CONTINUING CARE RESIDENT CARE MANUAL...

CONTINUING CARE RESIDENT CARE MANUAL POLICY

NUMBER __III-110 DATE August 17, 2010 PAGE 1 OF 1 __

APPROVED BY: Vice President, Seniors Health

SITE: Edmonton General, Youville Home, St. Joseph’s, Lethbridge

CATEGORY: Medication

TITLE: Warfarin Administration

The purpose of the Warfarin Monitoring Pathway is to optimize anticoagulant therapy outcomes for residents in continuing care. This is achieved by establishing consistent processes for systematic evaluation and monitoring using a coordinated team approach. Warfarin is administered by qualified nursing staff. The Warfarin Pathway is reviewed with staff as part of medication administration at the time of orientation. When a resident is on an anticoagulant such as Warfarin, management must be individualized dependent on the determination of risk of clotting versus that of bleeding. Residents at great risk of having clots are managed aggressively, while residents at great risk of bleeding are managed more conservatively. The evaluation of that risk is determined by the resident’s physician. The tool used for Warfarin Administration is the Interdisciplinary Warfarin Administration and Monitoring Pathway, developed by Senior’s Health (Edmonton Zone), Integrated Facility Living, March, 2010.

Seniors Health Edmonton Zone Integrated Facility Living (IFL)

Integrated Supportive Living (ISL)

Interdisciplinary Warfarin Administration and Monitoring Pathways

March 2010

Membership of the Working Group

• Dr. Mary Hurlburt; Medical Director, Alberta Health Services, Seniors Health (Edmonton Zone)

• Sandra Leung; Assistant Manager, Alberta Health Services, Seniors Health, Integrated Facility Living, Pharmacy Services (Edmonton Zone)

• Carol Anderson; Director, Quality Outcome, Alberta Health Services, Seniors Health • Katherine Gushaty; Clinical Quality Consultant, Alberta Health Services, Seniors

Health (Edmonton Zone), Integrated Supportive Living • Dr. Doug Faulder; Medical Director, CapitalCare • Laurie Modien, Pharmacist, CapitalCare Lynnwood • Gwen Bentley, Dietitian, Good Samaritan Society • Bonnie Hoyer, Director of Care, Jubilee Lodge Nursing Home

Disclaimer: Alberta Health Services is not responsible in any manner for direct, indirect, special or consequential damages, however caused, arising out of the use by anyone of this pathway. The information is provided for information only. Although care is taken to ensure accuracy, Alberta Health Services does not assume any responsibility for errors, omissions or effects of decisions based on the information provided.

March 2010 2

Background Warfarin is an anticoagulant used to prevent and treat thromboembolic disorders such as:

• Atrial Fibrillation • Cardioembolic Stroke • Deep Vein Thrombosis • Pulmonary Embolism • Valve Replacement • Genetic Disorders

Therapy with Warfarin is only efficacious within the desired therapeutic range, measured by the international normalized ratio (INR). Failure to adequately anticoagulate residents (INR < 2.0) consistently increases the risk of thromboembolic events (e.g. stroke or pulmonary embolism) in population at risk, while residents anticoagulated excessively (INR > 3.0 - 3.5) are at risk of bleeding. Numerous other factors complicate the management of therapy including: drug interactions, acute and chronic diseases, diet and inter-individual variability in responding to warfarin. Since Warfarin is a drug with a narrow therapeutic index, systematic review of the therapeutic regimen is essential to allow early identification of adverse reactions or toxicity. Warfarin dosages must be titrated accordingly and residents must be monitored to ensure optimal therapeutic outcome and to reduce or avoid potentially life-threatening adverse events. Purpose

To optimize anticoagulation therapy outcomes for residents in continuing care centres. Goals

• To reduce risks associated with anticoagulation therapy. • To establish consistent processes for systematic evaluation and monitoring. • To establish a focused, coordinated, and consistent team approach in managing

anticoagulation therapy. Risk Management Considerations: Clotting versus Bleeding When evaluating anticoagulation therapy in a resident, it is important to consider the risk of clotting versus the risk of bleeding. High risk of clotting is considered if one or more of the following diagnoses are present*:

