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Management of Direct Oral Anticoagulants in Anticoagulation Clinic - Adult - Ambulatory [152]

Management of Direct Oral Anticoagulants in Anticoagulation Clinic - Adult - Ambulatory [152] - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Delegation/Practice Protocols, Ambulatory Delegation Protocols


Delegation Protocol Number: 152

Delegation Protocol Title:
Management of Direct Oral Anticoagulants in the Anticoagulation Clinic – Adult – Ambulatory

Delegation Protocol Applies To:
UW Health Anticoagulation Clinics

Target Patient Population:
Adult patients referred to the UW Health Anticoagulation Clinic who have been initiated on or plan to
initiate on an oral anticoagulant commonly known as novel oral anticoagulants (NOAC) or direct oral
anticoagulants (DOAC) (i.e. dabigatran, rivaroxaban, apixaban or edoxaban)

Delegation Protocol Champion:
David Ciske, MD – Department of Medicine - Internal Medicine/Anticoagulation

Delegation Protocol Reviewers:
Anne Rose, PharmD - Pharmacy
Erin Robinson, PharmD, CACP - Pharmacy

Responsible Department:
Department of Pharmacy

Purpose Statement:
This protocol delegates authority from the referring provider to Pharmacists the initiation, assessment,
dose adjustment and monitoring of novel or direct oral anticoagulants. The protocol delegates authority to
Pharmacy Technicians to order laboratory tests and patient assessment questionnaire.
For the purpose of this protocol novel or non-vitamin K oral anticoagulants will be referred to as direct
oral anticoagulants or DOACs

Who May Carry Out This Delegation Protocol:
Pharmacists (RPh) and Pharmacy Technicians who have documented completion of training in the use of
this delegation protocol. Completion of protocol competency checklist to be maintained by the clinic
anticoagulation champion.

Guidelines for Implementation:

A. Protocol Initiation
1. The protocol is enacted when a patient is referred to the UW Health Anticoagulation Clinic for DOAC
education and/or medication management as indicated on the clinic referral form.
2. All patients receiving a DOAC and managed through this protocol should be entered into the
anticoagulation monitoring tool and will require the “Enroll in Anticoagulation” order to both
activate this tool and delegate protocol management. The “Enroll in Anticoagulation” order must be
sent for co-signature to the Anticoagulation Medical Director per protocol.

Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


B. Patient Assessment
1. Initial assessment – first interaction with the patient after protocol initiation the pharmacist will:
1.1. Verify or change to appropriate dose based on indication, age, weight, renal function, hepatic
function, drug interactions, and anticipated length of therapy as defined for the prescribed
agent in Tables 1-3.
1.2. Ensure the absence of contraindications (i.e. prosthetic heart valve or significant valvular
disease) to DOAC therapy.
1.3. Assist with transitioning between anticoagulants, if requested in consult, using Table 4.
1.4. Order/review baseline labs (see section D).
1.5. Ensure ability to acquire medication based on insurance coverage and/or available drug
discount options.
1.5.1 If patient unable to acquire medication then the prescriber will be contacted for an
alternative anticoagulation plan.
1.6. Provide patient education emphasizing the importance of compliance, drug interactions,
instructions for missed doses, and when to seek medical attention for
bleeding/thrombosis/stroke symptoms.
2. First 12 months of therapy the pharmacy technician will contact the patient at defined time intervals
during first year of therapy: (see Table 5).
• 1 week
• 1 month
• 3 month
• 6 month
• 12 month
2.1. At each patient contact the pharmacy technician will administer a pre-defined patient
assessment questionnaire and document the responses in the medical record (see Appendix A).
2.2. The questionnaire will assess the patient for:
2.2.1. Medication compliance
2.2.2. Medication changes
2.2.3. Signs and symptoms of bleeding
2.2.4. Signs and symptoms of thromboembolism or stroke
2.2.5. Need for periprocedural anticoagulation planning
2.3. If there are any positive findings from the questionnaire or the laboratory results (see section D)
the pharmacy technician will forward to the pharmacist in the Anticoagulation Clinic to
evaluate and contact the patient.
2.4. If all findings from the questionnaire or the laboratory results are negative or within normal
range (section D) the pharmacy technician will instruct the patient to continue with current
dosing regimen and schedule appropriate follow up. The pharmacy technician will forward the
encounter to the pharmacist for review and co-signature.
3. Maintenance therapy – beyond first 12 months of therapy the pharmacist and/or pharmacy
technician will have continued follow up, as described in 2.2, with the patient based on outlined
schedule: (see Table 6)
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


3.1. Patients with Creatinine Clearance CrCl > 60 mL/min: yearly
3.2. Patients with CrCl 30-60 mL/min, > 75 years old, or as directed by anticoagulation clinic medical
director: every 6 months
3.3. Patients with CrCl 15-29 mL/min: every 3 months

C. DOAC Dose Adjustments
1. Dose adjustments will be made by the pharmacist based on manufacturer recommendations.
(Tables 1-3)
2. Reasons for dose adjustments may include: patient age, weight, renal function, and concomitant
drug interactions.
3. If dose adjustment recommendations are unclear the pharmacist will discuss with the prescriber or
medical director of the anticoagulation clinic prior to making a dose adjustment.

