失調であるCataplexyは、笑い・怒り・驚き等を引き金として発生。 米国のナルコレプシー患者14万人の60-90%がCataplexyに悩む。米国Cataplexy市場は 推定年$125 million ※ORPHAN MEDICAL REPORTS HIGHEST QUARTERLY REVENUE IN COMPANY HISTORY[October 22, 2002] ※ORPHAN MEDICAL ANNOUNCES THE COMMERCIAL LAUNCH OF XYREM(R) (SODIUM OXYBATE)
ORAL SOLUTION THROUGH A DEDICATED SPECIALTY SALES FORCE[October 8, 2002] ※ORPHAN MEDICAL TO EXCEED THIRD QUARTER REVENUE EXPECTATIONS[October 3, 2002] ※ORPHAN MEDICAL NAMES EXPRESS SCRIPTS EXCLUSIVE DISTRIBUTOR OF XYREM(R)[August 22, 2002] ※ORPHAN MEDICAL ANNOUNCES FDA APPROVAL OF XYREM(R)[July 17, 2002] ※XYREM(R) RESPONSE ACCEPTED BY FDA FOR REVIEW[May 23, 2002] ※ORPHAN MEDICAL SUBMITS A COMPLETE RESPONSE TO THE XYREM(R) (SODIUM OXYBATE)
APPROVABLE LETTER[May 17, 2002] - FDA 2002.4.9 Approvable Letterに基づきデータを揃え、本日再申請。 ※ORPHAN MEDICAL LICENSES RIGHTS TO PAIN PRODUCT[April 25, 2002] - 癌性疼痛に用いるbutamben (butyl-p-aminobenzoate) suspensionの特許権とデータを 取得 ※ORPHAN MEDICAL RECEIVES FDA APPROVABLE LETTER FOR XYREM[April 10, 2002] ※ORPHAN MEDICAL REPORTS INCREASED FOURTH QUARTER AND 2001 YEAR END RESULTS[February 21, 2002] ※ORPHAN MEDICAL ANTICIPATES INCREASED REVENUE FOR 2001 FOURTH QUARTER AND YEAR END[January 28, 2002] ※ORPHAN MEDICAL ANNOUNCES TWO ADDITIONAL INTERNATIONAL APPROVALS[December 3, 2001] ※ORPHAN MEDICAL ANNOUNCES THAT XYREM(R) CONTRACT MANUFACTURER CLEARED BY FDA[November 8, 2001] ※ORPHAN MEDICAL ANNOUNCES XYREM(R) RESPONSE ACCEPTED FOR REVIEW BY THE FDA[October 23, 2001] ※ORPHAN MEDICAL SUBMITS COMPLETE RESPONSE TO THE XYREM(R)(SODIUM OXYBATE) NDA
APPROVABLE LETTER[October 9, 2001] ※ORPHAN MEDICAL ANNOUNCES FDA ACCEPTS COMPANY担 PROPOSED RESPONSE PLAN REGARDING
XYREM(R) NDA[August 28, 2001] ※ORPHAN MEDICAL RECEIVES FDA APPROVABLE LETTER FOR XYREM(R)[July 3, 2001] ※ORPHAN MEDICAL UPDATES ON INTERNATIONAL REGULATORY DEVELOPMENTS OF ANTIZOL(R)[June 13, 2001] ※ORPHAN MEDICAL ANNOUNCES FDA ADVISORY COMMITTEE FINDS XYREM(R) EFFECTIVE FOR
TREATING CATAPLEXY ASSOCIATED WITH NARCOLEPSY[June 6, 2001] - Peripheral and Central Nervous System Advisory Committee は、9g/日での効果は 6:3、6g/日は5:4、安全性でabstentionでは4:4、リスクマネージメントの必要性では8:1。 ※ADDITIONAL CLINICAL DATA FOR ORPHAN MEDICAL担 XYREM(R) DEMONSTRATE OVERALL
IMPROVEMENT FOR NARCOLEPSY PATIENTS[May 25, 2001] ※ORPHAN MEDICAL RECEIVES CORPORATE AWARD FROM THE NATIONAL ORGANIZATION OF RARE
DISORDERS (NORD)[May 22, 2001
(SODIUM OXYBATE) ORAL SOLUTION NDA[April 11, 2001] ※ORPHAN MEDICAL RECEIVES 90 DAY EXTENSION TO XYREM(R) NDA[March 30, 2001] ※ORPHAN MEDICAL REPORTS ON XYREM(R) NDA DEVELOPMENTS[March 1, 2001] ※OPRHAN MEDICAL UPDATES ON PROMISING REGULATORY DEVELOPMENTS WITHIN COMPANY'S
PRODUCT PIPELINE[January 25, 2001] ※ORPHAN MEDICAL ANNOUNCES XYREM(R) (SODIUM OXYBATE) ORAL SOLUTION NDA ACCEPTED
FOR FILING BY THE FDA[December 4, 2000] ※XYREM(R) (SODIUM OXYBATE) ORAL SOLUTION NDA RECEIVES PRIORITY REVIEW FROM THE FDA[October 17, 2000] ※XYREM(R) NDA FOR NARCOLEPSY SYMPTOMS SUBMITTED BY ORPHAN MEDICAL[October 2, 2000] - 本日申請。 ※President Clinton Signs H.R. 2130 Protecting the Medical use of GHB; Scheduling
of Orphan Medical's Xyrem Defined[February 21, 2000] ※Congressional Bill Supporting the Continued Development of Medically Formulated
GHB Moves to the President[February 1, 2000] ※Orphan Medical Reports Positive Clinical Trial Results for Xyrem(R), Potential
Treatment for Narcolepsy[January 19, 2000] ※U.S. Senate Approves Legislation Permitting Orphan Medical To Continue Developing
Narcolepsy Treatment Using Gamma Hydroxybutyrate (GHB)- Senate Bill Makes GHB
A Controlled Substance Except For Medical Uses[November 22, 1999] ※Orphan Medical Completes Licensing Agreement with Pierre Fabre Medicament for
European Marketing Rights of Busulfex(R) (busulfan) Injection -Company Provides
Update on FDA Meeting Regarding Development Timeline for Narcolepsy Drug-
Xyrem(R) (sodium oxybate)[October 19, 1999] ※Orphan Medical: Approval of H.R. 2130 By the House of Representatives Will Allow
for the Continued Research of Xyrem(R) (sodium oxybate) oral solution for the
Treatment of Narcolepsy[October 14, 1999] ※Orphan Medical Initiates Xyrem (sodium oxybate) oral solution Treatment IND[February 23, 1999] - 最初のIND用出荷。
●一般ニュース ●Gamma hydroxybutyrate: An Overview[2002.7.18] - GHBは悪名高い薬剤で、一時Discothequeでのレイブ"raves"シーン等で盛んに使われて いた。米麻薬取締局の記録では1990年以来58人が死亡、少なくとも5700人が過量摂取。 服用後数分で多幸症状態になり、理性・記憶・意識を喪失する。その習慣性の報告もあ る。特にアルコールと同時服用が危険。 本来GHBは、全身麻酔薬として開発されたが効果が低く中止、その後成長ホルモン放出 促進作用・筋肉増進作用が注目され、ボディビルダー達に人気となった。 2000.2.18 クリントン大統領がGHB保有を非合法とする連邦法(H.R. 2130) に署名、 ヘロインと同じSchedule 1 controlled substanceと指定。 その後ナルコレプシー治療 効果が認可され、医療目的に使用されるSchedule III Controlled Substanceに指定。 ●Date-Rape Drug For Narcolepsy ●Google Directory:Gamma-hydroxybutyrate
[1049]●製品：モダフィニル［プロビジル］ modafinil [Provigil] :Cephalon, Inc.