• Atrial fibrillation or evidence of valvular heart disease, prior stroke or systemic embolism and/or < 12 weeks therapy

• Deep vein thrombosis/pulmonary embolus and < 12 weeks of therapy • Mechanical prosthetic valve(s) • Bioprosthetic valve < 3 months • Malignancy

March 2010 3

• Antiphospholipid syndrome or the presence of > 1 hypercoagulable state • History of embolization on anticoagulant therapy • Acute MI and < 12 weeks of therapy

High risk of bleeding is considered if one or more of the following diagnoses are present*:

• Age > 65 years • History of falls • History of gastrointestinal bleed within the past year • History of hemorrhagic stroke within the past year • Initiation of warfarin within the last month • Presence of severe liver dysfunction • Presence of “uncontrolled” hypertension (i.e. Blood pressure > 160/90 mmHg) • Change of >2 INR units from most recent INR test • Renal insufficiency • Severe anemia

*Subject to individualized resident review. Criteria erred on the side of caution. NOTE:

• Individualized anticoagulation management of each resident is dependent upon the determination of the risk of clotting versus that of bleeding.

• Residents at great risk of having clots should be managed aggressively such that their INR does not fall below their target INR range.

• Residents at great risk of bleeding should be managed more conservatively. Warfarin Therapy

1. Clearly identify indication, establish the desired INR range and duration of therapy before initiating Warfarin

2. Order laboratory tests to establish baseline status. (E.g. blood coagulation status (INR), CBC, urinalysis, renal functions, liver function, and TSH).

3. Adjust Warfarin dosing in order to maintain appropriate intensity of therapy. 4. Systematically evaluate and document response to Warfarin through critical

assessment. Factors to be considered include: a. Risk versus benefit assessment b. Occurrence of thromboembolic or hemorrhagic events c. Acute changes in medical history d. Changes in medications e. Lifestyle assessment such as diet, ethanol intake, activity level f. Adherence with Warfarin therapy

5. A summary of Warfarin administration and laboratory values is to be included in the resident’s health record.

March 2010 4

Guidelines for Monitoring Establish a proactive medication regimen review process to monitor efficacy and minimize adverse drug reactions and interactions with Warfarin. The following systemic approach provides a list of factors to be evaluated in residents:

• Collect demographics and baseline information (e.g. Vital signs, history of smoking, history of alcohol use, and drug allergies and sensitivities).

• Determine acute and chronic medical conditions and their effects on Warfarin therapy. • Review medication history, medication start and stop dates, reasons for starting and

stopping the medications. • Current medications should be reviewed to determine appropriateness, and potential

for adverse effects and interactions with Warfarin. • Evaluate pertinent laboratory test results and determine whether the resident’s

condition is currently being managed with anticoagulation therapy. • Review resident’s current diet and relative contents of Vitamin K of selected foods. • Determine the primary indication for Warfarin therapy, ask attending physician to

clearly state the desired INR range and the expected duration of therapy.

Considerations when Initiating, Adjusting and Monitoring Therapy

• The elderly may require lower initiation and maintenance doses of Warfarin • Poor resident compliance; dietary, medication and activities changes; and acute

medical conditions may lead to out of range INR values. The cause of the abnormal values should be determined before dose changes are made.

• Warfarin dose changes may take 5-7 days or longer before reaching the new steady-state. This must be considered when requesting INRs after making subsequent maintenance dose changes.

• Residents starting on Warfarin should have INR done every 2-3 days. • Stabilized residents should have INR check at least monthly. • Monitor CBC every 3-6 months. • Bleeding is the most common adverse effect of Warfarin, signs include: excessive

bruising of the skin or blood in the urine or stools. • Other areas of consideration include: co-morbidities such as hypertension, diabetes

mellitus, and history of stroke or transient ischemic attack. Treatment of Critical INR (INR > 5)

1) Assess for presence of bleeding 2) Assess recent changes in medical conditions, medications and diet changes, discuss with pharmacist and dietitian. 3) Contact physician

Note: Refer to Appendix 1: Resident Assessment Algorithm • Vitamin K Orally (2-4 mg) can be administered in emergency situations.

