1 Warfarin Management – Adult– Ambulatory Consensus Care Practice Guideline Target Population: Adult patients receiving anticoagulation therapy with the oral vitamin K antagonist, warfarin Full Guideline: Warfarin Management – Adult - Ambulatory Guideline Overview • Target INR and duration of therapy are based on indication for warfarin use- see full guideline • Risk factors which alter sensitivity to warfarin • HAS-BLED Score- prediction tool for risk of major bleeding with warfarin • Warfarin dosing protocols for initiation and maintenance • Warfarin dosing pearls • Laboratory monitoring including INR frequency • Common signs and symptoms of major bleeding/clotting • Dose adjustments for drug interactions • Factors that increase INR and bleeding risk • Factors that decrease INR and increase clotting risk • Warfarin reversal • References Table 1: see guideline for INR goals and recommended duration of therapy by indication Risk factors which alter sensitivity to warfarin Table 2. Warfarin sensitivity factors Increases sensitivity (usually require lower doses) • Baseline (pre-warfarin) PT/INR (e.g., greater than 1.4) • Advanced age (e.g., 60 years of age or older)1-10 • Underweight (e.g., BMI less than 18kg/m2)9,11,12 • Nutritional status (e.g., malnourished, low vitamin K intake/stores) • Genetic factors (e.g., CYP2C9, VKORC1 phenotypes) • Drug-drug interactions • Hypoalbuminemia13,14 • Ethnicity (Asian)10,15,16 • Liver disease10,17 • Thyroid Disease (e.g., hyperthyroidism, Graves’ disease)18-21 • Heart Failure22,23 • Febrile illness • Prolonged vomiting and diarrhea • Cannabinoids • Alcohol Decrease warfarin sensitivity (may require higher doses) • Enteral feedings • High-vitamin K intake • Drug interactions • Chewing tobacco Copyright © 2022 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 05/2022 Effective 5-19-2022. Contact CCKM@uwhealth.org for previous versions. 2 Table 3. HAS-BLED Score24 Factors Points Scoring Hypertension (SBP >160 mmHg) 1 Score = 0-1: Low risk Score = 2: Moderate risk Score ≥3: High risk High bleed risk considerations: - Optimize blood pressure control - Check INRs frequently - Utilize anticoagulation clinic - Focus on fall prevention - Utilize direct oral anticoagulants Abnormal lab values - Creatinine >2.26 mg/dL - Bilirubin >2x the upper limit of normal (ULN) and AST/ALT/AP >3x ULN 1 Stroke history 1 Bleeding history or predisposition 1 Labile INRs: Time in Therapeutic Range <60% 1 Elderly: > 65 years 1 Drugs - EtOH abuse - ASA or NSAID use 1 Table 4. Dosing for Warfarin Initiation (Week 1) with INR Goal 2-325 Day Therapy INR Value Dose Adjustment Day 1 5 mg daily (2.5 mg daily if high sensitivity to warfarin identified) In 2-3 days after initiation < 1.5 1.5-1.9 2.0-2.5 > 2.5 5 – 7.5 mg daily 2.5 - 5 mg daily 1 - 2.5 mg daily Hold and recheck INR next day In additional 2-3 days after last INR check < 1.5 1.5-1.9 2.0-3.0 > 3.0 7.5 – 10 mg daily 5 – 10 mg daily 2.5 – 5 mg daily Hold warfarin, recheck in 1-2 days *If patient is started on 2.5 mg then target lower warfarin dose adjustments to avoid overshooting INR goal Table 5. Warfarin Maintenance Dosing Protocol with INR Goal 1.5-2.025 Table 6. Warfarin Maintenance Dosing Protocol with INR Goal 2-325 Copyright © 2022 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 05/2022 Effective 5-19-2022. Contact CCKM@uwhealth.org for previous versions. 3 Table 7. Warfarin Maintenance Dosing Protocol with INR Goal 2.5-3.525 Table 8. UW Health Dosing Pearls (UW Health GRADE very low quality evidence, C recommendation) Table 9. Laboratory Monitoring26,27 Baseline Within the past 30 days • Baseline INR • Pregnancy test* *Pregnancy test is not needed if: 1. Are postmenopausal (12 months of amenorrhea in a woman > 45 years old in the absence of other biological or physiological causes) 2. Had a hysterectomy or bilateral salpingo-oophorectomy 3. Have ovarian failure 4. Had a bilateral tubal ligation or other surgical sterilization procedure 5. Are known to be pregnant 6. Have had a miscarriage or abortion in the last 7 days 7. Have given birth within the past 4 weeks Within the past 90 days • Hemoglobin • Platelet count Annually • Hemoglobin • Platelet count Copyright © 2022 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 05/2022 Effective 5-19-2022. Contact CCKM@uwhealth.org for previous versions. 