日本語版註）モダフィニル［プロビジル］ modafinil [Provigil] :Cephalon, Inc.
【別名】Modiodal,CRL-40476 【開発元】創製開発Lafon[仏]→セファロン社Cephalon Incの子会社に(2001.12) [DBR_ID]24568
【化学名】2-[(diphenylmethyl)sulfinyl]acetamide; CAS : 68693-11-8
【承認】FDA申請=1996-12-27、FDA承認=1998-12-24 発売1999-2-16; [*追加適応]FDA申請=2002.12.20、FDA承認=2004.1.23 【製剤】Tabletes -100mg, 200mg(朝１回400mg) 【適応】ナルコレプシー、*OSAHS[閉塞型睡眠時無呼吸低呼吸症候群]および *SWSD[交代勤務睡眠障害]に伴う過眠症 (PROVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder.) 【製品情報】http://www.cephalon.com -http://www.provigil.com/ 【添付文書】http://www.fda.gov/cder/foi/label/1998/20717lbl.pdf|Provigil(modafinil) Prescribing Information
【EU】現在30か国以上で承認。英国PROVIGIL、仏・スペインMODIODAL(R)[Cepa Schwarz Pharma]、独VIGIL(R)[Merckle GmbH]、オーストリア・スイスMODASOMIL(R)[Merckle GmbH]。→2002.12セファロン社に移管
【日本】モディオダール錠１００ｍｇ[製造販売元／アルフレッサファーマ株式会社 提携／Ｃｅｐｈａｌｏｎ ]ＭＯＤＩＯＤＡＬ 申請2005.4.15-承認2007.1.26-発売2007.3.28 | モディオダール錠１００ｍｇ[製造販売元／アルフレッサファーマ株式会社 提携／Ｃｅｐｈａｌｏｎ 販売元／田辺三菱製薬株式会社]ＭＯＤＩＯＤＡＬ 発売2007.3.28 ；06.3.27田辺と共同販売契約 【製剤～日本】１錠中モダフィニル１００ｍｇ 【適応～日本】ナルコレプシーに伴う日中の過度の眠気 【用法用量～日本】通常、成人にはモダフィニルとして１日１回２００ｍｇを朝に経口投与する。なお、年齢、症状により適宜増減するが、１日最大投与量は３００ｍｇまでとする。 【添付文書～日本】アルフレッサ添付文書情報 田辺三菱添付文書 【その他】U.S. Patent Nos. 4,927,855 / RE37,516
●BIAM: Modafinil
【日本語版コメント1181】
睡眠障害は、大きくわけると、不眠症[Insomnia](患者21万人)、過眠症[Hypersomnia;ナルコレプシーを含む](1000-2000人)、睡眠時無呼吸症候群[Sleep Apnea](2.3万人)、レストレス・レッグ症候群[RLS: Restless Leg Syndrome]。 過眠症やRLS(就寝時脚が火照ったり、ムズムズする)は、患者調査にはあらわれなくとも潜在的に軽度の症状を持つ者は日本人も多いはず。 米国ではナルコレプシー25万人、RLS 1200万人と多い。
睡眠医学・医療は最近独立した専門領域として定着しつつあり、睡眠医療センターやクリニックができ日本睡眠学会会員数も1300名、2002年から導入された認定制度で認定医32名、認定検査技師22名、認定医療機関32施設。 因みに米国睡眠医学会[AASM]は参加施設536、個人会員数4,856(正会員2,556)睡眠医学を主とする専門医が1,546人。不眠症以外は、治療手段がなかったり、著しく制限されてきた。 最近ナルコレプシーによる過眠症治療薬の世界標準となっているモダフィニルが追加適応症「睡眠時無呼吸症候群(SAS)」を認可されたので、本号ではこれをテーマとして採択した。
SASはTV番組でも放映され話題になり、国土交通省が「睡眠時無呼吸症候群に注意しましょう」とのパンフレットをSAS対応可能な500施設に配布(2003.3)。 従来SAS治療には、主に鼻腔からのCPAP(経鼻持続陽圧呼吸療法)が用いられてきた。 薬物療法としてはこれまで認可されたものはなかった。→詳細は参考資料●MLリソース：催眠鎮静剤に纏めた。 Modafinilは●MLリソース：ナルコレプシー治療剤に纏めた。＜日本語版コメント用要約＞
・ナルコレプシーに伴う日中過眠の治療薬モダフィニルが、新たに閉塞型睡眠時無呼吸・低呼吸症候群(OSAHS)または交代勤務睡眠障害(SWSD)による過眠の治療薬としてもFDAに承認された。
・臨床試験において睡眠潜時や臨床症状評価の改善が示されたが、劇的な効果ではない。
・本剤はアンフェタミンと異なり心血管作用がなく、夜間睡眠にも影響を及ぼさない。
・12週間までの使用では忍容性は良好であったが、長期安全性に関しては不明である。
【日本語版コメント1049】
日本で適応症として「ナルコレプシー」を承認されているのは３成分のみ。 塩酸メチルフェニデート（リタリン[ノバルティス]）、塩酸メタンフェタミン、ペモリン（ベタナミン[三和化学研]）。
モダナフィルに関して、American Sleep Disorders Assn(ASDA;米国睡眠障害学会)前会長 Dr. Wolfgang Schmidt-Nowara,M.D.によると"ナルコレプシーに伴う昼間過眠症状excessive daytime sleepiness(EDS)の治療に大きな進歩"。 副作用は"mild to moderate"。 主な副作用としては、頭痛、眩暈、下痢。 米国では1993年にオーファンドラッグ指定。 英国でCephalon社はProvigil (modafinil)を発売(March 4, 1998)。 カナダでもMARCH 3, 1999にAlertec (modafinil)が承認。
●承認データ：FDA ●2004.5.1 以降 Drugs@FDA
Drug Name(s) =PROVIGIL FDA Application No. =NDA # 020717 Active Ingredient(s)=MODAFINIL Company =CEPHALON Dosage Form/Route =TABLET; ORAL: 100MG; 200MG Strength = - Approval Date=12/24/1998[000] :Label[添付文書]|Letter[承認書]|Review [承認] - Approval Date=01/23/2004[008] :Label[添付文書]|Letter[承認書]|[適応追加]
出典●FDA Drug Approvals List December 1998 Original Application #: 020717 Approval Date: 24-DEC-98 Trade Name: PROVIGIL Chemical Type: 1 Therapeutic Potential: S Dosage Form: TABLET Applicant: CEPHALON, INC Active Ingredient(s): MODAFINIL OTC/RX Status: RX Indication(s):For the treatment of narcolepsy 情報ソース●CDER New and Generic Drug Approvals: 1998-2004 Provigil (Modafinil) Tablets, Rx Cephalon, Inc. Application #=NDA 20-717/S9 Approval Date=7/29/03 Letter Posted=8/15/03 承認書※2003.3.28申請分 Label Posted = 添付文書 Review Posted= Provigil (Modafinil) Tablets, Rx Cephalon, Inc. Application #=NDA 20-717/S5/S8 Approval Date=1/23/04 Letter Posted=2/2/04 承認書※S5=2001.8.22申請[記述内容変更] /S8=2002.12.20申請[適応追加*] Label Posted =2/2/04 添付文書 Review Posted= * OSAHS[閉塞型睡眠時無呼吸低呼吸症候群] and shift work sleep disorder(SWSD；交代勤務睡眠障害) Provigil (Modafinil) Tablets, Rx Cephalon, Inc. Application #=NDA 20-717/S6 Approval Date=4/16/03 Letter Posted= 承認書 Label Posted = 添付文書 Review Posted= Provigil (Modafinil) Tablets, Rx Cephalon, Inc. Application #=NDA 20-717 Approval Date=12/24/98 Letter Posted=12/30/98 承認書 Label Posted =12/29/98 添付文書 Review Posted=6/19/00
