1. Goal Of Project To reduce adverse outcomes of warfarin therapy by developing and implementing an inpatient warfarin dosing protocol, and by instituting an education program with regard to diet and instructions for physician follow up at discharge.

2. Committees Med Use Team Pharmacy and Therapeutics Committee Patient Safety Committee Medical Executive Committee Team Members Sharon Lutz, Ph.D., Vice President, Quality Support Services Colleen Wheeler, Quality Support Services Jim Whipple, Nursing Education Dina Vankolpenberg, Dietary Daniel Malinowski, Dietary Mary Slater, Laboratory Bruce Read, PharmD, Clinical Director Sunny Choi, PharmD, Computer Interface Laura Uhl, PharmD, Computer Interface Allan Cohen, PharmD, Director

8. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol PURPOSE: To provide clarity and uniformity in the pharmacy directed dosing of Warfarin. SCOPE OF SERVICE: The Warfarin Therapy protocol must be initiated by a physician. For consulted patients, warfarin is initiated or home therapy is continued. Dosing is adjusted based upon patient condition and lab values. Dietary is informed of patients receiving warfarin. Education is provided to the patient prior to hospital discharge.

9. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) PROCEDURE: Prescriber orders Warfarin by Protocol order, including indication, anticipated duration of therapy and target INR range. All doses of warfarin shall be scheduled for 1800. For consults ordered after 2300 the first dose of warfarin shall be scheduled for the following evening unless the prescriber orders it as a “now” order. Initial Patient Assessment - Warfarin by Protocol The pharmacist will review the patient medical record to confirm indication for therapy, determine baseline coagulation parameters including PT, INR, and Hgb, and to identify any potential interacting medication therapy or patient conditions. If the most recent PT and INR were obtained more than 24 Hours prior to the planned initial warfarin dose, the pharmacist shall order a PT and INR per protocol and assess the results prior to administration of the initial warfarin dose. Baseline INR should be below or within the goal INR range prior to initiation of warfarin therapy.

10. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Initial Dosing Baseline INR< 1.2 Age =70KG7.5-10mg Post CVA patients5-7.5mg Age>=80(all patients)No > than 5mg(Age>90 consider <5mg) All others5-7.5mg Patients on amiodarone or with 3 or more risk factors, consider reducing initial dose by 2.5mg. If not currently treated with a parenteral anticoagulant, do not exceed 7.5mg for initial dose Baseline >=1.2 – Dose<=5mg or reduce above dose by up to 2.5mg. Whenever INR exceeds therapeutic goal and has increased by >.8, discuss options with MD.

11. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Monitoring Daily PT, INR, and Hgb should be monitored. These labs would be by the pharmacist per protocol if necessary. The pharmacist should review the clinical notes of the primary service daily to determine the presence of patient conditions that may interact with warfarin therapy and/or impact the dosing The pharmacist should discuss with the physician those patients with significant changes in the INR or patient condition, or if appropriate dosing is outside parameters of the protocol.

12. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Dose Adjustment The pharmacist must assess and adjust Warfarin dosing based on lab value and patient condition according to the Dose Adjustment Tables in this protocol. Changes will be documented in pharmacy HMM clinical notes Changes to dosing shall be ordered by the pharmacist per protocol as appropriate. Warfarin Risk Factors: Age >60 (moderate risk) Age >80 (high) Actual body weight (ABW) <70kg (low) ABW<Ideal Body Weight (IBW) (low) IBW<50kg(low) ABW<50kg(moderate) Significant renal failure (moderate) DDI (variable) Protein C or Protein S deficiency Anti-Phospholipid Antibody Syndrome or Lupus Anticoagulant Low Vit K intake (moderate) Reduced Vit K absorption Liver Disease (moderate) Hypermetabolic states (fever) CHF (Moderate) Malnutrition, Low alb (moderate) Potential Bleeding risk (high)

13. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Initial Dose: Baseline INR< 1.2 Age =70KG7.5-10mg Post CVA patients5-7.5mg Age>=80(all patients)No > than 5mg(Age>90 consider <5mg) All others5-7.5mg Patients on amiodarone or with 3 or more risk factors, consider reducing initial dose by 2.5mg. If not currently treated with a parenteral anticoagulant, do not exceed 7.5mg for initial dose Baseline >=1.2 – Dose<=5mg or reduce above dose by up to 2.5mg. Whenever INR exceeds therapeutic goal and has increased by >.8, discuss options with MD

14. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) INR Day 2 of TherapyDose INR increase< 0.2Same as initial dose - Consider slight increase only if initial dose reduced INR increase 0.2 to 0.4½ to ¾ dose - Consider holding if age>=80yo,risk factors INR increase 0.4 to 0.8¼ to ½ previous dose - Consider holding if multiple risk factors or age >=80yo INR increase > 0.8Hold dose INR Day 3 of TherapyDose INR increase <.4Increase dose up to 3/2 INR increase 0.4 to 0.8½ to same dose INR increase >0.8¼ to ½ dose - Consider holding If age>= 80yo or INR above goal INR Day 4 of TherapyDose (If third dose was held, use ½ of second dose as the reference) INR<1.5Increase by 3/2 INR 1.5 to 1.9 and INR increase<=0.4 INR increase 0.4 to 0.8 Same dose to 3/2 dose ½ to ¾ dose INR 2.0 to 3.0 and INR increase <=0.4 If INR increase 0.4 to 0.8 If INR increase >0.8 Same dose (If INR increase <=.2 above goal, consider slight increase) ½ to ¾ dose ¼ to ½ dose, consider holding (using risk factors as guide) INR > 3.0-3.5 and INR increase <=0.4 If INR increase >0.4 ½ to ¾ dose ¼ to ½ dose - Consider holding INR>3.5Hold Day 5 and on Subsequent dose should be based on trend established by the INR results from the third and fourth doses

15. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Hospital Discharge Planning Prior to discharge the patient will be provided appropriate prescriptions for outpatient Warfarin therapy, phlebotomy for INR and physician appointment. Notification of the Physician The physician should be notified if there is significant changes in the INR or the patient’s condition, or if appropriate dose or dose adjustment is outside parameters of the protocol. The physician should also be notified for the following: INR>4.5 Hgb 2g/DL from previous result Significant bleeding.

16. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Patient Education Patients should be educated by the nurse and dietician prior to discharge. Patient education should include the following: Importance of adherence to warfarin regimen Potential Side effects, especially the signs and symptoms of bleeding Possible effects of diet on therapy Potential for prescription and over-the-counter drug interactions Written educational materials Answers to patient’s questions and contact numbers if questions arise after discharge

17. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Documentation-Rx to Dose Pharmacy to document in a pharmacy clinical note prior to initiation of therapy. Therapy type and home regimen (if applicable) Indication for therapy, goal INR range, and anticipated duration. Presence of complicating diseases Baseline PT, INR, albumin, Hgb. After initial assessment, the note should include Medication Plan (including interacting medications, initial dosing, and monitoring plan. Daily clinical notes will be written by the pharmacist which will include the following: Therapy type and home regimen (if applicable) New medication therapy and its potential effect on the INR. Most recent PT, INR, and Hgb Assessment and therapy management plan (including laboratory result evaluation, dosing changes, and monitoring plan)

18. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Protocol (continued) Cottage Health System Minimum Requirements For Monitoring Warfarin Therapy Before initiation of warfarin therapy a baseline INR, H/H and platelet count must be obtained. INRs will be obtained daily until therapeutic for 2 consecutive draws, then at least weekly. HgB/HCT to be drawn at least every other day until INR is stable, then at least weekly. All INRs and coumadin doses will be documented by nursing on the Anticoagulation flow sheet (form 187) Pharmacy will dispense coumadin in the exact dosage prescribed, check the INR before dispensing and will contact the physician if the dose does not seem appropriate. Heparin anticoagulation is to be discontinued when the patient has been on warfarin a minimum of 3 days and the INR is therapeutic. MD will be contacted by nursing if the HgB decreases by more than 2gm/dL, for signs of bleeding or the INR is greater than 4.5 Dietary will be notified of all patients on Coumadin therapy. All patients will be provided discharge instructions, which will include the name of the physician coordinating the coumadin dose.

19. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Patient Instructions Warfarin (Oral) (Tablet) Warfarin (By mouth) Warfarin (WAR-far-in) Treats or prevents blood clots. This medicine is a blood thinner (anticoagulant). Brand Name(s):Coumadin, Jantoven, Warfarin There may be other brand names for this medicine. When This Medicine Should Not Be Used: You should not use this medicine if you have had an allergic reaction to warfarin, or if you are pregnant or planning to become pregnant. Ask your doctor about using this medicine if you are having or have recently had surgery. Usually, you should not use this medicine if you are having surgery on your eyes, brain, or spine, or major surgery that will leave you with large, open wounds. This medicine should not be used if you have certain heart problems, severe or uncontrolled high blood pressure, or any condition that may cause uncontrolled bleeding (such as a stomach ulcer or hemophilia).

20. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Patient Instructions (continued) How to Use This Medicine: Tablet Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to. You may take this medicine with or without food. If a dose is missed: If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose. How to Store and Dispose of This Medicine: Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine after you have finished your treatment. You will also need to throw away old medicine after the expiration date has passed. Keep all medicine away from children and never share your medicine with anyone.

21. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Patient Instructions (continued) Drugs and Foods to Avoid: Ask your doctor or pharmacist before using any other medicine, including over-the- counter medicines, vitamins, and herbal products. There are many other medicines, including nonprescription (over-the-counter) medicines and herbal products, that you should not use while you are taking warfarin. Make sure your doctor knows about ALL other medicines you are using. Carefully follow your doctor's instructions about any special diet. This medicine works best when you eat about the same amount of vitamin K in your food every day. Avoid big changes in how much vitamin K you eat. Some foods that have a high amount of vitamin K are broccoli, brussels sprouts, cabbage, and green leafy vegetables such as spinach and salad greens. You should avoid drinking cranberry juice or any other cranberry products. Do not drink alcohol while you are using this medicine.

22. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Patient Instructions (continued) Warnings While Using This Medicine: Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away. Make sure your doctor knows if you are breastfeeding, or if you have liver disease, kidney disease, congestive heart failure, high blood pressure, diabetes, any type of infection, or any other medical problems. Also tell your doctor if you have recently had a fall or other injury. You may bleed more easily while you are using this medicine. Stay away from rough sports or other situations where you could be bruised, cut, or injured. Brush and floss your teeth gently. Be careful when using sharp objects, including razors and fingernail clippers. Avoid picking your nose. If you need to blow your nose, blow it gently. Carry an ID card or wear a medical alert bracelet to let any emergency caregivers know that you are using warfarin. Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests. Your doctor will need to check your blood at regular visits while you are using this medicine. Be sure to keep all appointments.

23. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Warfarin Work Flow Order For Warfarin by MDOrder By MD for Pharmacy to Dose Pharmacist enters order for specific dose Then enters “COUMD”Enters COUMRX Pop up window with forced entry for required baseline data, and follow up dates Pop up with forced entry for required criteria for dosing. COUMD shows on MAR with message “contact physician if no routine order by 1800, chart dose on warfarin flowsheet” RX to dose on MAR Chart on Flow sheet Any new or continuing warfarin is summarized and printed for both pharmacy and dietary each morning for follow-up Same summary

24. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Warfarin Work Flow (continued) For both order entry modes, pharmacy documents doses, INR, Hgb/HCT, platelets, MD interventions, drug interactions in therapy attachment for each patient. Dietary initiates education of new and continuing patients, and documents in electronic CPOE interface. Warfarin handout given to patient. At discharge, nurse gives written discharge instructions, including the name of physician for subsequent follow up and INR. This is also documented in CPOE electronic interface. A copy of in-house flow sheet to go with patient to follow-up MD.

28. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Minimum requirements for warfarin dosing Baseline Hgb/HCT, platelets must be obtained before initiation of therapy. INR daily until two consecutive draws are therapeutic, then at least weekly. All INR and warfarin doses will be documented on Anticoagulation Flow Sheet. Exact doses will be dispensed, so that overdose will not occur. MD will be contacted if Hgb drops by more than 2gm/dl, signs of bleeding, or INR>4.5. Dietary department will be notified of all patients on warfarin therapy. All patients will be provided discharge instructions, which will include the name of the physician coordinating the dose.

30. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Goal Measurement 7 month inpatient data collection (March 2008 to September 2008) INR Inpatient Data Trauma Research ”Fall on Warfarin Data” Further research comparisons pending Current comparison data in process Preliminary results suggest Pharmacy department dosing reduces supratherapeutic INR’s by approximately 50% Further comparison data ongoing Onset to therapeutic range: Incidence of ADRs MD vs RX dosing Outpatient ADR’s

31. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Minimum Requirements Audit (Duration 3 Weeks) Results: 100% Compliance by Dietary Education 2 of 37 inappropriate for education (tube feeds, not cognitive) Nursing Education at Discharge: Unknown - means of documentation by nursing at discharge not implemented: Audit resulted in new interface to be created for documentation. 36 out of 37 patients had required baseline data prior to initiation of therapy (97% compliance) Exact Doses Dispensed (100% compliance)

32. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Minimum Requirements Audit (Duration 3 Weeks) (continued) Doses charted on flowsheet One of 37 had warfarin flowsheet completed: 3% compliance Lack of education Resistance to “charting in two places” Alternatives being investigated MAR documentation 100% compliance 34 of 37 had baseline data, doses charted in pharmacy notes (92% compliance) 36 of 37 had daily INRs until therapeutic (97% compliance) 2 of 37 had H/H drop: Verified by pharmacy that MD aware: Progress note notation by MD (100% compliance)

33. COTTAGE HEALTH SYSTEM Pharmacy Directed Warfarin Therapy Future Areas of Improvement More active participation with MD’s in dosing: Computer models Pharmacogenetic dosing based on CYP 2C9 and VKORC1 gene variations Standardize orthopedic dosing Outpatient follow-up Documentation