BUDDHACHINARAJ MEDICAL JOURNAL

59

Drug Insights

: Dabigatran
, .., ..

New Anticoagulant: Dabigatran

Napawan Jeanpeerapong, B.Sc.in Pharm., M.Sc.

Abstract

Traditional anticoagulants have limitations such as narrow therapeutic index, variable dose-response
among individuals, drug and food interaction. This article presents new anticoagulant in direct
thrombin inhibitor group. Generic name of this drug is dabigatran. Pharmacokinetic,
pharmacodynamic, adverse drug reaction, caution and precaution including clinical trials comparison
with traditional anticoagulants have been reviewed. In order to have an alternative treatment,
prevention of venous thromboembolism and also with stroke prevention in patients with atrial
fibrillation in a new anticoagulant drug which safer and easier administration than traditional
anticoagulant.

Keyword: anticoagulant, dabigatran, direct thrombin inhibitor

Buddhachinaraj Med J 2013;30(1):59-66.

thrombin

:
2556;30(1):59-66.

Department
of Pharmacy,
-

Buddhachinaraj
Phitsanulok Hospital

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60

New Anticoagulant

(anticoagulation)
(fibrin)
low
molecular weight heparin enoxaparin,
tinzaparin anti-Factor Xa inhibitor
fondaparinux, rivaroxaban direct thrombin
inhibitor lepirudin, argatroban, dabigatran

dabigatran


50 warfarin





international normalized ratio (INR)

50 1

thrombin
(dabigatran)

(venous
thromboembolism)

Dabigatran
C34H41N7O5-CH4O3S
12 Pradaxa
75, 110, 150
-

1 Dabigatran

(stroke)
(atrial fibrillation)
(systemic
embolism)
2

Postoperative thromboprophylaxis
(knee replacement)
110 1-4
220

(haemostasis) 220
10 3
(hip replacement)

28-35 3

(Stroke)

(non-valvular atrial fibrillation) CrCl

30 /: 150 2 , CrCl
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BUDDHACHINARAJ MEDICAL JOURNAL

15-30 /: 75 2
(CrCl 30-50 /
) 75 1-4 .

(CrCl 30 /)3

61

24

2-4
3 1

1 3
CrCl ( /)
80
50 < 80
30 < 50

(.)

13
15
18

2
2-3
4

1
1-2
2-3

thrombin (serine protease)
fibrinogen fibrin
thrombin (direct thrombin
inhibitor)
(anticoagulant)
(anticoagulation) dabigatran etexilate

(prodrug) dabigatran etexilate
dabigatran
hydrolysis esterase

dabigatran thrombin
4-6 (potent competitive,
reversible direct thrombin inhibitor)
thrombin fibrin-bound
7 heparin inactivate
thrombin fibrin-bound
binding site heparin 7
warfarin
factor II,VII, IX X
vitamin K-dependent coagulation factors
warfarin carboxylation
-

protein C protein S
9

Dabigatran
12-14
2-3
9 34-35
50-70 dabigatran etexilate
dabigatran esterase
dabigatran substrate, inhibitor, inducer
CYP450 dabigatran metabolize
hepatic glucuronidation
acyl glucuronides10
9-10 Stangier
11 13.8, 16.6,
18.7, 27.5 34


12
75
13
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62

Pregnancy Category C2

dabigatran

dabigatran

14

dabigatran

3

(Cardiovascular Effects)
Acute coronary syndrome
Dabigatran
acute coronary
syndrome (unstable angina, myocardial infarction,
and cardiac death) 3315

Rash
24
dabigatran 150 . 2
9
diphenhydramine ( Naranjo
probable)16
3
(esophagitis),
, gastritis, gastroesophageal reflux disease
6.1 dabigatran
150 2 warfarin
4

New Anticoagulant

3
16.6
dabigatran 150 2
warfarin 18.4
3
anaphylaxis, edema, allergy
hypersensitivity reaction 0.1
17
intracranial hemorrhage
0.3 dabigatran 150
2 warfarin
0.8

3
(Contraindication)
dabigatran
CrCl 30
/
hemorrhagic ischemic cerebral infarction
6 P-glycoprotein (P-gp)
inhibitors quinidine, amiodarone, verapamil,
ketoconazole, clarithromycin
(Warning and Precaution)
bacterial
endocarditis, bleeding disorder, thrombocytopenia,
stroke, ,

heparin, enoxaparin,
clopidrogrel, aspirin, NSAIDs
dabigatran

2
75 50

18

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BUDDHACHINARAJ MEDICAL JOURNAL

dabigatran substrate efflux
transporter P-glycoprotein (P-gp) dabigatran
P-gp inhibitors quinidine,
amiodarone, verapamil, ketoconazole, clarithromycin
dabigatran
18 P-gp
inducer rifampicin dabigatran
19 bioavailability
dabigatran
2 20

dabigatran

serum creatinine, BUN
Ecarin clotting time (ECT), activated
partial thromboplastin time (aPTT) thrombin
time (TT) INR
INR PT (prothrombin time)

warfarin biologic activity factors II, VII
X warfarin9
dabigatran
dabigatran
INR ( INR = 2.0
supra-therapeutic concentrations
dabigatran)21
dabigatran venous
thromboembolic events (VTE) 220

INR

dabigatran22
INR

dabigatran
ECT TT
-

63

dabigatran 400 ng/mL

aPTT
dabigatran
( )21

meta-analysis
dabigatran 220

enoxaparin 40
23
RE-LY trial17 atrial fibrillation 18,113
dabigatran
150 2 110
2 warfarin
3 1 warfarin
INR 2-3 2
dabigatran 150 2 3
dabigatran 110 2
2 3
(significant valvular
heart disease)
stroke systemic
embolism dabigatran 110
2
stroke systemic embolism atrial
fibrillation warfarin (relative risk 0.91,
95%CI 0.74-1.11, p = 0.34) major bleeding
warfarin dabigatran 150
2
stroke systemic embolism atrial
fibrillation warfarin (relative risk 0.66, 95% CI
0.53-0.82, p < 0.001) major bleeding

dabigatran 150
2 warfarin
75
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New Anticoagulant

dabigatran 110 2
warfarin
dabigatran 150 2
stroke dabigatran 110
2 major bleeding (
20 /
2

hemorrhagic stroke) dabigatran

110
(creatinin clearance 30-50
/) stroke
dabigatran 110 150
bleeding
24 2

2 75

/100
Dabigatran 110 .

Dabigatran 150 .

Warfarin

75 24
Stroke/embolism

1.89 (n = 87)

1.43 (n = 69)

2.14 (n = 101)

Major hemorrhage

4.43 (n = 204)

5.10 (n = 246)

4.87 (n = 206)

2.36 (n = 1,136)

1.23 (n = 1,157)

2.64 (n = 1,050)

5.42 (n = 1,136)

5.08 (n = 1,157)

5.28 (n = 1,050)

25
Stroke/embolism
Major hemorrhage

dabigatran
110

26-27
dabigatran 110 .. 2551
.. 2553



110

(non-valvular atrial fibrillation)

27

warfarin 50

(narrow therapeutic drug)

INR
direct
thrombin inhibitor warfarin

warfarin



dabigatran

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BUDDHACHINARAJ MEDICAL JOURNAL

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