●Electronic Orange Book Application Number: 020717 Active Ingredient : MODAFINIL Proprietary Name : PROVIGIL [CEPHALON] TABLET; ORAL 100MG ,200mg Approval Date : Dec 24, 1998 Exclusivity Data : ODE 12/24/2005 NCE 12/24/2003 Patent Data : RE37516 OCT 06,2014 U-255 4927855 MAY 22,2007 U-255
●Provigil Consumer Information
Summary: Review all medications that you are taking with your health care provider, including those that you take without a prescription, because certain other medications can interact with Provigil. Tell your health care provider if you are trying to become pregn
Provigil(R)
Brand Name: Provigil(R)
Active Ingredient: modafinil
Strength(s): 100mg and 200mg
Dosage Form(s): Tablets
Company Name: Cephalon, Inc.
Availability: Prescription only, Schedule IV Controlled Substance
*Date Approved by the FDA: December 24, 1998
*Approval by FDA does not mean that a new drug will be immediately marketed and available to consumers.
●What is Provigil used for? Provigil is used to improve wakefulness in people with excessive daytime sleepiness associated with narcolepsy.
●General Precautions with Provigil:
★Before taking Provigil:
・Tell your health care provider if you have:
any heart conditions, (including valve problems, irregular heart beat, recent heart attack, or unstable chest pain) a history of mental illness liver problems ・Review all medications that you are taking with your health care provider, including those that you take without a prescription, because certain other medications can interact with Provigil.
・Tell your health care provider if you are trying to become pregnant, are already pregnant, or are breast-feeding.
★While you are taking Provigil:
・Provigil can decrease the effectiveness of certain contraceptives including birth control pills, and implantable contraceptives. If you are using this type of contraceptive while taking Provigil and for 1 month after you stop treatment with Provigil you should etiher:
use an alternate birth control method, or use another effective birth control method together with your current contraceptive. ・Doses of your other medications may need to be adjusted or you may have to be monitored more closely.
・Do not drive or operate other complex machinery until you know how Provigil affects your ability to function.
・Avoid alcohol.
・Call your health care provider if you develop a skin rash, hives, or allergic reactions.
●How should I take Provigil?
Take Provigil once a day in the morning.
●What are some possible side effects of Provigil?
(This is NOT a complete list of side effects reported with Provigil. Your health care provider can discuss with you a more complete list of side effects.)
・Headache
・Infection
・Nausea
・Nervousness
・Feeling anxious
・Trouble sleeping
For more detailed information about Provigil, ask your health care provider.
Date Posted: 2/23/99
●Cephalon Inc
●http://www.provigil.com/ Provigil(modafinil) Prescribing Information[pdf,4p]［医薬品添付文書］ ●Cephalon: Annual Report 2001 The American Academy of Sleep Medicineは本剤を標準薬と認める 2001年度米国処方箋 685,000(+98%) ★適応追加P3 to treat the symptom of excessive sleepiness beyond narcolepsy. ★国際 仏Lafonを取得。 ●Product News
