17 PATIENT COUNSELING INFORMATION
DARZALEX 20 mg/mL concentrate for solution for infusion daratumumab
6. Contents of the pack and other information What DARZALEX contains
x The active substance is daratumumab. One mL of concentrate contains 20 mg daratumumab.
Each vial of 5 mL concentrate contains 100 mg of daratumumab. Each vial of 20 mL concentrate contains 400 mg of daratumumab.
x The other ingredients are glacial acetic acid, mannitol (E421), polysorbate 20, sodium acetate trihydrate, sodium chloride and water for injections (see “DARZALEX contains sodium” in section 2).
What DARZALEX looks like and contents of the pack
DARZALEX is a concentrate for solution for infusion and is a colourless to yellow liquid.
DARZALEX is supplied as a carton pack containing 1 glass vial.
Marketing Authorisation Holder Janssen-Cilag International NV Turnhoutseweg 30
B-2340 Beerse Belgium Manufacturer
Janssen Biologics B.V.
Einsteinweg 101 NL-2333 CB Leiden The Netherlands
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Janssen-Cilag NV Antwerpseweg 15-17 B-2340 Beerse
Tel/Tél: +32 14 64 94 11
Lietuva
UAB "JOHNSON & JOHNSON"
Geležinio Vilko g. 18A LT-08104 Vilnius Tel: +370 5 278 68 88 Ȼɴɥɝɚɪɢɹ
ÄȾɠɨɧɫɴɧ ȾɠɨɧɫɴɧȻɴɥɝɚɪɢɹ´ȿɈɈȾ ɠɤɆɥɚɞɨɫɬ
Ȼɢɡɧɟɫɉɚɪɤɋɨɮɢɹɫɝɪɚɞɚ ɋɨɮɢɹ
Ɍɟɥ
Luxembourg/Luxemburg Janssen-Cilag NV
Antwerpseweg 15-17 B-2340 Beerse Belgique/Belgien
Tél/Tel: +32 14 64 94 11
ýHVNiUHSXEOLND Janssen-Cilag s.r.o.
Karla Engliše 3201/06 CZ-150 00 Praha 5 - Smíchov Tel.: +420 227 012 227
Magyarország Janssen-Cilag Kft.
Nagyenyed u. 8-14 H-Budapest, 1123 Tel.: +36 1 884 2858 Danmark
Janssen-Cilag A/S Bregnerødvej 133 DK-3460 Birkerød Tlf: +45 45 94 82 82
Malta
AM MANGION LTD.
0DQJLRQ%XLOGLQJ7ULTƤGLGDIL7ULT9DOOHWWD MT-ƪDO-Luqa LQA 6000
Tel: +356 2397 6000 Deutschland
Janssen-Cilag GmbH Johnson & Johnson Platz 1 D-41470 Neuss
Tel: +49 2137 955 955
Nederland
Janssen-Cilag B.V.
Graaf Engelbertlaan 75 NL-4837 DS Breda Tel: +31 76 711 1111 Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal Lõõtsa 2
EE-11415 Tallinn Tel: +372 617 7410
Norge
Janssen-Cilag AS Postboks 144 NO-1325-Lysaker Tlf: +47 24 12 65 00 ǼȜȜȐįĮ
Janssen-CilagĭĮȡȝĮțİȣIJȚțȒǹǼǺǼ ȁİȦijȩȡȠȢǼȚȡȒȞȘȢ
GR-ȆİȪțȘǹșȒȞĮ TȘȜ
Österreich
Janssen-Cilag Pharma GmbH Vorgartenstraße 206B A-1020 Wien
Tel: +43 1 610 300 España
Janssen-Cilag, S.A.
Paseo de las Doce Estrellas, 5-7 E-28042 Madrid
Tel: +34 91 722 81 00
Polska
Janssen-Cilag Polska Sp. z o.o.
XO,áĪHFND
PL-02-135 Warszawa Tel.: +48 22 237 60 00 France
Janssen-Cilag
1, rue Camille Desmoulins, TSA 91003 F-92787 Issy Les Moulineaux, Cedex 9 Tél: 0 800 25 50 75 / +33 1 55 00 40 03
Portugal
Janssen-Cilag Farmacêutica, Lda.
Estrada Consiglieri Pedroso, 69 A Queluz de Baixo
PT-2734-503 Barcarena Tel: +351 21 43 68 835 Hrvatska
Johnson & Johnson S.E. d.o.o.
2UHãNRYLüHYDK 10010 Zagreb
Tel: +385 1 6610 700
România
Johnson & Johnson România SRL Str. Tipografilor nr. 11-15
&OăGLUHD6-Park, Corp B3-B4, Etaj 3
%XFXUHúWL520Æ1,$
Tel: +40 21 207 1800
Ireland
Janssen-Cilag Ltd.
50-100 Holmers Farm Way High Wycombe
Buckinghamshire HP12 4EG United Kingdom
Tel: +44 1 494 567 444
Slovenija
Johnson & Johnson d.o.o.
Šmartinska cesta 53 SI-1000 Ljubljana Tel: +386 1 401 18 30
Ísland
Janssen-Cilag AB c/o Vistor hf.
Hörgatúni 2 IS-210 Garðabær Sími: +354 535 7000
Slovenská republika Johnson & Johnson, s.r.o.
CBC III,.DUDGåLþRYD SK-821 08 Bratislava Tel: +421 232 408 400
Italia
Janssen-Cilag SpA Via M.Buonarroti, 23
I-20093 Cologno Monzese MI Tel: +39 02 2510 1
Suomi/Finland Janssen-Cilag Oy
Vaisalantie/Vaisalavägen 2 FI-02130 Espoo/Esbo Puh/Tel: +358 207 531 300 ȀȪʌȡȠȢ
ǺĮȡȞȐȕĮȢȋĮIJȗȘʌĮȞĮȖȒȢȁIJį ȁİȦijȩȡȠȢīȚȐȞȞȠȣȀȡĮȞȚįȚȫIJȘ ȁĮIJıȚȐ
CY-ȁİȣțȦıȓĮ ȉȘȜ
Sverige
Janssen-Cilag AB Box 4042
SE-169 04 Solna Tel: +46 8 626 50 00
Latvija
UAB "JOHNSON & JOHNSON"ILOLƗOH/DWYLMƗ Mnjkusalas iela 101
RƯJD/91004 Tel: +371 678 93561
United Kingdom Janssen-Cilag Ltd.
50-100 Holmers Farm Way High Wycombe
Buckinghamshire HP12 4EG - UK Tel: +44 1 494 567 444