March 2010 5

• If resident is not bleeding and not at high risk of bleeding, withholding Warfarin dose for a short time period may be adequate to return the INR to desired level.

Documentation of drug-regimen reviews and monitoring

• Ongoing documentation of resident’s clinical changes and subsequent Warfarin dose

adjustments establish resident’s response trends, improves overall resident care, and helps in reducing potential risks associated with anticoagulation therapy.

Drug Interactions with Warfarin Drugs may interact with Warfarin through pharmacodynamic or pharmacokinetic mechanisms. 1) Pharmacodynamic mechanisms:

• Synergistic – Impaired homeostasis, reduced clotting factor synthesis (hepatic disease)

• Competitively antagonistic (Vitamin K) • Altered physiologic control loop for vitamin K metabolism (hereditary resistance)

2) Pharmacokinetic mechanisms:

• Enzyme induction • Enzyme inhibition • Reduced plasma protein binding

Note: Some drugs may interact by more than one mechanism. Consult with the pharmacist for individualized medication review and any specific concerns. Dietary Considerations Pharmacodynamics of Warfarin can be affected by dietary intake, resulting in changes in anticoagulant efficacy or increased risks if bleeding is present. Dietary considerations can become a major factor in Warfarin therapy when the daily amount of Vitamin K fluctuates significantly. Residents do not necessarily have to avoid these foods entirely, but changes in consumption of Vitamin K rich foods (See examples in Appendix 3: Vitamin K Foods Summary Chart) should be noted and considered when managing anticoagulation therapy. Sudden increases in Vitamin K intake may decrease the effect of Warfarin. Foods high in Vitamin K, such as leafy greens, inhibit anticoagulant effect. Milk, meat, eggs, cereal, fruits and vegetables contain small amounts of Vitamin K. Consistency is the key. Do not make major changes in the diet without consultation with the doctor or the dietitian. Consult the doctor if the resident is unable to eat for several days, vomiting, have diarrhea or a fever. Any acute medical changes may cause an increase in INR, requiring an assessment and a change in the medication.

March 2010 6

References:

1. Capital Health LMWH Restrictions and Guidelines for Use. 2. Brown CH; the Consultant Pharmacist 1996; 11: 390-408; Risk Management in Long

Term Care: Consultative Services on Warfarin Therapy by Pharmacists. 3. Capital Health Anticoagulation Management Service Standard Operating Procedures. 4. Chest 2001; 119:1S-370S. 5. Brian F. Gage, MD, MSc; Carl van Walraven, MD, FRCPC, MSc; Lesly Pearce, MS:

Robert G. Hart, MD; Peter J. Koudstaal, MD; B.S.P. Boode, MD; Palle Petersen, MD, PhD; Selecting Patients With Atrial Fibrillation for Anticoagulation Stroke Risk Stratification in Patients Taking Aspirin. Circulations 2004;110:2287-2292.

6. USDA National Nutrient Database for Standard Reference, Release 20. 7. Drug-Nutrient Interactions, Coumadin and Vitamin K, Clinical Centre, National

Institutes of Health, Drug Nutrient Interaction Task Force. 8. Chest 2008

March 2010 7

Within Desired Therapeutic

Range****And Clinically

Stable

Continue with the same dose

As per physician's

ordersBelow Desired

Therapeutic Range

Assess signs of1. sub-therapeutic

complications*

2. Hemorrhage**

Contact Physician with above information

1. Obtain new order

2. Next INR date***

Above Desired Therapeutic

Range

Significant bleeding

High risk of bleeding

1. Contact physician for

further instructions

2. Rapid reversal is

not indicated

Contact physician to

discuss need for ER

transfer

Contact physician to discuss INR result and obtain new

order

Decrease dose or hold next

dose 1. Hold 1-2 doses

or2. Omit next

dose and administer 1-2.5 mg Vit K

po

Hold dose administer 3-5

mg Vit K po

INR < 5

INR 5-9

INR Value

Resident Assessment Algorithm

INR >9

NOYES

* Complications may include signs of DVT, TIA

** Epistaxis, bleeding gingiva, cloudy or coloured urine, melena, increased

ease of bruising

*** Practice Point: INR Level within 2 days of new

dosage is NOT recommended

**** Desired Therapeutic range should be clearly

identified by physician and documented in residents

record

Always consider the risk of bleeding when assessing the INR Values

Appendix 1

Notify physicianabout INR

result within 24 hrs

Arrange for ER Transfer

Rapid reversal required:

-Vitamin K 2-4 mg po.