●アルフレッサホールディングス株式会社 - http://www.alfresa.com/ 〒100-0004 東京都千代田区大手町一丁目1番3号 ●IR情報 ★IRライブラリー～決算短信、アニュアルレポート、有価証券報告書 ★IR説明資料 2005年3月期決算 補足資料[2005.5.13;pdf,17p] 2004年3月期決算 補足資料[2004.5.19;pdf,20p] ●決算公告 ●ニュースリリース ナルコレプシー治療剤モダフィニルの共同販売および適応症拡大に関する共同開発契約締結のお知らせ[2006.3.31]] 田辺製薬株式会社とアルフレッサ ホールディングス株式会社の完全子会社であるアルフ レッサ ファーマ株式会社は、3月27日、アルフレッサ ファーマ株式会社が製造販売承認申 請中のナルコレプシー治療剤モダフィニルの日本における共同販売および適応症拡大に関 する共同開発契約を締結いたしました。 モダフィニルは覚醒促進作用を有する薬剤で、アルフレッサ ファーマ株式会社が1998 年6 月に米国セファロン社より日本国内における開発、製造および販売の権利を取得した ものです。すでに欧米をはじめ世界30カ国以上で、ナルコレプシーに伴う日中の過度の眠 気に対する治療薬として発売され、さらに閉塞性睡眠時無呼吸症候群および交代勤務睡眠 障害患者における過度の眠気の治療薬として、米国および欧州主要国で承認されています。 国内では、アルフレッサ ファーマ株式会社がナルコレプシー治療剤として、厚生労働省よ り希少疾病用医薬品の指定を受けて開発を進め、現在、早期承認取得に向けて取り組んで おります。 本剤の承認取得後、両社はそれぞれの販売チャンネルを通じて、モダフィニルを同一商 品名｢モディオダール(R)｣で販売いたします。また、今後は、閉塞性睡眠時無呼吸症候群や、 小児ADHD（注意欠陥多動性障害）などの適応症拡大を目指した共同開発を行います。
●アルフレッサ ファーマ株式会社 - http://www.alfresa-pharma.co.jp/ 旧株式会社アズウェルの製造部門 〒540-8575 大阪市中央区石町二丁目2番9号 TEL. 06-6941-0300（代） FAX. 06-6947-1548 従業員数： 618人（2004年10月1日現在） 1998.10.1 日本商事㈱と昭和薬品㈱が合併し、㈱アズウェルが誕生。 2000.4.1 高木薬品㈱と合併。 2000.10.1 中川安㈱、中央興医会㈱と合併。 2003.9.29 福神㈱と経営統合し、共同持株会社アルフレッサホールディングズ㈱を設立。 2003.10.1 ㈱アズウェルの会社分割によりアルプレッサ ファーマ㈱誕生。 ●医療従事者向け情報 モディオダール錠１００ｍｇ[モダフィニル] - 添付文書情報 ●製品紹介 ●お知らせ ナルコレプシー治療剤「モディオダール錠100mg」新発売のお知らせ[2007.3.27] ナルコレプシー治療剤「モディオダール錠100mg」製造承認取得のお知らせ[2007.1.26] ナルコレプシー治療剤モダフィニルの共同販売および適応症拡大に関する共同開発契約締結のお知らせ[2006.3.31] ナルコレプシー治療剤モダフィニル製造承認申請のお知らせ[2005.4.15]
●田辺三菱製薬 - http://www.mt-pharma.co.jp/index.php ●会社情報 ●医療関係者向け情報 モディオダール - 添付文書 ●一般・患者向け情報 ●研究開発活動 ★研究開発パイプライン ●ニュースリリース ★ニュースリリース：旧田辺製薬～2001年～2007年 ナルコレプシー治療薬「モディオダールR錠100mg」新発売のお知らせ [2007.3.27] ナルコレプシー治療剤モダフィニルの共同販売および適応症拡大に関する共同開発契約締結のお知らせ [2006.3.31] ★ニュースリリース:旧三菱ウェルファーマ ～2001年～2007年 ■株主・投資家情報 ●決算発表資料～決算短信・決算説明資料 ★決算発表資料：旧田辺製薬～2002年3月期～2008年3月期第1四半期 ★決算発表資料：旧三菱ウェルファーマ～平成14年3月期(2002)～平成20年3月期第1四半期 ●IRミーティング ★IRミーティング：旧田辺製薬 ●有価証券報告書 ★有価証券報告書：旧田辺製薬～2001年3月期～2007年3月期 ★有価証券報告書：旧三菱ウェルファーマ～平成14年3月期(2002)～平成19年3月期 ●アニュアルレポート ★アニュアルレポート：旧田辺製薬 ★アニュアルレポート：旧三菱ウェルファーマ[英文] ●IRライブラリー～過去の決算短信や決算概要・参考資料、アニュアルレポート等 ★IRライブラリー：旧田辺製薬 ★IRライブラリー：旧三菱ウェルファーマ ★
■modafinil.com［modafinil専門サイト］
Modafinil is a mood-brightening and memory-enhancing psychostimulant which enhances wakefulness and vigilance. ここではナルコレプシーの情報、他のナルコレプシー治療薬についての情報もある。 http://www.modafinil.com/ BLTC Research
●
From
THE GOOD DRUG GUIDE
"....modafinil is a mood-brightening and memory-enhancing psychostimulant. It enhances wakefulness and vigilance, but its pharmacological profile is notably different from the amphetamines, methylphenidate (Ritalin) or cocaine. It is less likely to cause jitteriness, anxiety, or excess locomotor activity - or lead to a hypersomnolent 'rebound effect' - than traditional stimulants. Subjectively, it feels smoother and cleaner than the amphetamines.
Current research suggests modafinil, like its older and better-tested analogue adrafinil, is a safe, effective and well-tolerated agent. It is long-acting and doesn't tend to cause peripheral sympathetic stimulation. Yet its CNS action isn't fully understood. Modafinil induces wakefulness in part by its action in the anterior hypothalmus. Its dopamine-releasing action in the nucleus accumbens is weak and dose-dependent; the likelihood of dose-escalation and tolerance is apparently small. Modafinil has central alpha 1-adrenergic agonist effects i.e. it directly stimulates the receptors. More significant, perhaps, is its ability to increase excitatory glutamatergic transmission. This reduces local GABAergic transmission, thereby diminishing GABA-A receptor signalling on the mesolimbic dopamine terminals.
Modafinil is proving clinically useful in the treatment of narcolepsy, a neurological disorder marked by uncontollable attacks of daytime sleepiness. Experimentally, it is also used in the treatment of Alzheimer's disease, depression, attention-deficit disorder, age-related memory decline, idiopathic hypersomnia and everyday cat-napping.［実験的にはアルツハイマー病、うつ病、注意欠如障害等に有効］
sleep. Prolonged sleeplessness weakens immune function. Animals tortured in sleep-deprivation experiments eventually die from massive bacterial infections of the blood..."