This leaflet was last revised in MM/YYYY.
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.
---The following information is intended for healthcare professionals only:
This medicinal product is for single-use only.
Prepare the solution for infusion using aseptic technique as follows:
x Calculate the dose (mg), total volume (mL) of DARZALEX solution required and the number of DARZALEX vials needed based on patient weight.
x Check that the DARZALEX solution is colourless to yellow. Do not use if opaque particles, discolouration or other foreign particles are present.
x Using aseptic technique, remove a volume of 0.9% Sodium Chloride from the infusion bag/container that is equal to the required volume of DARZALEX solution.
x Withdraw the necessary amount of DARZALEX solution and dilute to the appropriate volume by adding to an infusion bag/container containing 0.9% Sodium Chloride. Infusion
bags/containers must be made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE) or polyolefin blend (PP+PE). Dilute under appropriate aseptic conditions. Discard any unused portion left in the vial.
x Gently invert the bag/container to mix the solution. Do not shake.
x Visually inspect parenteral medicinal products for particulate matter and discolouration prior to administration. The diluted solution may develop very small, translucent to white proteinaceous particles, as daratumumab is a protein. Do not use if visibly opaque particles, discolouration or foreign particles are observed.
x Since DARZALEX does not contain a preservative, diluted solutions should be administered within 15 hours (including infusion time) at room temperature (15°C - 25°C) and in room light.
x If not used immediately, the diluted solution can be stored prior to administration for up to 24 hours at refrigerated conditions (2°C - 8°C) and protected from light. Do not freeze.
x Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used.
x Do not infuse DARZALEX concomitantly in the same intravenous line with other agents.
x Do not store any unused portion of the infusion solution for reuse. Any unused product or waste material should be disposed of in accordance with local requirements.
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
1.7 ྠ✀ྠຠရ୍ぴ⾲
⏦ㄳࡍࡿ⸆ࡢ୍ぴ⾲ࢆ㸪⾲ 1.7-1♧ࡍࠋࡲࡓ㸪⌧ᅾᅜෆ࡛⏝ࡉࢀ࡚࠸ࡿ࡞ྠ✀ྠຠရ ࡢ୍ぴ⾲ࢆ㸪⾲ 1.7-2~ ⾲ 1.7-9♧ࡍࠋ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
⾲ 1.7-1 ⏦ㄳࡍࡿ⸆
୍⯡ⓗྡ⛠ ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧
㈍ྡ ࢲࣛࢨࣞࢵࢡࢫⅬ㟼ὀ100mg ࢲࣛࢨࣞࢵࢡࢫⅬ㟼ὀ400mg
♫ྡ ࣖࣥࢭࣥࣇ࣮࣐ᰴᘧ♫
ᢎㄆᖺ᭶᪥➼
つไ༊ศ ⏕≀⏤᮶〇ရ㸪⸆㸪ฎ᪉⟢་⸆ရ
Ꮫᵓ㐀ᘧ ࣄࢺCD38 ᑐࡍࡿ㑇ఏᏊ⤌࠼ࣄࢺIgG1 ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡿࠋࢳࣕࢽ
࣮ࢬࣁ࣒ࢫࢱ࣮༸ᕢ⣽⬊ࡼࡾ⏘⏕ࡉࢀࡿ452ಶࡢ࣑ࣀ㓟ṧᇶࡽ࡞ࡿH 㙐2 ᮏཬࡧ214ಶࡢ࣑ࣀ㓟ṧᇶࡽ࡞ࡿL 㙐2 ᮏ࡛ᵓᡂࡉࢀࡿ⢾ࢱࣥࣃࢡ㉁࡛࠶
ࡿࠋ
ᆺ㺃ྵ㔞 ࢲࣛࢨࣞࢵࢡࢫⅬ㟼ὀ100mg㸸ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧100mg㸦1 ࣂ
ࣝ୰㸧
ࢲࣛࢨࣞࢵࢡࢫⅬ㟼ὀ400mg㸸ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧400mg㸦1 ࣂ
ࣝ୰㸧
ຠ⬟㺃ຠᯝ Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘
ࠓຠ⬟࣭ຠᯝ㛵㐃ࡍࡿ⏝ୖࡢὀពࠔ
1. ᮏࡼࡿ⒪ࡣࠊᑡ࡞ࡃࡶ1 ࡘࡢᶆ‽ⓗ࡞⒪ࡀ↓ຠཪࡣ⒪ᚋⓎ
ࡋࡓᝈ⪅ࢆᑐ㇟ࡍࡿࡇࠋ
2. ⮫ᗋヨ㦂⤌ࡳධࢀࡽࢀࡓᝈ⪅ࡢ๓⒪Ṕ➼ࡘ࠸࡚ࠊࠕ⮫ᗋᡂ⦼ࠖࡢ㡯ࡢ ෆᐜࢆ⇍▱ࡋࠊᮏࡢ᭷ຠᛶཬࡧᏳᛶࢆ༑ศ⌮ゎࡋࡓୖ࡛ࠊ㐺ᛂᝈ⪅ࡢ㑅 ᢥࢆ⾜࠺ࡇࠋ
⏝ἲ㺃⏝㔞 ㏻ᖖࠊᡂேࡣࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧ࡋ࡚ࠊ1ᅇ16 mg/kgࢆ௨ୗࡢᢞ
㛫㝸࡛Ⅼ㟼ὀࡍࡿࠋ
ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࡢሙྜ㸸
1㐌㛫㛫㝸㸦1㹼8㐌┠㸧ࠊ2㐌㛫㛫㝸㸦9㹼24㐌┠㸧ཬࡧ4㐌㛫㛫㝸㸦25㐌┠௨ 㝆㸧
࣎ࣝࢸࢰ࣑ࣈཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࡢሙྜ㸸
1㐌㛫㛫㝸㸦1㹼9㐌┠㸧ࠊ3㐌㛫㛫㝸㸦10㹼24㐌┠㸧ཬࡧ4㐌㛫㛫㝸㸦25㐌┠௨ 㝆㸧
⏝ἲ㺃⏝㔞
㛵㐃ࡍࡿ
⏝ୖࡢὀព
1. ᮏࢆ༢⊂ᢞࡋࡓሙྜࡢ᭷ຠᛶཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
2. ᮏࡢᢞ㛫㝸ࠊᮏే⏝ࡍࡿᢠᝏᛶ⭘⒆➼ࡘ࠸࡚ࠊࠕ⮫ᗋᡂ⦼ࠖࡢ㡯ࡢ ෆᐜࢆ⇍▱ࡋࡓୖ࡛㑅ᢥࡍࡿࡇࠋࡲࡓࠊే⏝⸆ࡢῧᩥ᭩ࢆ⇍ㄞࡍࡿࡇࠋ 3. ᮏᢞࡼࡿinfusion reactionࢆ㍍ῶࡉࡏࡿࡓࡵࠊᮏᢞ㛤ጞ1㹼3㛫๓
⭈⓶㉁࣍ࣝࣔࣥࠊゎ⇕㙠③ཬࡧᢠࣄࢫࢱ࣑ࣥࢆᢞࡍࡿࡇࠋࡲࡓࠊ㐜
Ⓨᛶࡢinfusion reactionࢆ㍍ῶࡉࡏࡿࡓࡵࠊᚲせᛂࡌ࡚ᮏᢞᚋ⭈⓶
㉁࣍ࣝࣔࣥ➼ࢆᢞࡍࡿࡇࠋ࡞࠾ࠊ៏ᛶ㛢ሰᛶ⫵ᝈⱝࡋࡃࡣẼ⟶ᨭႍᜥࡢ࠶
ࡿᝈ⪅ཪࡣࡑࢀࡽࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅ࡣࠊᮏࡢᢞᚋฎ⨨ࡋ࡚Ẽ⟶ᨭᣑᙇ
⸆ཬࡧ྾ධࢫࢸࣟࢻ⸆ࡢᢞࢆ⪃៖ࡍࡿࡇࠋ
4. ᮏࡣ⏕⌮㣗ሷᾮࢆ⏝࠸࡚ᕼ㔘ᚋࡢ⥲㔞ࢆ1,000 mLࡋࠊ50mL/ࡢᢞ㏿ᗘ࡛
Ⅼ㟼ὀࢆ㛤ጞࡍࡿࠋInfusion reactionࡀㄆࡵࡽࢀ࡞ࡗࡓሙྜࡣࠊᝈ⪅ࡢ≧ែ
ࢆほᐹࡋ࡞ࡀࡽᕼ㔘ᚋࡢ⥲㔞ཬࡧᢞ㏿ᗘࢆ௨ୗࡢࡼ࠺ኚ᭦ࡍࡿࡇࡀ࡛ࡁ
ࡿࠋࡓࡔࡋࠊᢞ㏿ᗘࡢୖ㝈ࡣ200mL/ࡍࡿࠋ
ᮏࡢᕼ㔘ᚋࡢ⥲㔞ཬࡧᢞ㏿ᗘ
ᢞᮇ ᕼ㔘ᚋࡢ⥲㔞 ᢞ㛤ጞࡽࡢᢞ㏿ᗘ㸦mL/㸧 0㹼1㛫 1㹼2㛫 2㹼3㛫 3㛫௨㝆
