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Warfarin

What is warfarin

Warfarin is oral anticoagulant or ‘blood thinner’ with anti-vitamin K activity that is commonly used to treat and prevent blood clots. Warfarin has multiple FDA-approved and off-label clinical uses. Warfarin is used to prevent or treat blood clots, including deep venous thrombosis or pulmonary embolism. It is also used to prevent blood clots that may be caused by certain heart conditions like atrial fibrillation, prosthetic heart value placement, open-heart surgery, or after a heart attack (acute myocardial infarction). Warfarin is an anticoagulant (blood thinner) that decreases the clotting ability of the blood. Warfarin was approved for use in the United States in 1961 and remains in wide use with more than 30 million prescriptions filled yearly.

Warfarin is available only with your doctor’s prescription.

Warfarin comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take warfarin at around the same time every day. Warfarin typical dose is 5 mg daily for 2 to 4 days followed by 2 to 10 mg daily, based upon measurements of prothrombin time aiming at an international normalized ratio (INR) value of 2 to 3. Monitoring of the INR is essential during warfarin therapy, because bleeding is a common side effect and can be life-threatening and fatal.

Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take warfarin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Call your doctor immediately if you take more than your prescribed dose of warfarin. Make sure you understand any new dosing instructions from your doctor.

Continue to take warfarin even if you feel well. Do not stop taking warfarin without talking to your doctor.

Warfarin side effects not directly attributable to the anticoagulant activity of warfarin are not common, but can include nausea, abdominal discomfort, diarrhea, anorexia, fever, alopecia, skin necrosis and bluish discoloration. Finally, warfarin is very sensitive to drug-drug interactions involving its metabolism or function and great care must be given to starting or stopping concurrent medications in patients on warfarin therapy. Severe bleeding episodes can be caused by administration of another medication that prolongs its half-life or activity.

Warfarin was discovered after identification of the hemorrhagic activity that caused toxicity and bleeding in cattle after eating spoiled, sweet clover silage. Once the active component was shown to be bis-hydroxycoumarin, synthetic derivatives were developed and found to be effective rodenticides. Only thereafter were coumarin derivatives shown to be useful as anticoagulants in humans, and only with careful monitoring. Importantly, coumarin itself does not have anticoagulant activity but is used as an antineoplastic agent, and has different effects and side effects than its derivatives.

IMPORTANT WARNING

Warfarin may cause severe bleeding that can be life-threatening and even cause death. Tell your doctor if you have or have ever had a blood or bleeding disorder; bleeding problems, especially in your stomach or your esophagus (tube from the throat to the stomach), intestines, urinary tract or bladder, or lungs; high blood pressure; heart attack; angina (chest pain or pressure); heart disease; pericarditis (swelling of the lining (sac) around the heart); endocarditis (infection of one or more heart valves); a stroke or ministroke; aneurysm (weakening or tearing of an artery or vein); anemia (low number of red blood cells in the blood); cancer; chronic diarrhea; or kidney, or liver disease. Also tell your doctor if you fall often or have had a recent serious injury or surgery. Bleeding is more likely during warfarin treatment for people over 65 years of age, and it is also more likely during the first month of warfarin treatment. Bleeding is also more likely to occur for people who take high doses of warfarin, or take this medication for a long time. The risk for bleeding while taking warfarin is also higher for people participating in an activity or sport that may result in serious injury. Tell your doctor and pharmacist if you are taking or plan to take any prescription or nonprescription medications, vitamins, nutritional supplements, and herbal or botanical products (See SPECIAL PRECAUTIONS), as some of these products may increase the risk for bleeding while you are taking warfarin. If you experience any of the following symptoms, call your doctor immediately: pain, swelling, or discomfort, bleeding from a cut that does not stop in the usual amount of time, nosebleeds or bleeding from your gums, coughing up or vomiting blood or material that looks like coffee grounds, unusual bleeding or bruising, increased menstrual flow or vaginal bleeding, pink, red, or dark brown urine, red or tarry black bowel movements, headache, dizziness, or weakness.

Some people may respond differently to warfarin based on their heredity or genetic make-up. Your doctor may order a blood test to help find the dose of warfarin that is best for you.

Warfarin prevents blood from clotting so it may take longer than usual for you to stop bleeding if you are cut or injured. Avoid activities or sports that have a high risk of causing injury. Call your doctor if bleeding is unusual or if you fall and get hurt, especially if you hit your head.

Keep all appointments with your doctor and the laboratory. Your doctor will order a blood test (PT [prothrombin test] reported as INR [international normalized ratio] value) regularly to check your body’s response to warfarin.

If your doctor tells you to stop taking warfarin, the effects of this medication may last for 2 to 5 days after you stop taking it.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with warfarin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (https://www.fda.gov/) or the manufacturer’s website to obtain the Medication Guide.

Talk to your doctor about the risk(s) of taking warfarin.

