RISPERDAL CONSTA

Suspension for I.M. Injection

25 25 mg 023857
37.5 37.5 mg 023859
50 50 mg 023858

RISPERDAL CONSTA risperidone 25 mg37.5 mg50 mgRISPERDAL

CONSTA risperidonerisperidone
polylactide-co-glycoliderisperidone 381

(
)/(
)RISPERDAL CONSTA
()
Risperdal ConstaValproate(Rapid
cycling bipolar disorder)

risperidoneRISPERDAL CONSTA
risperidone
RISPERDAL CONSTA

2(
)

25 mgRISPERDAL CONSTA
50 mg
50 mg
RISPERDAL CONSTA 12

RISPERDAL CONSTA risperidone

RISPERDAL
CONSTA RISPERDAL CONSTA

RISPERDAL CONSTA valproate

25 mg50 mg
RISPERDAL CONSTA

12.5 mg
risperidone(
)12.5 mg

RISPERDAL CONSTA risperidone

()risperidone
()

RISPERDAL CONSTA

RISPERDAL CONSTA 25 mg
RISPERDAL CONSTA risperidone
()risperidone
()

()

RISPERDAL CONSTA
risperidonerisperidone 0.5 mg
1 mg2 mg
2 mgRISPERDAL CONSTA 25 mg
risperidonerisperidone
12.5 mg
RISPERDAL CONSTA 12.5 mg

risperidone
risperidone(free fraction)(
)

RISPERDAL CONSTA

RISPERDAL
CONSTA risperidone
RISPERDAL CONSTA
RISPERDAL CONSTA

RISPERDAL CONSTA risperidone

(
)
risperidoneRISPERDAL CONSTA
risperidone

RISPERDAL CONSTA
RisperidonecarbamazepineCYP 3A4 (phenytoinrifampin
phenobarbital)risperidone9-hydroxyrisperidone
RISPERDAL CONSTA
(
)carbamazepine CYP 3A4
RISPERDAL CONSTA
4-8risperidone
carbamazepineCYP 3A4RISPERDAL
CONSTA carbamazepine
CYP 3A42-4RISPERDAL
CONSTA risperidone9-hydroxyrisperidone
25 mg RISPERDAL CONSTA
carbamazepineCYP 3A425 mg
RISPERDAL CONSTA 12.5 mg
RISPERDAL CONSTA 12.5 mg

CYP 2D6fluoxetineparoxetinerisperidone
2.5-2.83-9fluoxetine9-hydroxyrisperidoneparoxetine
9-hydroxyrisperidone10%fluoxetineparoxetine
risperidonefluoxetineparoxetine
RISPERDAL CONSTA
fluoxetineparoxetinefluoxetineparoxetine2-4
RISPERDAL CONSTA risperidone
25 mg RISPERDAL CONSTA
fluoxetineparoxetine25 mg
RISPERDAL CONSTA 12.5 mgRISPERDAL CONSTA
fluoxetineparoxetineRISPERDAL
CONSTA 12.5 mg12.5 mg
fluoxetineparoxetinerisperidone
9-hydroxyrisperidone()

RISPERDAL CONSTA RISPERDAL

CONSTA

(Randomized Controlled TrialRCT)

(Retrospective Cohort Study)
(Conventional)(Atyptical)
(Dementia-Related Psychosis)

(Ketoacidosis)(Hyperglycemic Hyperosmolar
Nonketotic Coma)
(
)
()

risperidone RISPERDAL CONSTA

risperidone

RISPERDAL CONSTA
(risperidone)
17(RISPERDAL)

RISPERDAL
RISPERDAL4.0%3.1%
()86 (67-100 )
fuorosemide
RISPERDAL
furosemiderisperidone(7.3%8975-97)
risperidone (3.1%8470-96)furosemide
(4.1%8067-90)
furosemiderisperidone

risperidone

(CAE)
(8573-97)
risperidone
()

risperidonealphaRISPERDAL CONSTA ()

RISPERDAL CONSTA 0.8% (12/14991)