ึᅇᢞ 1,000mL
50 100 150 200 2ᅇ┠ᢞ 500mL*1
3ᅇ┠ᢞ௨㝆 500mL*1 100*2 150 200
*1㸸ึᅇᢞ㛤ጞࡽ3㛫௨ෆinfusion reactionࡀㄆࡵࡽࢀ࡞ࡗࡓሙྜࠊ 500mLࡍࡿࡇࡀ࡛ࡁࡿࠋ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧
*2㸸ึᅇཬࡧ2ᅇ┠ᢞ᭱⤊㏿ᗘࡀ100mL/௨ୖ࡛infusion reactionࡀㄆࡵࡽࢀ
࡞ࡗࡓሙྜࠊ100mL/ࡽ㛤ጞࡍࡿࡇࡀ࡛ࡁࡿࠋ
5. Infusion reactionࡀⓎ⌧ࡋࡓሙྜࠊ௨ୗࡢࡼ࠺ࠊᮏࡢᢞ୰᩿ࠊ୰Ṇࠊᢞ㏿
ᗘࡢኚ᭦➼ࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ࡞࠾ࠊGradeࡣNCI-CTCAE v4.0‽ࡌ
ࡿࠋ
1) Grade 1㹼3㸸ᮏࡢᢞࢆ୰᩿ࡍࡿࡇࠋInfusion reactionࡀᅇࡋࡓሙྜ
ࡣࠊinfusion reactionⓎ⌧ࡢ༙ศ௨ୗࡢᢞ㏿ᗘ࡛ᢞࢆ㛤ࡍࡿࡇࡀ࡛ࡁ
ࡿࠋInfusion reactionࡢⓎࡀㄆࡵࡽࢀ࡞ࡗࡓሙྜࡣࠊୖグࡢ⾲ ࠕᮏࡢᕼ 㔘ᚋࡢ⥲㔞ཬࡧᢞ㏿ᗘࠖࢆཧ↷ࡋࠊᢞ㏿ᗘࢆኚ᭦ࡍࡿࡇࡀ࡛ࡁࡿࠋࡓ ࡔࡋࠊGrade 3ࡢinfusion reactionࡀ3ᅇⓎ⌧ࡋࡓሙྜࡣᮏࡢᢞࢆ୰Ṇࡍࡿ
ࡇࠋ
2) Grade 4㸸ᮏࡢᢞࢆ୰Ṇࡍࡿࡇࠋ
⏝ୖࡢὀព
࠙㆙ ࿌ࠚ
ᮏࡢᢞࡣࠊ⥭ᛴ༑ศᑐᛂ࡛ࡁࡿ་⒪タ࠾࠸࡚ࠊ㐀⾑ჾᝏᛶ⭘⒆ࡢ
⒪ᑐࡋ࡚༑ศ࡞▱㆑࣭⤒㦂ࢆᣢࡘ་ᖌࡢࡶ࡛ࠊᮏࡢᢞࡀ㐺ษุ᩿
ࡉࢀࡿࡢࡳ⾜࠺ࡇࠋࡲࡓࠊ⒪㛤ጞඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘᭷
ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ࡚ࡽᢞࢆ㛤ጞࡍࡿࡇࠋ
࠙⚗ᚷ㸦ḟࡢᝈ⪅ࡣᢞࡋ࡞࠸ࡇ㸧ࠚ ᮏࡢᡂศᑐࡋ㐣ᩄࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
࠙⏝ୖࡢὀពࠚ
1㸬ៅ㔜ᢞ㸦ḟࡢᝈ⪅ࡣៅ㔜ᢞࡍࡿࡇ㸧
៏ᛶ㛢ሰᛶ⫵ᝈⱝࡋࡃࡣẼ⟶ᨭႍᜥࡢ࠶ࡿᝈ⪅ཪࡣࡑࢀࡽࡢ᪤ Ṕࡢ࠶ࡿᝈ
⪅㹙ᮏᢞᚋ㐜ⓎᛶࢆྵࡴẼ⟶ᨭ②ᨥࡢⓎ⌧ࣜࢫࢡࡀ㧗ࡃ࡞ࡿ࠾ࡑࢀࡀ࠶
ࡿࠋ㹛
2㸬㔜せ࡞ᇶᮏⓗὀព
1) ᮏᢞࡼࡾࠊࢼࣇࣛ࢟ࢩ࣮ࠊ㰯㛢ࠊတႿࠊᝏᐮࠊẼ⟶ᨭ②ᨥࠊప㓟
⣲ࠊ྾ᅔ㞴➼ࡢinfusion reactionࡀሗ࿌ࡉࢀ࡚࠾ࡾࠊከࡃࡢሙྜࡣࠊึᅇ ᢞⓎ⌧ࡀㄆࡵࡽࢀࡓࡀࠊ2ᅇ┠௨㝆ࡢᢞࡶㄆࡵࡽࢀ࡚࠸ࡿࠋᮏ
ᢞ୰ࡣࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢ ᢞࢆ୰᩿ཪࡣ୰Ṇࡋ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡶࠊ≧ࡀᅇࡍࡿࡲ࡛ᝈ⪅
ࡢ≧ែࢆ༑ศほᐹࡍࡿࡇࠋ㸦ࠕ⏝ἲ࣭⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀពࠖࠊ ࠕ㔜࡞స⏝ࠖࡢ㡯ཧ↷㸧
2) ዲ୰⌫ῶᑡࠊ⾑ᑠᯈῶᑡཬࡧࣜࣥࣃ⌫ῶᑡ➼ࡢ㦵㧊ᢚไࡀ࠶ࡽࢃࢀࡿࡇࡀ
࠶ࡿࡢ࡛ࠊᮏࡢᢞ๓ཬࡧᢞ୰ࡣࠊᐃᮇⓗ⾑ᾮ᳨ᰝ➼ࢆ⾜࠸ࠊᝈ⪅ࡢ
≧ែࢆ༑ศほᐹࡍࡿࡇࠋ㸦ࠕ㔜࡞స⏝ࠖࡢ㡯ཧ↷㸧
3) ᮏࡣࠊ㉥⾑⌫ୖⓎ⌧ࡋ࡚࠸ࡿCD38⤖ྜࡋࠊ㛫᥋ࢡ࣮࣒ࢫヨ㦂⤖ᯝࡀ ഇ㝧ᛶ࡞ࡿྍ⬟ᛶࡀ࠶ࡿࠋᙜヱᖸ΅ࡣᮏ᭱⤊ᢞࡼࡾ6ࣧ᭶ᚋࡲ࡛ᣢ⥆
ࡍࡿྍ⬟ᛶࡀ࠶ࡿࠋࡇࡢࡓࡵࠊᮏᢞ๓つ๎ᢠయࡢࢫࢡ࣮ࣜࢽࣥࢢࢆ
ྵࡵࡓ୍⯡ⓗ࡞㍺⾑๓᳨ᰝࡢᐇࢆࡍࡿࡇࠋ㍺⾑ࡀணᐃࡉࢀ࡚࠸ࡿሙྜ
ࡣࠊᮏࢆࡋࡓ㛫᥋ࢡ࣮࣒ࢫヨ㦂ࡢᖸ΅ࡘ࠸࡚㛵ಀ⪅࿘▱ࡍࡿࡇ
ࠋ1)㸦ࠕ⮫ᗋ᳨ᰝ⤖ᯝཬࡰࡍᙳ㡪ࠖࡢ㡯ཧ↷㸧
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧 3㸬స⏝
ࢲࣛࢶ࣒࣐ࣈࠊࣞࢼࣜࢻ࣑ࢻࠊࢹ࢟ࢧ࣓ࢱࢰࣥే⏝⒪ἲ㸸
1ࣞࢪ࣓ࣥ௨ୖࡢ๓⒪Ṕࢆ᭷ࡍࡿⓎཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ᝈ⪅ࢆᑐ
㇟ࡋࡓᅜ㝿ඹྠ➨III┦⮫ᗋヨ㦂࠾࠸࡚ࠊ283୰215㸦76.0㸣㸧
స⏝㸦⮫ᗋ᳨ᰝ್␗ᖖࢆྵࡴ㸧ࡀㄆࡵࡽࢀࡓࠋ࡞స⏝ࡣࠊinfusion reaction 158㸦55.8㸣㸧ࠊዲ୰⌫ῶᑡ43㸦15.2㸣㸧ࠊୖẼ㐨ឤᰁ43 㸦15.2㸣㸧ࠊ⑂ປ35㸦12.4㸣㸧ࠊတႿ34㸦12.0㸣㸧➼࡛࠶ࡗࡓࠋ㸦ᢎ ㄆ㸧
ࢲࣛࢶ࣒࣐ࣈࠊ࣎ࣝࢸࢰ࣑ࣈࠊࢹ࢟ࢧ࣓ࢱࢰࣥే⏝⒪ἲ㸸
1ࣞࢪ࣓ࣥ௨ୖࡢ๓⒪Ṕࢆ᭷ࡍࡿⓎཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ᝈ⪅ࢆᑐ
㇟ࡋࡓᾏእ➨III┦⮫ᗋヨ㦂࠾࠸࡚ࠊ243୰182㸦74.9㸣㸧స⏝
㸦⮫ᗋ᳨ᰝ್␗ᖖࢆྵࡴ㸧ࡀㄆࡵࡽࢀࡓࠋ࡞స⏝ࡣࠊinfusion reaction 120㸦49.4㸣㸧ࠊ⾑ᑠᯈῶᑡ73㸦30.0㸣㸧ࠊ྾ᅔ㞴34㸦14.0㸣㸧ࠊ တႿ30㸦12.3㸣㸧ࠊ⑂ປ27㸦11.1㸣㸧➼࡛࠶ࡗࡓࠋ㸦ᢎㄆ㸧 1㸧㔜࡞స⏝
(1) Infusion reaction㸸ࢼࣇࣛ࢟ࢩ࣮ࠊ㰯㛢ࠊတႿࠊᝏᐮࠊẼ⟶ᨭ②ᨥࠊప㓟
⣲ࠊ྾ᅔ㞴➼ࡢinfusion reaction㸦52.9%㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ
࡛ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋࠊ㔜ᗘࡢinfusion reactionࡀㄆࡵࡽࢀࡓሙ
ྜࠊᮏࡢᢞ୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ㸦ࠕ⏝ἲ࣭⏝㔞㛵㐃ࡍ
ࡿ⏝ୖࡢὀពࠖࠊࠕ㔜せ࡞ᇶᮏⓗὀពࠖࡢ㡯ཧ↷㸧
(2) 㦵㧊ᢚไ㸸⾑ᑠᯈῶᑡ㸦18.3%㸧ࠊዲ୰⌫ῶᑡ㸦11.6%㸧ཬࡧࣜࣥࣃ⌫ῶᑡ 㸦6.3%㸧➼ࡢ㦵㧊ᢚไࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᝈ⪅ࡢ≧ែࢆ༑ศ
ほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢᢞ୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺
ࡇࠋ㸦ࠕ㔜せ࡞ᇶᮏⓗὀពࠖࡢ㡯ཧ↷㸧
(3) ឤᰁ㸸⫵⅖㸦6.1%㸧➼ࡢ㔜⠜࡞ឤᰁࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᝈ
⪅ࡢ≧ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢᢞ୰Ṇ➼ࡢ 㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ
(4) ⭘⒆ᔂቯೃ⩌㸸⭘⒆ᔂቯೃ⩌㸦0.2㸣㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊ
⾑Ύ୰㟁ゎ㉁⃰ᗘཬࡧ⭈ᶵ⬟᳨ᰝࢆ⾜࠺➼ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿ
ࡇࠋ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣ㐺ษ࡞ฎ⨨㸦⏕⌮㣗ሷᾮࠊ㧗ᒀ㓟⾑
⒪➼ࡢᢞࠊ㏱ᯒ➼㸧ࢆ⾜࠺ࡶࠊ≧ࡀᅇࡍࡿࡲ࡛ᝈ⪅ࡢ≧ែ
ࢆ༑ศほᐹࡍࡿࡇࠋ 2㸧ࡑࡢࡢస⏝
10㸣௨ୖ 10㸣ᮍ‶5㸣௨ୖ 5㸣ᮍ‶
ឤᰁ࠾ࡼࡧᐤ⏕ ୖẼ㐨ឤᰁ ࣥࣇ࢚ࣝࣥࢨ
⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ ㈋⾑
⚄⤒⣔㞀ᐖ 㢌③ࠊᮎᲈᛶឤぬࢽ࣮ࣗࣟ
ࣃࢳ࣮
ᚰ⮚㞀ᐖ ᚰᡣ⣽ື
྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ ྾ᅔ㞴ࠊ တႿ
⫶⭠㞀ᐖ ୗ⑩ࠊᝏᚰࠊྤ
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ ➽②⦰
୍⯡࣭㌟㞀ᐖ࠾ࡼࡧᢞ㒊
ࡢ≧ែ
⑂ປ Ⓨ⇕ ᮎᲈᛶᾋ⭘
㢖ᗘࡣే⏝⒪ἲࡢᾏእ➨III┦⮫ᗋヨ㦂ཬࡧᅜ㝿ඹྠ➨III┦⮫ᗋヨ㦂ࡢ㞟ィ⤖ᯝࡼࡿࠋ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧 4㸬㧗㱋⪅ࡢᢞ
㧗㱋⪅࡛ࡣ୍⯡⏕⌮ᶵ⬟ࡀపୗࡋ࡚࠸ࡿࡢ࡛ࠊᝈ⪅ࡢ≧ែࢆほᐹࡋ࡞ࡀࡽៅ
㔜ᢞࡍࡿࡇࠋ
5㸬ዷ፬ࠊ⏘፬ࠊᤵங፬➼ࡢᢞ
1) ᮏࡢዷፎ୰ࡢᢞ㛵ࡍࡿᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࡢ࡛ࠊዷ፬ཪࡣዷፎࡋ
࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿዪᛶࡣࠊཎ๎ࡋ࡚ᢞࡋ࡞࠸ࡇࠋࡸࡴࢆᚓࡎᢞ
ࡍࡿሙྜࡣ⒪ୖࡢ᭷┈ᛶࡀ༴㝤ᛶࢆୖᅇࡿุ᩿ࡉࢀࡿሙྜࡢࡳᢞ
ࡍࡿࡇࠋࡲࡓࠊዷፎྍ⬟࡞ዪᛶཬࡧࣃ࣮ࢺࢼ࣮ࡀዷፎࡍࡿྍ⬟ᛶࡢ࠶ࡿ⏨
ᛶᑐࡋ࡚ࡣࠊᮏᢞ୰ཬࡧᮏᢞ⤊ᚋ୍ᐃᮇ㛫ࡣ㐺ษ࡞㑊ዷࢆ⾜࠺
ࡼ࠺ᣦᑟࡍࡿࡇࠋ㹙ᮏࢆ⏝࠸ࡓ⏕ṪⓎ⏕ẘᛶヨ㦂ࡣᐇࡉࢀ࡚࠸࡞࠸