- Check INR in 24 hours

NO

YES

APPENDIX 2

ANTICOAGULATION ADMINSTRATION RECORD

Warafin Administration Appendix 2 March 2010

e

*Please utilize this form for trending INR results. Document daily anticoagulant medication administration and unusual occurrence in medication administration record (MAR). DIRECTIONS: Plot INR results on the graph to demonstrate INR trends. Dat

9.0

8.5

8.0

7.5

INR 7.0

6.5

6.0

5.5

5.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

Coumadin dos e

Time : Initials (RN/LPN )

Continue with same dosage if INR result is between _________ and _________

*as per physician’s order

Indications

Resident Addressograph

Appendix 3

Vitamin K Foods Summary Chart


Food Item Vitamin K

In Milligrams

Weight In Grams

Common Measure

Asparagus, frozen, cooked, boiled, drained, no salt 144 180 235 ml (1 cup) Beet Greens, cooked, boiled, drained, no salt 697 144 235 ml (1 cup) Broccoli, cooked, boiled, drained, no salt 220 156 235 ml (1 cup) Broccoli, frozen, chopped, boiled, drained, no salt 183 184 235 ml (1 cup) Broccoli, raw 89 88 235 ml (1 cup) Broccoli, cooked, boiled, drained, no salt 52 37 1 spear Brussels Sprouts, frozen, cooked, boiled, drained, no salt 300 155 235 ml (1 cup) Brussels Sprouts, cooked, boiled, drained, no salt 219 156 235 ml (1 cup) Cabbage, chinese, (Pak-choi), boiled, drained, no salt 58 170 235 ml (1 cup) Cabbage, savoy, raw 48 70 235 ml (1 cup) Cabbage, raw 42 70 235 ml (1 cup) Celery, cooked, boiled, drained, no salt 57 150 235 ml (1 cup) Collards, frozen, chopped, boiled, drained, no salt 1,059 170 235 ml (1 cup) Collards, cooked, boiled, drained, no salt 836 190 235 ml (1 cup) Cow Peas, frozen, boiled, drained, no salt 63 170 235 ml (1 cup) Cow peas, immature, seeds, boiled, drained, no salt 44 165 235 ml (1 cup) Cucumber, with peel, raw 49 301 1 large Dandelion greens, cooked, boiled, drained, no salt 204 105 235 ml (1 cup) Endive, raw 116 50 235 ml (1 cup) Kale, frozen, cooked, boiled, drained, no salt 1,147 130 235 ml (1 cup) Kale, cooked, boiled, drained, no salt 1,062 130 235 ml (1 cup) Lettuce, Butterhead, Boston or Bibb, raw 167 163 1 head Lettuce, ice berg, raw 130 539 1 head Lettuce, green leaf, raw 97 56 235 ml (1 cup) Lettuce, Romaine, raw 57 56 235 ml (1 cup) Mustard Greens, cooked, boiled, drained, no salt 419 140 235 ml (1 cup) Okra, frozen, cooked, boiled, drained, no salt 88 184 235 ml (1 cup) Onions, spring or scallions (includes tops, bulbs), raw 207 100 235 ml (1 cup) Parsley, raw 164 10 10 sprigs Peas, frozen, boiled, drained, no salt 48 160 235 ml (1 cup) Prunes, stewed, no added sugar 65 248 235 ml (1 cup) Pumpkin, canned no salt 39 245 235 ml (1 cup) Rhubarb, frozen, cooked with sugar 51 240 235 ml (1 cup) Sauce, pasta, spaghetti/marinara, ready-to-serve 35 250 235 ml (1 cup) Soybeans, mature cooked, boiled, no salt 33 172 235 ml (1 cup) Spinach, frozen, chopped, boiled, drained, no salt 1,027 190 235 ml (1 cup) Spinach, canned, drained solids 988 214 235 ml (1 cup) Spinach, cooked, boiled, drained, no salt 889 180 235 ml (1 cup) Spinach, raw 145 30 235 ml (1 cup) Spinach soufflé 172 136 235 ml (1 cup) Turnip Greens, frozen, boiled, drained, no salt 851 164 235 ml (1 cup) Turnip Greens, cooked, boiled, drained, no salt 529 144 235 ml (1 cup) Vegetables, mixed, frozen, boiled, drained, no salt 43 182 235 ml (1 cup)