Warfarin mechanism of action

Warfarin competitively blocks the vitamin K epoxide reductase complex 1 (VKORC1) enzyme, which is an essential enzyme for activating the vitamin K to its active form in the body. Through this mechanism, warfarin can deplete functional vitamin K reserves and therefore reduce the synthesis of active clotting factors II, VII, IX and X. The hepatic synthesis of coagulation factors II, VII, IX, and X as well as regulatory factors protein C and protein S require the presence of vitamin K 1. Vitamin K is an essential cofactor for the synthesis of all of these vitamin K-dependent clotting factors. Warfarin causes a prolongation of the prothrombin time which is beneficial in preventing progression or recurrence of deep vein thrombosis and pulmonary embolism.

Warfarin contraindications

Warfarin has several contraindications and clinical considerations to its use 2.

Warfarin is contraindicated in patients with:

  • Hypersensitivity to warfarin or any component of the formulation
  • Hemorrhagic tendencies (e.g., active GI ulceration, patients bleeding from the GI, respiratory, or GU tract; a cerebral aneurysm; central nervous system (CNS) hemorrhage; dissecting aortic aneurysm; spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding)
  • Recent or contemplated surgery of the eye, central nervous system, or traumatic surgery resulting in large open surfaces
  • Bleeding tendencies associated with any of the following:
    • Active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract
    • Central nervous system hemorrhage
    • Cerebral aneurysms, dissecting aorta
    • Pericarditis and pericardial effusions
    • Bacterial endocarditis
  • Threatened abortion, eclampsia, or preeclampsia
  • Unsupervised patients with conditions associated with a high potential of non-adherence
  • Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding
  • Major regional or lumbar block anesthesia
  • Malignant hypertension
  • Pregnancy (exception: women with mechanical heart valves at high risk for thromboembolism)

Warfarin special precautions

Before taking warfarin:

  • tell your doctor and pharmacist if you are allergic to warfarin, any other medications, or any of the ingredients in warfarin tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  • do not take two or more medications that contain warfarin at the same time. Be sure to check with your doctor or pharmacist if you are uncertain if a medication contains warfarin or warfarin sodium.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take, especially acyclovir (Zovirax); allopurinol (Zyloprim); alprazolam (Xanax); antibiotics such as ciprofloxacin (Cipro), clarithromycin (Biaxin, in Prevpac), erythromycin (E.E.S., Eryc, Ery-Tab), nafcillin, norfloxacin (Noroxin), sulfinpyrazone, telithromycin (Ketek), and tigecycline (Tygacil); anticoagulants such as argatroban (Acova), dabigatran (Pradaxa), bivalirudin (Angiomax), desirudin (Iprivask), heparin, and lepirudin (Refludan); antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), miconazole (Monistat), posaconazole (Noxafil), terbinafine (Lamisil), voriconazole (Vfend); antiplatelet medications such as cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Persantine, in Aggrenox), prasugrel (Effient), and ticlopidine (Ticlid); aprepitant (Emend); aspirin or aspirin-containing products and other nonsteroidal anti-inflammatory drugs such as celecoxib (Celebrex), diclofenac (Flector, Voltaren, in Arthrotec), diflunisal, fenoprofen (Nalfon), ibuprofen (Advil, Motrin), indomethacin (Indocin), ketoprofen, ketorolac, mefenamic acid (Ponstel), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), and sulindac (Clinoril); bicalutamide; bosentan; certain antiarrhythmic medications such as amiodarone (Cordarone, Nexterone, Pacerone), mexiletine, and propafenone (Rythmol); certain calcium channel blocking medications such as amlodipine (Norvasc, in Azor, Caduet, Exforge, Lotrel, Twynsta), diltiazem (Cardizem, Cartia XT, Dilacor XR, Tiazac) and verapamil (Calan, Isoptin, Verelan, in Tarka); certain medications for asthma such as montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo); certain medications used to treat cancer such as capecitabine (Xeloda), imatinib (Gleevec), and nilotinib (Tasigna); certain medications for cholesterol such as atorvastatin (Lipitor, in Caduet) and fluvastatin (Lescol); certain medications for digestive disorders such as cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac); certain medications for human immunodeficiency virus (HIV) infection such as amprenavir, atazanavir (Reyataz), efavirenz (Sustiva), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir/ritonavir, nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase), and tipranavir (Aptivus); certain medications for narcolepsy such as armodafinil (Nuvigil) and modafinil (Provigil); certain medications for seizures such as carbamazepine (Carbatrol, Equetro, Tegretol), phenobarbital, phenytoin (Dilantin, Phenytek), and rufinamide (Banzel); certain medications to treat tuberculosis such as isoniazid (in Rifamate, Rifater) and rifampin (Rifadin, in Rifamate, Rifater); certain selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) such as citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), milnacipran (Savella), paroxetine (Paxil, Pexeva), sertraline (Zoloft), venlafaxine (Effexor) corticosteroids such as prednisone; cyclosporine (Neoral, Sandimmune); disulfiram (Antabuse); methoxsalen (Oxsoralen, Uvadex); metronidazole (Flagyl); nefazodone (Serzone), oral contraceptives (birth control pills); oxandrolone (Oxandrin); pioglitazone (Actos, in Actoplus Met, Duetact, Oseni); propranolol (Inderal) or vilazodone (Viibryd). Many other medications may also interact with warfarin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Do not take any new medications or stop taking any medication without talking to your doctor.
  • tell your doctor and pharmacist what herbal or botanical products you are taking, especially coenzyme Q10 (Ubidecarenone), Echinacea, garlic, Ginkgo biloba, ginseng, goldenseal, and St. John’s wort. There are many other herbal or botanical products which might affect your body’s response to warfarin. Do not start or stop taking any herbal products without talking to your doctor.
  • tell your doctor if you have or have ever had diabetes. Also tell your doctor if you have an infection, a gastrointestinal illness such as diarrhea, or sprue (an allergic reaction to protein found in grains that causes diarrhea), or an indwelling catheter (a flexible plastic tube that is placed into the bladder to allow the urine to drain out).
  • Tell your doctor if you are pregnant, think you might be pregnant, or plan to become pregnant while taking warfarin. Pregnant women should not take warfarin unless they have a mechanical heart valve. Talk to your doctor about the use of effective birth control while taking warfarin. If you become pregnant while taking warfarin, call your doctor immediately. Warfarin may harm the fetus.
  • tell your doctor if you are breast-feeding.
  • if you are having surgery, including dental surgery, or any type of medical or dental procedure, tell the doctor or dentist that you are taking warfarin. Your doctor may tell you to stop taking warfarin before the surgery or procedure or change your dosage of warfarin before the surgery or procedure. Follow your doctor’s directions carefully and keep all appointments with the laboratory if your doctor orders blood tests to find the best dose of warfarin for you.
  • ask your doctor about the safe use of alcoholic beverages while you are taking warfarin.
  • tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this medication.
  • Carry an identification card or wear a bracelet stating that you take warfarin. Ask your pharmacist or doctor how to obtain this card or bracelet. List your name, medical problems, medications and dosages, and doctor’s name and telephone number on the card.
  • Tell all your healthcare providers that you take warfarin.