ࡀࠊIgG1ࣔࣀࢡ࣮ࣟࢼࣝᢠయ⫾┙㏻㐣ᛶࡀ࠶ࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿࠋ⏨ᛶ ࡢཷ⫾⬟ᑐࡍࡿᙳ㡪ࡣ᳨ウࡉࢀ࡚࠾ࡽࡎ࡛᫂࠶ࡿࠋ㹛
2) ᤵங፬ᢞࡍࡿሙྜࡣᤵஙࢆ୰Ṇࡉࡏࡿࡇࠋ㹙ᮏࡢࣄࢺஙỒ୰ࡢ
⛣⾜ࡣ᳨ウࡉࢀ࡚࠸࡞࠸ࡀࠊࣄࢺIgGࡣஙỒ୰⛣⾜ࡍࡿࡢ࡛ࠊᮏࡶ⛣⾜
ࡍࡿྍ⬟ᛶࡀ࠶ࡿࠋ㹛 6㸬ᑠඣ➼ࡢᢞ
ᑠඣ➼ᑐࡍࡿᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸㸦⏝⤒㦂ࡀ࡞࠸㸧ࠋ 7㸬⮫ᗋ᳨ᰝ⤖ᯝཬࡰࡍᙳ㡪
1) ᮏࡣ㉥⾑⌫ୖࡢCD38⤖ྜࡋࠊᢠయࢫࢡ࣮ࣜࢽࣥࢢࡸᕪヨ㦂➼ࡢ㐺ྜ
ᛶヨ㦂ᖸ΅ࡍࡿࠋᮏࡼࡿ㛫᥋ࢡ࣮࣒ࢫヨ㦂ࡢᖸ΅ࢆᅇ㑊ࡍࡿࡓࡵ
ࠊࢪࢳ࢜ࢫࣞࢺ࣮ࣝ㸦DTT㸧ฎ⌮㸦ᮏ㉥⾑⌫ୖࡢCD38ࡢ⤖ྜࢆ
㜼ᐖࡍࡿ㸧ࢆ⪃៖ࡍࡿࡇࠋKellᢠཎࡣDTTฎ⌮࡛ኚᛶࡍࡿࡢ࡛ࠊつ๎ᢠ యࢫࢡ࣮ࣜࢽࣥࢢ࠾࠸࡚Kellᢠయࡢホ౯ࡀ⬟࡞ࡿࠋࡋࡓࡀࡗ࡚DTT
ࢆ⏝࠸࡚つ๎ᢠయࢆࢫࢡ࣮ࣜࢽࣥࢢࡋࡓሙྜࡣࠊKellᢠཎ㝜ᛶࡢ㉥⾑⌫〇
ࢆ⏝ࡍࡿࡇࠋ1)㸦ࠕ㔜せ࡞ᇶᮏⓗὀពࠖࡢ㡯ཧ↷㸧
2) ᮏࡣࣄࢺIgG Nᆺࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡾࠊ⾑Ύ୰Mࢱࣥࣃࢡࡢ⾑Ύ⺮
ⓑ㟁ẼὋືἲཬࡧ⾑Ύචᅛᐃἲࡢ⤖ᯝᖸ΅ࡍࡿྍ⬟ᛶࡀ࠶ࡿࠋIgG Nᆺከ
Ⓨᛶ㦵㧊⭘⣽⬊ࢆ᭷ࡍࡿᝈ⪅࠾ࡅࡿዌຠ㸦CR㸧ࡢホ౯ཬࡧCRࡽࡢ
Ⓨࡢホ౯ᙳ㡪ࢆཬࡰࡍྍ⬟ᛶࡀ࠶ࡿࡓࡵὀពࡍࡿࡇࠋ 8㸬㐺⏝ୖࡢὀព
1) ㄪ〇
(1) ᝈ⪅ࡢయ㔜ᇶ࡙࠸࡚ᮏࡢᢞ㔞ࢆ⟬ฟࡋࠊᢞᚲせ࡞ࣂࣝᩘࢆ
Ỵᐃࡍࡿࠋ
(2) ᮏࡀ↓Ⰽࡽ㯤Ⰽ࡛࠶ࡿࡇࢆ☜ㄆࡍࡿࠋ㏱᫂⢏ᏊࡸኚⰍཪࡣ␗≀ࡀ ㄆࡵࡽࢀࡓሙྜࡣ⏝ࡋ࡞࠸ࡇࠋ
(3) ↓⳦⎔ቃୗ࠾࠸࡚ࠊ᪥ᒁ⏕⌮㣗ሷᾮࡢⅬࣂࢵࢢཪࡣᐜჾࡼࡾࠊ㏣ຍࡍ
ࡿᮏྠ㔞ᢤࡁྲྀࡿࠋ
(4) ᮏࢆᚲせ㔞ᢤࡁྲྀࡾࠊ᪥ᒁ⏕⌮㣗ሷᾮࡢⅬࣂࢵࢢཬࡧᐜჾᮏࢆຍ
࠼ࡿࠋ࣏ࣜሷࣅࢽࣝࠊ࣏ࣜࣉࣟࣆࣞࣥࠊ࣏࢚ࣜࢳࣞࣥࠊ࣏ࣜ࢜ࣞࣇ
ࣥΰྜ〇ཪࡣ࢚ࢳࣞࣥࣅࢽࣝࢭࢸ࣮ࢺࡢⅬࣂࢵࢢཬࡧᐜჾࢆ⏝࠸ࡿ
ࡇࠋᕼ㔘ࡣ↓⳦⎔ቃୗ࡛⾜࠺ࡇࠋᮍ⏝ṧᾮࡘ࠸࡚ࡣ㐺ษᗫᲠ ࡍࡿࡇࠋ
(5) ✜ࡸΰࡋࠊ┞ཪࡣ⤖ࡉࡏ࡞࠸ࡇࠋ 2) ᢞ
(1) ᮏᢞ๓⢏ᏊࡸኚⰍࡢ᭷↓ࢆ┠ど࡛☜ㄆࡍࡿࡇࠋᮏࡣࢱࣥࣃࢡ㉁
࡛࠶ࡿࡓࡵࠊᮏࡢᕼ㔘ᾮࡣ༙㏱᫂ཪࡣⓑⰍࡢ⢏Ꮚࡀㄆࡵࡽࢀࡿྍ⬟ᛶ ࡀ࠶ࡿࠋ㏱᫂⢏ᏊࡸኚⰍཪࡣ␗≀ࡀㄆࡵࡽࢀࡓሙྜࡣ⏝ࡋ࡞࠸ࡇ
ࠋ
(2) ᮏࡣಖᏑࢆྵࢇ࡛࠸࡞࠸ࡓࡵࠊᐊෆගୗ࡚ᐊ ࡢࡶࠊᮏࡢᕼ㔘 ᾮࡣᢞ㛫ࡶྵࡵ15㛫௨ෆᢞࡍࡿࡇࠋ
(3) ᕼ㔘ᚋ┤ࡕᢞࡋ࡞࠸ሙྜࡣࠊ㐽ගୗ࡚2Υ㹼8Υ࡛24㛫ಖ⟶ࡍࡿ
ࡇࡀ࡛ࡁࡿࠋ෭ࡋ࡞࠸ࡇࠋ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢲࣛࢶ࣒࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧
(4) ᮏࡢᕼ㔘ᾮࢆᢞࡍࡿ㝿ࡣࠊࣃࣟࢪ࢙ࣥࣇ࣮࡛ࣜ⺮ⓑ⤖ྜᛶࡢప࠸
࣏࢚࣮ࣜࢸࣝࢫࣝ࣍ࣥ〇ࡢࣥࣛࣥࣇࣝࢱ࣮㸦࣏ࢧࢬ0.2ȣm㸧
ࢆ⏝࠸࡚ᢞࡍࡿࡇࠋࡲࡓࠊ࣏ࣜ࢘ࣞࢱࣥࠊ࣏ࣜࣈࢱࢪ࢚ࣥࠊ࣏ࣜሷ
ࣅࢽࣝࠊ࣏ࣜࣉࣟࣆࣞࣥཪࡣ࣏࢚ࣜࢳࣞࣥ〇࡛ࣇ࣮ࣟࣞࢠ࣮ࣗࣞࢱ࣮
ࢆഛ࠼ࡓᢞࢭࢵࢺࢆ⏝࠸ࡿࡇࠋ
(5) ࡢ⸆ྠࡌ㟼ὀ࡚ࣛࣥྠὀධࡣ⾜ࢃ࡞࠸ࡇࠋ
(6) ⏝ࡢࡓࡵࠊᮍ⏝ṧᾮࢆಖ⟶ࡋ࡞࠸ࡇࠋᮍ⏝ṧᾮࡘ࠸࡚ࡣ㐺 ษᗫᲠࡍࡿࡇࠋ
9㸬ࡑࡢࡢὀព
ᮏᑐࡍࡿᢠయ⏘⏕ࡀㄆࡵࡽࢀࡓᝈ⪅ࡢྜࡣࠊ0.7% 㸦2㸧࡛࠶ࡾࠊࡇࡢ
࠺ࡕ1࠾࠸࡚ࡣࠊᮏᑐࡍࡿ୰ᢠయࢆㄆࡵࡓࠋ ῧᩥ᭩ࡢ
సᡂᖺ᭶
㸫
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
⾲ 1.7-2 ྠ✀ྠຠရ
1୍⯡ⓗྡ⛠ ࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝ
㈍ྡ ࢽ࣮ࣥࣛࣟ࢝ࣉࢭࣝ2.3mg ࢽ࣮ࣥࣛࣟ࢝ࣉࢭࣝ3mg ࢽ࣮ࣥࣛࣟ࢝ࣉࢭࣝ4mg
♫ྡ Ṋ⏣⸆ရᕤᴗᰴᘧ♫
ᢎㄆᖺ᭶᪥➼ 2017ᖺ3᭶30᪥ つไ༊ศ ẘ⸆ࠊฎ᪉⟢་⸆ရ
Ꮫᵓ㐀ᘧ
ᆺ㺃ྵ㔞 ◳࢝ࣉࢭࣝ
ࢽ࣮ࣥࣛࣟ࢝ࣉࢭࣝ2.3mg㸸࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝࡋ࡚3.29mg㸦࢟
ࢧࢰ࣑ࣈࡋ࡚2.3mg㸧㸦1࢝ࣉࢭࣝ୰㸧
ࢽ࣮ࣥࣛࣟ࢝ࣉࢭࣝ3mg㸸࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝࡋ࡚4.30mg㸦࢟ࢧ ࢰ࣑ࣈࡋ࡚3.0mg㸧㸦1࢝ࣉࢭࣝ୰㸧
ࢽ࣮ࣥࣛࣟ࢝ࣉࢭࣝ4mg㸸࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝࡋ࡚5.73mg㸦࢟ࢧ ࢰ࣑ࣈࡋ࡚4.0mg㸧㸦1࢝ࣉࢭࣝ୰㸧
ຠ⬟㺃ຠᯝ Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘
㸺ຠ⬟࣭ຠᯝ㛵㐃ࡍࡿ⏝ୖࡢὀព㸼
(1)ᮏࡼࡿ⒪ࡣࠊᑡ࡞ࡃࡶ1 ࡘࡢᶆ‽ⓗ࡞⒪ࡀ↓ຠཪࡣ⒪ᚋⓎ
ࡋࡓᝈ⪅ࢆᑐ㇟ࡍࡿࡇࠋ
(2)⮫ᗋヨ㦂⤌ࡳධࢀࡽࢀࡓᝈ⪅ࡢ๓⒪Ṕ➼ࡘ࠸࡚ࠊ࠙⮫ᗋᡂ⦼ࠚࡢ㡯ࡢ ෆᐜࢆ⇍▱ࡋࠊᮏࡢ᭷ຠᛶཬࡧᏳᛶࢆ༑ศ⌮ゎࡋࡓୖ࡛ࠊ㐺ᛂᝈ⪅ࡢ㑅 ᢥࢆ⾜࠺ࡇࠋ
⏝ἲ㺃⏝㔞 ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࡢే⏝࠾࠸࡚ࠊ㏻ᖖࠊᡂேࡣ࢟ࢧࢰ࣑ࣈ
ࡋ࡚1 ᪥1 ᅇ4 mgࢆ✵⭡㐌1 ᅇࠊ3㐌㛫㸦 1 ࠊ8 ཬࡧ15᪥┠㸧⤒ཱྀᢞࡋ ࡓᚋࠊ13᪥㛫ఇ⸆㸦16㹼28᪥┠㸧ࡍࡿࠋࡇࡢ4 㐌㛫ࢆ1 ࢧࢡࣝࡋࠊᢞࢆ⧞
ࡾ㏉ࡍࠋ࡞࠾ࠊᝈ⪅ࡢ≧ែࡼࡾ㐺ᐅῶ㔞ࡍࡿࠋ
⏝ἲ㺃⏝㔞
㛵㐃ࡍࡿ
⏝ୖࡢὀព
(1)ᮏࢆ༢⊂ᢞࡋࡓሙྜࡢ᭷ຠᛶཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
(2)ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࡢᢞ㝿ࡋ࡚ࡣࠊ࠙⮫ᗋᡂ⦼ࠚࡢ㡯ࡢෆᐜ
ࢆ⇍▱ࡋࠊᢞࡍࡿࡇࠋࡲࡓࠊే⏝⸆ࡢῧᩥ᭩ࢆ⇍ㄞࡍࡿࡇࠋ (3)ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ௨እࡢᢠᝏᛶ⭘⒆ࡢే⏝࠾ࡅࡿ᭷ຠᛶ
ཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
(4)୰➼ᗘ௨ୖࡢ⫢ᶵ⬟㞀ᐖࡢ࠶ࡿᝈ⪅ཬࡧ㔜ᗘࡢ⭈ᶵ⬟㞀ᐖࡢ࠶ࡿᝈ⪅࡛ࡣࠊᮏ
ࡢ⾑୰⃰ᗘࡀୖ᪼ࡍࡿࡢሗ࿌ࡀ࠶ࡿࡓࡵࠊῶ㔞ࢆ⪃៖ࡍࡿࡶࠊᝈ⪅
ࡢ≧ែࢆࡼࡾៅ㔜ほᐹࡋࠊ᭷ᐖ㇟ࡢⓎ⌧༑ศὀពࡍࡿࡇࠋ㸦ࠕៅ㔜ᢞ
ࠖཬࡧ࠙⸆≀ືែࠚࡢ㡯ཧ↷㸧
(5)㣗ᚋᮏࢆᢞࡋࡓሙྜࠊᮏࡢCmaxཬࡧAUCࡀపୗࡍࡿࡢሗ࿌ࡀ࠶ࡿࠋ 㣗ࡢᙳ㡪ࢆ㑊ࡅࡿࡓࡵࠊ㣗ࡢ1 㛫๓ࡽ㣗ᚋ2 㛫ࡲ࡛ࡢ㛫ࡢ᭹⏝ࡣ㑊 ࡅࡿࡇࠋ㸦࠙⸆≀ືែࠚࡢ㡯ཧ↷㸧
(6)᪂ࡓ࡞ࢧࢡࣝࡢ㛤ጞ࠶ࡓࡗ࡚ࡣࠊ௨ୗࡢᇶ‽ࢆཧ⪃ᢞࡢྍྰࢆุ᩿ࡍ
ࡿࡇࠋ
ࢧࢡࣝ㛤ጞᇶ‽
ዲ୰⌫ᩘ 1,000/mm3௨ୖ
⾑ᑠᯈᩘ 75,000/mm3௨ୖ
㠀⾑ᾮẘᛶ ࣮࣋ࢫࣛࣥཪࡣGrade 1 ௨ୗᅇ
GradeࡣNCI-CTCAE v4.0ᇶ࡙ࡃ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝ
(7)ᮏᢞࡼࡾస⏝ࡀⓎ⌧ࡋࡓሙྜࡣࠊ௨ୗࡢᇶ‽ࢆཧ⪃ࠊᮏࢆఇ
⸆ࠊῶ㔞ࠊ୰Ṇࡍࡿࡇࠋ
ᮏࡢῶ㔞ࢫࢸࢵࣉ
㛤ጞ⏝㔞 4 mg
ࢫࢸࢵࣉ1㸦 1 ẁ㝵ῶ㔞㸧 3 mg
ࢫࢸࢵࣉ2㸦 2 ẁ㝵ῶ㔞㸧 2.3 mg
ࢫࢸࢵࣉ3 ᢞ୰Ṇ
ఇ⸆࣭ῶ㔞࣭୰Ṇᇶ‽
స⏝ ⛬ᗘ ฎ⨨
⾑ᑠᯈῶᑡ ⾑ᑠᯈᩘ
30,000/mm3ᮍ‶
30,000/mm3௨ୖᅇࡍࡿࡲ࡛ࠊఇ⸆ࡍࡿࠋ ᅇᚋࠊྠ୍⏝㔞࡛ᢞࢆ㛤࡛ࡁࡿࠋ
ࡧ30,000/mm3ᮍ‶ῶᑡࡋࡓሙྜࡣࠊ 30,000/mm3௨ୖᅇࡍࡿࡲ࡛ࠊఇ⸆ࡍࡿࠋ ᅇᚋࠊ1 ẁ㝵ῶ㔞ࡋ࡚ᢞࢆ㛤࡛ࡁࡿࠋ ዲ୰⌫ῶᑡ ዲ୰⌫ᩘ
500/mm3ᮍ‶
500/mm3௨ୖᅇࡍࡿࡲ࡛ࠊఇ⸆ࡍࡿࠋ ᅇᚋࠊྠ୍⏝㔞࡛ᢞࢆ㛤࡛ࡁࡿࠋ
ࡧ500/mm3ᮍ‶ῶᑡࡋࡓሙྜࡣࠊ500/mm3௨
ୖᅇࡍࡿࡲ࡛ࠊఇ⸆ࡍࡿࠋ
ᅇᚋࠊ1 ẁ㝵ῶ㔞ࡋ࡚ᢞࢆ㛤࡛ࡁࡿࠋ
⓶㞀ᐖ
Grade 2 ᑐ⒪ἲࢆ⾜࠸ࠊᢞࢆ⥅⥆࡛ࡁࡿࠋ
ᚸᐜ࡛ࡁ࡞࠸ሙྜࡣࠊୗグ㺀Grade 3 㺁ཧ↷ࠋ
Grade 3 Grade 1 ௨ୗᅇࡍࡿࡲ࡛ࠊఇ⸆ࡍࡿࠋ
ᅇᚋࠊ1 ẁ㝵ῶ㔞ࡋ࡚ᢞࢆ㛤࡛ࡁࡿࠋ
Grade 4 ᢞࢆ୰Ṇࡍࡿࠋ
ᮎᲈ⚄⤒㞀ᐖ
⑊③ࢆక࠺Grade 1 ཪ ࡣ⑊③ࢆకࢃ࡞࠸
Grade 2
࣮࣋ࢫࣛࣥཪࡣ⑊③ࢆకࢃ࡞࠸Grade 1௨ୗ
ᅇࡍࡿࡲ࡛ࠊఇ⸆ࡍࡿࠋ
ᅇᚋࠊྠ୍⏝㔞࡛ᢞࢆ㛤࡛ࡁࡿࠋ
⑊③ࢆక࠺Grade 2 ཪ ࡣGrade 3
࣮࣋ࢫࣛࣥཪࡣGrade1௨ୗᅇࡍࡿࡲ࡛ࠊఇ
⸆ࡍࡿࠋ
ᅇᚋࠊ1 ẁ㝵ῶ㔞ࡋ࡚ᢞࢆ㛤࡛ࡁࡿࠋ
Grade 4 ᢞࢆ୰Ṇࡍࡿࠋ
ୖ グ ௨ እ ࡢ స⏝
Grade 3 ࡢ㠀⾑ᾮẘᛶ
࣮࣋ࢫࣛࣥཪࡣGrade1௨ୗᅇࡍࡿࡲ࡛ࠊఇ
⸆ࡍࡿࠋ
ᅇᚋࠊ1 ẁ㝵ῶ㔞ࡋ࡚ᢞࢆ㛤࡛ࡁࡿࠋ Grade 4 ࡢ㠀⾑ᾮẘᛶ ᢞࢆ୰Ṇࡍࡿࠋ
