Download 1. Baseline assessment prior to initiation of dabigatran (Pradaxa®)

Clinical Guideline
Dabigatran for stroke prevention in Atrial Fibrillation
NICE TA249 published in March 2012 recommended dabigatran (Pradaxa®) as an option
for the prevention of stroke and systemic embolism within its licensed indication, that is, in
people with nonvalvular atrial fibrillation with one or more of the following risk factors:
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Previous stroke, transient ischaemic attack or systemic embolism
Left ventricular ejection fraction below 40%
Symptomatic heart failure of New York Heart Association (NYHA) class 2 or above
≥ 75 years old
≥ 65 years old with one of the following: diabetes mellitus, coronary artery disease or
hypertension.
1. Baseline assessment prior to initiation of dabigatran (Pradaxa®)
1.1 Baseline Activated Partial Prothrombin Time (aPTT), International Normalised Ratio
(INR), haemoglobin, urea & electrolytes and liver function tests
1.2 Weigh patient
1.3 Calculate baseline creatinine clearance (CrCL). The electronic calculator is available on
the intranet
1.4 Establish bleeding risk for individual patient – (See table 1)
1.5 Complete initiation checklist for dabigatran and file in patient records
1.6 Informed discussion with patient regarding risks and benefits of dabigatran (document
this in the patients notes).
This MUST include that there is currently no available antidote for reversing dabigatran
in the event of a major bleed
1.7 Confirm if patient already taking other anticoagulants and switch according to Section
3 (document action taken in medical notes)
1.8 ALL patients MUST be given the dabigatran alert card.
2. Dose of dabigatran (Pradaxa®) - 150mg hard capsule orally twice daily. Therapy
should be continued long term. Some patients require a lower dosage of dabigatran 110mg
twice daily (See table 1 and 2).
Dabigatran for stroke prevention in Atrial Fibrillation. Clinical Guideline V1.
Page 1 of 6
Principal Authors; R. Curran & G. McKerrell, Pharmacists WUTH.
Approved by: Wirral Drug and Therapeutics Committee Sep 2012. Review Sep 2013
Clinical Guideline
Table 1. Bleeding risks and recommended dosage adjustments
Patient Factors
Dose of dabigatran
If your patient has any of these MAJOR risk factors:
 Hypersensitivity to the active substance or to any of the
excipients
 Severe renal impairment (CrCL < 30 ml/min)
 Active clinically significant bleeding or organic lesion at risk of
bleeding
 High risk of falls that are likely to cause injury and
contraindicate the use of anticoagulation
 Hepatic impairment or liver disease expected to have any
impact on survival
 Concomitant treatment with systemic ketoconazole,
ciclosporin, itraconazole & tacrolimus (see table 2)
 Breastfeeding and pregnancy
 Diseases/procedures with special haemorrhagic risks
 Congenital or acquired coagulation disorders
 Thrombocytopenia or functional platelet defects
 Active ulcerative GI disease
 Recent GI bleeding
 Recent biopsy or major trauma
 Recent Intracerebral haemorrhage
 Brain, spinal, or ophthalmic surgery
 Bacterial endocarditis
If your patient has any of these increased AMBER bleeding
factors:
 Age > 80 years old
 Age 75 - 80 years when thromboembolic risk is low
bleeding risk high
 Weight < 50kg
 CrCL 30 - 50mls/min
 Concomitant treatment with interacting drugs see table 2
 History of gastritis, oesophageal reflux disease
oesophagitis
And all MAJOR risk factors have been excluded.
If more than two AMBER risk factors reconsider the overall
versus benefit of treatment with dabigatran
Avoid as contraindicated
risk
and
Initiate reduced
dabigatran dose of
110mg twice daily
and
risk
If your patient is:
 Age 18-80 years
 CrCL > 50mls/min
 Weight > 50kg
And all major and additional risk factors for bleeding have been
excluded as above
Initiate standard
dabigatran dose of
150mg twice daily
Dabigatran for stroke prevention in Atrial Fibrillation. Clinical Guideline V1.
Page 2 of 6
Principle Authors; R. Curran & G. McKerrell, Pharmacists WUTH.
Approved by: Wirral Drug and Therapeutics Committee Sep 2012. Review Sep 2013
Clinical Guideline
3. Switching anticoagulants
Dabigatran treatment to parenteral anticoagulant. It is recommended to wait 12 hours
after the last dose of dabigatran before switching to a parenteral anticoagulant. If CrCL <
30mls/min wait 24 hours before initiating parenteral treatment.