Information obtained from USDA National Nutrient Database for Standard Reference, Release 20

Appendix 4

WARFARIN INTERACTION TABLE


1

This table contains common drugs that may interact with warfarin. This tool is not inclusive of all warfarin drug interactions. It does not contain natural health products, vitamins, or supplements that may affect coagulation. Consult with pharmacist or drug interaction resources when starting, stopping, or titrating concurrent medications. This table also does not outline lifestyle factors that can influence warfarin therapy such as diet, exercise, alcohol, and illness.

ABBREVIATIONS: N/A = information not available; half life = (of precipitant drug); GI = gastrointestinal, = increase = decrease

DRUG

Effect on INR

( or ) and Severity

Mechanism Expected Onset

Expected Offset

Suggested Management

acetaminophen INR

Inhibits Warfarin metabolism NA NA Avoid total acetaminophen doses of >2 g/day

acetylsalicylic acid

INR

Inhibits platelets irreversibly; increases risk of peptic ulceration

Delayed NA Avoid ASA doses >325mg/day; use enteric-coated preparations. Consider use of Misoprostol

allopurinol

INR moderate

Unknown Delayed N/A Reports of interaction are inconsistent – monitor INR when initiating or discontinuing allopurinol

amiodarone INR moderate -

severe

Inhibition of warfarin metabolism (amiodarone may also increase or decrease INR by inducing hyper- or hypo-thyroidism, respectively)

~7-14 days up to 90 days Monitor INR at least weekly when starting amiodarone; dose will likely need to be decreased by ~25-60% when starting amiodarone (and vice versa) Monitor INR more frequently when stopping amiodarone (slow offset of interaction).

amitriptyline INR moderate

Inhibition of warfarin metabolism

Delayed N/A half life =

~15 hours

Monitor INR when starting or stopping amitriptyline

azathioprine

INR moderate

Possibly increased warfarin metabolism

~1-3 days N/A half life = 5 hours

Monitor INR; warfarin dose may require significant increase when given concurrently with azathioprine

azithromycin INR moderate

Possibly decreased warfarin metabolism; Literature reporting interaction often compounded by other factors that may increase INR (fever, decreased appetite, etc)

Delayed ~3-7 days

N/A half life = 68 hours

Inconsistent effect – monitor INR

carbamazepine INR moderate -

severe

Increase in warfarin metabolism

~10-35 days Delayed ~14-40 days

May require 50-100% increase in warfarin dosage when initiating carbamazepine; decrease warfarin by ~50% when stopping carbamazepine; monitor INR frequently when starting, stopping or adjusting doses of carbamazepine

celecoxib INR major

(especially in elderly)

Decreased CYP 2C9 mediated warfarin metabolism

Delayed N/A half life = 11 hours

Avoid combination if possible; monitor INR frequently when starting or stopping celecoxib.

chloral hydrate INR mild-

moderate

Protein-binding displacement Rapid 12-24 hours

N/A half life =

7-10 hours

Avoid combination if possible; monitor INR frequently when starting or stopping choral hydrate

Appendix 4



2

DRUG

Effect on INR

( or ) and Severity


Expected Offset


chloramphenical INR moderate

Decrease in warfarin metabolism

Delayed N/A half life = ~4 hours

Avoid concomitant use if possible; monitor INR closely when starting or stopping chloramphenicol

cholestyramine INR moderate

Decreased warfarin absorption

Delayed N/A Avoid administering cholestyramine within 2 hours of warfarin, monitor INR more frequently when staring or stopping cholestyramine

ciprofloxacin INR moderate

Unknown; possibly due to CYP 1A2 inhibition; interaction more prevalent in elderly patients on multiple medications

