WARFARIN SODIUM

WARFARIN SODIUM
(war'far-in)
Coumadin Sodium, Warfilone 
Classifications: anticoagulant;
Therapeutic: anticoagulant

Pregnancy Category: X

Availability

1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10 mg tablets; 2.5 mg/mL injection

Action

Indirectly interferes with blood clotting by depressing hepatic synthesis of vitamin K-dependent coagulation factors: II, VII, IX, and X.

Therapeutic Effect

Deters further extension of existing thrombi and prevents new clots from forming. Has no effect on already synthesized circulating coagulation factors or on circulating thrombi.

Uses

Prophylaxis and treatment of deep vein thrombosis and its extension, pulmonary embolism; treatment of atrial fibrillation with embolization. Also used as adjunct in treatment of coronary occlusion, cerebral transient ischemic attacks (TIAs), and as a prophylactic in patients with prosthetic cardiac valves. Used extensively as rodenticide.

Contraindications

Hemorrhagic tendencies, vitamin C or K deficiency, hemophilia, coagulation factor deficiencies, dyscrasias; active bleeding; open wounds, active peptic ulcer, visceral carcinoma, esophageal varices, malabsorption syndrome; hypertension (diastolic BP >110 mm Hg), cerebral vascular disease; heparin-induced thrombocytopenia (HIT); pericarditis with acute MI; severe hepatic or renal disease; continuous tube drainage of any orifice; subacute bacterial endocarditis; recent surgery of brain, spinal cord, or eye; regional or lumbar block anesthesia; threatened abortion; unreliable patients; pregnancy (category X).

Cautious Use

Alcoholism, allergic disorders, during menstruation, older adults, senility, psychosis; debilitated patients. Endogenous factors that may increase prothrombin time response (enhance anticoagulant effect): carcinoma, CHF, collagen diseases, hepatic and renal insufficiency, diarrhea, fever, pancreatic disorders, malnutrition, vitamin K deficiency. Endogenous factors that may decrease prothrombin time response (decrease anticoagulant response): edema, hypothyroidism, hyperlipidemia, hypercholesterolemia, chronic alcoholism, hereditary resistance to coumarin therapy.

Route & Dosage

Anticoagulant
Adult: PO/IV Usual dose 2–10 mg daily with dose adjusted to maintain a PT 1.2–2 x control or INR of 2–3
Child: PO 0.1–0.3 mg/kg/d, adjust to maintain INR of 2–3

Administration

Note: Antidote for bleeding—anticoagulant effect usually is reversed by omitting 1 or more doses of warfarin and by administration of specific antidote phytonadione (vitamin K1) 2.5–10 mg orally. Physician may advise patient to carry vitamin K1 at all times, but not to take it until after consultation. If bleeding persists or progresses to a severe level, vitamin K 15–25 mg IV is given, or a fresh whole blood transfusion may be necessary.

Oral
  • Give tablet whole or crushed with fluid of patient's choice.
Intravenous

PREPARE: Direct: Add 2.7 mL of sterile water for injection to the 5 mg vial.  

ADMINISTER: Direct: Give required dose over 1–2 min.  

INCOMPATIBILITIES Solution/additive: Ammonium chloride, 5% dextrose, lactated Ringer's, atropine, calcium chloride, calcium gluconate, chloramphenicol, chlorothiazide, chlortetracycline, erythromycin, methicillin, nitrofurantoin, oxacillin, oxytetracycline, penicillin, pentobarbital, phenobarbital, promethazine, sodium bicarbonate, succinyl chloride, vitamin B with C. Y-site: Aminophylline, ammonium chloride, bretylium, ceftazidime, cephalothin, cimetidine, ciprofloxacin, dobutamine, esmolol, gentamicin, labetalol, metronidazole, promazine, vancomycin.

  • Store at 15°–30° C (59°–86° F). Discard discolored or precipitated solutions. Protect all preparations from light and moisture.

Adverse Effects (≥1%)

Body as a Whole: Major or minor hemorrhage from any tissue or organ; hypersensitivity (dermatitis, urticaria, pruritus, fever). GI: Anorexia, nausea, vomiting, abdominal cramps, diarrhea, steatorrhea, stomatitis. Other: Increased serum transaminase levels, hepatitis, jaundice, burning sensation of feet, transient hair loss. Overdosage: Internal or external bleeding, paralytic ileus; skin necrosis of toes (purple toes syndrome), tip of nose, buttocks, thighs, calves, female breast, abdomen, and other fat-rich areas.

Diagnostic Test Interference

Warfarin (coumarins) may cause alkaline urine to be red-orange; may enhance uric acid excretion, cause elevation of serum transaminases, and may increase lactic dehydrogenase activity.