Merck Manual CERI Sources Search Medline
HedWeb
HerbWeb
BLTC Research
Victoria Pharmacy
The Good Drug Guide
How To Buy Almost Any Drug Legally Without A Prescription
■ニュース ●Provigil now available in the U.S. for narcolepsy
－Feb. 16, 1999発売。 American Sleep Disorders Assn(ASDA;米国睡眠障害学会)前会長 Dr. Wolfgang Schmidt-Nowara,M.D.によると"ナルコレプシーに伴う昼間過眠症状excessive daytime sleepiness(EDS)の治療に大きな進歩"。 副作用は"mild to moderate"。 米国でのナルコレプシー患者数は125,000●Provigil launched in the U.K. for narcolepsy
－March 4, 1998。 英国でCephalon社はProvigil (modafinil)を発売。 主な副作用としては、頭痛、眩暈、下痢。 英国でのナルコレプシー患者数は"数千人"（セファロン社推計）。 米国では1993年にオーファンドラッグ指定。●Alertec approved in Canada for the treatment of narcolepsy
－カナダMARCH 3, 1999。 Health Protection Branch of Health Canadaは Alertec (modafinil)を承認。 Dr. Roger Broughton,MD（Ottawa Hospital Sleep Medicine Centre）によると、"カナダには数千人のナルコレプシー患者がいるが、本剤はQOLの改善に顕著な改善効果がある。"
●modafinil
http://www.tcn-catv.ne.jp/~kuri/modafinil.html (Size 2.1K) 更新日: 1999.02.06 Modafinil
modafinilはフランスのLaboratoire L. Lafon社で、adrafinilの後継として開発された。adrafinilと同様、ノルアドレナリンに選択的に作用するらしい。α１レセプターとの関与が示唆されている。Ritalin（塩酸メチルフェニデート）がドパミン系（ドパミンの放出促進及び再取り込み阻害を持つと考えられている）の薬であることを考えるとこの違いは興味深い。modafinilはadrafinilの改良版であるといえ、adrafinilの副作用である肝機能障害を軽減した。modafinilはadrafinil同様、ナルコレプシーの治療に用いられる。ナルコレプシーは眠り病といわれる睡眠障害である。日本では、Ritalinがナルコレプシーに対して一日最大6錠用いられるが、イギリスではそれに加えadrafinilそしてmodafinilが用いられる。modafinilはイギリスのcephalon社がイギリス、合衆国、メキシコ、オーストラリア、ならびに日本での独占販売のライセンス契約を、Laboratoire L. Lafonから得ており、もしかしたら日本でも申請されるかもしれない。ただし、cephalon社は1987年に設立されたベンチャー企業であるため、日本での申請や認可は余程のことがない限り不可能であろう。しかしナルコレプシーの治療薬としてmodafinilの認可を求める動きもみられる。商品名はProvinilで、1998年内にも合衆国で認可される予定である。現時点では、modafinilならびにadrafinilはイギリスの代理店から個人輸入が可能である。
modafinilは、リタリン同様に覚醒作用をもたらすクスリである。modafinilの薬効として抗鬱作用、記憶力増大が報告されている。処方箋に頼ることなく合法的に入手できるクスリとしては注目に値するであろう。現在はナルコレプシーの治癒として処方されているmodafinilであるが、その抗鬱作用、記憶力増大効果に関しては今のところ未知数であるといえよう。
amineptine（ドパミンを選択的に再取り込み阻害する薬、なんか凄そう....）等、アッパー系向精神薬の今後の動向には注目である。amineptineについては今後リサーチを行う予定である。（99/02/23/KuRI）
●Just IN from the FDA
Date: 12 Jan 1999, Size 77.8K, http://www.modernmedicine.com/formulary/justintro.html ●Updates reported by Formulary from week of 1/1/99
●New Molecular Entities
●Provigil.
Modafinil tablets (Provigil, Cephalon) has received FDA approval to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. Two phase III clinical trials involving more than 550 patients found modafinil, a nonamphetamine drug, to be efficacious in improving daytime wakefulness. Improvement in objective and subjective measures of excess daytime sleepiness for both the 200 mg and 400 mg doses was seen compared with placebo. Subjects treated with modafinil experienced statistically significant greater ability to remain awake, a statistically significant improvement in disease symptom severity, a statistically significant decrease in the propensity to fall asleep, and a statistically significant decreased level of daytime sleepiness. Nighttime sleep was not affected by modafinil.Adverse effects, evaluated in more than 2,200 patients, were mild to moderate in severity. Five percent of patients discontinued therapy due to an adverse event.
The most commonly reported events (more frequently reported than among placebo recipients) were headache, infection, nausea, nervousness, anxiety, and insomnia.The recommended dose is 200 mg, once daily. The drug is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Approved December 28, 1998.
●1998 Year-End FDA Drug Approvals (MDXexchange)
Date: 6 Jan 1999, Size 75.5K, http://www.micromedex.com/cmdx-c/98cfda.htm MICROMEDEX 1998 U.S. FDA Drug Approvals To Date
●Updated January 4, 1999:
●MODAFINIL
(FDA Category 1 S)
Provigil® (Cephalon) is a central nervous system stimulant.
DOSING INFORMATION: To improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy, the usual oral dose of modafinil is 200 milligrams daily, administered as a single dose in the morning.
PHARMACOKINETICS: Modafinil is rapidly absorbed after oral administration, with peak plasma concentrations occurring in 2 to 4 hours. The volume of distribution is approximately 0.9 liter/kilogram. Protein binding is approximately 60%, primarily to albumin. The major route of elimination (90%) is metabolism; a half-life of 7.5 to 15 hours has been reported.
CAUTIONS: Adverse effects of modafinil have included headache, nausea, hypersalivation, insomnia, and euphoria; blood pressure is not significantly affected, although tachycardia has occurred in some patients. Tolerance and dependence have not been reported, but this requires confirmation.
CLINICAL APPLICATIONS: Modafinil has been used with success in narcolepsy and idiopathic hypersomnia; however, comparisons of the drug with other agents used in these disorders are needed to establish its place in therapy. There is some evidence of benefits of modafinil in alcoholic organic brain syndrome.
●製品methylphenidate 塩酸メチルフェニデート
日本語版註）methylphenidate HCl (Ritalin [Novartis]) 塩酸メチルフェニデート
【別名】 【開発元】Novartis [DBR_ID]02928
【化学名】methyl alpha-phenyl-alpha-(2-piperidyl) acetate HCl ;CAS : 298-59-9
【承認】FDA申請=、FDA承認= ;【製剤】 【適応】Attention Deficit Disorders, Narcolepsy 【適応～日本】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、遷延性うつ病 【製品情報】www.ADHDinfo.com;http://www.pharma.us.novartis.com/products/name/ritalin.jsp 【添付文書】http://www.pharma.us.novartis.com/product/pi/pdf/ritalin_ritalin-sr.pdf 【EU】Ritalin 【日本】リタリン錠「チバ」／1％リタリン散「チバ」[ノバルティスファーマ]薬価基準収載年月1961年11月/販売開始年月1958年11月 【その他】
