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. 

   !"

#$%&'$ 1 ()

 2

6



 Digoxin 0.25
 Moduretic

! ) 44 + ,-  42 /0


 $

12 
%&'
3
4%&' 50- 5
13 6

$

-6 
1 3


73 7528!32

730$ 0,
 1$$0, !
0 32 SORIN 27 mm 0
0, 
 32 SORIN 19 mm   27 .6.
2547 $
. 
 6

$

#$%&'$ 1 ()

"
 2 3D
!5)
$ !3 0E0
1x1
1x1

#$%&'$ 1 ()
 /3  /
/+

#$%&'$ 1

 /3  /
/+

INR

Medications

26 .6. 2548

2.05

25 .. 2548

1.41

24 . . 2549

1.59

Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1/2x1
(4 mg/d)
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1/2x1
(4 mg/d)
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1x1
(5.5 mg/d)

)

#$%&'$ 1 ()

INR

Medications

19 .6.2549
23 .. 2549
22 .. 2549

6.52
1.5
1.38

22 ".6. 2549

2.23

Warfarin 3 mg 1x1
Warfarin 3 mg 1x1
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1/2x1
(4 mg/d)
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1/2x1
(4 mg/d)

)

Problem list : high INR

Problem list : high INR ()


 6
  
2
24/02/49  INR 1.59  
b 3
Warfarin   37.5% 1 C3 hs + C5 hs (4
mg/d.) f C3 1 hs + C5 hs (5.5mg/d.)
7528

   !!32 b 3
 0"
0 

 
b3


 




#$%&'$ 1 ()

Problem list : high INR ()

 /3  /
/+

INR

26 .6. 2548

2.05

25 .. 2548

1.41

24 . . 2549

1.59

Medications
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1/2x1
(4 mg/d)
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1/2x1
(4 mg/d)
Warfarin 5 mg 1/2x1 +
Warfarin 3 mg 1x1
(5.5 mg/d)

)


 




Ketoconazole

 ,
$0g 2
Ketoconazole (200)
1x1 = 90

- PROTEIN BINDING 93-96%


- CYP3A3/4 SUBSTRATE,
- CYP1A2, 2C, 2C9, 2C19(WEAK) , 3A3/4 AND
3A5-7 INHIBITOR

KETOCONAZOLE

Problem list : high INR ()

Significance 1
 Onset  Delayed
 Severity
 Major
 Documentation  Probable
Mechanism
 Inhibition of warfarin metabolism
Management
 Monitor INR values frequently (every 2 days)


 

0$ 0 |




 

/3} 
$$ 65 7528!!32
0$ 0 |




 

$7 

 
~2
- 7528!$0 3
- !$
b00 3)3 $7 

Pharmacist
Pharmacists intervention

#$%&'$ 2

12 2 


4&)$- 26 INR 5
6
, $, 131


Ketoconazole 0 Warfarin

 
b 3 Warfarin 37.5%

!65 ) 42 + ,-  69 /0


 $

12 
%&'
3"%&' 2
50- 513 6

$

-6 
1 3


73 7528!32

730$ 0,
 1$$0, !
0 32 Edwards MIRA 31 mm
  5 .. 2543 $
. 
 6

$

#$%&'$ 2 ()

#$%&'$ 2 ()


 2
"
 2 3D

6 05)
$ 8 +
3 0E02f 6
,6



 Enalapril 5 mg 1x2
Target INR
2.02.0-3.0

#$%&'$ 2 ()

 /3  /
/+

INR

Medications

20 ".6. 2548

2.35

18 .. 2549

8.81

2 .6. 2549

1.75

Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
)3 4 
Warfarin 3 mg 1/2x1 +
Warfarin 5 mg 1/2x1
(4 mg/d)
Warfarin 3 mg 1/2x1 +
Warfarin 5 mg 1/2x1
(4 mg/d)

)

Problem list : high INR



 6
  
2
7528

   !!32 b 3
 0"
0 

 
b3

Problem list : high INR ()

PIROXICAM


 



7528$
301&!~ , Pox
(Piroxicam )

 Protein Binding 99%


 CYP2C9, 2C18 Substrate
 Significance 2
 Onset
 Delayed
 Severity  Moderate
 Documentation  Suspected

 Mechanism
 Gastric irritation/decreased platelet aggregation

 Management
 Monitor patients closely

Problem list : high INR ()

Pharmacist
Pharmacists intervention

 
 

