BONVIVA

3mg/3ml solution for injection

BONVIVA (ibandronate sodium)(osteoclast)

(bone resorption)Ibandronate sodium
3-(N-methyl-N-pentyl)amino-1-hydroxypropane-1,1-diphosphonic
acid,
monosodium salt, monohydrate C9H22NO7P2NaH2O
359.24Ibandronate sodium
Ibandronate sodium
OH
O
CH3 CH2 CH2 CH2 CH2 N
CH3

OH

CH2 CH2 C

OH

.H O
2

ONa

OH

BONVIVA BONVIVA
3
3.375 ibandronate monosodium salt monohydrate 3
ibandronate

Ibandronate (hydroxyapatite)
Ibandronate
(bone turnover)

 2 6 ibandronate

ibandronate
90
40% 50%ibandronate 20 2000 ng/mL (
ibandronate ) 86%

ibandronate
ibandronate P450 1A22A62C92C192D62E1
3A4

Ibandronate
( 50% 60%)
Ibandronate
3 8
Cmax 10%ibandronate
Ibandronate
2 2 4
ibandronate 4.6 15.3
5 25.5
ibandronate 84 160 /
( 60 /) 50% 60%

<18 ibandronate

Ibandronate

 ibandronate
ibandronate
()

Ibandronate
(CLcr)
0.5 ibandronate CLcr 40 70 /
(AUC) CLcr>90 /
55%CLcr<30 / 2
(

ibandronate
ibandronate

Ibandronate P450
Ibandronate ibandronate

Melphalan/Prednisolone

melphalan (10 /) prednisolone (10 /

) 6 ibandronate
Ibandronate melphalan prednisolone
Tamoxifen

30 tamoxifen 2 ibandronate

X
3

(formation)(resorption)

50
40%
0.5 3
BONVIVA
(cross-linked C-telopeptide of Type I collagen [CTX])

(
[osteocalcin])
BONVIVA 3 3 BONVIVA 2.5
1
36 12 CTX
ITT 6 () CTX
57% (BONVIVA ) 62% (BONVIVA 2.5 )
12

BONVIVA 2,946 55 80
21 (L1-L4)
(T ) 2 5 (SD) 1 4
()
2.5 20
BONVIVA 3 X

20%
4 400
D 500

BONVIVA 3 3
1,358 (L1-L4 BMD T
4

2.5 SD)(DIVA )
BONVIVA 2.5
1 BMD
400
D 500

BONVIVA 2.5
() 3
9.6% BONVIVA 2.5
4.7% (p<0.001) (
1) 9 10
20 BONVIVA ()
(50%) 2.5

3
BONVIVA
*

(%)

n=975

9.6

BONVIVA

2.5
(%)

(%)

95% CI
95% CI
n=977
4.7

0-3

10.4

5.1

0-3
()

0-3

5.3

2.8

4.9

52 **

(2.3, 7.4)

(29, 68)

5.3

52

(2.6, 7.9)

(30, 67)

2.5

49

(0.6, 4.5)

(14, 69)

*(3 )

**p=0.0003
5


3 BONVIVA 2.5
[9.1%(95% CI7.1%11.1%)]
[8.2%(95% CI6.3%10.2%)]

(-)
(BMD)

BONVIVA 2.5
BMD 3
BONVIVA 2.5 BMD
3 6
3 BONVIVA 2.5
BMD 6.4%
1.4% 2 BMD
BONVIVA 2.5
BMD BMD
2

BONVIVA 2.5
BMD

BONVIVA 2.5
1.4
6.4

(n=693)
(n=712)
-0.7
3.1

(n=638)
(n=654)
-0.7
2.6

(n=683)
(n=699)
0.2
5.3

(n=683)
(n=699)
*(3 )
BMD

DIVA ITT
1 BONVIVA 3 3
6

(n=429) BMD (4.5%)

(n=434) (3.5%) 1.05% (95% CI
0.53%1.57%p<0.001 1) 1 BONVIVA 3
3 BMD
2.1%BONVIVA 2.5 1.5%
BONVIVA 3 3
BMD BONVIVA 2.5

1
BONVIVA 2.5
BONVIVA 3 3

BMD
(95% CI)
10
9
8
7
6
BMD
5
4
(%)
3
2
1
0

2.5

3 3

* 3 3 2.5 p<0.001

16 22 20 34 (iliac
crest) BONVIVA 2.5

3 3 ibandronate
22 (n=30) 2 2 ibandronate 23
(n=27)

 ibandronate
Schenk (tibial
metaphyses)ibandronate
5 //()
(0.005 //
) 1000 5000
BONVIVA
ibandronate
3 3
8 4 ([/]
AUC ) BMD
Ibandronate
ibandronate

BMD T SCORE < -2.5 SD

BONVIVA BMD
(

(BMD 2.5
[ T ])

