Download Warfarin Administration Guidelines

BIDMC Guidelines for the use of Warfarin
Table of Contents
1. Initiation of Anticoagulation
2. Management of Variable and Supratherapeutic INRs
3. Management of Supratherapeutic INRs
4. Intensity and Duration of Therapy for Venous Thromboembolism
5. Intensity of Anticoagulation of Patients with Atrial Fibrillation
6. Intensity of Anticoagulation of Patients with Mechanical Heart Valves
7. CHADS2 Scoring Index
8. FDA Approved Mechanical Heart Valves
9. Warnings and Warfarin Drug-Drug Interactions
Approved by: The Pharmacy and Therapeutics Committee 08/09, Version 1.
TOC
Initiation and Maintenance Dosing
Before starting warfarin therapy, a baseline INR should be obtained. In patients beginning
therapy with warfarin, start with a dose of 5 mg for the first 1 or 2 days, with subsequent dosing
based on the international normalized ratio (INR) response. If treatment is not urgent (e.g.,
chronic stable atrial fibrillation without risk factors), warfarin administration, without concurrent
heparin administration, can be commenced out-of-hospital with a maintenance dose based on
subsequent INR response.
Initiation of Anticoagulation in Elderly or Other Populations
In elderly patients or patients who are debilitated, are malnourished, have congestive heart
failure, have liver disease, have had recent major surgery, or are taking medications known to
increase sensitivity to warfarin (e.g., amiodarone), consider using a starting dose of < 5 mg with
subsequent dosing based on the INR response.
Initiation and Maintenance Dosing for Patient at High Risk of Thrombosis
Therapeutic unfractionated or low molecular weight heparin should be administered concurrently
when a rapid anticoagulant effect is required and/or in patients with antiphospholipid antibody
syndrome, known protein deficiency (C, S, Antithrombin), > 1 genetic or allelic abnormality, or
another highly thrombophilic state, and its administration should be overlapped with warfarin
until the INR has been in the therapeutic range for 2 days. This will help to protect against a
possible early hypercoagulable state caused by a warfarin-mediated reduction in the vitamin Kdependent coagulation inhibitors.
Frequency of Monitoring
Following the administration of warfarin, an initial effect on -the INR usually occurs within the
first 2 or 3 days, depending on the dose administered. The full antithrombotic effect occurs
between days 4-6. In patients beginning therapy with warfarin, INR monitoring should be
started after the initial two or three daily doses. For patients who are receiving a stable dose of
warfarin, less frequent monitoring is required, but should be performed at an interval of no
longer than every 4 weeks.
Reference: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133 (6 Suppl):160S-198S.
This guideline has been designed to assist the clinician in decision making. It is not intended to replace
clinical judgment where individual patient characteristics may require modification of the recommendations
TOC
Management of Variable INRs
For patients receiving long-term warfarin therapy with a variable INR response not attributable
to any of the usual known causes for instability, consider a trial of daily low-dose oral vitamin K
(100 to 200 micrograms), with close monitoring of the INR and warfarin dose adjustment to
counter an initial lowering of the INR in response to vitamin K.
Management of Subtherapeutic INRs
For patients with subtherapeutic INRs during long-term therapy, no specific studies have
examined the optimal method of correction. Because the average daily risk of thrombosis for
most indications is quite small, except in exceptional circumstances, most patients do not need to
be covered with a rapidly acting anticoagulant, such as heparin or low-molecular-weight heparin.
Rather, the weekly cumulative dose of warfarin is usually increased by 10 to 20%, and more
frequent monitoring is instituted until the INR is stable. In some cases, patients may be given a
one-time larger dose followed by more frequent monitoring with or without a change in the
cumulative weekly dose.
Reference: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133 (6 Suppl):160S-198S.
This guideline has been designed to assist the clinician in decision making. It is not intended to replace
clinical judgment where individual patient characteristics may require modification of the recommendations
TOC
Management of Supratherapeutic INRs and/or
Critical Bleeding in Patients on Warfarin Condition
Description
INR above therapeutic
range but < 5
without significant bleeding
Lower dose or omit dose, monitor more frequently, and resume at lower
dose when INR therapeutic; if only minimally above therapeutic range,
no dose reduction may be required.
INR 5 but < 9
without significant bleeding
Omit next one or two doses, monitor more frequently and resume at lower
dose when INR in therapeutic range. Alternatively, omit dose and give vitamin
K1 (1-2.5 mg), particularly if at increased risk of bleeding.
If more rapid reversal is required because the patient requires urgent surgery,
vitamin K1 (2 to 4 mg orally) can be given with the expectation that a
reduction of the INR will occur in 24 h. If the INR is still high, additional
vitamin K1 (1 to 2 mg orally) can be given.
