1. Dabigatran: Medication Use Evaluation
Jenna M. Faircloth, PharmD
PGY1 Pharmacy Practice Resident
Vanderbilt University Medical Center
June 22, 2012

2. Situation
SBAR
Dabigatran is an oral direct thrombin inhibitor recently added to formulary
Of all drugs marketed in US, dabigatran had the highest number of serious adverse events reported to the FDA in 2011
3781 (2367 hemorrhages; 542 deaths) versus 1,106 events with warfarin (72 deaths)

3. Background SBAR Dabigatran (Pradaxa®)
MOA: Competitive, direct and reversible inhibitor of thrombin
Works on platelet-derived, clot-bound and free-floating thrombin
Absorption/Metabolism: Oral prodrug converted in the liver through esterases to the active compound
Elimination: Urine
Does not require routine lab monitoring

4. Background SBAR Key Monitoring Parameters
Adjustment for renal function
Conversions from anticoagulants to/from Dabigatran
Adjustment for drug-interactions
Holding prior to surgical procedures

5. Assessment SBAR Time period evaluated Data Collected
January January 2012
Data Collected
Age, weight, gender, BMI
Dose and frequency
Indication
If applicable, CHADS2 score
New initiation or home medication
Past medical history
Diagnosis of cancer
Creatinine Clearance (Cockgroft-Gault), Hgb, PCV
Acute kidney injury (AKI) events during admission
Active medications
Invasive procedure during admission
Bleeding event during admission
Readmission for bleeding event
Drug discontinuation due to adverse event

6. Assessment SBAR Evaluated 103 hospital admissions in 94 patients
Baseline Characteristics
(n=103)
Demographics
Gender
Male
Female
58 (56.3%)
45 (43.7%)
Race
White
Black
Other
98 (95.1%)
4 (3.9%)
1 (1%)
Mean age
66 ± 13.1
Mean BMI
32 ± 10.1 Obesity (Class 1)
Creatinine Clearance (mL/min)
< 15
15-29
30-50
> 50
0 (0%)
12 (11.7%)
26 (25.2%)
65 (63.1%)
Acute Kidney Injury episodes
7.8% (8/103)

7. Assessment SBAR Baseline Characteristics (n=103) New initiation
Home medication
48 (47.5%)
53(52.5%)
Indication
Atrial fibrillation
Atrial flutter
DVT/PE treatment
Other
93 (90.3%)
16 (15.5%)
13 (12.6%)
7 (6.8%)
CHADS2 Score (n=100) 1 2 3 4 5
14 (14%)
24 (24%)
33 (33%)
19 (19%)
3 (3%)
7 (7%)
If 0 or 1, CHA2DS2Vasc Score:
0 =4
1= 10
2= 13
3= 8
4= 2
Diagnosis of Cancer
12 (11.7%)
Concomitantly administered medications
Aspirin
Clopidogrel
NSAIDS
49 (79%)
15 (24.2%)
8 (12.9%)

8. Assessment
SBAR

9. Assessment SBAR Off-label doses (N =17) Low Dose 15
Post ablation procedure* 7
Due to ASA and Clopidogrel 1
Due to high dose ASA &
bruising with minimal contact
Other 6
High Dose 2
*Post-procedure dose reduction is single 75mg dose, therapy resumed at maintenance the follow day

10. Acute Kidney Injury 8/103 (7.8%) patients had an AKI event
Dose adjusted when AKI occurred: 62.5%
Pradaxa Dose Initial
Baseline Cr
Peak Cr
Change in CrCl
Drug Held (Y/N)
Dose changed (Y/N)
Dabigatran adjusted appropriately (Y/N)
Cause of AKI
Comments
150 mg BID
1.37
2.28
19 (47.5-> 28.5) No
Per nephrology note, dehydration due to poor intake; ATN due to intermittent low BP, CIN contrast, or AIN due to ABX
Scr not checked for 7 days. Obtained SCr prior to d/c (CrCl 28.5ml/min) and did not adjust to 75mgBID ; admitted to stallworth- Scr improved to with CrCl 35ml/min. Admitted for GI Bleed 5 days later;
0.63
1.3
36 (75-> 39)
Yes
unknown; had surgery 10 days prior
dose reduced to 75mg BID; Scr not rechecked to see if continued to trend up or down;
0.98
1.89
22 (46->24)
Y es(24 hrs late)
possibly overdiuresis with Furosemide
team did not adjust for 24 hours dose until 24hr after patient dropped below 30ml/min.