Pregnancy considerations

Warfarin has two different pregnancy categories depending on the presence of a mechanical heart valve. Warfarin is currently listed as a Category D drug for pregnant women with a mechanical heart valve and Category X for all other indications in pregnant women. Warfarin crosses the placental barrier, causing fetal plasma levels similar to maternal values. Warfarin can cause bleeding in the fetus, and use during pregnancy is commonly associated with spontaneous abortion, stillbirth, preterm birth, and neonatal death. In pregnant women with high-risk for thromboembolism from mechanical heart valves, the benefits and risks of warfarin therapy should be evaluated. Some experts recommend avoiding warfarin use during the first trimester and close to delivery.

Breastfeeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Warfarin diet

While there is no specific diet recommended for patients on warfarin, certain foods and beverages can either limit or enhance the anticoagulant effect of warfarin. Vitamin K decreases the effectiveness of warfarin in the body. Ask your doctor or pharmacist for a list of foods that contain vitamin K. Eat consistent amounts of vitamin K-containing food on a week-to-week basis. Do not eat large amounts of leafy, green vegetables or certain vegetable oils that contain large amounts of vitamin K. Be sure to talk to your doctor before you make any changes in your diet. Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking warfarin. Examples of foods that are high in vitamin K include kale, green tea leaves, Brussel sprouts, and spinach. Other dietary recommendations include limiting consumption of cranberry juice and alcohol while on warfarin therapy. Grapefruit juice and alcohol can enhance the anticoagulant effect of warfarin, thereby leading to increased bleeding complications.

Using warfarin with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Cranberry Juice
  • Pomegranate
  • Tobacco

Using warfarin with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Avocado
  • Black Tea
  • Enteral Nutrition
  • Green Tea
  • High Protein Food
  • Noni Juice
  • Soybean
  • Vitamin K Containing Food

Warfarin interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking warfarin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using warfarin with any of the following medicines is not recommended. Your doctor may decide not to treat you with warfarin or change some of the other medicines you take.

