Warfarin Management - Adult - Inpatient Consensus Care Practice Guideline Target Population: Adult inpatients receiving anticoagulation therapy with the oral vitamin K antagonist, warfarin Full Guideline: Warfarin Management - Adult - Inpatient 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 • Monitoring considerations • Warfarin dosing protocol with INR goal 2-3 • Warfarin dosing protocol with INR goal 2.5-3.5 • Laboratory monitoring • Dose adjustments for drug interactions • Factors that increase INR • Factors that decrease INR • Warfarin reversal • Transitioning to outpatient management • References- see full guideline for citations Table 1: see full guideline for INR goals and recommended duration of therapy by indication (with link when ready) 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) • Underweight (e.g. BMI less than 18kg/m2) • Nutritional status (e.g. malnourished, low vitamin K intake/stores) • Genetic factors (e.g. CYP2C9, VKORC1 phenotypes) • Drug-drug interactions • Hypoalbuminemia • Ethnicity (Asian) • Liver disease • Thyroid Disease (e.g. hyperthyroidism, Graves’ disease) • Heart Failure • Febrile illness • Prolonged vomiting and diarrhea • Surgery and blood loss • Cannabinoids • Alcohol • Drug interactions Decrease warfarin sensitivity (may require higher doses) • Enteral feedings • High-vitamin K intake • Estrogens • Chewing tobacco Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 07/2021 Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions. Table 3. Monitoring Considerations Table 3. Monitoring Considerations • Signs and symptoms of thrombosis progression or bleeding • PT/INR (daily during initiation or unstable, and at least weekly when stable) • CBC without differential prior to warfarin initiation and then at least every 3 days • Missed or held doses • Drug-drug and drug-food interactions • Nutrition • Activity level Table 4. Warfarin dosing protocol with INR Goal 2-3 High Sensitivity to Warfarin Low Sensitivity to Warfarin INR Value Dose INR Value Dose Day 1 <1.5 2.5 - 5 mg <1.5 5 - 7.5 mg Day 2 <1.5 ≥1.5 2.5 - 5 mg 0 - 2.5 mg <1.5 ≥1.5 5 - 7.5 mg 0 - 5 mg Day 3 <1.5 1.5-1.9 2-2.5 ≥2.6 5 mg 2.5 mg 1 mg 0 (no dose) <1.5 1.5-1.9 2-2.5 ≥2.6 7.5 mg 5 mg 2.5 mg 0 (no dose) Day 4 <1.5 1.5-1.9 2-3 > 3 7.5 mg 5 mg 2.5 mg 0 - 1 mg <1.5 1.5-1.9 2-3 >3 10 mg 7.5 mg 5 mg 0-2.5 mg Day 5 <1.5 1.5-1.9 2-3 3-3.5 >3.5 10 mg yesterday’s dose + 1 mg yesterday’s dose yesterday’s dose – 1 mg 0 (no dose) <1.5 1.5-1.9 2-3 3-3.5 >3.5 12.5 mg yesterday’s dose + 2.5 mg yesterday’s dose yesterday’s dose – 2.5 mg 0 (no dose) Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 07/2021 Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions. Table 5. Warfarin dosing protocol with INR Goal 2.5-3.5 High Sensitivity to Warfarin Low Sensitivity to Warfarin INR Value Dose INR Value Dose Day 1 < 1.5 2.5 - 5 mg < 1.5 5 - 7.5 mg Day 2 < 1.5 ≥ 1.5 2.5 - 5 mg 0 - 2.5 mg < 1.5 ≥ 1.5 5 - 7.5 mg 0 - 5 mg Day 3 < 1.5 1.5-1.9 2.0-2.5 ≥ 2.5 5 - 7.5 mg 5 mg 2.5 mg 0 ( no dose) < 1.5 1.5-1.9 2.0-2.5 ≥ 2.5 7.5 - 10 mg 7.5 mg 5 mg 0 (no dose) Day 4 < 1.9 2.0-2.4 2.5-3.5 ≥ 3.6 7.5 mg 5 mg 2.5 mg 0 - 1 mg < 1.9 2.0-2.4 2.5-3.5 ≥ 3.6 10 mg 7.5 mg 5 mg 0-2.5 mg Day 5 < 1.9 2.0-2.4 2.5-3.5 3.6-4.0 ≥ 4.0 10 mg yesterday’s dose + 2.5 mg yesterday’s dose yesterday’s dose – 2.5 mg 0 (no dose) < 1.9 2.0-2.4 2.5-3.5 3.6-4.0 ≥ 4.0 12.5 mg yesterday’s dose + 2.5 mg yesterday’s dose yesterday’s dose – 2.5 mg 0 (no dose) Laboratory Monitoring Baseline Within the past 30 days • Baseline INR • Pregnancy test* • CBC without diff *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 • ALT • Creatinine During Admission Daily • INR If providing a daily warfarin dose At least weekly • CBC without diff • INR If providing a weekly warfarin dose After Discharge Within 3-4 days • INR Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 07/2021 Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions. Dose Adjustment Recommendations for Common/Significant Warfarin-Drug Interactions 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 © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 07/2021 Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions. Table 6. Medications, Dietary Supplements, and Foods that INCREASE INR or bleeding risk 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 © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 07/2021 Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions. Table 7. Medications, Dietary Supplements, and Foods that DECREASE INR 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 Transitioning to outpatient management Communication to the next provider of care Indication Target INR range Warfarin dose Date for next INR check Name of the clinic or provider assuming warfarin management Length of therapy Potential drug, herbal, or supplement interactions Longitudinal record of inpatient INR values and warfarin doses Bridging therapy if needed Educational materials provided to the patient Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. 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