INR 9
without significant bleeding
Hold warfarin therapy and give higher dose of vitamin K1 (5–10 mg orally) with
the expectation that the INR will be reduced substantially in 24–48 h. Monitor
more frequently and use additional vitamin K1 if necessary.
Resume therapy at lower dose when INR therapeutic.
Major bleeding
at any elevation of INR
Hold warfarin therapy and give vitamin K1 (10 mg by slow IV infusion),
supplemented with fresh plasma or prothrombin complex
concentrate depending on the urgency of the situation.
Also guidelines:
Emergent Management of Critical Bleeding in Patients on Warfarin
Hold warfarin therapy and give prothrombin complex concentrate
supplemented with vitamin K1 (10 mg by slow IV infusion)
Life-threatening bleeding
Also see guidelines:
Emergent Management of Critical Bleeding in Patients on Warfarin
•
Oral and intravenous vitamin K are equally effective at reducing the INR, and are the
recommended route of administration. Subcutaneous vitamin K is significantly less effective
than either oral or intravenous administration, and is not recommended.
•
In patients for whom an INR of 1 is desired, higher doses (> 5 mg) of vitamin K may be
appropriate
•
In patients for whom the goal is to achieve a therapeutic INR (2-3.5), higher doses of vitamin
K (> 5 mg) can result in over correction and warfarin resistance, with significant delays in
achieving a therapeutic INR. For these patients, low dose (1-2 mg) of oral vitamin K is
preferred.
Reference: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133 (6 Suppl):160S-198S.
This guideline has been designed to assist the clinician in decision making. It is not intended to replace clinical
judgment where individual patient characteristics may require modification of the recommendations
TOC Intensity and Duration of Anticoagulation for Patients with
Venous Thromboembolism
1. Treatment
In acute DVT and/or PE, begin therapeutic doses of LMWH, UFH, or fondaparinux for at least 5
days and continue until the INR is > 2 for two consecutive days; begin warfarin together with
LMWH, UFH, or fondaparinux on the first treatment day. The goal INR is 2.5 (INR range, 2.0 to
3.0) for all treatment durations.
2. Duration of Therapy
A. VTE due to transient risk factor
For patients with DVT and/or PE secondary to a transient (reversible) risk factor,
therapeutic anticoagulation should be given for at least 3 months.
B. VTE unprovoked (not due to a transient reversible risk factor)
For patients with unprovoked (not due to a transient reversible risk factor) DVT and/or
PE, therapeutic anticoagulation should be given for at least 3 months, and patients should
be evaluated for the risks to benefits of indefinite therapy.
C. VTE in association with malignancy
For patients with DVT and/or PE in the setting of an active cancer, therapeutic
anticoagulation with LMWH should be given for at least 3 months, followed by treatment
with LMWH or warfarin for as long as the cancer is active.
Reference: Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133 (6 Suppl):454S-545S
This guideline has been designed to assist the clinician in decision making. It is not intended to replace
clinical judgment where individual patient characteristics may require modification of the recommendations
TOC
Intensity of Anticoagulation for Patients with Atrial Fibrillation
Risk Assessment and Recommendations for Anticoagulation Therapy
in Patients with Atrial Fibrillation
Risk for
embolism
Patient characteristics
Recommendation
Low Risk
Non-valvular, paroxysmal, or chronic atrial fibrillation,
with CHADS2 score < 2
Aspirin 81–325 mg
daily
High Risk
Valvular*; or non-valvular paroxysmal or chronic atrial
fibrillation, with CHADS2 score > 3
(or > 2 if prior transient ischemic attack, stroke, or
peripheral embolism)
Warfarin
INR 2 to 3g
* “Valvular” includes any native valve abnormality (e.g. aortic stenosis)
and/or any prosthetic heart valves. gIf mechanical valve, target INR > 2.5
CHADS2 INDEX
Stroke Risk In Patients With Nonvalvular
AF Not Treated With Anticoagulation
CHADS2 Risk Criteria
Score
C:
Congestive heart failure (regardless of ejection fraction)
1
H:
Hypertension (or treated hypertension)
1
A:
Age >75 years
1
D:
Diabetes
1
S:
Prior transient ischemic attack, stroke, or peripheral embolism
2
Reference: ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the
American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines. Circulation. 2006 Aug 15;114 (7):e257-354.
