一 PRADAXA 適應症與健保給付規範 4 二 PRADAXA 的用藥方法與建議劑量 7 三 如何由其他抗凝血藥物療程轉換使 用 PRADAXA 12 四 抗凝血效果的評估 15 五 藥物不良反應與併發症的處置 17 六 藥物交互作用與其他用藥注意事項 21 七 如何在手術 / 燒灼術 / 心臟整

Guidebook

一 PRADAXA 適應症與健保給付規範 4 二 PRADAXA 的用藥方法與建議劑量 7 三 如何由其他抗凝血藥物療程轉換使 用 PRADAXA 12 四 抗凝血效果的評估 15 五 藥物不良反應與併發症的處置 17 六 藥物交互作用與其他用藥注意事項 21 七 如何在手術 / 燒灼術 / 心臟整流術患者使 用 PRADAXA 23 2

-- Pradaxa Guidebook -- 八 使用 PRADAXA 患者發生急性中風的處置方式 27 九 如何在心房顫動和冠狀動脈疾病患者使用 PRADAXA 29 十 如何在慢性腎臟病患者使用 PRADAXA 32 十一 索引 34 3

PRADAXA (novel oral anti-coagulant, NOAC) PRADAXA (Dabigatran) (direct thrombin inhibitor) 1 PRADAXA 110 mg 150 mg 2 2012 6 3 4

-- Pradaxa Guidebook -- PRADAXA 3 PRADAXA 全民健保給付規定 (1) (1)14 (2) 40% (2) 6 (3) (3) (New York Heart Association Functional (4) Classification) 30 ml/min (5) (4) 75 ( ) (5) 65 74 5

1. PRADAXA : i. (prosthetic heart valve) 4-7 ii. (rheumatic mitral stenosis) 5-6 iii. 4 2. Rankin (modified Rankin Scale, mrs) = 5 6

-- Pradaxa Guidebook -- PRADAXA PRADAXA 110-150 mg 8 H 2 (H 2 -blocker) (proton pump inhibitor, PPI) 8 A B (A) PRADAXA 110 mg (B) PRADAXA 150 mg 7

PRADAXA 75 ( = 30-50 ml/min) (NSAIDs) verapamil quinidine amiodarone clarithromycin 110 mg 110 mg PRADAXA PRADAXA (CrCl) <30 ml/ min 9 PRADAXA 9 PRADAXA ( ) 9 8

-- Pradaxa Guidebook -- PRADAXA PRADAXA ( / ) (CrCl <30 ml/min) (hemorrhagic manifestations) (bleeding diathesis) / (organic lesions) 9

PRADAXA PRADAXA 1. PRADAXA 2. 3. 4. 5. 6 10

-- Pradaxa Guidebook -- 6. 7. PRADAXA 11

PRADAXA warfarin [ (unfractionated heparin)] PRADAXA PRADAXA 11 PRADAXA aspirin/clopidogrel 10, 11 warfarin PRADAXA warfarin (international normalized ratio, INR) 2.0 PRADAXA 11 停止使用 VKA 於 INR<2.0 之後, 立即服用第一劑 Pradaxa 12

-- Pradaxa Guidebook -- PRADAXA 0-2 PRADAXA 11 第一劑 Pradaxa 0 2 小時 下一劑注射型抗凝血劑的施打時間 ( 不再用藥 ) heparin PRADAXA PRADAXA 11 連續性治療 ( 例如,IV UFH) 結束連續性治療, 並開始服用第一劑 Pradaxa 13

PRADAXA warfarin CrCl warfarin 11 CrCl >50 ml/min PRADAXA 3 warfarin CrCl = 31-50 ml/min PRADAXA 2 warfarin PRADAXA PRADAXA 12 (CrCl 30 ml/min) 11 最後一劑 Pradaxa 12 小時 第一劑注射型抗凝血劑或開始進行連續性治療 14

-- Pradaxa Guidebook -- PRADAXA (coagulation assay) 11 : 1. 2. 3. 15

16 PRADAXA aptt INR (activated partial thromboplastin time) (international normalized ratio) * >2 >80 aptt PRADAXA PRADAXA * (trough value) (heparin) aptt

-- Pradaxa Guidebook -- PRADAXA 8, 12 H 2 -blocker PPI 8 11 PRADAXA 12-17 80% 11, 13 aptt 10, 11, 13 PRADAXA 9 Dabigatran etexilate dabigatran ( 14 ) 11, 13 PRADAXA 9, 11 17

PRADAXA 9-11 K K PRADAXA? ( )?? PRADAXA *( PRADAXA 2 ) ( ) PRADAXA 18

-- Pradaxa Guidebook -- / ( ) (clotting factor concentr ates) 1. (prothrombin complex concentrates PCC)* 2. VIIa (rfvlla)* 3. ( aspirin clopidogrel) (platelet concentrate) PRADAXA aptt 10, 13 19