Parenteral anticoagulants to dabigatran Dabigatran should be given 0 to 2 hours prior to
the time that the next dose of the alternate therapy would be due, or at the time of
discontinuation in case of continuous treatment (e.g. intravenous Unfractionated Heparin
(UFH)).
Dabigatran treatment to Vitamin K antagonists (VKA) e.g. warfarin. Adjust the starting
time of the VKA based on CrCL as follows:
•
CrCL ≥ 50 ml/min, start VKA three days before discontinuing dabigatran
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CrCL
30 - < 50 ml/min, start VKA two days before discontinuing dabigatran
VKA to dabigatran Stop the VKA. Give dabigatran when the INR is < 2.0.
4. Monitoring
There is no routine anticoagulant blood monitoring for dabigatran.
For patients at risk of bleeding the aPTT provides an approximate indication of the
anticoagulant intensity achieved with dabigatran. This test has limited sensitivity and is not
suitable for precise quantification of anticoagulant effect, especially at high plasma
concentrations of dabigatran. High aPTT values should be interpreted with caution.
Dabigatran is a black triangle drug. ANY adverse effects must be reported to the
Committee on Safety of Medicines (CSM). http://yellowcard.mhra.gov.uk/
4.1. Renal Function
Assess renal function at baseline and every six months thereafter.
Close clinical supervision is required in patients with stage 3 chronic kidney disease (CKD)
CrCL 30-60ml/min, e.g. monitor renal function every three months or more frequently if
clinically appropriate.
In clinical situations when it is suspected that renal function could deteriorate (such as
hypovolemia, dehydration) and with certain co-medications (e.g. high dose diuretics) renal
function should be assessed more frequently and the dose of dabigatran reviewed as
appropriate.
4.2. Bleeding risk
As with all anticoagulants, dabigatran should be used with caution in conditions with an
increased risk of bleeding. Bleeding may occur at any site during therapy with dabigatran.
An unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to an
investigation to identify any potential bleeding site. Haemaglobin levels and blood pressure
Dabigatran for stroke prevention in Atrial Fibrillation. Clinical Guideline V1.
Page 3 of 6
Principle Authors; R. Curran & G. McKerrell, Pharmacists WUTH.
Approved by: Wirral Drug and Therapeutics Committee Sep 2012. Review Sep 2013
Clinical Guideline
should be monitored regularly throughout the treatment period, especially if risk factors are
combined.
5. Problem Solving
5.1 Drug Interactions
Table 2. Selected interactions and recommended dosage adjustments:
(Refer to BNF/SPC for a full up-to-date list of interactions)
Drug Interactions
Amiodarone and quinidine
Plasma concentrations of dabigatran are increased so
reduce dose to 110mg twice daily.
Close clinical
surveillance is required.
Monitor for signs of bleeding or anaemia.
Verapamil
Plasma concentrations of dabigatran are increased so
reduce dose to 110mg twice daily.
Close clinical
surveillance is required.
Monitor for signs of bleeding or anaemia.
Dabigatran and verapamil should be taken at the same time.
Rifampicin,
carbamazepine,
phenytoin, St Johns Wort
Plasma concentrations of dabigatran decreased.
Avoid co-prescribing.
UFH, LMWH, heparin
derivatives, thrombolytic
agents (fondaparinux),
GPIIb/IIIa receptor
antagonists, dextran,
sulphinpyrazone,
rivaroxaban and vitamin K
antagonists
Increased risk of GI bleeding. Caution if co-prescribed
Use of thrombolytic agents for treatment of acute ischaemic
stroke – refer to “Time is Brain” pathway and consult with
Stroke consultant on call.
Dronedarone
Inadequate clinical data. Avoid concomitant use.
Clarithromycin
Plasma concentrations of dabigatran are increased. Close
monitoring required in particular in renal impairment. Monitor
for signs of bleeding or anaemia.
Systemic ketoconazole,
ciclosporin, itraconazole,
tacrolimus
Plasma concentrations of dabigatran
Dabigatran is contraindicated.
Antiplatelets, NSAIDs,
SSRIs and SNRIs.
Increased risk of GI bleeding. Consider risk vs benefit and
indications for treatment with both. Consider using the
reduced dose of dabigatran 110mg twice daily
Digoxin
No interactions reported to date
are
Dabigatran for stroke prevention in Atrial Fibrillation. Clinical Guideline V1.
