CONTINUING CARE RESIDENT CARE MANUAL POLICY

Transcription

1 CONTINUING CARE RESIDENT CARE MANUAL POLICY NUMBER III-110 DATE August 17, 2010 PAGE 1 OF 1 APPROVED BY: SITE: CATEGORY: TITLE: Vice President, Seniors Health Edmonton General, Youville Home, St. Joseph s, Lethbridge Medication 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.

2 Seniors Health Edmonton Zone Integrated Facility Living (IFL) Integrated Supportive Living (ISL) Interdisciplinary Warfarin Administration and Monitoring Pathways

3 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. 2

4 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 > ) 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 3

5 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. 4

6 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 steadystate. 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. 5

7 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 (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. 6

8 References: 1. Capital Health LMWH Restrictions and Guidelines for Use. 2. Brown CH; the Consultant Pharmacist 1996; 11: ; 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: USDA National Nutrient Database for Standard Reference, Release Drug-Nutrient Interactions, Coumadin and Vitamin K, Clinical Centre, National Institutes of Health, Drug Nutrient Interaction Task Force. 8. Chest

9 Appendix 1 Resident Assessment Algorithm INR Value Always consider the risk of bleeding when assessing the INR Values Within Desired Therapeutic Range****And Clinically Stable **** Desired Therapeutic range should be clearly identified by physician and documented in residents record Below Desired Therapeutic Range Assess signs of 1. sub-therapeutic complications* 2. Hemorrhage** * Complications may include signs of DVT, TIA Continue with the same dose As per physician's orders Notify physician about INR result within 24 hrs ** Epistaxis, bleeding gingiva, cloudy or coloured urine, melena, increased ease of bruising Significant bleeding High risk of bleeding Above Desired Therapeutic Range *** Practice Point: INR Level within 2 days of new dosage is NOT recommended Contact Physician with above information 1. Obtain new order 2. Next INR date*** YES Arrange for ER Transfer Contact physician to discuss need for ER transfer NO YES Rapid reversal required: -Vitamin K 2-4 mg po. - Check INR in 24 hours INR < 5 NO 1. Contact physician for further instructions 2. Rapid reversal is not indicated INR 5-9 INR >9 Contact physician to discuss INR result and obtain new order Decrease dose or hold next dose 1. Hold 1-2 doses or 2. Omit next dose and administer mg Vit K po Hold dose administer 3-5 mg Vit K po

10 APPENDIX 2 ANTICOAGULATION ADMINSTRATION RECORD Resident Addressograph *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. Continue with same dosage if INR result is between and *as per physician s order Indications Dat e INR Coumadin dos e Time : Initials (RN/LPN) Warafin Administration Appendix 2

11 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 ml (1 cup) Beet Greens, cooked, boiled, drained, no salt ml (1 cup) Broccoli, cooked, boiled, drained, no salt ml (1 cup) Broccoli, frozen, chopped, boiled, drained, no salt ml (1 cup) Broccoli, raw ml (1 cup) Broccoli, cooked, boiled, drained, no salt spear Brussels Sprouts, frozen, cooked, boiled, drained, no salt ml (1 cup) Brussels Sprouts, cooked, boiled, drained, no salt ml (1 cup) Cabbage, chinese, (Pak-choi), boiled, drained, no salt ml (1 cup) Cabbage, savoy, raw ml (1 cup) Cabbage, raw ml (1 cup) Celery, cooked, boiled, drained, no salt ml (1 cup) Collards, frozen, chopped, boiled, drained, no salt 1, ml (1 cup) Collards, cooked, boiled, drained, no salt ml (1 cup) Cow Peas, frozen, boiled, drained, no salt ml (1 cup) Cow peas, immature, seeds, boiled, drained, no salt ml (1 cup) Cucumber, with peel, raw large Dandelion greens, cooked, boiled, drained, no salt ml (1 cup) Endive, raw ml (1 cup) Kale, frozen, cooked, boiled, drained, no salt 1, ml (1 cup) Kale, cooked, boiled, drained, no salt 1, ml (1 cup) Lettuce, Butterhead, Boston or Bibb, raw head Lettuce, ice berg, raw head Lettuce, green leaf, raw ml (1 cup) Lettuce, Romaine, raw ml (1 cup) Mustard Greens, cooked, boiled, drained, no salt ml (1 cup) Okra, frozen, cooked, boiled, drained, no salt ml (1 cup) Onions, spring or scallions (includes tops, bulbs), raw ml (1 cup) Parsley, raw sprigs Peas, frozen, boiled, drained, no salt ml (1 cup) Prunes, stewed, no added sugar ml (1 cup) Pumpkin, canned no salt ml (1 cup) Rhubarb, frozen, cooked with sugar ml (1 cup) Sauce, pasta, spaghetti/marinara, ready-to-serve ml (1 cup) Soybeans, mature cooked, boiled, no salt ml (1 cup) Spinach, frozen, chopped, boiled, drained, no salt 1, ml (1 cup) Spinach, canned, drained solids ml (1 cup) Spinach, cooked, boiled, drained, no salt ml (1 cup) Spinach, raw ml (1 cup) Spinach soufflé ml (1 cup) Turnip Greens, frozen, boiled, drained, no salt ml (1 cup) Turnip Greens, cooked, boiled, drained, no salt ml (1 cup) Vegetables, mixed, frozen, boiled, drained, no salt ml (1 cup) Information obtained from USDA National Nutrient Database for Standard Reference, Release 20 Warafin Administration Appendix 3