  • Defibrotide
  • Tamoxifen

Using warfarin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Abciximab
  • Aceclofenac
  • Acemetacin
  • Acenocoumarol
  • Alefacept
  • Alipogene Tiparvovec
  • Allopurinol
  • Alteplase, Recombinant
  • Amiodarone
  • Amoxicillin
  • Ampicillin
  • Amtolmetin Guacil
  • Anagrelide
  • Anistreplase
  • Apalutamide
  • Apixaban
  • Aspirin
  • Azithromycin
  • Bemiparin
  • Betrixaban
  • Bicalutamide
  • Bivalirudin
  • Bromfenac
  • Bufexamac
  • Cabozantinib
  • Capecitabine
  • Caplacizumab-yhdp
  • Carbenicillin
  • Carboplatin
  • Cefadroxil
  • Cefdinir
  • Cefepime
  • Cefixime
  • Cefotaxime
  • Cefpodoxime
  • Ceftaroline Fosamil
  • Ceftazidime
  • Ceftibuten
  • Ceftizoxime
  • Celecoxib
  • Cephalexin
  • Cephalothin
  • Cephapirin
  • Cephradine
  • Ceritinib
  • Chamomile
  • Choline Salicylate
  • Ciprofibrate
  • Ciprofloxacin
  • Citalopram
  • Clarithromycin
  • Clonixin
  • Clopidogrel
  • Cloxacillin
  • Cobicistat
  • Collagenase, Clostridium histolyticum
  • Cyclophosphamide
  • Dabigatran Etexilate
  • Dabrafenib
  • Daclatasvir
  • Dalteparin
  • Danaparoid
  • Dapsone
  • Dasabuvir
  • Deferasirox
  • Desvenlafaxine
  • Dexibuprofen
  • Dexketoprofen
  • Diclofenac
  • Dicloxacillin
  • Diflunisal
  • Dihydroartemisinin
  • Dipyridamole
  • Dipyrone
  • Doxifluridine
  • Doxorubicin
  • Doxorubicin Hydrochloride Liposome
  • Dronedarone
  • Drotrecogin Alfa
  • Droxicam
  • Econazole
  • Edoxaban
  • Efavirenz
  • Elbasvir
  • Elvitegravir
  • Enoxacin
  • Enoxaparin
  • Entacapone
  • Enzalutamide
  • Eptifibatide
  • Erlotinib
  • Erythromycin
  • Escitalopram
  • Etodolac
  • Etofenamate
  • Etoposide
  • Etoricoxib
  • Etravirine
  • Felbinac
  • Fenofibrate
  • Fenofibric Acid
  • Fenoprofen
  • Fepradinol
  • Feprazone
  • Fish Oil
  • Floctafenine
  • Fluconazole
  • Flufenamic Acid
  • Fluorouracil
  • Fluoxetine
  • Flurbiprofen
  • Fluvoxamine
  • Fosnetupitant
  • Garlic
  • Gatifloxacin
  • Gemcitabine
  • Gemifloxacin
  • Ginkgo
  • Grazoprevir
  • Ibrutinib
  • Ibuprofen
  • Iloprost
  • Imatinib
  • Indomethacin
  • Infliximab
  • Influenza Virus Vaccine
  • Inotersen
  • Itraconazole
  • Ivosidenib
  • Ketoconazole
  • Ketoprofen
  • Ketorolac
  • Ledipasvir
  • Leflunomide
  • Lepirudin
  • Letermovir
  • Levocarnitine
  • Levofloxacin
  • Levomilnacipran
  • Linezolid
  • Lomitapide
  • Lornoxicam
  • Loxoprofen
  • Lumiracoxib
  • Lycium
  • Marijuana
  • Mechlorethamine
  • Meclofenamate
  • Mefenamic Acid
  • Meloxicam
  • Mercaptopurine
  • Methicillin
  • Methotrexate
  • Methyl Salicylate
  • Metronidazole
  • Miconazole
  • Milnacipran
  • Mirtazapine
  • Morniflumate
  • Moxalactam
  • Moxifloxacin
  • Nabumetone
  • Nadroparin
  • Nafcillin
  • Nalidixic Acid
  • Nandrolone
  • Naproxen
  • Nepafenac
  • Netupitant
  • Niflumic Acid
  • Nilotinib
  • Nimesulide
  • Nimesulide Beta Cyclodextrin
  • Nintedanib
  • Norfloxacin
  • Noscapine
  • Obeticholic Acid
  • Ofloxacin
  • Omadacycline
  • Ombitasvir
  • Oritavancin
  • Orlistat
  • Oseltamivir
  • Oxacillin
  • Oxandrolone
  • Oxaprozin
  • Oxyphenbutazone
  • Oxypurinol
  • Papaya
  • Parecoxib
  • Paritaprevir
  • Paroxetine
  • Peginterferon Alfa-2b
  • Penicillin G
  • Penicillin V
  • Pentosan Polysulfate Sodium
  • Phenindione
  • Phenprocoumon
  • Phenylbutazone
  • Piketoprofen
  • Piperacillin
  • Piracetam
  • Piroxicam
  • Pixantrone
  • Posaconazole
  • Pranoprofen
  • Prasugrel
  • Procarbazine
  • Proglumetacin
  • Proguanil
  • Propyphenazone
  • Proquazone
  • Regorafenib
  • Reteplase, Recombinant
  • Ribavirin
  • Rivaroxaban
  • Rofecoxib
  • Ropinirole
  • Roxithromycin
  • Rucaparib
  • Sarecycline
  • Secnidazole
  • Sertraline
  • Simeprevir
  • Simvastatin
  • Sitaxsentan
  • Sofosbuvir
  • St John’s Wort
  • Streptokinase
  • Sulfamethoxazole
  • Sulfisoxazole
  • Sulindac
  • Sultamicillin
  • Tan-Shen
  • Tegafur
  • Telithromycin
  • Tenecteplase
  • Tenoxicam
  • Teriflunomide
  • Testosterone
  • Tiaprofenic Acid
  • Ticarcillin
  • Ticlopidine
  • Tinzaparin
  • Tirofiban
  • Tocophersolan
  • Tolfenamic Acid
  • Tolmetin
  • Torsemide
  • Treprostinil
  • Urokinase
  • Valdecoxib
  • Valproic Acid
  • Velpatasvir
  • Venlafaxine
  • Vilazodone
  • Vincristine
  • Vincristine Sulfate Liposome
  • Vindesine
  • Vorapaxar
  • Voriconazole
  • Vortioxetine
  • Voxilaprevir