11. Drug Interactions Assessment SBAR
7.8% (8/103) concurrently taking Dronedarone

12. Conversion from anticoagulants to Dabigatran
Assessment
SBAR
Conversion from anticoagulants to Dabigatran
87.4% (90/103) of anticoagulants converted per FDA label
Anticoagulant Agent
Appropriately Converted
Inappropriately Converted
Comments
Heparin 23 11
7 overlap duration excessive
- 3 Heparin infusion
- 4 Heparin 5000 units SQ
4 withheld too long
- 3 Heparin 5000 units SQ
- 1 Heparin infusion
Warfarin 4 1
overlap duration excessive
Received Warfarin 15mg dose, dbl home dose, evening before first morning dose of Dabigatran
Enoxaparin 5
withheld too long
Warfarin dose was double home dose (15mg – 7 mg normal home dose)

13. Evaluation of holding prior to invasive procedures
Assessment
SBAR
Evaluation of holding prior to invasive procedures
Invasive procedures in 30.1% (31/103) of population
3 procedures were emergent
Procedure Type
Ablation 18
LHC/PCI 3
Orthopedic 2
AAA repair 1
AV balloon valvuloplasty
Bilateral thoracoscopy
Pacemaker implant
BiV ICD
Thyroid Biopsy

14. Evaluation of holding prior to invasive procedures
Assessment
SBAR
Evaluation of holding prior to invasive procedures
Dabigatran was held per FDA labeling based on CrCl in 19 of 31 procedures (61.3%)
In remaining 12 cases, medication was not held per labeling
RF ablation= 9*
Dual chamber pacemaker implant = 1
PCI with stent = 2
Orthopedic procedure= 1
*routine process for prevention of perioperative stroke

15. Bleeding Events Assessment SBAR
12.6% (13/103) patients experienced drop in Hgb ≥ 2mg/dL
Mean patient age: 73 years old
12 dosed per FDA labeling
1 under dosed
Site of bleed
9 Unknown
3 GI bleeds
1 Sub-dural
5 required transfusions
2 invasive procedures

16. Readmission for bleeding event
Assessment
SBAR
Readmission for bleeding event
3 readmissions (2.9%) for bleeding event
Site: GI bleed
Age
Dose
CHADS2 score
Renally adjusted
(Y/N)
Concomitant medications
Anticoag
Overlap excessive
Invasive procedures
Comments 63
150mg BID 2
Yes/No
Dronedarone No
Bilateral Amputee patient –CrCl unclear 69 1
Yes
n/a
Yes- Heparin infusion 76

17. Therapy Discontinuation
Assessment
SBAR
Therapy Discontinuation
6.8% (7/103)- discontinuation due to an adverse event
Reason for discontinuation
Approximate Days of therapy until d/c
Inpatient or outpatient d/c
Subdural hematoma, recurrent falls
28 days
Inpatient
Severe joint pain
122 days
Outpatient
Dyspepsia
50 days
GI complaints
210 days
GI bleed
91 days
Severe epigastric pain and possible GI bleed
16 days
Stomach pain and lightheadedness
150 days

18. Recommendations
SBAR
Require height and serum creatinine for prior to ordering therapy
During order processing, pharmacist to evaluate for drug interactions and renal function
Dispense message to provide reminder
Dashboard monitoring of appropriate dose for renal function, drug-interactions, Hgb/Hct

19. Recommendations SBAR Continue patient education prior to discharge
Education to providers regarding proper conversion of anticoagulants
Education to providers regarding proper holding prior to invasive procedures

20. Dabigatran: Medication Use Evaluation
Jenna M. Faircloth, PharmD
PGY1 Pharmacy Practice Resident
Vanderbilt University Medical Center
June 22, 2012

21. Appendix A. Key Monitoring Parameters Adjustments for renal function
150mg BID = estCrCl >30mL/min
75mg BID = estCrCl 15-30ml/min
Not Recommended = est CrCl <15ml/min and/or HD
Conversions from Anticoagulation to/from Dabigatran
LMWH/Fondaparinux to Dabigatran = Stop parenteral agent and administer dabigatran 0-2h before next parenteral dose due
Continuous parenteral anticoagulant to Dabigatran = Administer first dose of dabigatran at the time of discontinuation of IV anticoagulant
Dabigatran to parenteral anticoagulant = CrCl >30mL/min, start parenteral anticoagulant 12 hours after the last dose of dabigatran; CrCl <30mL/min: Start parenteral anticoagulant 24 hours after the last dose  of dabigatran
Warfarin to Dabigatran= initiate when INR < 2.0
Dabigatran to warfarin = CrCl >50mL/min, start warfarin 3 days before discontinuing dabigatran
                                           CrCl 30-50mL/min, start warfarin 2 days before discontinuing dabigatran
                                            CrCl 15-30mL/min, start warfarin 1 day before discontinuing dabigatran
                                            CrCl <15mL/min, no recommendations can be made
Adjustments for Drug Interactions
Ketoconazole: Switch 150mg BID to 75mg BID if estCrCl=30-50mL/min and D/C if estCrCl <30mL/min
Dronedarone: Switch 150mg BID to 75mg BID if estCrCl=30-50mL/min and D/C if estCrCl <30mL/min
Rifampin: Avoid concomitant use
NSAIDs: Use with caution; Increase risk of bleeding
Duloxetine: Use with caution; Increase risk of bleeding
Holding Prior to Surgical Procedures
estCrCl >50mL/min = Hold dabigatran 1 to 2 days
estCrCl <50mL/min = Hold dabigatran 3 to 5 days
May require doses to be held longer in patients undergoing major surgery, spinal puncture, or placement of a spinal /epidural catheter , port