12 Appendix 4 WARFARIN INTERACTION TABLE 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: = information not available; (of precipitant drug); GI = gastrointestinal, = increase = decrease DRUG Effect on INR ( or ) and Severity Warafin Administration Appendix 4 Mechanism Onset Offset Suggested Management acetaminophen Inhibits Warfarin NA NA Avoid total acetaminophen doses of >2 g/day acetylsalicylic acid Inhibits platelets irreversibly; increases risk of peptic NA Avoid ASA doses >325mg/day; use enteric-coated preparations. allopurinol amiodarone amitriptyline azathioprine azithromycin carbamazepine celecoxib chloral hydrate - severe - severe major (especially in elderly) mild ulceration Consider use of Misoprostol Unknown Reports of interaction are inconsistent monitor INR when initiating or discontinuing allopurinol Inhibition of warfarin (amiodarone may also increase or decrease INR by inducing hyper- or hypo-thyroidism, respectively) Inhibition of warfarin Possibly increased warfarin Possibly decreased warfarin ; Literature reporting interaction often compounded by other factors that may increase INR (fever, decreased appetite, etc) Increase in warfarin Decreased CYP 2C9 mediated warfarin Protein-binding displacement ~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). ~15 hours ~1-3 days 5 hours ~3-7 days 68 hours ~10-35 days ~14-40 days Rapid hours 11 hours 7-10 hours Monitor INR when starting or stopping amitriptyline Monitor INR; warfarin dose may require significant increase when given concurrently with azathioprine Inconsistent effect monitor INR May require % 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 Avoid combination if possible; monitor INR frequently when starting or stopping celecoxib. Avoid combination if possible; monitor INR frequently when starting or stopping choral hydrate 1

13 Appendix 4 WARFARIN INTERACTION TABLE DRUG chloramphenical Effect on INR ( or ) and Severity Mechanism Decrease in warfarin Onset Offset ~4 hours Suggested Management Avoid concomitant use if possible; monitor INR closely when starting or stopping chloramphenicol cholestyramine ciprofloxacin clarithromycin clopidogrel cloxacillin colchicine diclofenac erythromycin fenofibrate fluconazole risk of bleeding (no effect on INR) severe risk of bleeding (no effect on INR) major Decreased warfarin absorption Unknown; possibly due to CYP 1A2 inhibition; interaction more prevalent in elderly patients on multiple medications Inhibition of warfarin Antiplatelet effects of clopidogrel combined with warfarin s anticoagulant effect impair two of the body s clot-forming mechanisms Avoid administering cholestyramine within 2 hours of warfarin, monitor INR more frequently when staring or stopping cholestyramine ~2-5 days Literature reports suggest 2-4 days; 3-6 hours ~3-7 days ~2 hours (amount of time it takes for clopidogrel to inhibit platelet aggregation) ~5-7 hours; prolonged in renal impairment ~5-7 days (platelet aggregation is irreversibly inhibited by clopidogrel for the life of the platelet) Monitor INR more frequently when starting or stopping ciprofloxacin. Monitor INR more frequently when starting or stopping clarithromycin. Monitor INR; monitor clinically for bleeding signs and symptoms Unknown Monitor INR frequently when starting or stopping cloxacillin Diarrhea associated with colchicine causes the INR to increase Inhibition of platelets and gastroprotective prostaglandins Decreased warfarin Unknown Inhibition of CYP 2C9 and 3A4 medicated warfarin 1-3 days If experiencing significant diarrhea with colchicine (>3-4 loose stools per day), check INR and may need to decrease warfarin dose while on colchicine Minimize use; monitor clinically for bleeding signs and symptoms (especially GI) 5-10 days ~1.5 hours 2-3 days ~30 hours; prolonged in the elderly Monitor INR when starting or stopping erythromycin Monitor INR frequently; expect a ~30% warfarin dose decrease when starting fenofibrate. Monitor INR closely when starting or stopping fluconazole; effects more pronounced in patients with decreased renal function due to decreased clearance of fluconazole Warafin Administration Appendix 4 2

