The following recommendations should be followed for ALL patients started on warfarin:
1. Review the contraindications to therapy and the clinical conditions that may increase risks associated with warfarin therapy. Also make sure there is a valid indication for starting warfarin.
2. A thorough review of the following should be completed: diet, current drug therapy (interacting medications), OTC use (herbal products, NSAID use etc).
3. Initial doses of warfarin may range from 2.5 to 10 mg depending on the presence of risk factors for bleeding. Loading doses (e.g. doses >10mg) are NOT recommended (refer to the 8th ACCP- Chest guidelines).
Patients who are at an increased risk of bleeding such as the elderly (> 65 – 70 yo) or patients with CHF/ liver disease / debilitated / recent major surgery / or patients receiving medications known to potentiate the action of warfarin are usually started at the low end of this range e.g. 2.5 – 3 mg.
4. The following monitoring guidelines should be followed:
– A baseline INR should be obtained IN ALL CASES.
– Determine the INR daily after the administration of the initial dose until INR results stabilize in the therapeutic range.
– After stabilization, maintain dosing within the therapeutic range by performing periodic INRs. The frequency of performing INR
should be based on the clinical situation but generally acceptable intervals for INR determinations are 1 to 4 weeks.
– Perform additional INR tests when other warfarin products are interchanged with COUMADIN, as well as whenever other
medications are initiated, discontinued, or taken irregularly
———————————————————————-
CONTRAINDICATIONS
———————————————————————-
• Pregnancy
COUMADIN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism. COUMADIN can cause fetal harm when administered to a pregnant woman. COUMADIN exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. If COUMADIN is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus
• Hemorrhagic tendencies or blood dyscrasias
• Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces
• Bleeding tendencies associated with:
–Active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract
–Central nervous system hemorrhage
–Cerebral aneurysms, dissecting aorta
–Pericarditis and pericardial effusions
–Bacterial endocarditis
• Threatened abortion, eclampsia, and preeclampsia
• Unsupervised patients with conditions associated with potential high level of non-compliance
• Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding
• Hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis)
• Major regional or lumbar block anesthesia
• Malignant hypertension
———————————————————————-
The risks of COUMADIN therapy may be INCREASED with the following:
———————————————————————-
• Moderate to severe hepatic impairment
• Infectious diseases or disturbances of intestinal flora (e.g., sprue, antibiotic therapy)
• Use of an indwelling catheter
• Severe to moderate hypertension
• Deficiency in protein C-mediated anticoagulant response: COUMADIN reduces the synthesis of the naturally occurring anticoagulants, protein C and protein S. Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. Concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with COUMADIN may minimize the incidence of tissue necrosis in these patients.
• Eye surgery: In cataract surgery, COUMADIN use was associated with a significant increase in minor complications of sharp needle and local anesthesia block but not associated with potentially sight-threatening operative hemorrhagic complications. As COUMADIN cessation or reduction may lead to serious thromboembolic complications, the decision to discontinue COUMADIN before a relatively less invasive and complex eye surgery, such as lens surgery, should be based upon the risks of anticoagulant therapy weighed against the benefits.
• Polycythemia vera
• Vasculitis
• Diabetes mellitus
————————
Geriatric Use:
————————
Patients 60 years or older appear to exhibit greater than expected INR response to the anticoagulant effects of warfarin. COUMADIN is contraindicated in any unsupervised patient with senility. Observe caution with administration of COUMADIN to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. Consider lower initiation and maintenance doses of COUMADIN in elderly patients.
Elderly patients may have:
• nutritional deficiencies,
• comorbidities,
• multiple drug interactions,
• And, they are often at greater risk for falls.
=================================================================
Standard Warfarin Initiation Nomogram
=================================================================
Warfarin initiation nomogram for thrombosis treatment
Target INR (2 – 3) Based on Crowther et al. Ref: #2
==================================
Day 1
———————————————————————–
INR: Dosage:
Obtain baseline INR 5.0 mg
==================================
Day 2
———————————————————————–
INR Dosage
<1.5 5 mg
1.5 – 1.9 2.5 mg
2.0 – 2.5 1 – 2.5 mg
> 2.5 Omit dose
==================================
Day 3
———————————————————————–
INR Dosage
<1.5 5 – 10 mg
1.5 – 1.9 2.5 – 5mg
2.0 – 2.5 0 – 2.5 mg
> 3.0 Omit dose
==================================
Day 4
———————————————————————–
INR Dosage
<1.5 10 mg
1.5 – 1.9 5 – 7.5mg
2.0 – 2.5 0 – 5 mg
> 3.0 Omit dose
==================================
Day 5
———————————————————————–
INR Dosage
<1.5 10 mg
1.5 – 1.9 7.5 – 10mg
2.0 – 2.5 0 – 5 mg
> 3.0 Omit dose
==================================
Day 6
———————————————————————–
INR Dosage
<1.5 7.5 – 12.5 mg
1.5 – 1.9 5 – 10mg
2.0 – 2.5 0 – 7.5 mg
> 3.0 Omit dose
=================================================================
Warfarin Initiation Nomogram – HIGH Risk Patient (2.5 mg)
=================================================================
Warfarin initiation nomogram for thrombosis treatment –
Target INR (2 – 3) . Based on a modified version of Crowther et al. Ref: #2
Consider a starting dose of 2.5 mg
HIGH-risk patient defined: Patients who are at an increased risk of bleeding such as the elderly or patients with CHF/ liver disease / debilitated / recent major surgery / or patients receiving medications known to potentiate the action of warfarin.