Interactions

Drug: In addition to the drugs listed below, many other drugs have been reported to alter the expected response to warfarin; however, clinical importance of these reports has not been substantiated. The addition or withdrawal of any drug to an established drug regimen should be made cautiously, with more frequent INR determinations than usual and with careful observation of the patient and dose adjustment as indicated. The following may enhance the anticoagulant effects of warfarin: Acetohexamide, acetaminophen, alkylating agents, allopurinol, aminoglycosides, aminosalicylic acid, amiodarone, anabolic steroids, antibiotics (oral), antimetabolites, antiplatelet drugs, aspirin, asparaginase, capecitabine, celecoxib, chloramphenicol, chlorpropamide, chymotrypsin, cimetidine, clofibrate, co-trimoxazole, danazol, dextran, dextrothyroxine, diazoxide, disulfiram, erythromycin, ethacrynic acid, fluconazole, glucagons, guanethidine, hepatotoxic drugs, influenza vaccine, isoniazid, itraconazole, ketoconazole, mao inhibitors, meclofenamate, mefenamic acid, methyldopa, methylphenidate, metronidazole, miconazole, mineral oil, nalidixic acid, neomycin (oral), nonsteroidal anti-inflammatory drugs, oxandrolone, plicamycin, potassium products, propoxyphene, propylthiouracil, quinidine, quinine, rofecoxib, salicylates, streptokinase, sulindac, sulfonamides, sulfonylureas, tetracyclines, thiazides, thyroid drugs, tolbutamide, tricyclic antidepressants, urokinase, vitamin E, zileuton. The following may increase or decrease the anticoagulant effects of warfarin: Alcohol (acute intoxication may increase, chronic alcoholism may decrease effects), chloral hydrate, diuretics. The following may decrease the anticoagulant effects of warfarin: barbiturates, carbamazepine, cholestyramine, corticosteroids, corticotropin, ethchlorvynol, glutethimide, griseofulvin, laxatives, mercaptopurine, oral contraceptives, rifampin, spironolactone, vitamin C, vitamin K. Herbal: Boldo, capsicum, celery, chamomile, clove, coenzyme Q10, danshen, devil's claw, dong quai, echinacea, fenugreek, feverfew, fish oil, garlic, ginger, ginkgo, horse chestnut, licorice root, passionflower herb, turmeric, willow bark may increase risk of bleeding; ginseng, green tea, seaweed, soy, St. John's wort may decrease effectiveness of warfarin. Food: Cranberry juice may increase INR. Green leafy vegetables may affect efficacy. Avocado may decrease effectiveness of warfarin.

Pharmacokinetics

Absorption: Well absorbed from GI tract. Onset: 2–7 d. Peak: 0.5–3 d. Distribution: 97% protein bound; crosses placenta. Metabolism: In liver (CYP2C9). Elimination: In urine and bile. Half-Life: 0.5–3 d.

Nursing Implications

Assessment & Drug Effects

  • Determine PT/INP prior to initiation of therapy and then daily until maintenance dosage is established.
  • Obtain a CAREFUL medication history prior to start of therapy and whenever altered responses to therapy require interpretation; extremely IMPORTANT since many drugs interfere with the activity of anticoagulant drugs (see INTERACTIONS).
  • Adjust dose to maintain PT at 1?–2? times the control (12–15 sec), or 15–35% of normal prothrombin activity, or an INR of 2–4 depending on diagnosis.
  • Lab tests: For maintenance dosage, PT/INR determinations at 1–4-wk intervals depending on patient's response; periodic urinalyses, stool guaiac, and liver function tests. Blood samples should be drawn at 12–18 h after last dose (optimum).
  • Monitor closely older adult, psychotic, or alcoholic patients because they present serious noncompliance problems.
  • Note: Patients at greatest risk of hemorrhage include those whose PT/INR are difficult to regulate, who have an aortic valve prosthesis, who are receiving long-term anticoagulant therapy, and older adult and debilitated patients.

Patient & Family Education

  • Understand that bleeding can occur even though PT/INR are within therapeutic range. Stop drug and notify physician immediately if bleeding or signs of bleeding appear: Blood in urine, bright red or black tarry stools, vomiting of blood, bleeding with tooth brushing, blue or purple spots on skin or mucous membrane, round pinpoint purplish red spots (often occur in ankle areas), nosebleed, bloody sputum; chest pain; abdominal or lumbar pain or swelling, profuse menstrual bleeding, pelvic pain; severe or continuous headache, faintness or dizziness; prolonged oozing from any minor injury (e.g., nicks from shaving).
  • Stop drug and report immediately any symptoms of hepatitis (dark urine, itchy skin, jaundice, abdominal pain, light stools) or hypersensitivity reaction (see Appendix F).
  • Avoid brand interchange, take drug at same time each day, and do NOT alter dose.
  • Notify physician if there is an unusual increase in menstrual bleeding (slightly increased or prolonged). Note: PT/INR are checked at least monthly in menstruating women.
  • Risk of bleeding is increased for up to 1 mo after receiving the influenza vaccine.
  • Fever, prolonged hot weather, malnutrition, and diarrhea lengthen PT/INR (enhanced anticoagulant effect).
  • A high-fat diet, sudden increase in vitamin K–rich foods (cabbage, cauliflower, broccoli, asparagus, lettuce, turnip greens, onions, spinach, kale, fish, liver), coffee or green tea (caffeine), or by tube feedings with high vitamin K content shorten PT/INR.
  • Maintain a well-balanced diet and avoid excess intake of alcohol.
  • Inform dentist or any new physician about anticoagulant therapy and duration of treatment.
  • Use a soft toothbrush and floss teeth gently with waxed floss.
  • Use barrier contraceptive measures; if you become pregnant while on anticoagulant therapy the fetus is at great potential risk of congenital malformations.
  • Do not take any other prescription or OTC drug unless specifically approved by physician or pharmacist. Carry medical identification at all times. It needs to indicate medical diagnosis, medication(s), physician's name, address, and telephone number.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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