PRADAXA ( [colloids]) ( 60 10 9 /L) PCC* 25 U/kg ( 1-2 ) apcc* 50 IE/kg ( 200 IE/kg/day) rfviia* 90 μg/kg ( ) ( NOAC ) *PCC PRADAXA PRADAXA 20

-- Pradaxa Guidebook -- PRADAXA 9, 11, 15 PRADAXA 9-11, 15 PRADAXA PRADAXA P-gp (P-glycoprotein antagonists) Systemic ketoconazole, itraconazole, tacrolimus, cyclosporine, dronedarone HIV protease inhibitors (ritonavir, saquinavir) P-gp (P-glycoprotein inducers) rifampin, St. John's wort (Hypericum perforatum), carbamazepine, phenytoin, pentobarbital/ phenobarbital, prazosin, tenofovir 21

PRADAXA 110 mg aspirin, clopidogrel, ticagrelor NSAIDs diclofenac, ibuprofen, piroxicam P-gp verapamil, quinidine, amiodarone, clarithromycin PRADAXA atorvastatin, pantoprazole, ranitidine, digoxin, diltiazem 22

-- Pradaxa Guidebook -- / / PRADAXA / PRADAXA( ) 9, 11 PRADAXA (CrCl, ml/min) PRADAXA 80 1 2 50 - <80 2 3 30 - <50 3 4 PRADAXA (onset) (offset) (bridging therapy) 11 23

10 ( ) ( biopsy) / ICD ( ) Pulmonary vein isolation VT ablation / / (TURP) 24

-- Pradaxa Guidebook -- 6, 16 (TIA) 6 PRADAXA 3 12-24 ( 1-2 PRADAXA) 6 heparin heparin 3-4 ( ) PRADAXA PRADAXA 6 5, 6 PRADAXA PRADAXA 3 4 5, 6 25

10 PRADAXA 6-8 48-72 * * unfractionated heparin low molecular weight heparin 15 26

-- Pradaxa Guidebook -- PRADAXA (acute phase) PRADAXA ( ) 10 (post-acute phase) 10-14 PRADAXA ( ) 10 27

(acute phase) PRADAXA 3 48 PRADAXA (recombinant tissue plasminogen activator) 10 (post-acute phase) PRADAXA 10 TIA 1 3 6 2-3 28 ( )

-- Pradaxa Guidebook -- PRADAXA PCI(percutaneous coronary intervention) (dual anti-platelet therapy) (triple therapy) 5, 6, 10 PCI (bare metal stent, BMS) triple therapy BMS 2-4 (drugeluting stent, DES) 3-6 PRADAXA 110 mg 17 PRADAXA 110 mg 1 5, 6, 10 1 PRADAXA 5, 6, 10 PRADAXA 110 mg 5, 6, 9-10 29

AF * Low or intermediate haemorrhagic risk (HAS-BLED 0-2) Elective PCI ACS BMS Triple therapy 1 mon DES Triple therapy 3-6 mons BMS/DES Triple therapy 6 mons OAC+ 1 AP up to 12th mon OAC+ 1 AP up to 12th mon OAC+ 1 AP up to 12th mon OAC = OAC Lifelong OAC Lifelong OAC Lifelong 30 * AF patients with moderate to high thromboembolic risk, PCI= percutane DES=Drug-eluting stent, Triple therapy=oac+ ASA 100mg/day+ clopido AP= clopidogrel 75mg/day or ASA 100mg/day, OAC= Vitamin K antagon Adapted from: Eur Heart J (2012) 33, 2719-2747. (2012 ESC guidelines)

-- Pradaxa Guidebook -- High haemorrhagic risk (HAS-BLED 3) Elective PCI ACS BMS Triple therapy 2-4 weeks BMS Triple therapy 4 weeks VKA or NOAC OAC+ 1 AP up to 12th mon OAC Lifelong OAC Lifelong ous coronary intervention, BMS= Bare-metal stent, grel 75mg/day ist or NOAC (novel oral anticoagulant) 31

PRADAXA (chronic kidney disease, CKD) PRADAXA CKD 10 PRADAXA CrCl >30 ml/min 9, 11 PRADAXA (CrCl, ml/min) 50 PRADAXA 150 mg 30-50 110 mg <30 PRADAXA 32