BIAM: Methylphenidate HCl ●添付文書：リタリン錠「チバ」／1％リタリン散「チバ」[ノバルティスファーマ] 日本標準商品分類番号 871179 中枢神経興奮剤 薬価基準収載年月 1961年11月 販売開始年月 1958年11月 規制区分 劇薬、向精神薬、指定医薬品、要指示医薬品 組成 １錠中塩酸メチルフェニデート 10mg；１g中塩酸メチルフェニデート 10mg 効能又は効果 ナルコレプシー 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、遷延性うつ病TC=1170 By Ciba-Geigy[SZ] In 1944
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) = FDA Application No. = Active Ingredient(s)= Company = Dosage Form/Route = Strength = - Approval Date= :Label[添付文書]|Letter[承認書]|Review
●Electronic Orange Book /2006.8.28/
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 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 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: 021284 Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE Proprietary Name : RITALIN LA [NOVARTIS] CAPSULE, EXTENDED RELEASE; ORAL 20MG,30MG,40MG Approval Date : Jun 5, 2002 Exclusivity Data : NP 6/7/2005 Patent Data : 6228398 MAY 01,2019 U-472 5837284 MAY 15,2016 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 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 : - Application Number: 018029 Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE Proprietary Name : RITALIN-SR [NOVARTIS] TABLET, EXTENDED RELEASE; ORAL 20MG Approval Date : Mar 30, 1982 Exclusivity Data : - Patent Data : - Application Number: 010187 Active Ingredient : METHYLPHENIDATE HYDROCHLORIDE Proprietary Name : RITALIN [NOVARTIS] TABLET; ORAL 5MG ,10MG,20MG Approval Date : Approved Prior to Jan 1, 1982 Exclusivity Data : - Patent Data : -
Appl
NoTE Code RLD Active
IngredientDosage Form;
RouteStrength Proprietary
NameApplicant 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 021514 Yes METHYLPHENIDATE FILM, EXTENDED RELEASE; TRANSDERMAL 10MG/9HR (1.1MG/HR) DAYTRANA SHIRE 021514 Yes METHYLPHENIDATE FILM, EXTENDED RELEASE; TRANSDERMAL 15MG/9HR (1.6MG/HR) DAYTRANA SHIRE 021514 Yes METHYLPHENIDATE FILM, EXTENDED RELEASE; TRANSDERMAL 20MG/9HR (2.2MG/HR) DAYTRANA SHIRE 021514 Yes METHYLPHENIDATE FILM, EXTENDED RELEASE; TRANSDERMAL 30MG/9HR (3.3MG/HR) DAYTRANA SHIRE 021284 BX No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 10MG RITALIN LA NOVARTIS 021284 BX No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 20MG RITALIN LA NOVARTIS 021284 BX No METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 30MG RITALIN LA NOVARTIS 021284 BX Yes METHYLPHENIDATE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE; ORAL 40MG RITALIN LA NOVARTIS 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 021419 Yes METHYLPHENIDATE HYDROCHLORIDE SOLUTION; ORAL 10MG/5ML METHYLIN MALLINCKRODT 021419 Yes METHYLPHENIDATE HYDROCHLORIDE SOLUTION; ORAL 5MG/5ML METHYLIN MALLINCKRODT 021475 Yes METHYLPHENIDATE HYDROCHLORIDE TABLET, CHEWABLE; ORAL 10MG METHYLIN MALLINCKRODT 021475 No METHYLPHENIDATE HYDROCHLORIDE TABLET, CHEWABLE; ORAL 2.5MG METHYLIN MALLINCKRODT 021475 No METHYLPHENIDATE HYDROCHLORIDE TABLET, CHEWABLE; ORAL 5MG METHYLIN MALLINCKRODT 075450 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 20MG METHYLPHENIDATE HYDROCHLORIDE ACTAVIS ELIZABETH 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 075629 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 10MG METHYLIN ER MALLINCKRODT 075629 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 20MG METHYLIN ER MALLINCKRODT 018029 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 20MG RITALIN-SR NOVARTIS 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 040410 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET, EXTENDED RELEASE; ORAL 20MG METHYLPHENIDATE HYDROCHLORIDE WATSON LABS 040321 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 10MG METHYLPHENIDATE HYDROCHLORIDE ACTAVIS ELIZABETH 040321 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 20MG METHYLPHENIDATE HYDROCHLORIDE ACTAVIS ELIZABETH 040321 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 5MG METHYLPHENIDATE HYDROCHLORIDE ACTAVIS ELIZABETH 040300 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 10MG METHYLPHENIDATE HYDROCHLORIDE MALLINCKRODT 040300 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 20MG METHYLPHENIDATE HYDROCHLORIDE MALLINCKRODT 040300 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 5MG METHYLPHENIDATE HYDROCHLORIDE MALLINCKRODT 010187 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 10MG RITALIN NOVARTIS 010187 AB Yes METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 20MG RITALIN NOVARTIS 010187 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 5MG RITALIN NOVARTIS 085799 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 10MG METHYLPHENIDATE HYDROCHLORIDE UCB INC 086428 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 20MG METHYLPHENIDATE HYDROCHLORIDE UCB INC 086429 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 5MG METHYLPHENIDATE HYDROCHLORIDE UCB INC 040220 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 10MG METHYLPHENIDATE HYDROCHLORIDE WATSON LABS 040220 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 20MG METHYLPHENIDATE HYDROCHLORIDE WATSON LABS 040220 AB No METHYLPHENIDATE HYDROCHLORIDE TABLET; ORAL 5MG METHYLPHENIDATE HYDROCHLORIDE WATSON LABS