This guideline has been designed to assist the clinician in decision making. It is not intended to replace
clinical judgment where individual patient characteristics may require modification of the recommendations
TOC
Intensity of Anticoagulation for Patient with Mechanical Heart Valves
Antithrombotic Therapy in Patients with Prosthetic Heart Valves
Type and Position of Valve
Goal INR and
Antiplatelet Therapy
• Bioprosthetic MVR or AVR without risk factors
Aspirin 75-100mg
• Bileaflet mechanical AVR without risk factors
• Medtronic Hall disc AVR without risk factors
• Bioprosthetic AVR with risk factors*
Warfarin
INR 2 to 3
AND
Aspirin 75-100mg
• Bileaflet mechanical AVR with risk factors
• Medtronic Hall disc AVR with risk factors
• Bioprosthetic MVR with risk factors
• Any mechanical MVR or TVR
• Ball or Disc valve (excluding Medtronic Hall AVR without risk factors)
Warfarin
INR 2.5 to 3.5
AND
Aspirin 75-100mg
Risk factors: Atrial fibrillation, previous thromboembolism, LV systolic dysfunction (LVEF < 40%),
hypercoagulable conditions, or > 1 prosthetic valves. MVR = mitral valve replacement,
AVR = Aortic valve replacement, TVR = Tricuspid valve replacement
Reference: ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease:
Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines J Am Coll Cardiol, 2006; 48:598-675.
This guideline has been designed to assist the clinician in decision making. It is not intended to replace
clinical judgment where individual patient characteristics may require modification of the recommendations
TOC
FDA-Approved Prosthetic Heart Valves
Type
Mechanical
Ball
Single Disc
Bileaflet
Manufacturer
Baxter Edwards
Medtronic
Medical Inc.
Alliance
St. Jude
Baxter Edwards
CarboMedics
Model
Starr-Edwards
Medtronic Hall
Omniscience
Monostrut
St. Jude
Duromedics
CarboMedics
Biological
Medtronic
Porcine
Pericardial
Homograft
Autologous
Baxter Edwards
St. Jude
Medtronic
Baxter Edwards
Noncommercial
Cryolife
Noncommercial
Hancock Standard
Hancock Modified Orifice
Carpentier-Edwards Standard
Carpentier-Edwards Supra-Annular
Toronto Stentless (TSP)
Free Style
Carpentier-Edwards
Pulmonary autograft
Reference
ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive
Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines J Am Coll Cardiol, 2006; 48:598-675
This guideline has been designed to assist the clinician in decision making. It is not intended to replace
clinical judgment where individual patient characteristics may require modification of the recommendations
TOC
Warnings and Warfarin Drug-Drug Interactions
Warfarin has numerous drug and food interactions which can potentiate or inhibit its anticoagulant effect.
Similarly, warfarin may potentiate or inhibit the effects of other medications. The following list includes
many of the major warfarin drug-drug interactions, but it is not comprehensive, and therefore should not
serve as a substitute for a complete review of all of drug-drug interactions by the prescriber. Please ask
for assistance from pharmacy as needed.
Caution should be used when prescribing warfarin to patients on other anticoagulant or antiplatelet
therapy as this may increase the risk of bleeding.
Patients should be counseled to maintain consistency in their intake of foods rich in vitamin K.
Significant changes in diet may lead to a subtherapeutic or supratherapeutic INR.
Medications that INCREASE
warfarin’s anticoagulant effect
Medications that DECREASE
warfarin’s anticoagulant effect
Anti-Infectives:
•
amoxicillin-clavulanate
•
azithromycin
•
ciprofloxacin
•
clarithromycin
•
cotrimazole
•
sulfamethoxazole/trimethoprim
•
erythromycin
•
fluconazole
•
levofloxacin
•
metronidazole
•
voriconazole
Anti-Infectives:
•
nafcillin
•
rifampin
•
ritonavir
Cardiovascular:
•
amiodarone
•
fenofibrate
•
simvastatin
Analgesics/anti-inflammatories:
•
acetaminophen (doses greater than 2g/day)
•
NSAID’s / COX-2 inhibitors
•
phenylbutazone
•
piroxicam
CNS Medications:
•
alcohol (if concomitant liver disease)
•
citalopram
•
entacapone
•
fluoxetine
•
sertraline
GI Medications
•
cimetidine
•
omeprazole
Other:
•
•
•
•
•
fluorouracil
gemcitabine
imatinib
paclitaxel
tamoxifen
Cardiovascular:
•
cholestyramine
CNS Medications:
•
barbiturates
•
carbamazepine
Other:
•
•
•
Vitamin supplements with vitamin K
enteral feeds with vitamin k
sucralfate
Adapted from: Ansell, J. et al. Pharmacology
and Management of the Vitamin K Antagonists.
Chest 2008;133;160S-198S