14 DRUG fluoxetine fluvastatin fluvoxamine gemfibrozil glyburide Effect on INR ( or ) and Severity Appendix 4 WARFARIN INTERACTION TABLE Mechanism Inhibition of CYP 2C9 mediated warfarin ; possible protein binding displacement Inhibition of CYP 2C9 mediated warfarin Inhibition of CYP 2C9 and 1A2 medicated warfarin Inhibition of warfarin ; displacement of warfarin from plasma protein binding sites Onset 1-3 weeks Offset ~4-9 days 2.5 hours NA 16 hours; prolonged in elderly 1.3 hours Suggested Management Monitor INR Use another statin agent (pravastatin and atorvastatin have not been reported to interact with warfarin); monitor INR Monitor INR Monitor INR Unknown Monitor INR frequently when starting or stopping glyburide griseofulvin ibuprofen indomethacin isoniazid risk of bleeding (no effect on INR) risk of bleeding (potential INR) Unknown enzyme induction Inhibition of platelet function and gastroprotective prostaglandins Inhibition of platelet aggregation and gastroprotective prostaglandins Inhibition of CYP 2C9- mediated warfarin ~1-2 weeks Monitor INR at weekly intervals when starting, stopping, or doseadjustment griseofulvin until INR stabilized Minimize use; take with food; monitor clinically for bleeding signs and symptoms (especially GI) Minimize use; take with food; monitor clinically for bleeding signs and symptoms (especially GI); monitor INR ~1-4 hours Monitor INR when starting or stopping isoniazid itraconazole ketoconazole lactulose lansoprazole levofloxacin mild Decreased warfarin Decreased warfarin ~64 hours +/- 32 hours 2-12 hours Monitor INR; consider empiric warfarin dosage reduction Monitor INR; consider empiric warfarin dosage reduction Decreased intestinal Monitor INR frequently when absorption of vitamin K starting or stopping lactulose Unknown Monitor INR Unknown; possible CYP 1A2 inhibition ~3-5 days ~5-10 days Monitor INR closely when initiating or discontinuing levofloxacin. Warafin Administration Appendix 4 3

15 DRUG levothyroxine lovastatin mercaptopurine methimazole methylphenidate methyl salicylate (topical) metronidazole miconazole (topical and vaginal included) Effect on INR ( or ) and Severity bleeding major Appendix 4 WARFARIN INTERACTION TABLE Mechanism 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 Unknown Possibly increased warfarin Increased catabolism of clotting factors with the introduction of methimazole and return of euthyroidism; increased warfarin requirements Onset Offset Suggested Management Monitor INR frequently when introducing, adjusting, and discontinuing levothyroxine; warfarin adjustments as necessary 1-3 weeks Monitor INR ~1-3 days Monitor INR 5 hours Monitor INR frequently when starting, stopping, or adjusting doses of methimazole Unknown Monitor INR Inhibition of warfarin ; inhibition of platelet aggregation Decreased warfarin Inhibition of warfarin Avoid concurrent use (topical capsaicin preferred alternative) ~2-5 days 8 hours 24 hours Consider an empiric dose reduction of 25-50%; monitor INR closely when staring or stopping metronidazole. Monitor INR closely when starting or stopping topical, vaginal, or oral miconazole moxifloxacin naproxen major risk of bleeding (no effect on INR) major Unknown; possible inhibition of CYP 1A2 Inhibition of platelet aggregation and production of gastroprotective prostaglandins 2-7 days Use caution when using moxifloxacin in combination with warfarin, especially in the elderly; monitor INR closely. Avoid/minimize concurrent use; take with food; monitor clinically for bleeding signs and symptoms (especially GI) nortriptyline Decreased warfarin hours; prolonged in the elderly Monitor INR Warafin Administration Appendix 4 4