GradeࡣNCI-CTCAE v4.0ᇶ࡙ࡃ
⏝ୖࡢὀព
࠙㆙࿌ࠚ
ᮏࡣࠊ⥭ᛴ༑ศᑐᛂ࡛ࡁࡿ་⒪タ࠾࠸࡚ࠊ㐀⾑ჾᝏᛶ⭘⒆ࡢ⒪
ᑐࡋ࡚༑ศ࡞▱㆑⤒㦂ࢆᣢࡘ་ᖌࡢࡶ࡛ࠊᮏࡀ㐺ษุ᩿ࡉࢀࡿ
ࡘ࠸࡚ࡢࡳᢞࡍࡿࡇࠋࡲࡓࠊ⒪㛤ጞඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘᭷ຠ
ᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ࡚ࡽᢞࡍࡿࡇࠋ
࠙⚗ᚷࠚ㸦ḟࡢᝈ⪅ࡣᢞࡋ࡞࠸ࡇ㸧 (1)ᮏࡢᡂศᑐࡋ㐣ᩄࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
(2)ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿዪᛶ㸦㺀ዷ፬ࠊ⏘፬ࠊᤵங፬➼ࡢᢞ㺁 ࡢ㡯ཧ↷㸧
1. ៅ㔜ᢞ㸦ḟࡢᝈ⪅ࡣៅ㔜ᢞࡍࡿࡇ㸧
(1)୰➼ᗘ௨ୖࡢ⫢ᶵ⬟㞀ᐖࡢ࠶ࡿᝈ⪅㹙ᮏࡢ⾑୰⃰ᗘࡀୖ᪼ࡋࠊస⏝ࡀᙉ ࡃ࠶ࡽࢃࢀࡿ࠾ࡑࢀࡀ࠶ࡿࠋ㹛㸦㸺⏝ἲ࣭⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀព㸼ࠊ
࠙⸆≀ືែࠚࡢ㡯ཧ↷㸧
(2)㔜ᗘࡢ⭈ᶵ⬟㞀ᐖࡢ࠶ࡿᝈ⪅㹙ᮏࡢ⾑୰⃰ᗘࡀୖ᪼ࡋࠊస⏝ࡀᙉࡃ࠶ࡽ
ࢃࢀࡿ࠾ࡑࢀࡀ࠶ࡿࠋ㹛㸦㸺⏝ἲ࣭⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀព㸼ࠊ࠙⸆≀
ືែࠚࡢ㡯ཧ↷㸧
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝ
2. 㔜せ࡞ᇶᮏⓗὀព
⾑ᑠᯈῶᑡࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᮏࡢᢞ୰ࡣᐃᮇⓗ⾑ᾮᏛⓗ
᳨ᰝࢆ⾜࠸ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿࡇࠋ㸦㸺⏝ἲ࣭⏝㔞㛵㐃ࡍࡿ
⏝ୖࡢὀព㸼ࠊࠕ㔜࡞స⏝ࠖࡢ㡯ཧ↷㸧 3. ┦స⏝
ే⏝ὀព㸦ే⏝ὀពࡍࡿࡇ㸧
⸆ྡ➼ ⮫ᗋ≧࣭ᥐ⨨᪉ἲ ᶵᗎ࣭༴㝤ᅉᏊ CYP3Aㄏᑟ
ࣜࣇࣥࣆࢩࣥࠊ࢝
ࣝࣂ࣐ࢮࣆࣥࠊࣇ࢙
ࢽࢺࣥࠊࢭࣚ࢘
࢜ࢺࢠࣜࢯ࢘
㸦St.John’sWortࠊࢭ
ࣥࢺ࣭ࢪ࣮ࣙࣥࢬ࣭
࣮࣡ࢺ㸧ྵ᭷㣗ရ➼
ᮏࡢ⾑୰⃰ᗘࡀపୗࡋࠊຠᯝࡀ ῶᙅࡍࡿ࠾ࡑࢀࡀ࠶ࡿࡢ࡛ࠊ CYP3Aㄏᑟస⏝ࡢ࡞࠸⸆ࡢ ௦᭰ࢆ⪃៖ࡍࡿࡇࠋ㸦࠙⸆≀ື
ែࠚࡢ㡯ཧ↷㸧
ࣜࣇࣥࣆࢩࣥࡢ⸆≀௦ㅰ㓝⣲
㸦CYP3A➼㸧ᑐࡍࡿㄏᑟస⏝
ࡼࡾࠊᮏࡢ௦ㅰࡀಁ㐍ࡉࢀ
ࡿࠋ
4. స⏝
Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ᝈ⪅ࢆᑐ㇟ࡋࡓᅜ㝿ඹྠ➨Ϫ┦⮫ᗋヨ㦂࠾
࠸࡚ࠊᮏࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࢆే⏝ࡋࡓ361㸦᪥ᮏே20
ࢆྵࡴ㸧୰ࠊ335㸦93㸣㸧స⏝ࡀㄆࡵࡽࢀࡓࠋ࡞స⏝㸦20㸣௨ୖ㸧 ࡣࠊୗ⑩110㸦30㸣㸧ࠊዲ୰⌫ῶᑡ107㸦30㸣㸧ࠊ⾑ᑠᯈῶᑡ101 㸦28㸣㸧ࠊᮎᲈ⚄⤒㞀ᐖ81㸦22㸣㸧ཬࡧ⑂ປ75㸦21㸣㸧࡛࠶ࡗࡓ㸦ᢎㄆ
㸧ࠋ
(1)㔜࡞స⏝ὀ2㸧
1㸧⾑ᑠᯈῶᑡ㸦28㸣㸧㸸⾑ᑠᯈῶᑡࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᝈ⪅
ࡢ≧ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢఇ⸆ࠊῶ㔞ࠊ ᢞ୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ㸦㸺⏝ἲ࣭⏝㔞㛵㐃ࡍࡿ⏝ୖࡢ ὀព㸼ࠊࠕ㔜せ࡞ᇶᮏⓗὀពࠖࡢ㡯ཧ↷㸧
2㸧㔜ᗘࡢୗ⑩㸦5㸣㸧㸸㔜ᗘࡢୗ⑩ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᝈ⪅ࡢ≧
ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢఇ⸆ࠊῶ㔞ࠊᢞ
୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ㸦㸺⏝ἲ࣭⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀព 㸼ࡢ㡯ཧ↷㸧
3㸧⓶⢓⭷║ೃ⩌㸦Stevens-Johnsonೃ⩌㸧㸦㢖ᗘ᫂㸧㸸⓶⢓⭷║
ೃ⩌㸦Stevens-Johnsonೃ⩌㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᝈ⪅ࡢ≧ែ
ࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢᢞࢆ୰Ṇࡋࠊ㐺ษ
࡞ฎ⨨ࢆ⾜࠺ࡇࠋ
4㸧ᮎᲈ⚄⤒㞀ᐖ㸸ᮎᲈᛶឤぬࢽ࣮ࣗࣟࣃࢳ࣮㸦16㸣㸧ࠊᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ
࣮㸦7㸣㸧ࠊᮎᲈᛶឤぬ㐠ືࢽ࣮ࣗࣟࣃࢳ࣮㸦1㸣ᮍ‶㸧➼ࡀ࠶ࡽࢃࢀࡿࡇ
ࡀ࠶ࡿࡢ࡛ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊ ᮏࡢఇ⸆ࠊῶ㔞ࠊᢞ୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ㸦㸺⏝ἲ࣭⏝㔞
㛵㐃ࡍࡿ⏝ୖࡢὀព㸼ࡢ㡯ཧ↷㸧
5㸧ྍ㏫ᛶᚋⓑ㉁⬻ೃ⩌㸦㢖ᗘ᫂㸧㸸ྍ㏫ᛶᚋⓑ㉁⬻ೃ⩌㸦≧㸸
②ᨥⓎసࠊ⾑ᅽୖ᪼ࠊ㢌③ࠊព㆑ኚᐜࠊどぬ㞀ᐖ➼㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ
࠶ࡿࡢ࡛ࠊྍ㏫ᛶᚋⓑ㉁⬻ೃ⩌ࡀࢃࢀࡓሙྜࡣᮏࡢᢞࢆ୰Ṇ ࡋࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ
ὀ2㸧స⏝ࡢⓎ⌧㢖ᗘࡣࠊᅜ㝿ඹྠ➨Ϫ┦ヨ㦂ࡢ⤖ᯝࡽ㞟ィࡋࠊࡑࢀ௨እ࡛ሗ࿌ࡉࢀࡓస
⏝ࡣ㢖ᗘ᫂ࡋࡓࠋ
(2)ࡑࡢࡢస⏝ὀ3㸧
10㸣௨ୖ 5㹼10㸣ᮍ‶ 5㸣ᮍ‶
1㸧ឤᰁ ⫵⅖ Ẽ⟶ᨭ⅖ࠊୖẼ㐨ឤᰁࠊᖏ≧⑁⑈ࠊẼ
㐨ឤᰁࠊ㰯ဗ㢌⅖ࠊཱྀ⭍࢝ࣥࢪࢲࠊ
ཱྀ⭍࣊ࣝ࣌ࢫࠊࣥࣇ࢚ࣝࣥࢨࠊẼ⟶
ᨭ⫵⅖ࠊឤᰁࠊཱྀ⭍┿⳦ឤᰁࠊဗ㢌⅖ 2㸧⾑ᾮ㸭
ࣜࣥࣃ⣔
ዲ୰⌫ῶᑡࠊ
㈋⾑
ⓑ⾑⌫ῶᑡ ࣜࣥࣃ⌫ῶᑡࠊỗ⾑⌫ῶᑡ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢟ࢧࢰ࣑ࣈࢡ࢚ࣥ㓟࢚ࢫࢸࣝ
10㸣௨ୖ 5㹼10㸣ᮍ‶ 5㸣ᮍ‶
3㸧⚄⤒⣔ ぬ␗ᖖࠊᾋື
ᛶࡵࡲ࠸ࠊ㘒ឤ ぬࠊከⓎࢽ࣮ࣗ
ࣟࣃࢳ࣮
㢌③ࠊᡓࠊഴ╀ࠊὀពຊ㞀ᐖࠊႴ
╀ࠊぬῶ㏥ࠊ⚄⤒③
4㸧║ ⓑෆ㞀 㟝どࠊ║⇱ࠊ║่⃭
5㸧⾑⟶ ῝㒊㟼⬦⾑ᰦࠊ㧗⾑ᅽࠊ₻⣚ࠊప⾑
ᅽ
6㸧྾ჾ ྾ᅔ㞴ࠊࡋࡷࡗࡃࡾࠊ⫵ሰᰦࠊ㰯
ฟ⾑ࠊတႿ
7㸧ᾘჾ ᝏᚰ㸦19㸣㸧ࠊ
ྤ㸦16㸣㸧ࠊ
౽⛎
ᾘⰋ ୖ⭡㒊③ࠊ⭡③ࠊ⫶㣗㐨㏫ὶᛶᝈࠊ
⭡㒊⭾‶ࠊ⫶⅖ࠊཱྀෆ⅖ࠊ⭡㒊ᛌ ឤࠊཱྀෆ⇱ࠊᨺᒂࠊཱྀ⭍ෆ₽⒆ᙧᡂ
8㸧⫢⮚ ALT㸦GPT㸧ቑຍࠊAL-Pቑຍ
9㸧⓶ Ⓨ⑈㸦15㸣㸧 ⒍ ⣚ᩬᛶ⓶⑈ࠊ⣚ᩬࠊ⬺ᛶ⓶⅖ࠊ⸆
⑈ࠊከờࠊ㌟ᛶ⒍ࠊ⒍ᛶ⓶
⑈ࠊᛴᛶ⇕ᛶዲ୰⌫ᛶ⓶㸦Sweet
ೃ⩌㸧
10㸧ࡑࡢ ⑂ປࠊ╀ࠊ
ᮎᲈᛶᾋ⭘ࠊ➽
②⦰
↓ຊࠊ㣗ḧῶ
㏥
Ⓨ⇕ࠊ➽ຊపୗࠊ㧗⾑⢾ࠊప࣒࢝ࣜ࢘
⾑ࠊᛰឤࠊẼศኚࠊ⃭㉺ࠊయ㔜 ῶᑡࠊയࠊ่⃭᫆ᛶࠊయ㔜ቑຍࠊ㘒
≧ែࠊࢡࢵࢩࣥࢢᵝ≧ࠊ࠺ࡘࠊ 㢦㠃ᾋ⭘ࠊ➽⫗③ࠊᅄ⫥③ࠊᏳࠊ⫼
㒊③ࠊ⾑୰ࢡࣞࢳࢽࣥቑຍࠊప࢝ࣝ
ࢩ࣒࢘⾑ࠊẼศືᦂࠊືࠊ⭈
ࠊ⪥㬆ࠊᅇ㌿ᛶࡵࡲ࠸
ὀ3㸧స⏝ࡢⓎ⌧㢖ᗘࡣࠊᅜ㝿ඹྠ➨Ϫ┦ヨ㦂ࡢ⤖ᯝࡽ㞟ィࡋࡓࠋ
5. 㧗㱋⪅ࡢᢞ
୍⯡㧗㱋⪅࡛ࡣ⏕⌮ᶵ⬟ࡀపୗࡋ࡚࠸ࡿࡇࡀከ࠸ࡢ࡛ࠊᝈ⪅ࡢ≧ែࢆほᐹ ࡋ࡞ࡀࡽᢞࡍࡿࡇࠋ
6. ዷ፬ࠊ⏘፬ࠊᤵங፬➼ࡢᢞ
(1)ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿዪᛶࡣᢞࡋ࡞࠸ࡇࠋࡲࡓࠊዷፎྍ
⬟࡞ዪᛶཬࡧࣃ࣮ࢺࢼ࣮ࡀዷፎࡍࡿྍ⬟ᛶࡢ࠶ࡿ⏨ᛶᑐࡋ࡚ࡣࠊᮏᢞ
୰ཬࡧᢞ⤊ᚋ୍ᐃᮇ㛫ࡣ㐺ษ࡞㑊ዷࢆ⾜࠺ࡼ࠺ᣦᑟࡍࡿࡇࠋ㹙࢘ࢧࢠ
࠾࠸࡚ࠊAUCẚ㍑࡛⮫ᗋ᭚㟢㔞ࡢ1.8ಸ┦ᙜࡍࡿ⏝㔞࡛ദወᙧᛶ㸦⫾ඣ ࡢᑿ᳝␗ᖖཬࡧ▷ᑿ㸧ࡀㄆࡵࡽࢀࡓࠋࡲࡓࠊࣛࢵࢺ࠾࠸࡚AUCẚ㍑࡛⮫ᗋ
᭚㟢㔞ࢆୗࡲࢃࡿ⏝㔞࡛⢭ᕢẘᛶࡀㄆࡵࡽࢀࡓࠋ㹛
(2)ᤵங୰ࡢዪᛶᢞࡍࡿࡇࢆ㑊ࡅࠊࡸࡴࢆᚓࡎᢞࡍࡿሙྜࡣᤵஙࢆ୰
Ṇࡉࡏࡿࡇࠋ㹙ࣄࢺஙỒ୰ࡢ⛣⾜ࡣ࡛᫂࠶ࡿࠋ㹛 7. ᑠඣ➼ࡢᢞ
పฟ⏕య㔜ඣࠊ᪂⏕ඣࠊஙඣࠊᗂඣཪࡣᑠඣᑐࡍࡿᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸
㸦⏝⤒㦂ࡀ࡞࠸㸧ࠋ 8. 㐣㔞ᢞ
ᮏࡢ㐣㔞ᢞࡼࡾࠊ㔜ᗘࡢᝏᚰࠊྤࠊୗ⑩ࠊ⾑ᑠᯈῶᑡ➼ࡀሗ࿌ࡉࢀ
࡚࠸ࡿࠋ
ᮏࡢ㐣㔞ᢞᑐࡍࡿゎẘࡣᏑᅾࡋ࡞࠸ࠋ㐣㔞ᢞࡀㄆࡵࡽࢀࡓሙྜࡣࠊ
≧ᛂࡌ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ࡞࠾ࠊᮏࡣ⾑ᾮ㏱ᯒࡼࡾ㝖ཤࡉࢀ࡞
࠸ࠋ
9. 㐺⏝ୖࡢὀព
ㄪ 㸸ㄪ⬺࢝ࣉࢭࣝࢆࡋ࡞࠸ࡇࠋ
⸆㸸྾‵ࢆ㜵ࡄࡓࡵPTPໟࡢࡲࡲಖᏑࡋࠊ᭹⏝PTPࢩ࣮ࢺࡽ
ྲྀࡾฟࡍࡼ࠺ᣦᑟࡍࡿࡇࠋ