~2-5 days Literature reports

suggest 2-4 days; half life =

3-6 hours

Monitor INR more frequently when starting or stopping ciprofloxacin.

clarithromycin INR moderate


Delayed ~3-7 days

N/A half life = ~5-7 hours; prolonged in

renal impairment

Monitor INR more frequently when starting or stopping clarithromycin.

clopidogrel risk of bleeding (no

effect on INR) severe

Antiplatelet effects of clopidogrel combined with warfarin’s anticoagulant effect impair two of the body’s clot-forming mechanisms

~2 hours (amount of

time it takes for clopidogrel to inhibit platelet aggregation)

~5-7 days (platelet

aggregation is irreversibly inhibited by

clopidogrel for the life of the

platelet)

Monitor INR; monitor clinically for bleeding signs and symptoms

cloxacillin INR moderate

Unknown Delayed N/A Monitor INR frequently when starting or stopping cloxacillin

colchicine INR moderate

Diarrhea associated with colchicine causes the INR to increase

1-3 days N/A If experiencing significant diarrhea with colchicine (>3-4 loose stools per day), check INR and may need to decrease warfarin dose while on colchicine

diclofenac risk of bleeding (no

effect on INR)

moderate

Inhibition of platelets and gastroprotective prostaglandins

Delayed N/A Minimize use; monitor clinically for bleeding signs and symptoms (especially GI)

erythromycin INR moderate

Decreased warfarin metabolism


~1.5 hours

Monitor INR when starting or stopping erythromycin

fenofibrate INR major

Unknown Delayed 5-10 days

N/A Monitor INR frequently; expect a ~30% warfarin dose decrease when starting fenofibrate.

fluconazole INR moderate

Inhibition of CYP 2C9 and 3A4 medicated warfarin metabolism

2-3 days N/A half life =

~30 hours; prolonged in the elderly

Monitor INR closely when starting or stopping fluconazole; effects more pronounced in patients with decreased renal function due to decreased clearance of fluconazole

Appendix 4



3

DRUG

Effect on INR

( or ) and Severity


Expected Offset


fluoxetine INR moderate

Inhibition of CYP 2C9 mediated warfarin metabolism; possible protein binding displacement

Delayed N/A half life = ~4-9 days

Monitor INR

fluvastatin INR moderate

Inhibition of CYP 2C9 mediated warfarin metabolism

Delayed 1-3 weeks

N/A half life = 2.5 hours

Use another statin agent (pravastatin and atorvastatin have not been reported to interact with warfarin); monitor INR

fluvoxamine INR moderate

Inhibition of CYP 2C9 and 1A2 medicated warfarin metabolism

Delayed NA half life = 16 hours;

prolonged in elderly

Monitor INR

gemfibrozil INR moderate

Inhibition of warfarin metabolism; displacement of warfarin from plasma protein binding sites

Delayed N/A half life = 1.3 hours

Monitor INR

glyburide INR moderate

Unknown Delayed N/A Monitor INR frequently when starting or stopping glyburide

griseofulvin INR moderate

Unknown – enzyme induction Delayed ~1-2 weeks

N/A Monitor INR at weekly intervals when starting, stopping, or dose-adjustment griseofulvin until INR stabilized

ibuprofen risk of bleeding (no

effect on INR)

moderate

Inhibition of platelet function and gastroprotective prostaglandins

Delayed N/A Minimize use; take with food; monitor clinically for bleeding signs and symptoms (especially GI)

indomethacin risk of bleeding

(potential INR)

moderate

Inhibition of platelet aggregation and gastroprotective prostaglandins

Delayed N/A Minimize use; take with food; monitor clinically for bleeding signs and symptoms (especially GI); monitor INR

isoniazid INR moderate

Inhibition of CYP 2C9-mediated warfarin metabolism


~1-4 hours

Monitor INR when starting or stopping isoniazid

itraconazole INR moderate



~64 hours +/- 32 hours

Monitor INR; consider empiric warfarin dosage reduction

ketoconazole INR moderate



2-12 hours

Monitor INR; consider empiric warfarin dosage reduction

lactulose INR moderate

Decreased intestinal absorption of vitamin K

N/A N/A Monitor INR frequently when starting or stopping lactulose

lansoprazole INR mild-

moderate

Unknown Delayed N/A Monitor INR

levofloxacin INR moderate

Unknown; possible CYP 1A2 inhibition

Delayed ~3-5 days

~5-10 days Monitor INR closely when initiating or discontinuing levofloxacin.