0$ 0 |







/3} 
$$ 65 7528!!32
0$ 0 |




 
$7 
 
 
~2
- 7528$0 3-3!0 ) $!f 0 3 1 6
,
  2 3$7 
- !$
b00 3)3 $7 

 12 2 


4&)$- 26 INR 5 6
, $,
31

 Piroxicam 0 Warfarin 0
!32  2!b3 $,

#$%&'$ 3

#$%&'$ 3 ()

!65 ) 63 + ,-  46 /0


 $
-  
%&'
3
4%&' 50- 5
13)
$


-6 
1 3


73 7528!32

730$ 0,
 1$$0, !
0 32 Edwards MIRA 27 mm
00, 
32 Edwards MIRA 21 mm  
12 .6. 2548 $
. 
 6

$

 )3 Warfarin 4  0


03b 30f Warfarin 3
hs + Warfarin 5 hs (4 mg/d) F/U 
gb&, f 2 wk.
 26
527528$ warfarin 0
  2 ,-


~ ,

 


 2 "
 2 3D

6
!5)
$
!3 0E0


 Enalapril 5 mg 1x2
Target INR 2.0-3.0


#$%&'$ 3 ()
 /3  /+

INR

6 .6. 2549

2.76

5 .6. 2550

2.82

30 $.6. 2550

4.53

29 .. 2550

2.68

27 .. 2550

3.33

Medications

)

#$%&'$ 3 ()

Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)

Problem list : high INR

Problem list : high INR ()

 
 6
  
2
7528

   !!32 b 3
0"
0 

 
b3

 
 



3   7528$
f !b2 ! 1&!  $
60  !32 Ciprofloxacin (500 mg) 1 x 2

CIPROFLOXACIN

CIPROFLOXACIN

 Protein Binding 1616-43%


 CYP 1A2 Inhibitor
 Significance 4
 Onset
 Delayed
 Severity  Moderate
 Documentation  Possible
 Mechanism
 Unknown
 Management
 Monitor patients closely

,
- b DNA gyrase $|"f
bactericidal - 203 gut flora 70 2


2 Vitamin K 030 - 2  risk of
bleeding

Problem list : high INR ()

Pharmacist
Pharmacists intervention

 
 

0$ 0 |







/3} 
$$ 65 7528!!32
0$ 0 |




 
$7 
 
 
~2
7528!$0 3 0!$
b00 3
)3 $7 

#$%&'$ 4

#$%&'$ 3 ()
 /3  /+

INR

6 .6. 2549

2.76

5 .6. 2550

2.82

30 $.6. 2550

4.53

29 .. 2550

2.68

27 .. 2550

3.33

 12 2 


4&)$- 26 INR 5 6
, $,
31

 Ciprofloxacin 0 Warfarin
0!32  2)3 1-2  02
 32b 3
3 6  Warfarin 3 mg 1 x 1 037528
gb&,

Medications

)

Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)

#$%&'$ 4 ()
 
 2
"
 2 3D
 
6 !5)
$ !3 0E0
 


 Moduretic
1x1
 Digoxin 0.25 mg
1x1
 Target INR
2.0-3.0

!3$ ) 22 + ,-  59 Kg $ %&'


50- 513 6

$

1 3
 
-6
 

73 7528!32

730$ 0,  1$
$0, !
0 32 Edwards MIRA 27 mm   19 .. 2547
$
. 
 6

$

#$%&'$ 4 ()
 /3  /+

INR

Medications

20 ".6. 2548

2.56

14 $.6. 2549

2.35

4 .6. 2549

4.18

29 .6. 2549

2.53

Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
3 3 
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)
Warfarin 3 mg 1+1/2x1
(4.5 mg/d)

)


#$%&'$ 4 ()

Problem list : high INR


 
 6
  
2
7528

   !!32 b 3
0"
0 

 
b3

Problem list : high INR ()


 
 



$7 7528$
32!~ ,


 !32 cimetidine

CIMETIDINE
 Protein Binding 20%
 CYP3A3/4 Substrate
 CYP 1A2 , 2C9, 2C18, 2C19, 2D6 AND 3A3/4 Inhibitor
 Significance 1
 Onset  Delayed
 Severity  Major
 Documentation  Established

 Mechanism
 Inhibition of warfarin metabolism

 Management
 Avoid if possible; alternative NIZATIDINE , FAMOTIDINE

Problem list : high INR ()


 
 

0$ 0 |




 