᭹ ⏝ 㸸࢝ࣉࢭࣝࡣࡘࡪࡋࡓࡾࠊჶࢇࡔࡾࠊ㛤ࡅࡓࡾࡏࡎࠊࡑࡢࡲࡲỈ
ࡶ᭹⏝ࡍࡿࡼ࠺ᣦᑟࡍࡿࡇࠋ ῧᩥ᭩ࡢ
సᡂᖺ᭶
2017ᖺ5 ᭶ᨵゞ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
⾲ 1.7-3 ྠ✀ྠຠရ
2୍⯡ⓗྡ⛠ ࢚ࣟࢶࢬ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧
㈍ྡ ࢚࣒ࣉࣜࢩࢸⅬ㟼ὀ⏝300mg
࢚࣒ࣉࣜࢩࢸⅬ㟼ὀ⏝400mg
♫ྡ ࣈࣜࢫࢺ࣭࣐࣮ࣝࣖࢬ ࢫࢡࣈᰴᘧ♫
ᢎㄆᖺ᭶᪥➼ 2016ᖺ9᭶28᪥
つไ༊ศ ⏕≀⏤᮶〇ရ㸪⸆㸪ฎ᪉⟢་⸆ရ
Ꮫᵓ㐀ᘧ ࢚ࣟࢶࢬ࣐ࣈࡣ㸪㑇ఏᏊ⤌࠼ࣄࢺࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡾ㸪࣐࢘ࢫᢠࣄࢺ SLAMࣇ࣑࣮࣓ࣜࣥࣂ࣮7㸦SLAMF7㸧ᢠయࡢ┦⿵ᛶỴᐃ㒊㸪୪ࡧࣄࢺIgG1ࡢ
ࣇ࣮࣒࣮ࣞ࣡ࢡ㒊ཬࡧᐃᖖ㒊ࡽ࡞ࡿࠋ࢚ࣟࢶࢬ࣐ࣈࡣ㸪࣐࢘ࢫ࣑࢚࣮࣐ࣟ
㸦NS0㸧⣽⬊ࡼࡾ⏘⏕ࡉࢀࡿࠋ࢚ࣟࢶࢬ࣐ࣈࡣ㸪449ಶࡢ࣑ࣀ㓟ṧᇶࡽ࡞ࡿ
H㙐㸦Ȗ1㙐㸧2ᮏཬࡧ214ಶࡢ࣑ࣀ㓟ṧᇶࡽ࡞ࡿL㙐㸦N㙐㸧2ᮏ࡛ᵓᡂࡉࢀࡿ
⢾ࢱࣥࣃࢡ㉁㸦ศᏊ㔞㸸⣙148,000㸧࡛࠶ࡿࠋ
ᆺ㺃ྵ㔞 ⤖⇱ὀᑕ
࢚࣒ࣉࣜࢩࢸⅬ㟼ὀ⏝300mg㸸࢚ࣟࢶࢬ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧340mg㸦1ࣂ
ࣝ୰㸧
࢚࣒ࣉࣜࢩࢸⅬ㟼ὀ⏝400mg㸸࢚ࣟࢶࢬ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧440mg㸦1ࣂ
ࣝ୰㸧
ຠ⬟㺃ຠᯝ Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘
ࠑຠ⬟ཪࡣຠᯝ㛵㐃ࡍࡿ⏝ୖࡢὀពࠒ
օᮏࡼࡿ⒪ࡣ㸪ᑡ࡞ࡃࡶ1ࡘࡢᶆ‽ⓗ࡞⒪ࡀ↓ຠཪࡣ⒪ᚋⓎ
ࡋࡓᝈ⪅ࢆᑐ㇟ࡍࡿࡇࠋ
ֆ⮫ᗋヨ㦂⤌ࡳධࢀࡽࢀࡓᝈ⪅ࡢ๓⒪Ṕ➼ࡘ࠸࡚㸪ࠕ⮫ᗋᡂ⦼ࠖࡢ㡯ࡢ ෆᐜࢆ⇍▱ࡋ㸪ᮏࡢ᭷ຠᛶཬࡧᏳᛶࢆ༑ศ⌮ゎࡋࡓୖ࡛㸪㐺ᛂᝈ⪅ࡢ 㑅ᢥࢆ⾜࠺ࡇࠋ
⏝ἲ㺃⏝㔞 ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࡢే⏝࠾࠸࡚㸪㏻ᖖ㸪ᡂேࡣ࢚ࣟࢶࢬ࣐ࣈ
㸦㑇ఏᏊ⤌࠼㸧ࡋ࡚1ᅇ10mg/kgࢆⅬ㟼ὀࡍࡿࠋ28᪥㛫ࢆ1ࢧࢡࣝ
ࡋ㸪᭱ึࡢ2ࢧࢡࣝࡣ1㐌㛫㛫㝸࡛4ᅇ㸦1㸪8㸪15㸪22᪥┠㸧㸪3ࢧࢡࣝ௨㝆 ࡣ2㐌㛫㛫㝸࡛2ᅇ㸦1㸪15᪥┠㸧Ⅼ㟼ὀࡍࡿࠋ
⏝ἲ㺃⏝㔞
㛵㐃ࡍࡿ
⏝ୖࡢὀព
օᮏే⏝ࡍࡿࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࡢᢞ㝿ࡋ࡚ࡣ㸪ࠕ⮫ᗋᡂ
⦼ࠖࡢ㡯ࡢෆᐜࢆ⇍▱ࡋ㸪ᢞࡍࡿࡇࠋࡲࡓ㸪ే⏝⸆ࡢῧᩥ᭩ࢆ⇍ㄞࡍࡿ
ࡇࠋ
ֆᮏ༢⊂ᢞ࡛ࡢ᭷ຠᛶཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
ևࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥ௨እࡢᢠᝏᛶ⭘⒆ࡢే⏝ࡼࡿ᭷ຠᛶཬࡧ Ᏻᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
ֈᮏᢞ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿinfusion reactionࢆ㍍ῶࡉࡏࡿࡓࡵ㸪ᮏࡢ ᢞ๓㸪ᢠࣄࢫࢱ࣑ࣥ㸦ࢪࣇ࢙ࣥࣄࢻ࣑ࣛࣥ➼㸧㸪H2ཷᐜయᣕᢠ㸦ࣛࢽࢳ ࢪࣥ➼㸧ཬࡧゎ⇕㙠③㸦ࢭࢺ࣑ࣀࣇ࢙ࣥ➼㸧ࢆᢞࡍࡿࡇࠋࡲࡓ㸪ᮏ
ే⏝ࡍࡿࢹ࢟ࢧ࣓ࢱࢰࣥࡣ㸪⤒ཱྀᢞ㸦28mgࢆᮏᢞࡢ3㹼24㛫๓ᢞ
㸧㟼⬦ෆᢞ㸦8mgࢆᮏᢞࡢ45ศ๓ࡲ࡛ᢞ㸧ศࡋ࡚ᢞ
ࡍࡿࡇࠋ㸦ࠕ㔜せ࡞ᇶᮏⓗὀពࠖཬࡧࠕ㔜࡞స⏝ࠖࡢ㡯ཧ↷㸧
։ᮏࡣ0.5mL/ศࡢᢞ㏿ᗘ࡛Ⅼ㟼ὀࢆ㛤ጞࡋ㸪ᝈ⪅ࡢᚸᐜᛶࡀⰋዲ࡞ሙྜࡣ㸪 ᝈ⪅ࡢ≧ែࢆほᐹࡋ࡞ࡀࡽ㸪ᢞ㏿ᗘࢆ௨ୗࡢࡼ࠺ẁ㝵ⓗୖࡆࡿࡇࡀ࡛ࡁ
ࡿࠋࡓࡔࡋ㸪ᢞ㏿ᗘࡣ2mL/ศࢆ㉸࠼࡞࠸ࡇࠋ
ᢞᮇ
ᢞ㏿ᗘ㸦mL/ศ㸧 ᢞ㛤ጞ
0㹼30ศ
ᢞ㛤ጞ 30㹼60ศ
ᢞ㛤ጞ 60ศ௨㝆
➨1ࢧࢡࣝ ึᅇᢞ 0.5 1 2
2㹼4ᅇ┠ᢞ 1 2
➨2ࢧࢡࣝ௨㝆 2
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢚ࣟࢶࢬ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧
֊ᮏᢞࡼࡾinfusion reactionࡀⓎ⌧ࡋࡓሙྜࡣ㸪௨ୗࡢࡼ࠺㸪ᮏࡢᢞ
୰Ṇ㸪୰᩿㸪ᢞ㏿ᗘࡢኚ᭦➼ࢆ⾜࠺ࡇࠋ㸦ࠕ㔜せ࡞ᇶᮏⓗὀពࠖཬࡧࠕ㔜
࡞స⏝ࠖࡢ㡯ཧ↷㸧
NCI-CTCAE㸨
ࡼࡿGradeุᐃ ฎ⨨
Grade 4 ┤ࡕᮏࡢᢞࢆ୰Ṇࡍࡿࡇࠋ
Grade 3 ┤ࡕᮏࡢᢞࢆ୰᩿ࡍࡿࡇࠋཎ๎㸪ᢞࡋ࡞࠸ࡇࠋ
Grade 2
┤ࡕᮏࡢᢞࢆ୰᩿ࡍࡿࡇࠋGrade 1௨ୗᅇࡋࡓሙྜࡣ㸪ᮏࡢ ᢞ㏿ᗘࢆ0.5mL/ศࡋ㸪ᢞ࡛ࡁࡿࠋᮏࡢᢞ㏿ᗘࢆ0.5mL/ศࡋ㸪 ᝈ⪅ࡢᚸᐜᛶࡀ༑ศ☜ㄆࡉࢀࡓሙྜࡣ㸪30ศࡈ0.5mL/ศࡎࡘᮏࡢ ᢞ㏿ᗘࢆୖࡆࡿࡇࡀ࡛ࡁࡿࠋࡓࡔࡋ㸪infusion reactionࡀⓎ⌧ࡋࡓᢞᅇ࡛
ࡣinfusion reactionࡀⓎ⌧ࡋࡓᢞ㏿ᗘࢆ㉸࠼࡞࠸ࡇࠋᮏࡢᢞᚋ㸪 infusion reactionࡀⓎ⌧ࡋࡓሙྜࡣ㸪┤ࡕᮏࡢᢞࢆ୰᩿ࡋ㸪୰᩿᪥
ᢞࡋ࡞࠸ࡇࠋ
Grade 1
ᅇࡍࡿࡲ࡛ᮏࡢᢞ㏿ᗘࢆ0.5mL/ศࡍࡿࡇࠋᮏࡢᢞ㏿ᗘࢆ
0.5mL/ศࡋ㸪ᝈ⪅ࡢᚸᐜᛶࡀ༑ศ☜ㄆࡉࢀࡓሙྜࡣ㸪30ศࡈ
0.5mL/ศࡎࡘᮏࡢᢞ㏿ᗘࢆୖࡆࡿࡇࡀ࡛ࡁࡿࠋ
㸨㸸NCI-CTCAE v4.0ࡼࡾGradeࢆุᐃ
ࢹ࢟ࢧ࣓ࢱࢰࣥࡢᢞࢆᘏᮇཪࡣ୰Ṇࡋࡓሙྜࡣ㸪infusion reactionࡢࣜࢫࢡࢆ
⪃៖ࡋࡓୖ࡛㸪ᮏࡢᢞࡢྍྰࢆุ᩿ࡍࡿࡇࠋ
ὀᑕᾮࡢㄪ〇ἲ
ᮏࡣ㸪300mg〇ࡢሙྜࡣ13mL㸪400mg〇ࡢሙྜࡣ17mLࡢὀᑕ⏝Ỉ࡛⁐
ゎࡋ㸪25mg/mLࡢ⃰ᗘࡋࡓᚋ㸪ᝈ⪅ࡢయ㔜ࡽィ⟬ࡋࡓᚲせ㔞ࢆ㸪㏻ᖖ 230mLࡢ⏕⌮㣗ሷᾮཪࡣ5㸣ࣈࢻ࢘⢾ὀᑕᾮ࡛ᕼ㔘ࡋ࡚⏝ࡍࡿࡇࠋ㸦ࠕ㐺⏝
ୖࡢὀពࠖࡢ㡯ཧ↷㸧
⏝ୖࡢὀព
࠙㆙࿌ࠚ
ᮏࡣ㸪⥭ᛴ༑ศᑐᛂ࡛ࡁࡿ་⒪タ࠾࠸࡚㸪㐀⾑ჾᝏᛶ⭘⒆ࡢ⒪
ᑐࡋ࡚༑ศ࡞▱㆑࣭⤒㦂ࢆᣢࡘ་ᖌࡢࡶ࡛㸪ᮏࡢᢞࡀ㐺ษุ᩿ࡉࢀࡿ
ࡘ࠸࡚ࡢࡳᢞࡍࡿࡇࠋࡲࡓ㸪⒪㛤ጞඛ❧ࡕ㸪ᝈ⪅ཪࡣࡑࡢᐙ᪘
᭷ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋ㸪ྠពࢆᚓ࡚ࡽᢞࢆ㛤ጞࡍࡿࡇࠋ
࠙⚗ᚷ㸦ḟࡢᝈ⪅ࡣᢞࡋ࡞࠸ࡇ㸧ࠚ օᮏࡢᡂศᑐࡋ㐣ᩄࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
ֆዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿዪᛶ㸦ࠕዷ፬㸪⏘፬㸪ᤵங፬➼ࡢᢞ
ࠖࡢ㡯ཧ↷㸧
࠙⏝ୖࡢὀពࠚ 1. 㔜せ࡞ᇶᮏⓗὀព
օⓎ⇕㸪ᝏᐮ㸪㧗⾑ᅽ➼ࡢinfusion reactionࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᮏ
ࡢᢞࡣ㸪㔜ᗘࡢinfusion reactionഛ࠼࡚⥭ᛴ༑ศ࡞ᑐᛂࡢ࡛ࡁࡿ‽ഛ
ࢆ⾜ࡗࡓୖ࡛㛤ጞࡍࡿࡇࠋInfusion reactionࡣ㸪ᮏࡢึᅇᢞከࡃሗ࿌
ࡉࢀ࡚࠸ࡿࡀ㸪2ᅇ┠௨㝆ࡢᮏᢞࡶ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᮏ
ᢞ୰ࡣᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋ㸪␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣᢞ୰Ṇ➼ࡢ 㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡶ㸪≧ࡀᅇࡍࡿࡲ࡛ᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿ
ࡇࠋ㸦ࠕ⏝ἲཬࡧ⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀពࠖཬࡧࠕ㔜࡞స⏝ࠖࡢ㡯 ཧ↷㸧
ֆࣜࣥࣃ⌫ῶᑡ➼ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᮏࡢᢞ㛤ጞ๓ཬࡧᢞ୰ࡣ ᐃᮇⓗ⾑ᾮ᳨ᰝࢆ⾜࠸㸪ᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿࡇࠋ㸦ࠕ㔜࡞స
⏝ࠖࡢ㡯ཧ↷㸧 2. స⏝
Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ᝈ⪅ࢆᑐ㇟ࡋࡓᅜ㝿ඹྠ➨3┦ヨ㦂࠾࠸࡚㸪 ᮏࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࢆే⏝ࡋࡓ318㸦᪥ᮏேᝈ⪅31ࢆ
ྵࡴ㸧ㄆࡵࡽࢀࡓ࡞స⏝㸦10㸣௨ୖ㸧ࡣ㸪⑂ປ㸦28.9㸣㸧㸪ዲ୰⌫ῶᑡ 㸦27.0㸣㸧㸪ୗ⑩㸦18.6㸣㸧㸪⾑ᑠᯈῶᑡ㸦17.6㸣㸧㸪➽②⦰㸦16.4㸣㸧㸪