Using warfarin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acarbose
  • Acetaminophen
  • Aminoglutethimide
  • Amitriptyline
  • Amprenavir
  • Apazone
  • Aprepitant
  • Argatroban
  • Atovaquone
  • Azathioprine
  • Balsalazide
  • Bee Pollen
  • Benorilate
  • Benzbromarone
  • Bosentan
  • Butabarbital
  • Butalbital
  • Carbamazepine
  • Carbimazole
  • Cefamandole
  • Cefazolin
  • Ceftriaxone
  • Chitosan
  • Chloral Hydrate
  • Chlorthalidone
  • Cholestyramine
  • Choline Magnesium Trisalicylate
  • Chondroitin
  • Cimetidine
  • Cisapride
  • Cisplatin
  • Coenzyme Q10
  • Colesevelam
  • Curcumin
  • Cyclosporine
  • Danazol
  • Desogestrel
  • Dexamethasone
  • Dexlansoprazole
  • Dienogest
  • Disopyramide
  • Disulfiram
  • Dong Quai
  • Doxepin
  • Drospirenone
  • Duloxetine
  • Eslicarbazepine Acetate
  • Esomeprazole
  • Estradiol Cypionate
  • Estradiol Valerate
  • Eterobarb
  • Ethinyl Estradiol
  • Ethynodiol Diacetate
  • Etonogestrel
  • Exenatide
  • Felbamate
  • Fluoxymesterone
  • Fluvastatin
  • Fosaprepitant
  • Gefitinib
  • Gemfibrozil
  • Ginger
  • Ginseng
  • Glucagon
  • Glucosamine
  • Glyburide
  • Griseofulvin
  • Heparin
  • Ifosfamide
  • Indoprofen
  • Isoniazid
  • Isoxicam
  • Ivermectin
  • Lactulose
  • Lansoprazole
  • Levamisole
  • Levonorgestrel
  • Lopinavir
  • Medroxyprogesterone Acetate
  • Melatonin
  • Menatetrenone
  • Menthol
  • Mephobarbital
  • Mesalamine
  • Mesna
  • Mestranol
  • Methimazole
  • Methylprednisolone
  • Methyltestosterone
  • Methylthiouracil
  • Mitotane
  • Moricizine
  • Nelfinavir
  • Nevirapine
  • Niacin
  • Nilutamide
  • Norelgestromin
  • Norethindrone
  • Norgestimate
  • Norgestrel
  • Omeprazole
  • Pantoprazole
  • Pentoxifylline
  • Phenobarbital
  • Phytonadione
  • Polyacrylamide
  • Potassium Iodide
  • Prednisone
  • Primidone
  • Propafenone
  • Propoxyphene
  • Propylthiouracil
  • Quetiapine
  • Ranitidine
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Ritonavir
  • Rosuvastatin
  • Salicylamide
  • Salicylic Acid
  • Salsalate
  • Saquinavir
  • Secobarbital
  • Sodium Salicylate
  • Sodium Thiosalicylate
  • Sorafenib
  • Stanozolol
  • Sucralfate
  • Sulfasalazine
  • Sulfinpyrazone
  • Tenidap
  • Terbinafine
  • Tigecycline
  • Tolterodine
  • Tramadol
  • Trastuzumab
  • Trolamine Salicylate
  • Vancomycin
  • Venetoclax
  • Vitamin A
  • Vitamin E
  • Vorinostat
  • Zafirlukast
  • Zileuton

Other Medical Problems

The presence of other medical problems may affect the use of warfarin. Make sure you tell your doctor if you have any other medical problems, especially:

  • Anemia or
  • Catheter insertion or
  • Congestive heart failure or
  • Deep venous thrombosis, heparin-induced or
  • Diabetes or
  • Falls or blows to the body or head or
  • Hypertension (high blood pressure) or
  • Infection or
  • Kidney disease, or history of or
  • Major surgery, any type or
  • Polycythemia vera (blood disease) or
  • Protein C deficiency (rare hereditary disease), known or suspected or
  • Stomach or bowel problems, including bleeding or
  • Thrombocytopenia, heparin-induced or
  • Trauma or
  • Vasculitis (inflammation of blood vessel)—Use with caution. May cause side effects to become worse.
  • Blood disease or bleeding problems or
  • Heart infection or
  • High blood pressure (high blood pressure), severe or
  • Spinal anesthesia, recent or
  • Stomach or intestinal ulcer, active or
  • Stroke, history of or
  • Surgery, recent or scheduled (eg, surgery of the eye, brain, or spine) or
  • Threatened miscarriage—Should not be used in patients with these conditions. The risk of bleeding from warfarin may be increased.
  • Diarrhea or
  • Liver disease or
  • Malnutrition or
  • Steatorrhea (fats in the stool) or
  • Vitamin K deficiency—Use with caution. May increase risk of bleeding.

Warfarin uses

Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung).