RISPERDAL CONSTA (1)

()
()(2)

risperidone

(RISPERDAL CONSTA )

(<1/10,000)
/
(CBC)
RISPERDAL
CONSTA

( 1X10 9/L)
RISPERDAL CONSTA

RISPERDAL
CONSTA

(Tardive Dyskinesia)/(EPS)
dopamine
(/)
risperidone

(Dyskinesia)

RISPERDAL CONSTA

RISPERDAL CONSTA

RISPERDAL CONSTA
(NMS)

(
)
( )
risperidone
RISPERDAL CONSTA risperidone()

()
(EPS)

(1)
(2)(3)

Lewy
(RISPERDAL CONSTA )
Lewy(DLB)

RISPERDAL

(RISPERDAL CONSTA )
()

()

RISPERDAL CONSTA

QT
,RISPERDAL CONSTA
QTQT

alpha-adrenergic
RISPERDAL
()

RISPERDAL CONSTA
(
)

Risperidone

RISPERDAL CONSTA 0.3%

(5/1499 )RISPERDAL CONSTA

dopamine D2 receptorrisperidone

risperidone

risperidone
(
)()

5%RISPERDAL CONSTA
risperidone
RISPERDAL CONSTA

RISPERDAL CONSTA (-
- )
(TTP)
(1300)28
RISPERDAL
RISPERDAL

RISPERDAL CONSTA
RISPERDAL CONSTA

RISPERDAL CONSTA

RISPERDAL CONSTA
RISPERDAL CONSTA

RISPERDAL
CONSTARISPERDAL CONSTA

(creatinine<30 mL/min/1.73 m2)RISPERDAL

risperidone9-hydroxyrisperidone
risperidone
RISPERDAL CONSTA 25 mgrisperidone
()12.5 mg
()

RISPERDAL CONSTA 40 mg/kg

RISPERDAL CONSTA 40 mg/kg
()
RISPERDAL CONSTA 40 mg/kg

RISPERDAL CONSTA 40 mg/kg

(effect dose)RISPERDAL
CONSTA (MRHD)(50 mgmg/m2)8
(AUC)
(no-effect dose)5 mg/kg
(mg/m2)

risperidone
14(AUC
)

RISPERDAL CONSTA
RISPERDAL
risperidone RISPERDAL CONSTA

RISPERDAL CONSTA levodopadopamine

risperidone

RISPERDAL CONSTA QT
carbamazepinerisperidone
CYP3A4
carbamazepineCYP3A4RISPERDAL
CONSTA
CarbamazepineRISPERDAL risperidone9-hydroxyrisperidone
50%carbamazepine
CYP3A4 (Phenytoin,RifampinPhenobarbital)risperidone
risperidone9-hydroxyrisperidon
RISPERDAL CONSTA carbamazepine
4-8
RISPERDAL CONSTA carbamazepine
CYP3A4RISPERDAL CONSTA
carbamazepineCYP3A4
2-4RISPERDAL CONSTA
risperidone9-hydroxyrisperidon
25 mg RISPERDAL CONSTA carbamazepine
CYP3A425 mg
RISPERDAL CONSTA 12.5 mgRISPERDAL CONSTA
12.5 mg( )
CYP2D6Fluoxetine (20 mg)paroxetine (20 mg)
risperidone2.5-2.83-9
Fluoxetine9-hydroxyrisperidoneparoxetine
9-hydroxyrisperidone10%
fluoxetineparoxetineRISPERDAL CONSTA
fluoxetineparoxetinefluoxetine
paroxetine2-4RISPERDAL CONSTA
risperidone25 mg RISPERDAL
CONSTA fluoxetineparoxetine25 mg
RISPERDAL CONSTA 12.5 mg
RISPERDAL CONSTA fluoxetineparoxetine
RISPERDAL CONSTA 12.5 mg
12.5 mg()
fluoxetineparoxetinerisperidone9-hydroxyrisperidone