Appendix 4



4

DRUG

Effect on INR

( or ) and Severity


Expected Offset


levothyroxine INR moderate

Hypothyroid patients have higher warfarin requirements due to decreased catabolism of clotting factors; correcting hypothyroidism therefore decreases warfarin requirements due to increased catabolism of clotting factors

Delayed N/A Monitor INR frequently when introducing, adjusting, and discontinuing levothyroxine; warfarin adjustments as necessary

lovastatin INR moderate

Unknown Delayed 1-3 weeks

N/A Monitor INR

mercaptopurine

INR moderate

Possibly increased warfarin metabolism

~1-3 days N/A half life = 5 hours

Monitor INR

methimazole INR moderate

Increased catabolism of clotting factors with the introduction of methimazole and return of euthyroidism; increased warfarin requirements

Delayed N/A Monitor INR frequently when starting, stopping, or adjusting doses of methimazole

methylphenidate INR moderate


methyl salicylate (topical)

INR bleeding

moderate

Inhibition of warfarin metabolism; inhibition of platelet aggregation

Delayed N/A Avoid concurrent use (topical capsaicin preferred alternative)

metronidazole INR major


Delayed N/A half life = 8 hours

Consider an empiric dose reduction of 25-50%; monitor INR closely when staring or stopping metronidazole.

miconazole (topical and vaginal included)

INR moderate


Delayed ~2-5 days

N/A half life = 24 hours

Monitor INR closely when starting or stopping topical, vaginal, or oral miconazole

moxifloxacin INR major

Unknown; possible inhibition of CYP 1A2

Delayed 2-7 days

N/A Use caution when using moxifloxacin in combination with warfarin, especially in the elderly; monitor INR closely.

naproxen risk of bleeding (no

effect on INR) major

Inhibition of platelet aggregation and production of gastroprotective prostaglandins

Delayed N/A Avoid/minimize concurrent use; take with food; monitor clinically for bleeding signs and symptoms (especially GI)

nortriptyline INR moderate



15-39 hours; prolonged in the elderly

Monitor INR

Appendix 4



5

DRUG

Effect on INR

( or ) and Severity


Expected Offset


paroxetine risk of bleeding; may not

effect INR moderate

Unknown – possible pharmacodynamic interaction

Unknown N/A Avoid concurrent use if possible; monitor clinically for bleeding signs and symptoms

phenobarbital INR moderate

Induction of hepatic metabolism of warfarin

Delayed N/A Avoid combination if possible; monitor INR frequently especially when starting or stopping phenobarbital

phenytoin

Initially –transient in bleeding risk;

Chronic dosing –

INR moderate

Initially – displacement of warfarin from protein binding sites; Subsequently – induction of hepatic metabolism of warfarin

Initial – 1-3 days;

Subsequent – 2-4 weeks

N/A Minimum

10-14 days

Monitor INR frequently when starting, stopping or adjusting doses of phenytoin

primidone INR moderate


Delayed N/A Avoid combination if possible; monitor INR frequently, especially when starting or stopping primidone

propafenone INR moderate

decreased warfarin metabolism


2-10 hours

Monitor INR

quetiapine INR moderate

competitive inhibition of CYP 3A4 and 2C9 by quetiapine

Delayed ~7-14 days

N/A half life = ~6 hours

Monitor INR when starting or stopping quetiapine

ranitidine INR moderate

Inhibition of hepatic metabolism of warfarin

1-2 weeks 3-7 days Avoid concurrent use; famotidine not shown to have same interaction; monitor INR

ribavirin INR moderate –

severe

Unknown 2-4 weeks 2-4 weeks Monitor INR frequently when initiating or discontinuing ribavirin in patients taking warfarin until INR stabilizes (~4 weeks); consider empiric warfarin dosage increase

rifampin INR moderate -

severe


1-3 weeks ~1-5 weeks Monitor INR very carefully when starting or stopping rifampin; patients may require 2-3x their weekly warfarin dose when rifampin is added.