D. Laboratory Monitoring
1. Baseline laboratory monitoring – resulted within the 3 months prior to starting DOAC (See Table 4).
1.1. Hemoglobin (HGB)
1.2. Platelet Count (PLT)
1.3. Alanine aminotransferase (ALT)
1.4. Creatinine (CRET)
1.5. Creatinine clearance (HCCCLR): See – Renal Function Based Dose Adjustments Guidelines
• For patients with a BMI < 30 kg/m
2
, use Cockcroft-Gault equation
• For patients with a BMI > 30 kg/m
2
, use Salazar-Corcoran equation or adjusted weight
Cockcroft-Gault equation
2. Maintenance laboratory monitoring (See Table 4).
2.1. At 3 and 6 months of therapy
2.1.1. HGB and PLT
2.1.2. CRET and HCCCLR
2.2. At 12 months of therapy
2.2.1. HGB and PLT
2.2.2. CRET and HCCCLR
2.2.3. ALT
2.3. After 12 months if above lab(s) listed in 2.2 are within normal ranges they may be repeated
yearly (See Table 5).
2.4. If above lab(s) listed in 2.2 are abnormal then the abnormal lab must be repeated at least every
3-6 months as directed by the prescriber or anticoagulation medical director.
3. If baseline labs and maintenance labs are not already resulted, the pharmacist or pharmacy
technician may place these orders and send to anticoagulation medical director for co-signature.

E. Documentation
1. For all patients managed per this protocol the following must be documented in the health record:
1.1. Initial Documentation Completed by Pharmacist
1.1.1. Indication for anticoagulation
1.1.2. Anticoagulant medication and dose
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


1.1.3. Patient assessment (Appendix A)
1.1.4. Monitoring and management plan
2. Documentation will occur for each patient assessment time point as defined in Section B.
3. Documentation completed by a pharmacy technician will be routed to the pharmacist for co-sign.

F. Transition Therapy
1. Transitioning from one anticoagulant (subcutaneous or PO) to a DOAC will be directed by the
pharmacist based on manufacturer recommendations (Table 6).

G. Periprocedural Planning
1. For patients undergoing surgery or a procedure that requires the temporary discontinuation of
anticoagulation, the pharmacist will utilize recommendations in the UW Periprocedural and
Regional Anesthesia Guideline to develop a hold plan and communicate this plan to the surgeon or
proceduralist.
2. The pharmacist will communicate the pre-procedure anticoagulation plan to the patient and
document in the health record.
3. If recommendations in the UW Periprocedural guidelines are unclear the pharmacist will discuss
with the prescriber, medical director of the anticoagulation clinic or proceduralist/surgeon to
develop an anticoagulation hold plan.
Order Mode: Laboratory Orders: Consign Required, Protocol/Policy
Medication Orders: Protocol/Policy, Without Cosign
References:
1. Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2011; 365:981-992
2. Agnelli G, Buller HR, Cohen A, et al Oral apixaban for the treatment of acute venous
thromboembolism. N Engl J Med. 2013; 369(9):799-808
3. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism.
N Engl J Med. 2013; 368(8):699-708
4. Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2009; 361:1139-1151
5. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous
thromboembolism. N Engl J Med. 2009; 361:2342-52
6. Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin or placebo in venous
thromboembolism. N Engl J Med. 2013; 368:709-18
7. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban verus warfarin in patients with atrial fibrillation.
N Engl J Med. 2013; 369:2093-104
8. The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous
thromboembolism. N Engl J Med. 2013; 369:1406-15
9. Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N
Engl J Med. 2001; 365:883-891
10. Buller HR, Prins MH, Lensing AW, et al. Oral rivaroxaban for the treatment of symptomatic
pulmonary embolism. N Engl J Med. 2012; 366:1287-97
11. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous
thromboembolism. N Engl J Med. 2010; 363:2499-510
12. Patel J, White R, Finley K. Effect of target-specific oral anticoagulants on a pharmacist-managed
anticoagulation clinic. Am J Health Syst Pharm. 2015; 72:16-17
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