BONVIVA
(

BONVIVA
(
)

BONVIVA BONVIVA

BONVIVA
BONVIVA

BONVIVA D
D
D

()
1530BONVIVA

BONVIVA

BONVIVA (>200
mol/L [2.3 mg/dL][] <30 /
)

()

()
()

(ONJ)

ONJ
/

()(
)

BONVIVA (ibandronate sodium)

BONVIVA
BONVIVA

BONVIVA 3
3
BONVIVA 3
D

ibandronate

104 Wistar 37 15 /
/( AUC
3 3 3 1 )
78
NMRI 520 40 //(
AUC 3
3 96 14 )
90
NMRI 520 80 //
/ 80
//( AUC 3 3
10

 32 51 )

ibandronate
Salmonella typhimurium Escherichia coli
(Ames ) V79

Ibandronate

14 1.2 //
( AUC 3 3
117 )
28
0.3 //( AUC /
3 3 40 )

C
17 20 0.05
0.15 0.5 //(
AUC / 3 3
2 ) ibandronate
0.15 0.5 //( AUC /
3 3 4 )
0.15 0.5 //( AUC
/ 3 3
18 )

(
)class effect
1 //( AUC
/ 3 3
47 )(RPU)
11


/ 0.1 //(
AUC / 3 3
5 )
0.030.07 0.2 //
0.2 //([/]
3 3 19 )

(
)
(
)

BONVIVA

0.08 / 2 24
ibandronate 8.1 0.4 ng/mL
1.5 BONVIVA

BONVIVA

BONVIVA 3 3 1
(DIVA ) 51% 65

12

3 3,900
BONVIVA 2.5 BONVIVA 2.5

20% BONVIVA 2.5

23%BONVIVA 2.5
17%
BONVIVA

3 2% BONVIVA 2.5

2%
BONVIVA 2.5

%
(n=1134)

BONVIVA 2.5
%
(n=1140)

12.2
6.4
3.4
2.3
1.9

13.5
7.8
4.3
3.5
2.5

9.8
5.0
2.3
2.1
1.9

11.9
6.8
3.5
2.7
2.2

4.2

4.8

13

5.1
3.3
2.7

5.7
3.6
3.2

5.8
2.6
2.5
1.9

6.5
3.7
3.0
2.2

33.2
6.8
4.3
1.5

33.7
10.0
5.9
2.5

4.2

5.5

DIVA
BONVIVA 3 3
BONVIVA 2.5 1

BONVIVA 2.5
8.0% BONVIVA 3 3 7.5%
BONVIVA 2.5
6.7% BONVIVA 3 3
8.5%
>2% 4
4

BONVIVA
(3
3 )

BONVIVA
)
(2.5

2%

BONVIVA
2.5 (
)

%
(n=465)

BONVIVA
3 3 (
)

%
(n=469)

8.0
6.0

4.7
3.4
14

3.4
3.4
3.2
2.8
2.8

1.9
1.5
2.6
2.1
1.1

5.6
4.3
4.3
4.1
2.4
2.2

5.1
3.6
2.1
3.4
2.8
1.9

8.6
7.5
2.4
2.2
0.9

9.6
7.0
1.5
2.8
2.8

2.8
2.6

1.9
3.6

7.1

5.3

2.6
2.2

1.1
1.3

1.1
1.1

4.9
2.8

2.8

2.3

4.3

1.5

15

Acute Phase Reaction-like Events

(APR)
APR ( BONVIVA
2.5 4% BONVIVA 3 3
10%)
3 33 APR
7 24 48

() BONVIVA
3 3 (<2%8/469)
(<1%1/465)

ibandronate

2.5 ibandronate

BONVIVA 2.5
BONVIVA 3 3

BONVIVA

16

BONVIVA 3
15 30 3 (
)

15 30 BONVIVA

(
)

BONVIVA
BONVIVA (
)

BONVIVA

BONVIVA
BONVIVA
BONVIVA

BONVIVA

BONVIVA
3 BONVIVA
(3 ) 3
D (

30 /

BONVIVA
>200 mol/L (2.3 mg/dL)[] <30 mL/min
(

)
17


3 /3 BONVIVA (ibandronate
sodium)
5 (5 cc) 23 3/4

25 (77) 15 30 (59 86) [

]

3 ml
100
024630

US 2006 1
10.06-BON-3A01

Vetter Pharma-Fertigung GmbH & Co. KG.

Eisenbahnstrasse 2-4, D-88085 Langenargen, Germany.

Roche Diagnostics GmbH

Sandhoferstrasse 116, D-68305 Mannheim, Germany.

F. Hoffmann-La Roche Ltd

Grenzacherstrasse 124, CH-4070 Basel, Switzerland.


3 134 9
(02)27153111

18