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Warfarin Dosing Calculator
Beta Version - Initial version requires daily monitoring of INR during initiation phase
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Initial Warfarin Review

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 9th ACCP- Chest guidelines).
    9th ACCP suggestion:   Patients healthy enough to be treated as outpatients:  Give warfarin 10 mg daily x 2 days. Further dosing should be based on INR monitoring. (Preferred to starting with an estimated maintenance dose.)   (Grade 2C)

    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 / Clinical Conditions (REVIEW)

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.

A] Assess bleeding risk: check all that apply:

  1. [] Abnormal renal function ( defined as the presence of chronic dialysis or renal transplantation  or serum creatinine geq200µmol/L (>~2.3 mg/dL))
  2. [] Abnormal liver function ( defined as chronic hepatic disease (eg. cirrhosis) or biochemical evidence of significant hepatic derangement (eg. bilirubin >2x upper limit of normal, in association with AST/ALT/ALP >3x upper limit normal)
  3. [] Stroke (Previous history of stroke)
  4. [] Bleeding (Major bleeding history (anemia or predisposition to bleeding)) 
  5. [] Hypertension -( systolic blood pressure >160 mmHg
  6. [] Alcohol abuse / Alcohol intake (consuming 8 or more alcoholic drinks per week) 
  7. [] Malignancy
  8. Elderly (age geq 65) []   is patient also >75?  []
  9. [] Labile INRs (refers to unstable/high INRs or poor time in therapeutic range(eg<60%)
  10. [] Drug Therapy (concomitant therapy such as antiplatelet agents,  or NSAID's that may increase risk)
  11. Reduced platelet count or function [ ]  and/ or  Anemia  [ ]
  12. [] Excessive fall risk?
  13. [] Genetic factors (CYP2C9 variant) 

 
B]  Gender

C]  Select NOMOGRAM
      
          Note: If a custom nomogram is selected please select the
          starting dose
: mg
                 (Starting dose should be based on patient age; presence of  interacting medications;
                   and bleeding risk of patient.)



Baseline INR and CBC  should be obtained prior to initiation of  warfarin therapy.

Overview:  [all nomograms are based on INR values obtained daily in order to predict/determine the maintenance dose requirements.]   Once a patient stabilized (two therapeutic levels 24 hours apart),  follow-up monitoring should occur approximately weekly for the first month (initiation phase). 

Standard:   Initiation regimen for most patients unless factors are present that may significantly increase or decrease the response to warfarin.  Using higher doses e.g. 7.5 to 10mg for an average patient with no known risk factors for bleeding is more likely to result in overanticoagulation.

High-risk:  Patients who are at an increased risk of bleeding such as the elderly (> 70-75) or patients with CHF/ liver disease / debilitated  / recent major surgery / impaired
nutritional intake/ or patients receiving medications known to potentiate the action of warfarin (e.g. amiodarone or similar medications).   Increased baseline INR.

Low-risk:  Young patients with a LOW risk of bleeding, especially if very large; receiving medications known to decrease the response to warfarin;  concurrent medical condition(s) such as clinical hypothyroidism that may reduce response to warfarin.  In selected patients (e.g., very large individuals or those on medications known to antagonize warfarin), a Day 1 warfarin  dose of 7.5 mg may be appropriate.


The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.    PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  
You must confirm that you have READ and AGREE with the terms and conditions listed above before continuing: led
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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;127:332-333.
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. )

Available tablet strengths:  1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10 mg

Disclaimer

All calculations must be confirmed before use. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgement. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.   Read the disclaimer
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