==================================
Day 1
———————————————————————–
INR: Obtain baseline INR
Initial Dosage: 2.5 mg
==================================
Day 2
———————————————————————–
INR Dosage
<1.5 2.5 mg
1.5 – 1.9 1 – 1.5 mg
2.0 – 2.5 0.5 – 1.5 mg
> 2.5 Omit dose
==================================
Day 3
———————————————————————–
INR Dosage
<1.5 2.5 – 5 mg
1.5 – 1.9 1 – 2.5 mg
2.0 – 2.5 0 – 1.5 mg
> 3.0 Omit dose
==================================
Day 4
———————————————————————–
INR Dosage
<1.5 5 mg
1.5 – 1.9 2.5 – 4mg
2.0 – 2.5 0 – 2.5 mg
> 3.0 Omit dose
==================================
Day 5
———————————————————————–
INR Dosage
<1.5 5 mg
1.5 – 1.9 3.5 – 5 mg
2.0 – 2.5 0 – 2.5 mg
> 3.0 Omit dose
==================================
Day 6
———————————————————————–
INR Dosage
<1.5 3.5 – 6.5 mg
1.5 – 1.9 2.5 – 5mg
2.0 – 2.5 0 – 3.75 mg
> 3.0 Omit dose
=================================================================
Warfarin Initiation Nomogram – HIGH Risk Patient (3 mg)
=================================================================
Warfarin initiation nomogram for thrombosis treatment –
Target INR (2 – 3) . Based on a modified version of Crowther et al. Ref: #2
Consider a starting dose of 3 mg
HIGH-risk patient defined: Patients who are at an increased risk of bleeding such as the elderly or patients with CHF/ liver disease / debilitated / recent major surgery / or patients receiving medications known to potentiate the action of warfarin.
==================================
Day 1
———————————————————————–
INR: Obtain baseline INR
Initial Dosage: 3 mg
==================================
Day 2
———————————————————————–
INR Dosage
<1.5 3 mg
1.5 – 1.9 1.5 mg
2.0 – 2.5 0.5 – 1.5 mg
> 2.5 Omit dose
==================================
Day 3
———————————————————————–
INR Dosage
<1.5 3 – 6 mg
1.5 – 1.9 1.5 – 3 mg
2.0 – 2.5 0 – 1.5 mg
> 3.0 Omit dose
==================================
Day 4
———————————————————————–
INR Dosage
<1.5 6 mg
1.5 – 1.9 3 – 4.5mg
2.0 – 2.5 0 – 3 mg
> 3.0 Omit dose
==================================
Day 5
———————————————————————–
INR Dosage
<1.5 6 mg
1.5 – 1.9 4.5 – 6 mg
2.0 – 2.5 0 – 3 mg
> 3.0 Omit dose
==================================
Day 6
———————————————————————–
INR Dosage
<1.5 4.5 – 7.5 mg
1.5 – 1.9 3 – 6mg
2.0 – 2.5 0 – 4.5 mg
> 3.0 Omit dose
=================================================================
Warfarin Initiation Nomogram – LOW Risk Patient
=================================================================
Warfarin initiation nomogram for thrombosis treatment
Target INR (2 – 3) Based on Crowther et al. Ref: #2
Warfarin nomogram for low-risk patients based on a slightly modified version of Crowther et al. Ref: #2 and Kovacs et al. Ref: #7
Consider a starting dose of 7.5mg to 10 mg.