RISPERDAL 1-6 mgtopiramate400 mg

risperidone23%AUC0-12hr33%risperidone9hydroxyrisperidone9-hydroxyrisperidone
RISPERDAL Topiramate

Phenothiazinesrisperidone
Amitriptylinerisperidone
Cimetidineranitidinerisperidone
64%26%cimetidinerisperidone9hydroxyrisperidoneAUCranitidinerisperidone9-hydroxyrisperidone
AUC20%Erythromycin (CYP3A4 )risperidone
(galantaminedonepezil)
risperidone
risperidone

Clozapinerisperidonerisperidone
RISPERDAL (3mg)(lithium)
(AUC)(Cmaxn=13)
RISPERDAL (4 mg)valproate
(1000 mg)valproate
(Cmax)RISPERDAL 20% (n=21)
RISPERDAL (0.25 mg)digoxin
furosemide

RisperidoneC
risperidonerisperidone
prolactinCNS
risperidone
risperidoneSprague-DawleyWistar
(0.63-10 mg/kgmg/m20.4-6)
(0.31-5 mg/kgmg/m2
0.4-6)
(mg/m2) 0.4-6
()
0.16-5 mg/kgmg/m20.1-3

2.5 mg/kgmg/m21.5
Wistar(
)

(Day 1)Risperidone
(
)risperidone (5 mg/kg
mg/m23)
RISPERDAL CONSTA
Risperidone
risperidone
RISPERDAL

(RISPERDAL)
/

RISPERDAL CONSTA

risperidone9-hydroxyrisperidone
risperidone9-hydroxyrisperidone
RISPERDAL CONSTA 12

Risperidone

RISPERDAL CONSTA
RISPERDAL CONSTA 2392
33212RISPERDAL
CONSTA 33220225 mg50 mg
RISPERDAL CONSTA
()
(12)(4)

ECGsRISPERDAL CONSTA
RISPERDAL CONSTA

DSM-IV
risperidone ()
risperidone(n=440)
risperidonerisperidone (
)26RISPERDAL CONSTA
(n=501)24
RISPERDAL CONSTA (n=154)
(n=149)
8RISPERDAL CONSTA (n=160)

DSM-IV
124 /(
62)(n=275)
16(
valproate)/RISPERDAL CONSTA
16(n=139)
52
RISPERDAL CONSTA (n=72)(n=67)16
RISPERDAL CONSTA
36(
52)(n=70)

-
12RISPERDAL CONSTA
2%
1. 12 RISPERDAL CONSTA
2%
RISPERDAL RISPERDAL
Placebo
CONSTA
CONSTA
(N=98)
/
25 mg
50 mg
%

(N=99)
(N=103)
%
%

2
0
1

15
21
12
*
8
15
9

7
11
6
*
4
11
6

4
4
0

0
3
0

2
2
3

2
1
0

2
0
0

2
3
0

4
2
3

2
0
0

5
7
1

0
7
1

6
6
0

3
4
5

1
3
0

4
1
0

2
2
0

2
0
0

6
2
1

3
6
0

0
3
0

2
3
1

4
1
0

2
1
0

5
4
2

4
1
1
*

-
RISPERDAL CONSTA 24
RISPERDAL CONSTA
2%
2. 24RISPERDAL
CONSTA 2%

RISPERDAL CONSTA
Placebo
/
(N=154)
(N=149)

%
%

3
1

3
1

5
1
RISPERDAL CONSTA 52
RISPERDAL CONSTA
4%
3. 52RISPERDAL
CONSTA 4%

RISPERDAL CONSTA
/
+
Placebo +

a
(N=67)a
(N=72)

6
3

6
1

4
0

24
16
b
15
6
b
6
3

6
0

4
0

4
1

4
3

4
1

4
0

7
1
a (/
RISPERDAL CONSTA
b

Paliperidonerisperidone(
)risperidone/paliperidone
RISPERDAL CONSTA
2%risperidone/paliperidonea
4a. RISPERDAL CONSTA 2%
risperidone/paliperidone
/