You might be given warfarin if you have:

  • A blood clot in or near your heart that could trigger stroke, heart attack or organ damage
  • A blood clot in your lungs (pulmonary embolism)
  • A blood clot elsewhere in your body (venous thrombosis)
  • A high risk of blood clots forming in the heart, which can be a complication of some heart rhythm abnormalities (arrhythmias)
  • A mechanical artificial heart valve that is prone to forming blood clots

FDA-approved clinical uses for warfarin 3:

  • Prophylaxis and treatment of venous thrombosis and arising pulmonary embolisms
  • Prophylaxis and treatment of thromboembolic complications from atrial fibrillation or cardiac valve replacement
  • Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events (e.g., stroke, systemic embolization) after myocardial infarction

Off-label clinical uses of warfarin include:

  • Secondary prevention of recurrent stroke and transient ischemic attacks

Monitoring

Patients receiving treatment with warfarin should be closely monitored to ensure safety and efficacy of the medication. Periodic blood testing is recommended to assess the patient’s prothrombin time (PT) and the international normalized ratio (INR).

The laboratory parameter utilized to monitor warfarin therapy is the PT/INR. The PT is the number of seconds it takes the blood to clot, and the INR allows for the standardization of the PT measurement depending on the thromboplastin reagent used by a laboratory. Therefore monitoring a patient’s INR while on warfarin is strongly preferred over PT because it allows for a standardized measurement without variations due to different laboratory sites. Routine assessment of INR is essential in the management of patients receiving warfarin therapy. The INR of a patient who is not on anticoagulation therapy is approximately 1.0. If a patient has an INR of 2.0 or 3.0, that would indicate that it takes two or three times longer for that individual’s blood to clot than someone who is not taking any anticoagulants The therapeutic INR goal for patients on warfarin therapy is dependent on the indication, but may vary based on the patient’s clinical presentation and provider preference. Most patients on warfarin have an INR goal of 2 to 3. However, certain indications such as a mechanical mitral valve require an INR goal of 2.5 to 3.5.

Close monitoring of a patient’s INR is strongly recommended when initiating warfarin. The INR should be monitored more frequently when initiating warfarin. For hospitalized patients, INR is commonly monitored on a daily basis. Once a patient has reached the maintenance phase of therapy, the INR is typically assessed at least every four weeks. More frequent monitoring is necessary for patients with supratherapeutic or subtherapeutic INR in order to assess safety and efficacy. In addition, the INR may be assessed when initiating, discontinuing, or changing doses of medications that are known to interact with warfarin.

Patients should also be closely monitored for signs and symptoms of active bleeding throughout their treatment. Close monitoring for signs and symptoms of bleeding such as dark tarry stools, nosebleeds, and hematomas is necessary. The patient’s hemoglobin and hematocrit level should be assessed before initiating warfarin and approximately every six months while on therapy. Other laboratory tests may be recommended based on the patient’s clinical presentation and INR result. Monitoring liver function, renal function, and occult blood may be indicated in certain patient populations.

Warfarin dosage

The dose of warfarin medication will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of warfarin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of warfarin that you take depends on the strength of the warfarin. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take warfarin depend on the medical problem for which you are using warfarin.

For oral dosage form (tablets):

  • For prevention or treatment of blood clots:
    • Adult—At first, 2 to 5 milligrams (mg) as a single dose once per day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 10 mg per day.
      • Initial dose: 2 to 5 mg orally once a day
      • Maintenance dose: 2 to 10 mg orally once a day
      • Target INR: 2.5 (range: 2 to 3)
    • Children—Use and dose must be determined by your doctor.
      • The American College of Chest Physicians provides the following dosage guidelines for antithrombotic therapy in neonates and children:
        • Initial dose (if baseline INR is 1 to 1.3): 0.2 mg/kg orally; subsequent dose adjustments should be made to maintain an INR between 2 and 3.
        • Comments:
          • Infants required an average of 0.33 mg/kg to maintain an INR of 2 to 3.
          • Teenagers required an average of 0.09 mg/kg to maintain an INR of 2 to 3.

Adult dose for Prevention of Thromboembolism in Atrial Fibrillation

Use: Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy: Indefinite

Comments:

  • For patients with atrial fibrillation (AF) and prosthetic heart valves, target INR may be increased depending on valve type, valve position, and patient factors.
  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for thromboembolic stroke prophylaxis

Use: Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy: Indefinite

Comments:

  • For patients with atrial fibrillation (AF) and prosthetic heart valves, target INR may be increased depending on valve type, valve position, and patient factors.
  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Myocardial Infarction

Use: Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2 to 3

Duration of therapy: At least 3 months after myocardial infarction

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Myocardial Infarction – Prophylaxis

Use: Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2 to 3

Duration of therapy: At least 3 months after myocardial infarction

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Deep Vein Thrombosis – Prophylaxis

Use: Prophylaxis and treatment of venous thrombosis and pulmonary embolism (PE).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy:

  • Deep venous thrombosis (DVT) or pulmonary embolism (PE) secondary to a reversible risk factor: 3 months
  • Unprovoked DVT or PE: At least 3 months; evaluate risk-benefit ratio of long-term treatment after 3 months.
  • Two episodes of unprovoked DVT or PE: Indefinite; periodically reassess risk-benefit ratio of continuing such treatment.