13. Cockroft DW, Gault MH Prediction of creatinine clearance from serum creatinine. Nephron. 1976;
16(1):31-41.
14. Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients
from estimated fat-free body mass. Am J Med; 1988 Jun;84(6):1053-60.
15. Xarelto [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 12/2014
16. Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.;
12/2014
17. Eliquis [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 8/2014
18. Savaysa [prescribing information]. Parsippany, NJ: Daiichi Sankyo, Inc; 1/2015
19. Heidbuchel H, Verhamme P, Alings M, et al. EHRA practical guide on the use of new oral
anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;
34(27):2094-106.
20. Streiff MB, Agnelli G, Connors JM, et al. Guidance for the treatment of deep vein thrombosis and
pulmonary embolism. J Thromb Thrombolysis. 2016; 41:32-67.
21. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical
management of the direct oral anticoagulants (DOACS) in VTE treatment. J Thromb Thrombolysis.
2016; 41:206-232.

Collateral Documents/Tools: NA

Approved By:
UW Health Ambulatory Protocol Committee: September 2016
UW Health Lab Practices Committee: October 2016
UWHC Pharmacy and Therapeutics Committee: November 2016
UWHC Medical Board: December 2016
UW Health Chief Clinical Officer: January 2017

Effective Date: January 2017

Scheduled for Review: January 2020


Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


Table 1. DOAC Dosing Recommendations – Listed Alphabetically
Drug Indication Patient Characteristic Dose
Apixaban Non-valvular Atrial
Fibrillation (NVAF)
CrCl ≥ 15 mL/min
ESRD on hemodialysis
5 mg PO BID
If ≥ 2 of the following:
- Age ≥ 80 years
- Weight ≤ 60 kg
- SCr ≥ 1.5 mg/dL
- ESRD on hemodialysis
2.5 mg PO BID
Venous
Thromboembolism
(VTE) Treatment
CrCl > 15 mL/min 10 mg PO BID x 7 days then 5 mg
PO BID for at least 6 months
VTE Prevention CrCl > 15 mL/min 2.5 mg PO BID (after at least 6
months of a treatment dose)
Dabigatran NVAF CrCl > 30 mL/min 150 mg PO BID
CrCl 15 – 30 mL/min 75 mg PO BID
CrCl 30 – 50 mL/min AND
Dronedarone or
ketoconazole
75 mg PO BID
VTE CrCl > 30 mL/min 150mg PO BID after 5-10 days of
parenteral anticoagulation
Edoxaban NVAF CrCl: > 95 mL/min Contraindicated
(increased stroke risk)
CrCl: 51-95 mL/min 60 mg PO daily
CrCl: 15-50 mL/min 30 mg PO daily
VTE CrCl: > 50 mL/min 60 mg PO daily after at least 5
days of parenteral anticoagulation
CrCl: 15-50 mL/min 30 mg PO daily after at least 5
days of parenteral anticoagulation
Rivaroxaban NVAF CrCl > 50 mL/min 20 mg PO daily with evening
(largest) meal
CrCl 15-50 mL/min 15 mg PO daily with evening
(largest) meal
VTE CrCl > 30 mL/min 15 mg PO BID (with food )x 21
days then 20 mg PO daily (with
food) for remainder of therapy

Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


Table 2. DOAC Dosing Recommendations for Hepatic Impairment – Listed Alphabetically
Mild Hepatic Impairment
Child-Pugh Class A
Moderate to Severe Hepatic Impairment
Child-Pugh Class B/C
Apixaban No dose change Avoid use
Dabigatran No recommendations No recommendations
Edoxaban No dose change Avoid use
Rivaroxaban No dose change Avoid use

Table 3. DOAC Dosing Recommendations for Common Drug Interactions*
Drug Apixaban Dabigatran Edoxaban Rivaroxaban
Amiodarone No specific
recommendations
NVAF: Avoid use if CrCl
< 30 mL/min

VTE: Avoid use if CrCl
< 50 mL/min
No specific
recommendations
No specific
recommendations
Azithromycin No specific
recommendations
No specific
recommendations

NVAF: no dose
adjustment
recommended

VTE: reduce dose
to 30mg PO daily
No specific
recommendations
Clarithromycin Reduce dose by
50%