**

*
*

RISPERDAL CONSTA <2%risperidone

/paliperidoneb
4b. RISPERDAL CONSTA <2%
risperidone/paliperidone
/

QT

-glutamyltransferase

RISPERDAL CONSTA (25 mg50 mg)

risperidone/paliperidonec
4c. RISPERDAL CONSTA (25 mg50 mg)
risperidone/paliperidone

*
*

creatine phosphokinase

risperidone/paliperidone

1/10

1/100<1/10

1/1,000<1/100

1/10,000<1/1,000

<1/10,000

5. risperidone/paliperidone

a RISPERDAL CONSTA
()

()

QT
RISPERDALparoxetinetorsade de
pointes
,

Risperidone
/(
epinephrinedopaminerisperidone
)

ATC codeN05AX08
Risperidoneserotoninergic 5HT 2
dopaminergic D2Risperidone1-adrenergic
H1-histaminergic2-adrenergiccholinergic
risperidoneD2(
)
serotonindopamine

DSM-IV
RISPERDAL CONSTA (25 mg50 mg)
(/)1
RISPERDAL CONSTA

RISPERDAL CONSTA
(DSM-IV )
RISPERDAL CONSTA (50)

1. PANSS(LOCF)

RISPERDAL CONSTA

DSM-IV

50126RISPERDAL CONSTA
(25 mg37.550 mg
25 mg12.5 mg)303 (60%)
24RISPERDAL CONSTA
(
)RISPERDAL
CONSTA (p<0.001log rank test)
25%82RISPERDAL CONSTA
1732430%RISPERDAL
CONSTA 56%
RISPERDAL CONSTA 2.5
RISPERDAL CONSTA

()

RISPERDAL CONSTA

DSM-IV12 4
/(62)
164
5216
(valproate)
/RISPERDAL CONSTA
RISPERDAL CONSTA
()
RISPERDAL CONSTA

RISPERDAL CONSTA (1%

)
RISPERDAL CONSTA

risperidone()RISPERDAL
CONSTA risperidone9-hydroxyrisperidone ()
risperidone9-hydroxyrisperidone12.5 mg50 mg

RISPERDAL CONSTA ()

4-6RISPERDAL CONSTA 25 mg50 mg

risperidone9-hydroxyrisperidonerisperidone9-hydroxyrisperidone

Risperidone1-2L/kgRisperidone
1Risperidone90%
9-hydroxyrisperidone77%Risperidone9-hydroxyrisperidone
sulfamethazine (100 g/mL)
warfarin (10 g/mL)carbamazepine (10 g/mL)risperidone (10 ng/mL)
9-hydroxyrisperidone (50 ng/mL)

RisperidoneCYP2D6risperidone
9-hydroxyrisperidoneN-dealkylation
9-hydroxyrisperidonerisperidone
risperidone9-hydroxyrisperidone
CYP2D6debrisoquinhydroxylase
CYP2D66-8%
)
(quinidine)CYP2D
(extensive metabolizers)risperidone9-hydroxyrisperidone
CYP2D(poor metabolizers)risperidone
risperidone9-hydroxyrisperidone
risperidone9-hydroxyrisperidone

RISPERDAL CONSTA
RISPERDAL Risperidone
CYP2D6risperidone9-hydroxyrisperidone
(- CYP2D6 CYP)quinidine
risperidone
RISPERDAL quinidine
70RISPERDAL
carbamazepine
(phenytoinrifampine phenobarbital)RISPERDAL
risperidone9-hydroxyrisperidone( CarbamezepineCYP3A4)Risperidone
CYP2D6risperidone
(-CYP2D6CYP
)

Risperidone
1 mg14C-risperidone
84%74%14%
RISPERDAL CONSTA risperidone9-hydroxyrisperidone
3-6(monoexponential decline)3-6
risperidoneRisperidone(risperidone
9-hydroxyrisperidone)CYP2D613.7L/h5.0L/h
CYP2D63.3L/h3.2L/hRISPERDAL
CONSTA (25 mg50 mg)12risperidone
7-8