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Pulmonary Embolism

Use: Prophylaxis and treatment of venous thrombosis and pulmonary embolism (PE).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy:

  • Deep venous thrombosis (DVT) or pulmonary embolism (PE) secondary to a reversible risk factor: 3 months
  • Unprovoked DVT or PE: At least 3 months; evaluate risk-benefit ratio of long-term treatment after 3 months.
  • Two episodes of unprovoked DVT or PE: Indefinite; periodically reassess risk-benefit ratio of continuing such treatment.

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Deep Vein Thrombosis – First Event

Use: Prophylaxis and treatment of venous thrombosis and pulmonary embolism (PE).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy:

  • Deep venous thrombosis (DVT) or pulmonary embolism (PE) secondary to a reversible risk factor: 3 months
  • Unprovoked DVT or PE: At least 3 months; evaluate risk-benefit ratio of long-term treatment after 3 months.
  • Two episodes of unprovoked DVT or PE: Indefinite; periodically reassess risk-benefit ratio of continuing such treatment.

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Deep Vein Thrombosis – Recurrent Event

Use: Prophylaxis and treatment of venous thrombosis and pulmonary embolism (PE).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy:

  • Deep venous thrombosis (DVT) or pulmonary embolism (PE) secondary to a reversible risk factor: 3 months
  • Unprovoked DVT or PE: At least 3 months; evaluate risk-benefit ratio of long-term treatment after 3 months.
  • Two episodes of unprovoked DVT or PE: Indefinite; periodically reassess risk-benefit ratio of continuing such treatment.

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Pulmonary Embolism – First Event

Use: Prophylaxis and treatment of venous thrombosis and pulmonary embolism (PE).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy:

  • Deep venous thrombosis (DVT) or pulmonary embolism (PE) secondary to a reversible risk factor: 3 months
  • Unprovoked DVT or PE: At least 3 months; evaluate risk-benefit ratio of long-term treatment after 3 months.
  • Two episodes of unprovoked DVT or PE: Indefinite; periodically reassess risk-benefit ratio of continuing such treatment.

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Pulmonary Embolism – Recurrent Event

Use: Prophylaxis and treatment of venous thrombosis and pulmonary embolism (PE).

  • Initial dose: 2 to 5 mg orally once a day
  • Maintenance dose: 2 to 10 mg orally once a day
  • Target INR: 2.5 (range: 2 to 3)

Duration of therapy:

  • Deep venous thrombosis (DVT) or pulmonary embolism (PE) secondary to a reversible risk factor: 3 months
  • Unprovoked DVT or PE: At least 3 months; evaluate risk-benefit ratio of long-term treatment after 3 months.
  • Two episodes of unprovoked DVT or PE: Indefinite; periodically reassess risk-benefit ratio of continuing such treatment.

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Prosthetic Heart Valves – Tissue Valves

Uses:

  • Prophylaxis and treatment of thromboembolic complications in patients with a bileaflet mechanical valve or a Medtronic Hall (Minneapolis, MN) tilting disk valve in the aortic position who are in sinus rhythm and without left atrial enlargement (target INR: 2.5; range: 2 to 3).
  • Prophylaxis and treatment of thromboembolic complications in patients with tilting disk valves and bileaflet mechanical valves in the mitral position (target INR: 3; range: 2.5 to 3.5).
  • Prophylaxis and treatment of thromboembolic complications in patients with caged ball or caged disk valves (target INR: 3; range: 2.5 to 3.5).
  • Prophylaxis and treatment of thromboembolic complications in patients with a bioprosthetic valve in the mitral position (target INR: 2.5; range: 2 to 3) for the first 3 months after valve insertion is recommended. If additional risk factors for thromboembolism are present (atrial fibrillation, previous thromboembolism, left ventricular dysfunction), a target INR of 2.5 (range: 2 to 3) is recommended.

Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Adult dose for Prosthetic Heart Valves – Mechanical Valves

Uses:

  • Prophylaxis and treatment of thromboembolic complications in patients with a bileaflet mechanical valve or a Medtronic Hall (Minneapolis, MN) tilting disk valve in the aortic position who are in sinus rhythm and without left atrial enlargement (target INR: 2.5; range: 2 to 3).
  • Prophylaxis and treatment of thromboembolic complications in patients with tilting disk valves and bileaflet mechanical valves in the mitral position (target INR: 3; range: 2.5 to 3.5).
  • Prophylaxis and treatment of thromboembolic complications in patients with caged ball or caged disk valves (target INR: 3; range: 2.5 to 3.5).
  • Prophylaxis and treatment of thromboembolic complications in patients with a bioprosthetic valve in the mitral position (target INR: 2.5; range: 2 to 3) for the first 3 months after valve insertion is recommended. If additional risk factors for thromboembolism are present (atrial fibrillation, previous thromboembolism, left ventricular dysfunction), a target INR of 2.5 (range: 2 to 3) is recommended.

Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day

Comments:

  • Initial dose is influenced by age, race, body weight, gender, concomitant medications, comorbidities, genetic variation, and possibly other factors.
  • Dosage and administration must be individualized according to the patient’s INR and condition being treated.

Renal Dose Adjustments

  • No adjustment recommended

Liver Dose Adjustments

  • Use with caution

What should I do if I forget a dose?

Take the missed dose as soon as you remember it, if it is the same day that you were to take the dose. Do not take a double dose the next day to make up for a missed one. Call your doctor if you miss a dose of warfarin.

Warfarin side effects

Serious adverse effects of warfarin include bleeding and major hemorrhage. A major hemorrhage (e.g., intracranial hemorrhage, gastrointestinal (GI) bleed, hematemesis, intraocular bleeding, hemarthrosis) can occur at virtually any site on the body. Patients should thoroughly be educated about the easy bleeding or bruising that is a common adverse effect. A physician should also counsel patients about the proper management of cuts, bruises, and nosebleeds. The risk of bleeding and hemorrhage is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility. Individuals should be assessed for their risk and adjustments to their treatment plan should be made accordingly.

Other adverse effects include nausea, vomiting, abdominal pain, bloating, flatulence, and altered sense of taste.

Rare cases of purple toe syndrome, warfarin-induced skin necrosis, and calciphylaxis have been reported with warfarin therapy. Purple toe syndrome is complication characterized by cholesterol microembolization that causes purple lesions to develop on the toes and sides of the feet. Purple toe syndrome usually develops 3 to 8 weeks after the initiation of warfarin therapy. Warfarin-induced skin necrosis is a serious condition in which the subcutaneous tissue necrosis occurs due to an acquired protein C deficiency following treatment with warfarin. The risk of necrosis is increased in patients with protein C or protein S deficiency. The skin necrosis usually occurs within the first week of therapy and management strategies including discontinuing treatment with warfarin, administering fresh frozen plasma and vitamin K, and initiating anticoagulation therapy with either unfractionated heparin or a low molecular weight heparin. Calciphylaxis or calcium uremic arteriolopathy is another rare adverse effect that can occur in patients with or without end-stage renal disease.

Warfarin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • gas
  • abdominal pain
  • bloating
  • change in the way things taste
  • loss of hair
  • feeling cold or having chills

If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING section, call your doctor immediately:

  • hives
  • rash
  • itching
  • difficulty breathing or swallowing
  • swelling of the face, throat, tongue, lips, or eyes
  • hoarseness
  • chest pain or pressure
  • swelling of the hands, feet, ankles, or lower legs
  • fever
  • infection
  • nausea
  • vomiting
  • diarrhea
  • extreme tiredness
  • lack of energy
  • loss of appetite
  • pain in the upper right part of the stomach
  • yellowing of the skin or eyes
  • flu-like symptoms

You should know that warfarin may cause necrosis or gangrene (death of skin or other body tissues). Call your doctor immediately if you notice a purplish or darkened color to your skin, skin changes, ulcers, or an unusual problem in any area of your skin or body, or if you have a severe pain that occurs suddenly, or color or temperature change in any area of your body. Call your doctor immediately if your toes become painful or become purple or dark in color. You may need medical care right away to prevent amputation (removal) of your affected body part.

Warfarin may cause other side effects. Call your doctor if you have any unusual problems while taking warfarin.

Symptoms of warfarin overdose may include the following:

  • bloody or red, or tarry bowel movements
  • spitting or coughing up blood
  • heavy bleeding with your menstrual period
  • pink, red, or dark brown urine
  • coughing up or vomiting material that looks like coffee grounds
  • small, flat, round red spots under the skin
  • unusual bruising or bleeding
  • continued oozing or bleeding from minor cuts

Warfarin toxicity can be assessed through signs and symptoms of bleeding as well as the determination of a supratherapeutic INR level. The risk of bleeding is significantly greater with increased INR, especially above 5.0. When managing warfarin toxicity, the initial step would be to discontinue warfarin and then administer vitamin K (phytonadione). The vitamin K may be administered either the oral, intravenous, or subcutaneous route. However, initial administration of oral vitamin K is often preferred in patients without major bleeding or extremely elevated INR. A reduction in INR is expected to occur within 24 hours of administration. After that, intravenous vitamin K administration is recommended if necessary. Subcutaneous vitamin K is often not recommended for warfarin toxicity or reversal due to erratic and unpredictable absorption. Administering agents like prothrombin complex concentrate (PCC), fresh frozen plasma (FFP), and activated Factor VII may be considered for cases of major bleeding.

References
  1. Patel S, Preuss CV, Patel N. Warfarin. [Updated 2019 Apr 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470313
  2. Divito A, Kerr K, Wilkerson C, Shepard S, Choi A, Kitagawa RS. Use of Anticoagulation Agents After Traumatic Intracranial Hemorrhage. World Neurosurg. 2019 Mar;123:e25-e30.
  3. Doliner B, Jaller JA, Lopez AJ, Lev-Tov H. Treatments to prevent primary venous ulceration after deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2019 Mar;7(2):260-271.e1
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