rosuvastatin INR moderate

Unknown Delayed N/A Avoid combination (use atorvastatin or pravastatin instead); monitor INR frequently when starting or stopping rosuvastatin

sertraline INR mild-

moderate


Appendix 4



6

DRUG

Effect on INR

( or ) and Severity


Expected Offset


simvastatin INR mild-

moderate

Competition for CYP 3A4 mediated metabolism

Delayed N/A Use another statin (atorvastatin or pravastatin); monitor INR (interaction unlikely to be clinically significant in most patients); monitor patients for signs and symptoms of rhabdomyolysis (interaction works the other way as well)

sulfamethoxazole (with or without trimethoprim)

INR severe

Inhibition of warfarin metabolism and displacement of warfarin from protein binding sites

2-7 days 2-14 days Avoid use if possible – if not, monitor INR more frequently when starting or stopping sulfamethoxazole containing drug regimens.

sulfasalazine

INR moderate

Unknown Unknown N/A Monitor INR frequently when starting or stopping sulfasalazine; One case report required a 250% increase in weekly warfarin dose when sulfasalazine was started

terbinafine Both and have been reported moderate

Unknown Unknown N/A Monitor INR

tetracycline INR moderate

Reduced plasma prothrombin activity by tetracycline

Delayed NA half life =

~8-10 hours

Monitor INR

tolterodine INR moderate

Inhibition of CYP 3A4 mediated warfarin metabolism

Delayed 1-2 weeks

~2 weeks Monitor INR

Tramadol INR moderate

Unknown – possible inhibition of CYP 3A4 medicated warfarin metabolism

Delayed ~1-2 weeks

N/A Monitor INR; Dose decrease of 25-30% may be required when Tramadol initiated in patients of warfarin

voriconazole INR major

Inhibition of S-warfarin’s CYP 2C9 mediated metabolism by voriconazole

Unknown N/A Consider empiric warfarin dose reduction (25-50%); monitor INR carefully.

References:

1. 2008 PHARMALearn, University of Alberta (Unit 6, Anticoagulation Tools) 2. Table adopted from AHS Calgary Zone, Supported Living Services September 12, 2009 Warfarin Drug Interaction

document.

Appendix 5

Resident Assessment & Management of Critical INR (Provided as a guideline, may need individualized resident assessment of medical status)

INR Clinical Setting Therapeutic Concerns

<5 No significant bleeding, rapid reversal is not indicated

Reduce Warfarin dose, or hold the next Warfarin dose

5.0 – 9.0 No significant bleeding Hold the next 1-2 doses of Warfarin, or omit the next dose of Warfarin and administer vitamin K1 (1-2.5 mg PO)*

5.0 – 9.0 Rapid reversal required (i.e. urgent surgery/dental extraction)

Vitamin K1 2-4 mg PO ( INR within 24 hours), if INR remains high at 24 hours then vitamin K1 1-2 mg PO

>9** No significant bleeding Hold Warfarin and administer Vitamin K1 3-5 mg PO ( INR within 24-48 hours)

>9** Serious bleeding, major Warfarin overdose

Refer patient to Emergency Department. Vitamin K1 10 mg IV slow infusion (may repeat every 12 hours – expect INR within 6-8 hours), supplemented with fresh plasma transfusion or prothrombin complex concentrate

>9** Life-threatening bleeding Refer patient to Emergency Department. Prothrombin complex concentrate, supplemented with Vitamin K1 10 mg IV

Reference: Criteria for the Use of Vitamin K/Guidelines for Correction of Over-Anticoagulation. Chest 2001; 119: 2S-38S. * Oral vitamin K1 is preferred in patients having additional risk factors for bleeding ** Vitamin K1 2.5 mg PO has been reported to be less effective than higher doses in reducing the

INR to <5 amongst patients that have INRs ≥ 10


CONTINUING CARE RESIDENT CARE MANUAL...

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