RisperidoneRISPERDAL
60%
RISPERDAL CONSTA , RISPERDAL
CONSTA 25 mgRISPERDAL
12.5 mg(
)

RISPERDAL
risperidone1
35%RISPERDAL CONSTA
RISPERDAL CONSTA 25 mg
RISPERDAL
12.5 mg()

(65)RISPERDAL
CONSTA 12risperidone9-hydroxyrisperidone

()

risperidone()
/
PANSS()ESRS
()Phase III

risperidone ()RISPERDAL CONSTA

(12 )
(risperidone )

40risperidone
(6 mg/day)
4(AUC)7(mg/m2)
40 mg/kg/2RISPERDAL CONSTA 1224
mg/m2
8
220 mg/kg/2RISPERDAL CONSTA 12
14

dopamine D2,Wistar (Hannover)

(5~40 mg/kg)5~40 mg/kg
40 mg/kg

40 mg/kg/2

Wistar (Hannover)RISPERDAL CONSTA

Wistar (Wiga)Swiss
risperidone
Wistar (Hannover)
Wistar (Wiga)
risperidone
RISPERDAL CONSTA

RISPERDAL CONSTA
24

Wistar()
risperidone (0.16-5 mg/kg)mg/m2
(16 mg)0.1-3
risperidone
risperidone
0.31-5 mg/kg0.6-10(mg/m2
),

(no-effect dose)
RISPERDAL CONSTA

RISPERDAL CONSTA
7525 DL JN1 [poly-(d,1-lactide-co-glycolide)] polymer

Polysorbate 20 carmellose sodium 40mPa.s disodium hydrogen phosphate

dihydratecitric acid anhydroussodium chloridesodium hydroxide

RISPERDAL CONSTA

362~8C
25C24

,25C

(2~8C)25C
2~8CRISPERDAL CONSTA 25C
RISPERDAL CONSTA 25C

- RISPERDAL CONSTA
- RISPERDAL CONSTA
- Alaris SmartSite needle-free Vial Access Device
- (21G UTW 1()
20G TW 2 ())Needle-Pro
(Rxonly=)

RISPERDAL CONSTA

RISPERDAL CONSTA
Needle-Pro(1 )
(2 )
risperidone

RISPERDAL CONSTA (
30)

RISPERDAL CONSTA
Alaris SmartSite Needle-Free Vial Access Device
RISPERDAL CONSTA
Needle-Pro(21G UTW(
)2 20G TW())
1.

2. SmartSite Needle-Free Vial Access Device

12. Needle-Pro
Needle-Pro

13.
Needle-Pro
Needle-Pro

14. RISPERDAL CONSTA

RISPERDAL CONSTA

15.

16.

Needle-Pro
Needle-Pro
Needle-Pro
Needle-ProNeedle-Pro

17. Needle-Pro
Needle-ProNeedle-Pro

Needle-Pro

1 Microspheres : Alkermes Controlled Therapeutics II

2 Diluent : Cilag AG
3 Packaging and Labeling : Cilag AG
4 Office : Janssen Pharmaceutica N.V.
1 265 Olinger Circle Wilmington, Ohio 45177 USA
2 Hochstrasse 201, CH-8200, Schaffhausen, Switzerland
3 Hochstrasse 201, CH-8200, Schaffhausen, Switzerland
4 Turnhoutseweg 30, B-2340, Beerse, Belgium

319 8
0800-211-688

3. SmartSite Needle-Free Vial Access Device

SmartSite Needle-Free Vial

Access Device

SmartSite Needle-Free Vial Access Device,

4. SmartSite Needle-Free Vial

Access Device()

5.
(
)

6. SmartSite Needle-Free Vial Access

DeviceSmartSite
Needle-Free Vial Access Device()
SmartSite Needle-Free Vial Access Device

SmartSite Needle-Free Vial Access Device

7. ()

8.

9.

10. SmartSite Needle-Free Vial Access

Device

11.

20G TW 2()
21G UTW 1()

1302