16 Appendix 4 WARFARIN INTERACTION TABLE DRUG paroxetine phenobarbital Effect on INR ( or ) and Severity risk of bleeding; may not effect INR phenytoin Initially transient in bleeding risk; Chronic dosing primidone propafenone quetiapine ranitidine Mechanism Unknown possible pharmacodynamic interaction Induction of hepatic of warfarin Initially displacement of warfarin from protein binding sites; Subsequently induction of hepatic of warfarin Induction of hepatic of warfarin decreased warfarin competitive inhibition of CYP 3A4 and 2C9 by quetiapine Inhibition of hepatic of warfarin Onset Offset Suggested Management Unknown Avoid concurrent use if possible; monitor clinically for bleeding signs and symptoms Avoid combination if possible; monitor INR frequently especially when starting or stopping phenobarbital Initial 1-3 days; Subsequent 2-4 weeks Minimum days Monitor INR frequently when starting, stopping or adjusting doses of phenytoin Avoid combination if possible; monitor INR frequently, especially when starting or stopping primidone Monitor INR ~7-14 days 2-10 hours ~6 hours Monitor INR when starting or stopping quetiapine 1-2 weeks 3-7 days Avoid concurrent use; famotidine not shown to have same interaction; monitor INR ribavirin rifampin rosuvastatin sertraline severe - severe mild 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 Induction of hepatic of warfarin 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. Unknown Avoid combination (use atorvastatin or pravastatin instead); monitor INR frequently when starting or stopping rosuvastatin Unknown Monitor INR Warafin Administration Appendix 4 5

17 Appendix 4 WARFARIN INTERACTION TABLE DRUG simvastatin Effect on INR ( or ) and Severity mild Mechanism Competition for CYP 3A4 mediated Onset Offset Suggested Management 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) sulfasalazine terbinafine tetracycline tolterodine Tramadol voriconazole severe Both and have been reported major Inhibition of warfarin 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. Unknown Unknown Monitor INR frequently when starting or stopping sulfasalazine; One case report required a 250% increase in weekly warfarin dose when sulfasalazine was started Unknown Unknown Monitor INR Reduced plasma prothrombin activity by tetracycline Inhibition of CYP 3A4 mediated warfarin Unknown possible inhibition of CYP 3A4 medicated warfarin Inhibition of S-warfarin s CYP 2C9 mediated by voriconazole 1-2 weeks ~1-2 weeks NA Monitor INR ~8-10 hours ~2 weeks Monitor INR Monitor INR; Dose decrease of 25-30% may be required when Tramadol initiated in patients of warfarin Unknown Consider empiric warfarin dose reduction (25-50%); monitor INR carefully. References: 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. Warafin Administration Appendix 4 6

18 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 No significant bleeding Hold the next 1-2 doses of Warfarin, or omit the next dose of Warfarin and administer vitamin K 1 (1-2.5 mg PO)* Rapid reversal required (i.e. urgent surgery/dental extraction) Vitamin K mg PO ( within 24 hours), if INR remains high at 24 hours then vitamin K mg PO >9** No significant bleeding Hold Warfarin and administer Vitamin K mg PO ( within hours) >9** Serious bleeding, major Warfarin overdose Refer patient to Emergency Department. Vitamin K 1 10 mg IV slow infusion (may repeat every 12 hours expect 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 K 1 10 mg IV Reference: Criteria for the Use of Vitamin K/Guidelines for Correction of Over-Anticoagulation. Chest 2001; 119: 2S-38S. * Oral vitamin K 1 is preferred in patients having additional risk factors for bleeding ** Vitamin K mg PO has been reported to be less effective than higher doses in reducing the INR to <5 amongst patients that have INRs 10 Warafin Administration Appendix 5