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢚ࣟࢶࢬ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧
╀㸦16.0㸣㸧㸪㈋⾑㸦15.1㸣㸧㸪౽⛎㸦14.5㸣㸧㸪ᮎᲈᛶᾋ⭘㸦14.5㸣㸧㸪㧗
⾑⢾㸦13.8㸣㸧㸪Ⓨ⇕㸦12.6㸣㸧㸪ᝏᚰ㸦12.3㸣㸧㸪↓ຊ㸦11.6㸣㸧࡛࠶ࡗࡓࠋ 㸦ᢎㄆ㸧
օ㔜࡞స⏝
1㸧Infusion reaction㸦46.9㸣㸧㸸Ⓨ⇕㸪ᝏᐮ㸪㧗⾑ᅽ➼ࡢinfusion reactionࡀ࠶ࡽ
ࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋ㸪㔜ᗘࡢinfusion reactionࡀㄆࡵࡽࢀࡓሙྜࡣ㸪┤ࡕᮏࡢᢞࢆ୰Ṇࡋ㸪㐺ษ࡞ฎ⨨ࢆ
⾜࠺ࡇࠋ㸦ࠕ⏝ἲཬࡧ⏝㔞㛵㐃ࡍࡿ⏝ୖࡢὀពࠖཬࡧࠕ㔜せ࡞ᇶᮏ
ⓗὀពࠖࡢ㡯ཧ↷㸧
2㸧ឤᰁ㸸⫵⅖㸦8.5㸣㸧➼ࡢ㔜⠜࡞ឤᰁࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᝈ
⪅ࡢ≧ែࢆ༑ศほᐹࡋ㸪␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣ㸪ᢞ୰Ṇ➼ࡢ㐺ษ
࡞ฎ⨨ࢆ⾜࠺ࡇࠋ
3㸧ࣜࣥࣃ⌫ῶᑡ㸦9.7㸣㸧㸸ࣜࣥࣃ⌫ῶᑡࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᝈ⪅
ࡢ≧ែࢆ༑ศほᐹࡋ㸪␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣ㸪ᢞ୰Ṇ➼ࡢ㐺ษ࡞
ฎ⨨ࢆ⾜࠺ࡇࠋ㸦ࠕ㔜せ࡞ᇶᮏⓗὀពࠖࡢ㡯ཧ↷㸧
4㸧㛫㉁ᛶ⫵ᝈ㸦0.9㸣㸧㸸㛫㉁ᛶ⫵ᝈࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛㸪ᝈ⪅
ࡢ≧ែࢆ༑ศほᐹࡋ㸪␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣ㸪ᢞ୰Ṇ➼ࡢ㐺ษ࡞
ฎ⨨ࢆ⾜࠺ࡇࠋ ֆࡑࡢࡢస⏝
ᮏࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥࢆే⏝ࡋࡓ㝿ࡢస⏝ࡣ௨ୗࡢ࠾
ࡾ࡛࠶ࡿࠋḟࡢࡼ࠺࡞స⏝ࡀ࠶ࡽࢃࢀࡓሙྜࡣ㸪≧ᛂࡌ࡚㐺ษ࡞ฎ
⨨ࢆ⾜࠺ࡇࠋ
✀㢮㹚㢖ᗘ 5㸣௨ୖ 5㸣ᮍ‶ 㢖ᗘ᫂
㌟ ⑂ປ㸪ᮎᲈᛶᾋ⭘㸪Ⓨ⇕㸪↓
ຊ ⬚③
ᾘჾ ୗ⑩㸪౽⛎㸪ᝏᚰ
ච⣔ 㐣ᩄ
⾑ᾮ ዲ୰⌫ῶᑡ㸪⾑ᑠᯈῶᑡ㸪㈋
⾑
║ ⓑෆ㞀
⢭⚄࣭⚄⤒⣔ ╀ Ẽศኚ㸪ឤぬ㕌㯞
ឤᰁ ᖏ≧⑁⑈㸪㰯ဗ㢌⅖㸪ୖẼ㐨
ឤᰁ ௦ㅰ 㧗⾑⢾
⓶ ᐷờ
➽㦵᱁ ➽②⦰
྾ჾ တႿ ‵ᛶတႿ
ࡑࡢ య㔜ῶᑡ㸪⓶᭷Ჲ⣽⬊⒴㸪
ᇶᗏ⣽⬊⒴
స⏝ࡢⓎ⌧㢖ᗘࡣ㸪ᅜ㝿ඹྠ➨3┦ヨ㦂ࡢ⤖ᯝࡽ㞟ィࡋ㸪ࡑࢀ௨እࡢ⮫ᗋヨ㦂࡛ࡢሗ࿌ࡣ㢖 ᗘ᫂ࡋࡓࠋ
3. 㧗㱋⪅ࡢᢞ
୍⯡㧗㱋⪅࡛ࡣ⏕⌮ᶵ⬟ࡀపୗࡋ࡚࠸ࡿࡢ࡛㸪ᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋ࡞ࡀ
ࡽៅ㔜ᢞࡍࡿࡇࠋ 4. ዷ፬㸪⏘፬㸪ᤵங፬➼ࡢᢞ
օዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿዪᛶࡣᢞࡋ࡞࠸ࡇࠋዷፎࡍࡿྍ⬟ᛶ ࡢ࠶ࡿዪᛶཬࡧࣃ࣮ࢺࢼ࣮ࡀዷፎࡍࡿྍ⬟ᛶࡢ࠶ࡿ⏨ᛶࡣ㸪ᮏᢞ୰ཬࡧ ᮏᢞᚋ୍ᐃᮇ㛫㸪㐺ษ࡞㑊ዷࢆ⾜࠺ࡼ࠺ᣦᑟࡍࡿࡇࠋ㹙⏕ṪⓎ⏕ẘᛶヨ 㦂ࡣᐇࡉࢀ࡚࠸࡞࠸㸦ᮏࡀࣄࢺSLAMF7≉␗ⓗ࡛ື≀ᐇ㦂ࡀᐇ࡛ࡁ࡞
࠸ࡓࡵ㸧ࠋ㹛
ֆᤵங୰ࡢዪᛶᢞࡍࡿࡇࢆ㑊ࡅ㸪ࡸࡴࢆᚓࡎᢞࡍࡿሙྜࡣᤵஙࢆ୰Ṇ ࡉࡏࡿࡇࠋ㹙ᮏࡢࣄࢺẕங୰ࡢ⛣⾜㛵ࡍࡿࢹ࣮ࢱࡣ࡞࠸ࡀ㸪ࣄࢺIgG ࡣẕங୰⛣⾜ࡍࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿࠋ㹛
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢚ࣟࢶࢬ࣐ࣈ㸦㑇ఏᏊ⤌࠼㸧 5. ᑠඣ➼ࡢᢞ
పฟ⏕య㔜ඣ㸪᪂⏕ඣ㸪ஙඣ㸪ᗂඣཪࡣᑠඣᑐࡍࡿᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ 㹙⏝⤒㦂ࡀ࡞࠸㹛
6. ⮫ᗋ᳨ᰝ⤖ᯝཬࡰࡍᙳ㡪
ᮏࡣ㸪ࣄࢺIgGNࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡿࡇࡽ㸪⾑Ύ୰Mࢱࣥࣃࢡࡢ
⾑Ύ⺮ⓑ㟁ẼὋືἲཬࡧචᅛᐃἲࡢ୧᪉᳨࡛ฟࡉࢀࡿྍ⬟ᛶࡀ࠶ࡿࠋࡇࡢᖸ΅
ࡀ㸪IgGNᆺࡢከⓎᛶ㦵㧊⭘ᝈ⪅࠾࠸࡚㸪ዌຠࡢホ౯ཬࡧዌຠࡽࡢ
Ⓨࡢホ౯ᙳ㡪ࢆཬࡰࡍྍ⬟ᛶࡀ࠶ࡿࡇὀពࡍࡿࡇࠋ 7. 㐺⏝ୖࡢὀព
օㄪ〇
1㸧ᝈ⪅ࡢయ㔜ᇶ࡙ࡁᚲせ࡞ࡿࣂࣝᩘࢆ‽ഛࡍࡿࠋ
2㸧18G௨ୗࡢὀᑕ㔪ࢆ╔ࡋࡓὀᑕ⟄ࢆ⏝࠸࡚㸪300mg〇ࡢሙྜࡣ13mL㸪 400mg〇ࡢሙྜࡣ17mLࡢὀᑕ⏝Ỉ࡛⁐ゎࡋ㸪25mg/mLࡢ⃰ᗘࡍࡿࡇ
ࠋ
3㸧ࣂࣝࢆ❧࡚ࡓ≧ែ࡛ࡺࡗࡃࡾ⁐ᾮࢆᅇ㌿ࡉࡏ࡚⁐ゎࡋ㸪✜ࡸᩘ
ᅇ㌿ࡉࡏࡿࠋࣂࣝࡣ࠺ࡏࡎ㸪⃭ࡋࡃ᧠ᢾࡋ࡞࠸ࡇࠋ
4㸧⁐ゎࡋࡓᚋ㸪5㹼10ศ㛫㟼⨨ࡍࡿࠋ⁐ゎᾮࡣ↓Ⰽ㹼ᚤ㯤Ⰽࡢ᫂㹼ங
ⓑගࢆ࿊ࡍࡿᾮ࡛࠶ࡿࠋ⁐ゎᾮᚤ⢏ᏊࡸኚⰍࡀ࡞࠸┠ど࡛☜ㄆࡍࡿࡇ
ࠋᚤ⢏ᏊཪࡣኚⰍࡀㄆࡵࡽࢀࡓሙྜࡣ⏝ࡋ࡞࠸ࡇࠋ
5㸧ᝈ⪅ࡢయ㔜ࡽィ⟬ࡋࡓᚲせ㔞ࢆࣂࣝࡽᢤࡁྲྀࡾ㸪㏻ᖖ230mLࡢ⏕
⌮㣗ሷᾮཪࡣ5㸣ࣈࢻ࢘⢾ὀᑕᾮ࡛ᕼ㔘ࡍࡿࡇࠋ
6㸧⏝ㄪ〇ࡋ㸪ㄪ〇ᚋࡣ㏿ࡸ⏝ࡍࡿࡇࠋࡲࡓ㸪ṧᾮࡣᗫᲠࡍࡿࡇ
ࠋ ֆᢞ
1㸧ᕼ㔘ᾮࡢ㔞ࢆ㸪㍺ᾮ࣏ࣥࣉࢆ⏝࠸࡚㸪0.22࣑ࢡࣟࣥ௨ୗࡢ࣓ࣥࣈࣛࣥࣇ
ࣝࢱ࣮ࢆ⏝࠸ࡓࣥࣛࣥࣇࣝࢱ࣮ࢆ㏻ࡋ࡚ᢞࡍࡿࡇࠋ 2㸧ࡢ⸆➼ࡢ㓄ྜཪࡣΰὀࡣࡋ࡞࠸ࡇࠋ
3㸧ᮏࡣⅬ㟼ὀ⏝ࡋ࡚ࡢࡳ⏝࠸㸪ᛴ㏿㟼ὀࡣ⾜ࢃ࡞࠸ࡇࠋ 8. ࡑࡢࡢὀព
චཎᛶ㸸Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ᝈ⪅ࢆᑐ㇟ࡋࡓᅜ㝿ඹྠ➨3┦ヨ㦂
࠾࠸࡚㸪299୰45㸦15.1㸣㸧࡛ᮏᑐࡍࡿ⤖ྜᢠయࡀ᳨ฟࡉࢀ㸪ࡑࡢ࠺
ࡕ19㸦ᣢ⥆㝧ᛶࡣ2㸧࡛୰ᢠయࡢⓎ⌧ࡀㄆࡵࡽࢀࡓࠋ ῧᩥ᭩ࡢ
సᡂᖺ᭶
2016ᖺ11᭶సᡂ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
⾲ 1.7-4 ྠ✀ྠຠရ
3୍⯡ⓗྡ⛠ ࢝ࣝࣇࣝࢰ࣑ࣈ
㈍ྡ ࢝ࣉࣟࣜࢫⅬ㟼ὀ⏝10mg
࢝ࣉࣟࣜࢫⅬ㟼ὀ⏝40mg
♫ྡ ᑠ㔝⸆ရᕤᴗᰴᘧ♫
ᢎㄆᖺ᭶᪥➼ 2016ᖺ7᭶4᪥ つไ༊ศ ẘ⸆ࠊฎ᪉⟢་⸆ရ
Ꮫᵓ㐀ᘧ
ᆺ㺃ྵ㔞 ὀᑕ㸦ࣂࣝ㸧
࢝ࣉࣟࣜࢫⅬ㟼ὀ⏝10mg㸸࢝ࣝࣇࣝࢰ࣑ࣈ10mg㸦1ࣂࣝ୰㸧
࢝ࣉࣟࣜࢫⅬ㟼ὀ⏝40mg㸸࢝ࣝࣇࣝࢰ࣑ࣈ40mg㸦1ࣂࣝ୰㸧
ຠ⬟㺃ຠᯝ Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘
ࠑຠ⬟࣭ຠᯝ㛵㐃ࡍࡿ⏝ୖࡢὀពࠒ
㸦1㸧ᮏࡼࡿ⒪ࡣࠊᑡ࡞ࡃࡶ1ࡘࡢᶆ‽ⓗ࡞⒪ࡀ↓ຠཪࡣ⒪ᚋ
Ⓨࡋࡓᝈ⪅ࢆᑐ㇟ࡍࡿࡇࠋ
㸦2㸧⮫ᗋヨ㦂⤌ࡳධࢀࡽࢀࡓᝈ⪅ࡢ๓⒪Ṕ➼ࡘ࠸࡚ࠊࠕ⮫ᗋᡂ⦼ࠖࡢ㡯 ࡢෆᐜࢆ⇍▱ࡋࠊᮏࡢ᭷ຠᛶཬࡧᏳᛶࢆ༑ศ⌮ゎࡋࡓୖ࡛ࠊ㐺ᛂᝈ
⪅ࡢ㑅ᢥࢆ⾜࠺ࡇࠋ
⏝ἲ㺃⏝㔞 ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࡢሙྜ㸸
㏻ᖖࠊᡂேࡣ1 ᪥1 ᅇࠊᮏࢆ1ࠊ2ࠊ8ࠊ9ࠊ15ཬࡧ16 ᪥┠Ⅼ㟼ὀࡋࠊ12
᪥㛫ఇ⸆ࡍࡿࠋࡇࡢ28᪥㛫ࢆ1ࢧࢡࣝࡋࠊ12ࢧࢡࣝࡲ࡛ᢞࢆ⧞ࡾ㏉ࡍࠋ 13ࢧࢡࣝ௨㝆ࡣࠊ1᪥1ᅇࠊ1ࠊ2ࠊ15ཬࡧ16᪥┠ᮏࢆⅬ㟼ὀࡋࠊ12᪥㛫 ఇ⸆ࡍࡿࠋᮏࡢᢞ㔞ࡣ࢝ࣝࣇࣝࢰ࣑ࣈࡋ࡚ࠊ1ࢧࢡࣝ┠ࡢ1ཬࡧ2᪥┠
ࡢࡳ20mg/m2㸦య⾲㠃✚㸧ࠊࡑࢀ௨㝆ࡣ27mg/m2㸦య⾲㠃✚㸧ࡋࠊ10ศࡅ࡚Ⅼ
㟼ὀࡍࡿࠋ࡞࠾ࠊᝈ⪅ࡢ≧ែࡼࡾ㐺ᐅῶ㔞ࡍࡿࠋ ࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࡢሙྜ㸸
㏻ᖖࠊᡂேࡣ1 ᪥1 ᅇࠊᮏࢆ1ࠊ2ࠊ8ࠊ9ࠊ15ཬࡧ16 ᪥┠Ⅼ㟼ὀࡋࠊ12
᪥㛫ఇ⸆ࡍࡿࠋࡇࡢ28᪥㛫ࢆ1ࢧࢡࣝࡋࠊᢞࢆ⧞ࡾ㏉ࡍࠋᮏࡢᢞ㔞ࡣ
࢝ࣝࣇࣝࢰ࣑ࣈࡋ࡚ࠊ1ࢧࢡࣝ┠ࡢ1ཬࡧ2᪥┠ࡢࡳ20mg/m2㸦య⾲㠃
✚㸧ࠊࡑࢀ௨㝆ࡣ56mg/m2㸦య⾲㠃✚㸧ࡋࠊ30ศࡅ࡚Ⅼ㟼ὀࡍࡿࠋ࡞࠾ࠊ ᝈ⪅ࡢ≧ែࡼࡾ㐺ᐅῶ㔞ࡍࡿࠋ
⏝ἲ㺃⏝㔞
㛵㐃ࡍࡿ
⏝ୖࡢὀព
㸦1㸧ᮏࢆ༢⊂ᢞࡋࡓሙྜࡢ᭷ຠᛶཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
㸦2㸧ࣞࢼࣜࢻ࣑ࢻཪࡣࢹ࢟ࢧ࣓ࢱࢰࣥࡢᢞ㝿ࡋ࡚ࡣࠊࠕ⮫ᗋᡂ⦼ࠖࡢ㡯ࡢෆ ᐜࢆ⇍▱ࡋࠊᢞࡍࡿࡇࠋࡲࡓࠊే⏝⸆ࡢῧᩥ᭩ࢆ⇍ㄞࡍࡿࡇࠋ 㸦3㸧ࣞࢼࣜࢻ࣑ࢻཪࡣࢹ࢟ࢧ࣓ࢱࢰࣥ௨እࡢᢠᝏᛶ⭘⒆ࡢే⏝࠾ࡅࡿ᭷ຠ
ᛶཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
㸦4㸧య⾲㠃✚ࡀ2.2m2ࢆ㉸࠼ࡿᝈ⪅࡛ࡣࠊయ⾲㠃✚2.2m2ࡋ࡚ᢞ㔞ࢆ⟬ฟࡍࡿ
ࡇࠋ
㸦5㸧ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࡢሙྜࠊᮏࢆ18ࢧࢡࣝࢆ㉸࠼࡚ᢞ
ࡋࡓሙྜࡢ᭷ຠᛶཬࡧᏳᛶࡣ☜❧ࡋ࡚࠸࡞࠸ࠋ