4 Figure 1. Frequency of INR Monitoring after initiation of warfarin26-29 Table 10. Common Signs and Symptoms of Major Bleeding and Clotting30,31 Signs and Symptoms of Bleeding Signs and Symptoms of Clotting Blood in sputum Chest or unilateral leg pain Bloody emesis (bright red or coffee ground-like) Unilateral lower extremity swelling Blood in urine or stool (enough to color toilet water) Warm, red or discolored skin of lower extremity Bleeding that has not resolved or slowed within 10 minutes Elevated heart rate (HR > 100 bpm) Shortness of breath Coughing or coughing up blood Table 11. Dose Adjustment Recommendations for Common/Significant Warfarin-Drug Interactions26 Medication INR check after starting Adjustment Amiodarone Every 7 days Target a 25-50% weekly dose reduction over 2-4 weeks Rifampin Every 7 days Target a 50% weekly dose increase over 2 weeks Fluconazole 2 – 3 days Target a 30% weekly dose decrease Metronidazole 2 – 3 days Target a 30% weekly dose decrease Sulfamethoxazole/ Trimethoprim 2 days Target a 30% weekly dose decrease Should reduce dose prior to starting medication to avoid critical INR elevation Copyright © 2022 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 05/2022 Effective 5-19-2022. Contact CCKM@uwhealth.org for previous versions. 5 Table 12. Medications, Dietary Supplements, and Foods that INCREASE INR or bleeding risk10,26,27,32 Drug Class Known Interaction Probable Interaction Possible Interaction Unlikely Interaction Anti-Infective Ciprofloxacin Erythromycin Fluconazole Isoniazid Metronidazole Miconazole Miconazole Vaginal Suppository Moxifloxacin Sulfamethoxazole Voriconazole Amoxicillin/clavulanate Azithromycin Clarithromycin Itraconazole Ketoconazole Levofloxacin Ritonavir Tetracycline Amoxicillin Chloramphenicol Darunavir Daptomycin Etravirine Ivermectin Nitrofurantoin Norfloxacin Ofloxacin Saquinavir Telithromycin Terbinafine Cefotetan Cefazolin Tigecycline Cardiovascular Amiodarone* Clofibrate Diltiazem Fenofibrate Propafenone Propranolol Aspirin Fluvastatin Quinidine Ropinirole Simvastatin Disopyramide Gemfibrozil Metolazone Analgesics, Anti- Inflammatory Piroxicam Acetaminophen Aspririn Celecoxib Tramadol Indomethacin Propoxyphene Sulindac Tolmentin Topical Salicylates Methylprednisolone Nabumetone CNS Drugs Alcohol Citalopram Entacapone Sertraline Disulfiram Chloral hydrate Fluvoxamine Phenytoin Felbamate Diazepam Fluoxetine Quetiapine GI Drugs and Food Cimetidine Mango Omeprazole Grapefruit Orlistat Herbal Supplement Fenugreek Feverfew Fish Oil Ginkgo Quilinggao Dandelion Danshen Don Quai Lycium PC-SPES Red or Sweet Clover Capsicum Forskolin Garlic Ginger Turmeric Other Anabolic Steroids Capecitabine Zileuton Fluorouracil Gemcitabine Levamisole Paclitaxel Tamoxifen Tolterodine Acarbose Cyclophosphamide Danazol Iphosphamide Trastuzumab Etoposide Carboplatin Levonorgestrel *Indicates significant interaction Copyright © 2022 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 05/2022 Effective 5-19-2022. Contact CCKM@uwhealth.org for previous versions. 6 Table 13. Medications, Dietary Supplements, and Foods that DECREASE INR10,26,27,32 Drug Class Known Interaction Probable Interaction Possible Interaction Unlikely Interaction Anti-Infective Griseofulvin Nafcillin Ribavirin Rifampin* Dicloxacillin Ritonovir Rifapentine Terbinafine Nelfinavir Nevirapine Cloxacillin Rifaximin Teicoplanin Cardiovascular Cholestyramine Bosentan Telmisartan Furosemide Analgesics, Anti- Inflammatory Mesalamine Azathioprine Sulfasalazine CNS Drugs Barbiturates Carbamazepine Chlordiazepoxide Propofol GI Drugs and Food High content vitamin K food Avocado Soy milk Sucralfate Sushi containing seaweed Herbal Supplement Alfalfa Ginseng Multivitamin St. John’s Wort Parsley Chewing Tobacco Co-Enzyme Q10 Yarrow Licorice Green Tea Other Mercaptopurine Chelation Therapy Influenza vaccine Raloxifene Cyclosporine Etretinate Ubidecarenone *Indicates significant interaction Click here for information on Warfarin Reversal Copyright © 2022 University of Wisconsin Hospitals and Clinics Authority. 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