■メーカー情報
●ノバルティス
●Novartis製品情報：リタリン - 添付文書|使用上の注意改訂のお知らせ|くすりのしおリ|製剤写真|過量投与情報| 適正使用情報|再審査・再評価結果 を公開
●Novartis - http://www.novartis.com/ Ritalin Hydrochloride (methylphenidate hydrochloride tablets, USP) Integral part of total treatment program for a stabilizing effect in ADHD/ADD www.ADHDinfo.com (US residents only) Ritalin LA (methylphenidate hydrochloride extended-release capsules) Integral part of total treatment program for a stabilizing effect in ADHD/ADD www.ADHDinfo.com (US residents only) Ritalin SR (methylphenidate hydrochloride sustained-release tablets, USP) Integral part of total treatment program for a stabilizing effect in ADHD/ADD www.ADHDinfo.com (US residents only)
●Novartis -US Data Presented At APA Meeting Suggest RitalinR La (Methylphenidate Hydrochloride)
Extended-Release Capsules Are An Effective Once-Daily Treatment For ADHD[2002.5.22] - http://www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=283 ●Novartis-US Press Release ★Ritalin® Hydrochloride関連
●一般サイト
●安全性問題 Ritalin foes lose two rounds against drug maker, APA[2001.6.11] - http://www.ama-assn.org/sci-pubs/amnews/pick_01/gvsc0611.htm Ritalinの副作用に関する訴訟 Ritalin In The News - http://www.resultsproject.net/in_the_news.html ●リタリン - http://www.dango.ne.jp/nofuture/ritalin.html bytes, 1998/04/26 ●◎新採用薬紹介：リタリン錠 10mg, 1997/07/28 - 本剤は白色の裸錠で、１錠中に塩酸メチルフェニデート10mgを含有する。 中枢神経 興奮作用を有し、軽症うつ病、抑うつ神経症及びナルコレプシー(睡眠発作)の治療に用い られる。［略］国立療養所愛媛病院 薬剤科 ●リタリンの添付文書改訂について [適応]ナルコレプシー 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［略］
●他の製品
■pemoline ペモリン 日本語版註）pemoline (Cylert[Abbott]) ペモリン
【別名】phenyl-5-isohydantoin; LA 956 【開発元】Abbott [DBR_ID]02588
【化学名】imino-2 phenyl-5 oxazolidinone-4
【承認】FDA申請=、FDA承認= ,Oct-1998[ADHD追加];【製剤】 【適応】Attention Deficit Hyperactivity Disorder (ADHD). 【適応～日本】(1) 軽症うつ病、抑うつ神経症 (2) 次の疾患に伴う睡眠発作、傾眠傾向、精神的弛緩の改善：ナルコレプシー、ナルコレプシーの近縁傾眠疾患 【製品情報】 【添付文書】[RxList] Pemoline 【EU】 【日本】ベタナミン錠[三和化学研究所]薬価基準収載年月=1969年1月[錠]、1981年9月[錠25mg,錠50mg] 販売開始年月=1969年1月[錠]、1981年9月[錠25mg,錠50mg] 【その他】
MEDLINEplus Drug Information: Pemoline MEDLINEplus Drug Information: Pemoline(Systemic) BIAM: Pemoline ●添付文書：ベタナミン錠／ベタナミン錠25mg／ベタナミン錠50mg[株式会社三和化学研究所] 日本標準商品分類番号 871179 薬価基準収載年月 1969年1月[錠]、1981年9月[錠25mg,錠50mg] 販売開始年月 1969年1月[錠]、1981年9月[錠25mg,錠50mg] 規制区分 向精神薬、指定医薬品、要指示医薬品 組成 1錠中、ペモリン10mg、25mg、50mgを含有する製剤 効能又は効果 ベタナミン錠 (1) 軽症うつ病、抑うつ神経症 (2) 次の疾患に伴う睡眠発作、傾眠傾向、精神的弛緩の改善 ナルコレプシー、ナルコレプシーの近縁傾眠疾患 ベタナミン錠25mg、ベタナミン錠50mg 次の疾患に伴う睡眠発作、傾眠傾向、精神的弛緩の改善 ナルコレプシー、ナルコレプシーの近縁傾眠疾患TC=1330 DC=*****
AZOXODONE;BETANAMIN[;SANWA];CENTRAMIN ｾﾝﾄﾗﾐﾝ;CYLERT;DEADYN;DETAMINE;KETHAMED;LA956;MYAMIN ﾏｲｱﾐﾝ;PEMOLINE[INN][USAN][BAN][DCF][NFN][FDA];PHENIMINOOXAZOLIDINONE;PHENOXAZOLE;PHENYLISOHYDANTOIN;PHENYLPSEUDOHYDANTOIN;PIO;PSICOBLITZ;PSICODELTA;RONYL;SIGMADYN;STIMUL;TRADON;VOLITAL;YHL;ｾﾝﾄﾗﾐﾝ;ﾍﾞﾀﾅﾐﾝ;ﾍﾟﾓﾘﾝ;ﾏｲｱﾐﾝ
《JA》MYAMIN ﾏｲｱﾐﾝ（大日本製薬㈱）11-60＊(DISC∥CENTRAMIN ｾﾝﾄﾗﾐﾝ（吉富製薬㈱）11-60＊(DISC∥《US》CYLERT（ABBOTT LABS）03-75＊∥《UK》CYLERT（ABBOTT LABS）07-75＊∥RONYL（RONA LABS）-62＊∥VOLITAL（APPLIED BIOL）-63＊∥KETHAMED（MEDO CHEM）-60＊∥《FR》DETAMINE（ARON SARL,LABS）-60＊∥《WG》STIMUL（NADROL）10-66＊∥TRADON（BEIERSDORF AG）-58＊∥《IT》DEADYN（DE ANGELI S.P.A.,IST）-61＊(W+LEVO∥PSICOBLITZ（VON BOCH IST FARM）-65＊(W+LEVO∥PSICODELTA（CHIESI FARM SPA）-67＊(W+LEVO∥SIGMADYN（SPEMSA）-62＊(LIC FO【日本語版コメント】 Cylertはナルコレプシー治療薬として、かつて繁用されたものの、肝臓毒性のため 使われなくなった。[MedWatch Safety Summaries - Cylert] その代替えとしてはRitalinが使われた。
●承認データ：FDA
情報ソース●DDPA April 1996 16-832 CYLERT ABBOTT PEMOLINE 11-APR-96 (TABLET) ABBOTT PARK, IL 18.75MG 60064 37.5MG 75MG (LABELING REVISION -- OVERDOSAGE) 17-703 CYLERT ABBOTT PEMOLINE 11-APR-96 (TABLET, CHEWABLE) ABBOTT PARK, IL 37.5MG 60064 (LABELING REVISION -- OVERDOSAGE) 情報ソース●1997 New Drug Application (NDA) Cylert Tablets/Pemoline Abbott Laboratories 16832/S013 承認12/12/1997 Post=10/23/1998 Cylert Tablets/Pemoline Abbott Laboratories 16832/S015 承認12/12/1997 Post=10/23/1998 情報ソース●FDA Drug Approvals List May 1999 Application #: 016832 Labeling Supplement#: 018 To Original New Drug Application Approval Date: 28-MAY-99 Trade Name: CYLERT Dosage Form: TABLET Applicant: ABBOTT LABORATORIES PHARMACEUTICAL PRODUCTS DIV Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●Drug Approvals for December 1997 Application #: 016832 Labeling Supplement#: 015 To Original New Drug Application Approval Date: 12-DEC-97 Trade Name: CYLERT Dosage Form: TABLET Applicant: ABBOTT LABORATORIES PHARMACEUTICAL PRODUCTS DIV Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●FDA Drug Approvals List March 2001 Original Abbreviated Application # 075726 Approval Date: 30-MAR-01 Trade Name: PEMOLINE Dosage Form: TABLET Applicant: MALLINCKRODT INC Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●FDA Drug Approvals List July 2000 Original Abbreviated Application # 075678 Approval Date: 26-JUL-00 Trade Name: PEMOLINE Dosage Form: TABLET Applicant: AMIDE PHARMACEUTICAL INC Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●FDA Drug Approvals List April 2000 Original Abbreviated Application # 075328 Approval Date: 19-APR-00 Trade Name: PEMOLINE Dosage Form: TABLET Applicant: VINTAGE PHARMACEUTICALS INC Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●FDA Drug Approvals List February 2000 Original Abbreviated Application # 075555 Approval Date: 18-FEB-00 Trade Name: PEMOLINE Dosage Form: TABLET, CHEWABLE Applicant: COPLEY PHARMACEUTICAL, INC Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●FDA Drug Approvals List June 1999 Original Abbreviated Application # 075286 Approval Date: 30-JUN-99 Trade Name: PEMOLINE Dosage Form: TABLET Applicant: INVAMED INC Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●FDA Drug Approvals List January 1999 Original Abbreviated Application # 075030 Approval Date: 29-JAN-99 Trade Name: PEMOLINE Dosage Form: TABLET Applicant: COPLEY PHARMACEUTICAL INC Active Ingredient(s): PEMOLINE OTC/RX Status: RX 情報ソース●Drug Approvals - C Cylert Chewable Tablets (Pemoline), 18.75, 37.5 mg, and 75 mg Abbott Laboratories Application #=NDA 16-832/ S-016 Approval Date=5/8/98 Letter Posted= Label Posted = Review Posted=10/23/98 Cylert Chewable Tablets (Pemoline), 37.5 mg Abbott Laboratories Application #=NDA 17-703/ S-014 Approval Date=5/13/98 Letter Posted= Label Posted = Review Posted=10/23/98 Cylert Indication: Treatment of Attention Deficit Disorder 情報ソース●Drug Approvals - P Pemoline Tablets, 18.75 mg, 37.5 mg, and 75 mg, Rx only Mallinckrodt, Inc. Application #=ANDA 75-726 Approval Date=3/30/01 Letter Posted=4/2/01 Label Posted = Review Posted= Pemoline Chewable Tablets, 37.5 mg, Rx Amide Pharmaceutical, Inc. Application #=ANDA 75-678 Approval Date=7/26/00 Letter Posted=11/7/00 Label Posted = Review Posted= Pemoline Chewable Tablets, 37.5 mg, Rx Copley Pharamceutical, Inc Application #=ANDA 75-555 Approval Date=2/18/00 Letter Posted=2/24/00 Label Posted = Review Posted= Pemoline Tablets, 18.75 mg, 37.5 mg & 75 mg., Rx Amide Pharmaceutical, Inc. Application #=ANDA 75-595 Approval Date=2/28/00 Letter Posted=2/29/00 Label Posted = Review Posted= Pemoline Tablets, 18.75 mg, 37.5 mg, 75 mg, Rx Vintage Pharmaceuticals Inc. Application #=ANDA 75-328 Approval Date=4/19/00 Letter Posted=4/24/00 Label Posted = Review Posted= Pemoline Tablets, 37.5 mg & 75 mg., Rx Watson Laboratories Inc. Application #=ANDA 75-287 Approval Date=9/18/00 Letter Posted=10/30/00 Label Posted = Review Posted= Pemoline Tablets, 37.5 mg & 75 mg. Invamed Inc Application #=ANDA 75-286 Approval Date=6/30/99 Letter Posted=7/2/99 Label Posted = Review Posted= Pemoline Tablets, 37.5 mg, and 75 mg, Rx only Copley Pharmaceutical, Inc Application #=ANDA 75-030 Approval Date=1/29/99 Letter Posted=1/29/99 Label Posted = Review Posted=
●Electronic Orange Book
updated : May 4,2004 Application Number: 017703 Active Ingredient : PEMOLINE Proprietary Name : CYLERT [ABBOTT] TABLET, CHEWABLE; ORAL 37.5MG Approval Date : Approved Prior to Jan 1, 1982 Exclusivity Data : - Patent Data : - Application Number: 016832 Active Ingredient : PEMOLINE Proprietary Name : CYLERT [ABBOTT] TABLET; ORAL 18.75MG ,37.5MG,75MG Approval Date : Exclusivity Data : Patent Data :
Appl
NoTE Code RLD Active
IngredientDosage Form;
RouteStrength Proprietary
NameApplicant 017703 AB Yes PEMOLINE TABLET, CHEWABLE; ORAL 37.5MG CYLERT ABBOTT 075678 AB No PEMOLINE TABLET, CHEWABLE; ORAL 37.5MG PEMOLINE AMIDE PHARM 075555 AB No PEMOLINE TABLET, CHEWABLE; ORAL 37.5MG PEMOLINE COPLEY PHARM 016832 AB Yes PEMOLINE TABLET; ORAL 18.75MG CYLERT ABBOTT 016832 AB No PEMOLINE TABLET; ORAL 37.5MG CYLERT ABBOTT 016832 AB Yes PEMOLINE TABLET; ORAL 75MG CYLERT ABBOTT 075595 AB No PEMOLINE TABLET; ORAL 18.75MG PEMOLINE AMIDE PHARM 075595 AB No PEMOLINE TABLET; ORAL 37.5MG PEMOLINE AMIDE PHARM 075595 AB No PEMOLINE TABLET; ORAL 75MG PEMOLINE AMIDE PHARM 075030 AB No PEMOLINE TABLET; ORAL 18.75MG PEMOLINE COPLEY PHARM 075030 AB No PEMOLINE TABLET; ORAL 37.5MG PEMOLINE COPLEY PHARM 075030 AB No PEMOLINE TABLET; ORAL 75MG PEMOLINE COPLEY PHARM 075726 AB No PEMOLINE TABLET; ORAL 18.75MG PEMOLINE MALLINCKRODT 075726 AB No PEMOLINE TABLET; ORAL 37.5MG PEMOLINE MALLINCKRODT 075726 AB No PEMOLINE TABLET; ORAL 75MG PEMOLINE MALLINCKRODT 075286 AB No PEMOLINE TABLET; ORAL 18.75MG PEMOLINE SANDOZ 075286 AB No PEMOLINE TABLET; ORAL 37.5MG PEMOLINE SANDOZ 075286 AB No PEMOLINE TABLET; ORAL 75MG PEMOLINE SANDOZ 075328 AB No PEMOLINE TABLET; ORAL 18.75MG PEMOLINE VINTAGE PHARMS 075328 AB No PEMOLINE TABLET; ORAL 37.5MG PEMOLINE VINTAGE PHARMS 075328 AB No PEMOLINE TABLET; ORAL 75MG PEMOLINE VINTAGE PHARMS 075287 AB No PEMOLINE TABLET; ORAL 18.75MG PEMOLINE WATSON LABS 075287 AB No PEMOLINE TABLET; ORAL 37.5MG PEMOLINE WATSON LABS 075287 AB No PEMOLINE TABLET; ORAL 75MG PEMOLINE WATSON LABS
●Abbott Labs
- http://abbott.com/ ●News & Media Center ●CylertはAbbott社取り扱い品目だが、医薬品添付文書は同社サイト内にはない。
●ニュース[1997.3.17 米国、ペモリンのドクターレター！！]
http://www.nichiyaku.or.jp/news/N960317.HTM
Ｆ－Ｄ－Ｃ Ｒｅｐｏｒｔｓ（Ｔｈｅ Ｐｉｎｋ Ｓｈｅｅｔ）の１月２７日号によると、アボット社が、米国で注意力欠損傷害に使われるペモリンの致死的肝障害に関してドクターレターを出したということです。
このペモリンは、１９７５年に市販されて以来、１３例の急性肝不全に関する報告がＦＤＡになされており、うち１１例は徴候があらわれてから４週間以内に死または肝移植の経緯をたどっています。このことから、ドクターレターでこの適応では通常、第一次選択薬としないこと、また使用したとしても使用中に臨床上の肝障害が認められたときには薬を中止することなどの注意喚起がなされたようです。
このペモリンは、軽症のうつ病やナルコレプシー等による睡眠発作、傾眠傾向、精神的弛緩の改善の効能で日本でも医療用医薬品として承認されています。使用にあたっては治療前から治療中を通して継続的に肝機能検査を実施し、肝障害の発現に十分注意する必要がありそうです。
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- 作成：1999.4.1 最終更新:2008.5.19 小菅博之
The Medical Letter日本語版
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On Drugs and Therapeutics
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