Low-risk patient defined: Patient less than 60 years of age with a LOW bleeding risk and no concurrent use of interacting medications. Based on criteria listed in Haines et al. Ref: #5
==================================
Day 1
———————————————————————–
INR: Obtain baseline INR
Dosage: 7.5 – 10 mg
==================================
Day 2
———————————————————————–
INR Dosage
<1.5 7.5 – 10 mg
1.5 – 1.9 2.5 mg
2.0 – 2.5 1 – 2.5 mg
> 2.5 Omit dose
==================================
Day 3
———————————————————————–
INR Dosage
<1.5 5 – 10 mg
1.5 – 1.9 2.5 – 5mg
2.0 – 2.5 0 – 2.5 mg
> 3.0 Omit dose
==================================
Day 4
———————————————————————–
INR Dosage
<1.5 7.5 – 10 mg
1.5 – 1.9 5 – 7.5mg
2.0 – 2.5 0 – 5 mg
> 3.0 Omit dose
==================================
Day 5
———————————————————————–
INR Dosage
<1.5 7.5 – 10 mg
1.5 – 1.9 7.5 – 10mg
2.0 – 2.5 0 – 5 mg
> 3.0 Omit dose
==================================
Day 6
———————————————————————–
INR Dosage
<1.5 7.5 – 12.5 mg
1.5 – 1.9 5 – 10mg
2.0 – 2.5 0 – 7.5 mg
> 3.0 Omit dose
=================================================================
Warfarin Initiation Nomogram – Daily INR Monitoring Possible
=================================================================
Warfarin initiation nomogram for thrombosis treatment –
Target INR (2 – 3). Based on criteria listed in Haines et al. Ref: #5
Required monitoring: Daily PT/INR
Setting: Inpatient
(Starting dose should be based on patient age; presence of interacting medications; and bleeding risk of patient.)
==================================
Day 1
———————————————————————–
INR: Obtain baseline INR
Dosage: Determined by user
==================================
Day 2
———————————————————————–
INR Dosage
<1.5 -No dosage change
1.5 – 1.9 -Decrease dose 25 – 50 %
2.0 – 2.5 -Decrease dose 50 – 75 %
> 2.5 -Hold next dose
==================================
Day 3
———————————————————————–
INR Dosage
<1.5 -Increase dose 0 – 25 %
1.5 – 1.9 -No dosage change
2.0 – 2.5 -Decrease dose 25 – 50 %
> 2.5 -Decrease dose 50% or hold next dose
==================================
Day 4
———————————————————————–
INR Dosage
<1.5 -Increase dose 0 – 25 %
1.5 – 1.9 -No dosage change or increase 10 – 25%
2.0 – 3.0 -Decrease dose 0 – 25 %
> 3.0 -Decrease dose 50% or hold next dose
==================================
Day 5
———————————————————————–
INR Dosage
<1.5 -Increase dose 25%
1.5 – 1.9 -Increase dose 0 – 25 %
2.0 – 3.0 -No dosage change or decrease 10 – 25%
> 3.0 -Decrease dose 25 – 50 %
———————————————————————–
References
———————————————————————–
1. Ansell J, Hirsh J, Hylek E, Jacobson A, et al. Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 (suppl 6);133:160s-198s.
2. Crowther MA, Harrison L, Hirsh J. Warfarin: less may be better. Ann Intern Med. 1997;127:332-3.
[ Crowther et al. (Comments: Initial development of a warfarin initiation nomogram for thrombosis treatment. Provided guidance for dosage adjustments from day#2 through day #6 starting with an initial dose of 5mg on day #1 of therapy).]
3. Crowther MA, Ginsberg JB, Kearon C, et al. A Randomized Trial Comparing 5-mg and 10-mg Warfarin Loading Doses. Arch Intern Med. 1999;159:46-8.
4. Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349:1133–1138.
5. Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw-Hill Inc; 2005:373-413.
[Haines et al. (Comments: Listed two nomograms with common dosage reduction patterns found in other nomograms. Because the listed dosage modifications are listed as percentages, this type of dosing scheme can be easily manipulated by a computer program to accept any starting dose and then dynamically create a new nomogram based on the initial starting dose. Further enhancements can be added such as sophisticated rounding methods that generate common warfarin dosages as well as additional guidance based on a few simple web-form inputs. ) ]
6. Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg Loading Doses in Initiation of Warfarin Therapy. Ann Intern Med. 1997;126:133-6.
7. Kovacs MJ, Rodger M, Anderson DR, et al. Comparison of 10-mg and 5-mg Warfarin Initiation Nomograms Together with Low-Molecular-Weight Heparin for Outpatient Treatment of Acute Venous Thromboembolism. Ann Intern Med. 2003;138:714-719.
[Kovacs et al. (Comments: Modified the 5mg nomogram developed by Crowther et al (1997): The new nomogram started with two initial 5mg doses followed by potential dosage modification on day #3 instead of day #2. Also developed a10mg warfarin initiation nomogram with mandatory monitoring and potential modification on Day #3 and Day #5 of therapy. ) ]