/3} 
$$ 65 7528!!32
0$ 0 |




 
$7 
 
 
~2
-7528$1,-0 3$b 2 b2 b 32 7%5 0 2-3 ~.
1-  3 1)3 7528g   2  $02
- !$
b00 3)3 $7 

Pharmacist
Pharmacists intervention
 12 2 
4&)$- 26 INR 5 6
, $,
31

 cimetidine 0 warfarin 0
!32  2!b3 $,
   2)3 2  02
 32b 33
6  Warfarin 3 mg 1+1/2x1


#$%&'$ 5

#$%&'$ 5 ()

!65 ) 75 + ,-  68 /0


 $
!!32- 50- 513 6

$

-6 
1 3

 2 "
 2 3D

6
!5)
$ !3 0E0

 
61g8
8 . 6. 2550 Atrial fribillation , TIA , CHF
 


 Irbesartan 150 mg
1x1
 Furosemide 40 mg
1x1
 Dilatrend 25 mg
x1
 Target INR
2.0-3.0

#$%&'$ 5 ()

#$%&'$ 5 ()

 /3  /+
8 .6. 2550
22 .6. 2550

24 .6. 2550

INR
1.28

1.0

Medications
Warfarin 3 mg 1/2x1
Warfarin 3 mg
1/2x1 1 
4&
 ,
1x1  1 g3
Warfarin 3 mg
1/2x1 1 
4&%)
 ,
1x1 
0 

#$%&'$ 5 ()

)

 /3  /+

INR

Medications

24 .. 2550

0.98

13 .. 2550

0.99

Warfarin 3 mg
1/2x1 1 
4& | ,
1x1 %)
 4& 
Warfarin 3 mg
1x1 1 
4&%)
 ,
1/2x1 
0 

)

Problem list : low INR


 
 6
  
2
7528

   "
0 


 
b3 0!!32 b 3

Problem list : low INR ()



 



7528$
01g0$
+
32 
.  & 2
carbamazepine (200) 1x2

CARBAMAZEPINE





Protein Binding 7575-90%


CYP 2C8 AND 3A3/4 Substrate
CYP 1A2 , 2C AND 3A3/4 Inducer
Significance 2
Onset
 Delayed
Severity
 Moderate
Documentation  Suspected

 Mechanism
Induction of warfarin metabolism

 Management
Monitor PT when beginning or stopping

Problem list : low INR ()



  
enzyme inducer  !
CYP 3A4 (  warfarin
metabolism1234 warfarin

5167894 9
:93;4 < 10-35 ABC BD E

enzyme inducer
B!4
( E9<
100%  A G9< 45 ABC B95167

Pharmacists intervention
 12 2 
4&)$- 26 INR - 6
, $,
31

 carbamazepine 0 warfarin
0!32  2!b3 $,
   2)3 carbamazepine 06b 336 
Warfarin 3 mg 1/2x1 1 
4& | %)
 4&  1 g3
 2 2 carbamazepine  2 b 3 20% f 18
mg/week /3 2f Warfarin 3 mg 1x1 1 
4&%)
 , 

0 1/2x1

Problem list : low INR ()



  H (5!
AI1

:9J(
1 !KLM (IM4N8894
  H (5!AI1
3; 1

OH1P4

M4N8
E
O   
9
G9!AH O
 
9

3; 1 

0
1
#
 (B<QBBA
 R ; 834K
33;4
 E91 894AI8L
 ( 3
G93;491 3;4 A
 !BL
IASTM2BA9B 
 8
 !BL
IH! U substrate , inhibitor

inducer
  8(C L KX1 9AIM4NASLA(A6XAI
1 894AI

 
2!b
  20$ 
1-f 2 2

 26
52
 37528  023
 
b 3

Drug info resource for interaction


Drug Interaction Textbook
Drug Information (AHFS, Lexicomp, etc. )
CCIS or Micromedex
Monograph (Prescribing Information,
package insert)
If no info, look at PK, make best judgement
for monitoring

Pharmacist intervention
Policy
 Find the way to identify and communicate
 Education session for other healthcare personnel

Individual care
 Set up clinic
 Make rounds focus at high alert drugs

Intervention directed to patients


 Education ; Drugs, herbal, vitamin, nutritional
supplement, food, drinks, etc.

Pharmacist intervention
Policy
 Find the way to identify and communicate
 Education session for other healthcare personnel

Individual care
 Set up clinic
 Make rounds focus at high alert drugs

Intervention directed to patients


 Education ; Drugs, herbal, vitamin, nutritional
supplement, food, drinks, etc.

Thank you

10