Avoid use if
already on 2.5mg
BID dose
NVAF: Avoid use if CrCl
< 30 mL/min

VTE: Avoid use if CrCl
< 50 mL/min
NVAF: no dose
adjustment
recommended

VTE: reduce dose
to 30mg PO daily
No specific
recommendations
Carbamazepine Avoid use Avoid use Avoid use Avoid use
Diltiazem No specific
recommendations
No specific
recommendations
No specific
recommendations
Do not use if CrCl
15-80 mL/min
unless benefit
outweighs risk
Dronedarone No specific
recommendations
NVAF: CrCl 30-50
mL/min: Consider
75mg PO BID
Do not use if CrCl < 30
mL/min

VTE: Avoid use if CrCl
< 50 mL/min
No specific
recommendations
Do not use if CrCl
15-80 mL/min
unless benefit
outweighs risk
Erythromycin No specific
recommendations
No specific
recommendations
NVAF: no dose
adjustment
recommended

VTE: reduce dose
to 30mg PO daily
Do not use if CrCl
15-80 mL/min
unless benefit
outweighs risk
Phenytoin Avoid use Avoid use Avoid use Avoid use
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


Drug Apixaban Dabigatran Edoxaban Rivaroxaban
Rifampin Avoid use Avoid use Avoid use Avoid use
Ritonavir Reduce dose by
50%

Avoid use if
already on 2.5mg
BID dose
NVAF: Avoid use if CrCl
< 30 mL/min

VTE: Avoid use if CrCl
< 50 mL/min
No specific
recommendations

Avoid use
Verapamil No specific
recommendations
NVAF: Do not use if
CrCl < 30 mL/min

VTE: Do not use if CrCl
< 50 mL/min
NVAF: no dose
adjustment
recommended

VTE: reduce dose
to 30mg PO daily
Do not use if CrCl
15-80 mL/min
unless benefit
outweighs risk
*This table is NOT all inclusive **NVAF = Nonvalvular atrial fibrillation

Table 4. DOAC Transitioning Recommendations
Apixaban Dabigatran Edoxaban Rivaroxaban
Warfarin
to:
Start when INR < 2 Start when INR < 2 Start when INR < 2.5 Start when INR < 3
Warfarin
From:
Stop apixaban and
start warfarin*
CrCl > 50: start warfarin
and stop dabigatran
after 6 more doses

CrCl 31-50: start
warfarin and stop
dabigatran after 4 more
doses

CrCl < 30: start warfarin
and stop dabigatran
after 2 more doses
Stop edoxaban and
start warfarin*

Stop rivaroxaban
and start warfarin*
LMWH to: Start DOAC at the time of the next scheduled LMWH dose
DOAC to: Start new DOAC at the time of the next scheduled former DOAC dose
* May need parenteral anticoagulation until INR > 2

Table 5. DOAC Monitoring: First 12 Months
AC Clinic Visit Assessment Hgb/Plts Cr (w/ CrCl) ALT
Baseline    
1 week 
1 month 
3 months   
6 months   
12 months    

Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


Table 6. DOAC Monitoring: > 12 Months
Patient AC Clinic Visit Assessment Hgb/Plts Cr (w/ CrCl) ALT
CrCl: 15-29 mL/min Q 3 months  
Annually   
CrCl: 30-60 mL/min
or
Age ≥ 75 years
Q 6 months  
Annually   
CrCl: > 60 mL/min Annually    
*Lab results that fall outside of normal limits should be repeated at least every 3-6 months
Appendix A. Patient Assessment Tool
Question Response
1. Able to afford medication Yes or No
2. Missed doses Yes or No
3. Recent medication, over the counter or supplement changes Yes or No
4. Unusual bruising, bleeding or serious fall or injury Yes or No
5. New or unexplained trouble breathing, pain or swelling in the legs, sudden confusion
or weakness along one side of the body or difficulty speaking
Yes or No
6. Upcoming procedures or surgery Yes or No


Appendix B. Calculating Creatinine Clearance
Refer to Renal Function-Based Dose Adjustments – Adult – Inpatient/Ambulatory Clinical Practice
Guideline:
https://uconnect.wisc.edu/clinical/cckm-tools/content/?path=/content/cpg/medications/name-97583-
en.cckm

Cockcroft-Gault equation: for patients with BMI < 30
CrCl = [(140-age) x Weight (kg)]/[SCr x 72] x 0.85 if female

Salazar-Corcoran equation: for patient with a BMI > 30
Males - CrCl = {(137-age) x [(0.285 x weight (kg)) + (12.1 x height
2
)]}/ (SCr x 51)
Females – CrCl = {(146-age) x [(0.287 x weight (kg)) + (9.74 x height
2
)]}/ (SCr x 60)


Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org