-- Pradaxa Guidebook -- References 1. Stangier J et al. Br J Clin Pharmacol 2007; 64:292-303. 2.. http://www.fda.gov.tw 3.. http://www.nhi.gov.tw 4. Wann LS et al. J Am Coll Cardiol 2011; 57:1330-7. 5. Camm AJ et al. Eur Heart J 2012; 33:2719-47. 6. January CT et al. J Am Coll Cardiol 2014 Mar 28. doi: 10.1016/ j.jacc.2014.03.022. 7. Van de Werf F et al. Am Heart J 2012; 163:931-7.e1. doi: 10.1016/ j.ahj.2012.03.011. 8. Nieuwlaat R, et al. 2013 ESC Poster: P549. 9. PRADAXA (Dabigatran) Prescriber Guide (Updated July 2014). 10. Heidbuchel H et al. Europace 2013; 15:625-51. doi: 10.1093/ europace/eut083. 11. PRADAXA (Dabigatran) ( 025458/025459 ). 12. Connolly SJ et al. N Engl J Med 2009; 361:1139-51. 13. van Ryn J et al. Thromb Haemost 2010; 103:1116-27. 14. Schiele F et al. Blood 2013; 121:3554-62. 15. Queensland Health: Guideline for Managing Patients on Dabigatran (PRADAXA ), May 21, 2013. http://www.health.qld.gov.au/qhcss/mapsu/documents/ dabigatran_info.pdf 16. Calkins H et al. Heart Rhythm 2012; 9:632-696.e21. doi: 10.1016/ j.hrthm.2011.12.016. 17. 17. You JJ et al. Chest 2012; 141(2 Suppl):e531S-75S. doi: 10.1378/ chest.11-2304. 33

34 A amiodarone amiodarone 8, 22 anaphylactic shock 9 angiography 24 aspirin 12, 19, 22 atorvastatin atorvastatin 22 B bare metal stent (BMS) 29, 31 bladder biopsy 24 bleeding/hemorrhage 5, 9, 11, 15, 16, 17, 18, 19, 20, 21, 23, 24, 26, 27, 28, 32 bleeding diathesis 9 bleeding disorders 9 blood transfusion 19 blood volume replacement 19, 20 C chronic kidney disease (CKD) 32 clarithromycin clarithromycin 8, 22 clopidogrel clopidogrel 12, 19, 22, 30, 31 clotting factor concentrates 19

-- Pradaxa Guidebook -- coagulation 15, 16, 17 coagulation assay 15, 16 colloids 20 continuous anti-coagulation therapy 12, 13, 14 coronary artery disease (CAD) 29, 30 creatinine clearance (CrCl) 5, 8, 23, 32 D dehydration 8 diabetes mellitus 5 dialysis 18, 20 digoxin digoxin 22 diltiazem diltiazem 22 dizziness 11 drug-eluting stent (DES) 29 drug overdose 17 dyspepsia 11, 17 E ecchymosis 11 electroablation 23, 24, 25 electrosurgery 24 embolism 4, 5, 27, 28, 32 epistaxis 11 F fatigue 11 35

G gastralgia 11 gastritis-like symptoms 17 gastrointestinal adverse event 17 gastrointestinal discomfort 7, 10, 11 H H 2 -blocker H 2 7, 17 headache 11 heart failure 5 heart valve disease 5, 6 hematemesis 11 hemodialysis 18, 20 hemoptysis 11 hemorrhagic manifestations 9 hepatic disease 5, 9 hepatic dysfunction 9 hypersensitivity reaction 9 hypertension 5, 27 I international normalized ratio (INR) 12, 16 intracranial hemorrhage 27 ischemic stroke 28 36

-- Pradaxa Guidebook -- L long-term anti-platelet therapy 19 lumbar puncture 24 M major plastic surgery 24 modified Rankin Scale (mrs) Rankin 6 N New York Heart Association (NYHA) Functional Classification non-steroidal antiinflammatory drug (NSAID) novel oral anti-coagulant (NOAC) O 8 4, 20, 31 organic lesions 9 overdose 10 P pantoprazole pantoprazole 22 pathological bleeding 9 P-glycoprotein antagonists P-gp 21, 22 P-glycoprotein inducers P-gp 21 platelet concentrate 19 prostate biopsy 24 5 37

prosthetic heart valve 6 prothrombin complex concentrates (PCC) proton pump inhibitor (PPI) 7, 17 R ranitidine ranitidine 22 recombinant Factor VIIa (rfvlla) VIIa 19 19, 20 renal impairment 8, 9 rheumatic mitral stenosis 6 S spinal or epidural anesthesia 24 T thrombosis 26, 28, 30 transient ischemic attack (TIA) 25, 28 transurethral resection of the prostate (TURP) 24 triple therapy 29, 30, 31 trough value 16 U ulemorrhagia 11 unfractionated heparin 12, 26 V verapamil verapamil 8, 22 W warfarin warfarin 12, 14 38

-- Pradaxa Guidebook -- This publication is sponsored by Boehringer Ingelheim Taiwan Ltd. as a service to the medical profession. No responsibility is assumed by Elsevier, its licensors or associates, for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Because of rapid advances in the medical sciences, in particular, independent verify cation of diagnoses and drug dosages should be made. Although advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. Produced by Elsevier 2014 Elsevier 14ET037 39

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