Page 4 of 6
Principle Authors; R. Curran & G. McKerrell, Pharmacists WUTH.
Approved by: Wirral Drug and Therapeutics Committee Sep 2012. Review Sep 2013
increased.
Clinical Guideline
Beta - blockers
No interactions reported to date
Ritonavir and
combinations
Plasma concentrations of dabigatran are decreased. Coprescribing is not recommended
5.2. Acute Bleeding
Please see the clinical guideline Dabigatran guideline for management of acute bleeding.
5.3. Surgery
If an acute intervention is required, dabigatran should be temporarily discontinued. Surgery
or intervention should be delayed if possible until at least 12 hours after the last dose. If
surgery cannot be delayed the risk of bleeding may be increased and this should be
weighed against the urgency of intervention.
Prior to elective surgical procedures and interventions temporarily discontinue dabigatran
as there is an increased risk of bleeding. Clearance depends on renal function which will
affect how long before the procedure to discontinue dabigatran.
The table below can be used as a guide, but the opinion of the operating surgeon should
be sought.
Table 3. Stopping dabigatran prior to elective surgery.
Stop dabigatran before elective surgery
CrCL
(ml/min)
Estimated
half-life
(hours)
High risk of bleeding
or major surgery
Standard risk
of bleeding
≥80
50 - <80
30 - <50
~13
~15
~18
2 days before
2–3 days before
4 days before
24 hours before
1-2 days before
2-3 days before
5.4. Acutely unwell patients
While on treatment with dabigatran renal function should be assessed in clinical situations
where it is suspected that renal function could decline or deteriorate.
Consider temporarily substituting dabigatran with prophylactic low molecular weight
heparin in patients who are admitted to hospital with sepsis, acute kidney injury,
hypovolaemia, dehydration or who are started on high dose diuretics. It is recommended
to wait at least 12 hours after the last dose of dabigatran before starting parenteral
anticoagulation.
5.5. Compliance Aids - Dabigatran capsules must be stored within the manufacturers
original packaging (aluminium foil strips/bottles) to prevent physical instability. It is
therefore not suitable for dispensing in compliance aids.
5.6. Swallowing difficulties - Bioavailability of dabigatran is increased if removed from
the capsule. Patients should be instructed not to open the capsule as this may increase
the risk of bleeding. Alternative agents should be used in patients with swallowing
difficulties.
Dabigatran for stroke prevention in Atrial Fibrillation. Clinical Guideline V1.
Page 5 of 6
Principle Authors; R. Curran & G. McKerrell, Pharmacists WUTH.
Approved by: Wirral Drug and Therapeutics Committee Sep 2012. Review Sep 2013
Clinical Guideline
5.7. Overdose with dabigatran
Overdose exposes the patient to an increased risk of bleeding. The aPTT gives an
indication of the bleeding risk and the patient should be closely monitored for signs of
bleeding. There is no specific antidote for dabigatran overdose. Please refer to the clinical
guideline Dabigatran – Guideline for management of acute bleeding.
6. Patient information
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All patients should be given the dabigatran alert card and counselled on the details.
This should be documented on the initiation checklist and filed in the patients medical
notes.
Patient understands the potential bleeding risks with dabigatran and is aware that
there is currently no readily available antidote for its effects and the potential
ramifications of this.
All patients should be advised on what to do if they miss a dose of dabigatran:
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A missed dose of dabigatran may still be taken up to 6 hours prior to the
next scheduled dose. From 6 hours prior to the next scheduled dose on, the
missed dose should be omitted
Dabigatran should be swallowed as a whole capsule with water, with or without food.
Instruct patient not to open the capsule as this may increase the risk of bleeding.
All patients should be counselled to inform their dentist or any other healthcare
professional performing invasive treatments or surgery that they are taking dabigatran.
7. References
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Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation.
NICE TA 249 (March 2012). Available from http://publications.nice.org.uk/dabigatranetexilate-for-the-prevention-of-stroke-and-systemic-embolism-in-atrial-fibrillation-ta249
Summary of product characteristics for Pradaxa available online at www.medicines.org.uk
British National Formulary 63, March 2012
Pradaxa patient alert card available at http://www.pradaxa.co.uk/downloads/patient-alertcard.pdf
Dabigatran for stroke prevention in Atrial Fibrillation. Clinical Guideline V1.
Page 6 of 6
Principle Authors; R. Curran & G. McKerrell, Pharmacists WUTH.
Approved by: Wirral Drug and Therapeutics Committee Sep 2012. Review Sep 2013