㸦6㸧ࢡࣞࢳࢽࣥࢡࣜࣛࣥࢫ㸦Ccr㸧ࡀ15mL/ศᮍ‶࡞ࡗࡓሙྜࡣࠊᮏࢆ
ఇ⸆ࡍࡿࡇࠋCcrࡀ15mL/ศ௨ୖࡲ࡛ᅇࡋࡓሙྜࡣࠊᢞࡢ㛤ࢆ᳨
ウࡍࡿࡇࠋ㏱ᯒࢆせࡍࡿሙྜࡣࠊ㛤ࡢ⏝㔞ࡋ࡚20mg/m2ࢆ㉸࠼࡞
࠸ࡇࡋࠊࡲࡓ㏱ᯒᚋᢞࡍࡿࡇࠋ
㸦7㸧ᮏࡢᢞࡘ࠸࡚ࡣࠊ௨ୗᚑࡗ࡚ࠊ㐺ษఇ⸆ࠊῶ㔞ཪࡣᢞ୰Ṇࡢุ
᩿ࢆ⾜࠺ࡇࠋ
⾑ᾮẘᛶ㸦Grade4㸨ࡢ⾑ᑠᯈῶᑡࠊࣜࣥࣃ⌫ῶᑡࠊ㈋⾑ཪࡣGrade3㸨௨ୖࡢዲ
୰⌫ῶᑡ㸧ཪࡣGrade3㸨௨ୖࡢ㠀⾑ᾮẘᛶ㸦⬺ẟཪࡣGrade3㸨ࡢᝏᚰ࣭
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢝ࣝࣇࣝࢰ࣑ࣈ
ྤࠊୗ⑩ཬࡧ⑂ປࢆ㝖ࡃ㸧ヱᙜࡍࡿస⏝ࡀⓎ⌧ࡋࡓሙྜࡣࠊᅇࡍࡿ
ࡲ࡛ᮏࢆఇ⸆ࡍࡿࠋఇ⸆ᚋᢞࢆ㛤ࡍࡿሙྜࡣࠊᮏࡼࡿ᭷┈ᛶ
༴㝤ᛶࢆៅ㔜᳨ウࡋࡓୖ࡛ୗ⾲ࢆ┠Ᏻࡋ࡚ῶ㔞➼ࢆ⪃៖ࡍࡿࠋ
࡞࠾ࠊࡧస⏝ࡀⓎ⌧ࡋࠊఇ⸆ᚋᢞࢆ㛤ࡍࡿሙྜࡣࠊୗ⾲ࢆ┠Ᏻ
ࡋ࡚ᮏࢆῶ㔞ཪࡣᢞ୰Ṇࡍࡿࡇࠋ 㸨㸸NCI-CTCAE v4.0
ࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥే⏝
స⏝Ⓨ⌧ࡢᢞ㔞 ᢞ㛤ࡢᢞ㔞┠Ᏻ
27mg/m2 20mg/m2
20mg/m2 15mg/m2
15mg/m2 ᢞ୰Ṇ
ࢹ࢟ࢧ࣓ࢱࢰࣥే⏝
స⏝Ⓨ⌧ࡢᢞ㔞 ᢞ㛤ࡢᢞ㔞┠Ᏻ
56mg/m2 45mg/m2
45mg/m2 36mg/m2
36mg/m2 27mg/m2
27mg/m2 ᢞ୰Ṇ
㸦8㸧ὀᑕࡢㄪ〇᪉ἲ
ᮏࡣࠊ10mg〇ࡢሙྜࡣ5mLࠊ40mg〇ࡢሙྜࡣ20mLࡢὀᑕ⏝Ỉ࡛⁐
ゎࡋ࡚2mg/mLࡢ⃰ᗘࡋࡓᚋࠊయ⾲㠃✚ࡽィ⟬ࡋࡓᚲせ㔞ࢆ5㸣ࣈࢻ࢘
⢾ᾮ࡚ᕼ㔘ࡍࡿࡇࠋ㸦ࠕ㐺⏝ୖࡢὀពࠖࡢ㡯ཧ↷㸧
⏝ୖࡢὀព
ࠝ㆙ ࿌ࠞ
ᮏࡣࠊ⥭ᛴ༑ศᑐᛂ࡛ࡁࡿ་⒪タ࠾࠸࡚ࠊ㐀⾑ჾᝏᛶ⭘⒆ࡢ⒪
ᑐࡋ࡚༑ศ࡞▱㆑⤒㦂ࢆᣢࡘ་ᖌࡢࡶ࡛ࠊᮏࡢ⏝ࡀ㐺ษุ᩿ࡉࢀࡿ
ᝈ⪅ࡘ࠸࡚ࡢࡳᢞࡍࡿࡇࠋࡲࡓࠊ⒪㛤ጞඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘
᭷ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ࡚ࡽᢞࢆ㛤ጞࡍࡿࡇࠋ
ࠝ⚗ᚷ㸦ḟࡢᝈ⪅ࡣᢞࡋ࡞࠸ࡇ㸧ࠞ
㸦1㸧ᮏࡢᡂศᑐࡋ㐣ᩄࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
㸦2㸧ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿዪᛶ㸦ࠕዷ፬ࠊ⏘፬ࠊᤵங፬➼ࡢᢞ
ࠖࡢ㡯ཧ↷㸧
ࠝ⏝ୖࡢὀពࠞ
1㸬ៅ㔜ᢞ㸦ḟࡢᝈ⪅ࡣៅ㔜ᢞࡍࡿࡇ㸧
㸦1㸧ᚰ㞀ᐖࢆྜేࡋ࡚࠸ࡿᝈ⪅ཪࡣࡑࡢ᪤ Ṕࡀ࠶ࡿᝈ⪅ࠝ≧ࡀᝏཪࡣⓎ
ࡍࡿ࠾ࡑࢀࡀ࠶ࡿࠋ㸦ࠕ㔜࡞స⏝ࠖࡢ㡯ཧ↷㸧ࠞ
㸦2㸧㔜ᗘࡢ⫢ᶵ⬟㞀ᐖࡢ࠶ࡿᝈ⪅ࠝ⏝⤒㦂ࡀᑡ࡞࠸ࠋ㸦ࠕ⸆≀ືែࠖࡢ㡯ཧ
↷㸧ࠞ
2㸬㔜せ࡞ᇶᮏⓗὀព
㸦1㸧⫢ࠊAST㸦GOT㸧ࠊALT㸦GPT㸧ࠊࣅࣜࣝࣅࣥ➼ࡢୖ᪼ࢆక࠺⫢ᶵ⬟㞀 ᐖࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᮏࡢᢞ㛤ጞ๓ཬࡧᢞ୰ࡣᐃᮇⓗ⫢
ᶵ⬟᳨ᰝࢆ⾜࠸ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿࡇࠋ㸦ࠕ㔜࡞స⏝ࠖࡢ 㡯ཧ↷㸧
㸦2㸧㦵㧊ᢚไࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᮏࡢᢞ㛤ጞ๓ཬࡧᢞ୰ࡣᐃᮇ
ⓗ⾑ᾮ᳨ᰝࢆ⾜࠸ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿࡇࠋ㸦ࠕ㔜࡞స
⏝ࠖࡢ㡯ཧ↷㸧
㸦3㸧QT㛫㝸ᘏ㛗ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᮏࡢᢞ㛤ጞ๓ཬࡧᢞ୰ࡣᐃ ᮇⓗᚰ㟁ᅗ᳨ᰝཬࡧ㟁ゎ㉁᳨ᰝࢆ⾜࠸ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡍࡿࡇ
ࠋࡲࡓࠊᚲせᛂࡌ࡚ࠊ㟁ゎ㉁㸦࣒࢝ࣜ࢘ࠊ࣐ࢢࢿࢩ࣒࢘ࠊࣜࣥ➼㸧ࢆ⿵
ṇࡍࡿࡶࠊQT㛫㝸ᘏ㛗➼ࡢᩚ⬦ࡀㄆࡵࡽࢀࡓሙྜࡣࠊ㐺ษ࡞ฎ
⨨ࢆ⾜࠺ࡇࠋ
ࢲࣛࢶ࣒࣐ࣈ 1.7 ྠ✀ྠຠရ୍ぴ⾲
୍⯡ⓗྡ⛠ ࢝ࣝࣇࣝࢰ࣑ࣈ
3㸬స⏝
ࠑࣞࢼࣜࢻ࣑ࢻཬࡧࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࠒ
࣭Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ࢆᑐ㇟ࡋࡓᅜෆ➨Ϩ┦ヨ㦂㸦ONO-7057-05ヨ 㦂㸧࠾࠸࡚ࠊᮏࡀᢞࡉࢀࡓ26୰26㸦100㸣㸧స⏝㸦⮫ᗋ᳨ᰝ್
ࡢ␗ᖖࢆྵࡴ㸧ࡀㄆࡵࡽࢀࡓࠋ࡞స⏝㸦10㸣௨ୖ㸧ࡣࠊ⾑ᑠᯈῶᑡ12 㸦46.2㸣㸧ࠊࣜࣥࣃ⌫ῶᑡ11㸦42.3 㸣㸧ࠊ㧗⾑⢾10 㸦38.5 㸣㸧ࠊALT 㸦GPT㸧ቑຍ7 㸦26.9㸣㸧ࠊⓎ⑈7 㸦26.9㸣㸧ࠊ౽⛎6 㸦23.1㸣㸧ࠊ➽②
⦰6 㸦23.1㸣㸧ࠊపࣜࣥ㓟⾑5 㸦19.2㸣㸧ࠊⓑ⾑⌫ቑຍ5㸦19.2㸣㸧ࠊ AST㸦GOT㸧ቑຍ4㸦15.4 㸣㸧ࠊዲ୰⌫ῶᑡ4㸦15.4㸣㸧ࠊዲ୰⌫ቑຍ4 㸦15.4㸣㸧ࠊⓎ⇕4 㸦15.4㸣㸧ࠊᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮4㸦15.4㸣㸧ࠊ⾑୰
ࣅࣜࣝࣅࣥቑຍ4㸦15.4㸣㸧ࠊⓑ⾑⌫ῶᑡ4㸦15.4㸣㸧ࠊ㧗࣒࢝ࣜ࢘⾑3
㸦11.5 㸣㸧ࠊప࣒࢝ࣜ࢘⾑3 㸦11.5 㸣㸧ࠊᝏᚰ3 㸦11.5㸣㸧ࠊ㧗⾑ᅽ3
㸦11.5㸣㸧ࠊୗ⑩3 㸦11.5㸣㸧ࠊ⫵⅖3 㸦11.5㸣㸧ࠊୖẼ㐨ࡢ⅖3 㸦11.5㸣㸧ࠊぬ␗ᖖ3㸦11.5㸣㸧ࠊ⣚ᩬ3 㸦11.5㸣㸧ࠊ⾑୰ࢥࣞࢫࢸ࣮ࣟ
ࣝቑຍ3 㸦11.5㸣㸧ࠊ࣊ࣔࢢࣟࣅࣥῶᑡ3㸦11.5㸣㸧ཬࡧపࢼࢺ࣒ࣜ࢘⾑
3㸦11.5 㸣㸧࡛࠶ࡗࡓࠋ㸦ᢎㄆ㸧
࣭Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ࢆᑐ㇟ࡋࡓᾏእ➨Ϫ┦ヨ㦂㸦PX-171-009ヨ 㦂㸧࠾࠸࡚ࠊᮏࡀᢞࡉࢀࡓ392୰332㸦84.7㸣㸧స⏝㸦⮫ᗋ᳨ᰝ
್ࡢ␗ᖖࢆྵࡴ㸧ࡀㄆࡵࡽࢀࡓࠋ࡞స⏝㸦10㸣௨ୖ㸧ࡣࠊዲ୰⌫ῶᑡ142
㸦36.2㸣㸧ࠊ㈋⾑104㸦26.5㸣㸧ࠊ⾑ᑠᯈῶᑡ99㸦25.3㸣㸧ࠊ⑂ປ88 㸦22.4㸣㸧ࠊୗ⑩74 㸦18.9㸣㸧ࠊ➽②⦰72 㸦18.4㸣㸧ࠊ╀56 㸦14.3㸣㸧ࠊẼ㐨ឤᰁ50 㸦12.8㸣㸧ࠊప࣒࢝ࣜ࢘⾑43 㸦11.0㸣㸧ࠊ㧗⾑
⢾41 㸦10.5㸣㸧ཬࡧ↓ຊ41㸦10.5㸣㸧࡛࠶ࡗࡓࠋ㸦ᢎㄆ㸧
స⏝ࡢ㢖ᗘࡘ࠸࡚ࡣࠊᾏእ➨Ϫ┦ヨ㦂㸦PX-171-009ヨ㦂㸧ࡢᡂ⦼ᇶ࡙ࡁ グ㍕ࡋࡓࠋ
ࠑࢹ࢟ࢧ࣓ࢱࢰࣥే⏝ࠒ
࣭Ⓨཪࡣ㞴ᛶࡢከⓎᛶ㦵㧊⭘ࢆᑐ㇟ࡋࡓᅜ㝿ඹྠ➨Ϫ┦ヨ㦂㸦2011-003ヨ 㦂㸧࠾࠸࡚ࠊᮏࡀᢞࡉࢀࡓ463㸦᪥ᮏே22ྵࡴ㸧୰404
㸦87.3㸣㸧స⏝㸦⮫ᗋ᳨ᰝ್ࡢ␗ᖖࢆྵࡴ㸧ࡀㄆࡵࡽࢀࡓࠋ࡞స⏝
㸦10㸣௨ୖ㸧ࡣࠊ⾑ᑠᯈῶᑡ126㸦27.2㸣㸧ࠊ㈋⾑107 㸦23.1㸣㸧ࠊ⑂ປ97
㸦21.0 㸣㸧ࠊ╀93 㸦20.1 㸣㸧ࠊ྾ᅔ㞴74 㸦16.0㸣㸧ࠊୗ⑩69 㸦14.9㸣㸧ࠊ㧗⾑ᅽ62 㸦13.4㸣㸧ࠊᝏᚰ57 㸦12.3㸣㸧ࠊ↓ຊ55 㸦11.9㸣㸧ࠊᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮49㸦10.6㸣㸧ࠊࣜࣥࣃ⌫ῶᑡ48 㸦10.4㸣㸧ࠊⓎ⇕48 㸦10.4㸣㸧ཬࡧ㧗⾑⢾47㸦10.2 㸣㸧࡛࠶ࡗࡓࠋ㸦ᢎㄆ
㸧
స⏝ࡢ㢖ᗘࡘ࠸࡚ࡣࠊᾏእ➨Ϫ┦ヨ㦂㸦PX-171-009ヨ㦂㸧ཬࡧᅜ㝿ඹྠ➨
Ϫ┦ヨ㦂㸦2011-003ヨ㦂㸧ࡢᡂ⦼ᇶ࡙ࡁグ㍕ࡋࡓࠋ
ͤ㸸PX-171-009ヨ㦂ཬࡧ2011-003ヨ㦂௨እ࡛ሗ࿌ࡉࢀࡓస⏝ࡘ࠸࡚ࡣ㢖ᗘ
᫂ࡋࡓࠋ 㸦1㸧㔜࡞స⏝
1㸧ᚰ㞀ᐖ
ᚰ㸦2.7㸣㸧ࠊQT㛫㝸ᘏ㛗㸦0.1㸣㸧ࠊᚰ➽᱾ሰ㸦0.1㸣㸧ࠊᚰᄞᾮ㈓␃
㸦0.1㸣㸧ࠊᚰ⭷⅖㸦㢖ᗘ᫂ͤ㸧➼ࡢᚰ㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊ ᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢఇ⸆ࠊῶ㔞 ཪࡣᢞ୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ
2㸧㛫㉁ᛶ⫵ᝈ
㛫㉁ᛶ⫵ᝈ㸦0.9㸣㸧㸦⫵⮚⅖㸦0.5㸣㸧ࠊ㛫㉁ᛶ⫵⅖㸦0.4㸣㸧ࠊᛴᛶ྾
❓㏕ೃ⩌ࠊᛴᛶ྾㸦࠸ࡎࢀࡶ㢖ᗘ᫂ͤ㸧➼㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶
ࡿࡢ࡛ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹࡋࠊ␗ᖖࡀㄆࡵࡽࢀࡓሙྜࡣࠊᮏࡢఇ
⸆ࠊῶ㔞ཪࡣᢞ୰Ṇ➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇࠋ 3㸧⫵㧗⾑ᅽ
⫵㧗⾑ᅽ㸦0.5㸣㸧ࡀ࠶ࡽࢃࢀࡿࡇࡀ࠶ࡿࡢ࡛ࠊᝈ⪅ࡢ≧ែࢆ༑ศほᐹ ࡋࠊ྾ᅔ㞴ࠊ⬚③➼ࡢ≧ࡀ࠶ࡽࢃࢀࡓሙྜࡣࠊᮏࡢᢞࢆ୰Ṇࡍࡿ