WARFARIN SODIUM
(war′far-in)
Coumadin Sodium, Warfilone
Classification: ANTICOAGULANT
Therapeutic: ANTICOAGULANT
Pregnancy Category: X
AVAILABILITY
Tablet; solution for injection
ACTION & THERAPEUTIC EFFECT
Indirectly interferes with blood clotting by depressing hepatic synthesis of vitamin K-dependent coagulation factors: II, VII, IX, and X. Deters further extension of existing thrombi and prevents new clots from forming.
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.
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; uncontrolled hypertension, 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 × control or INR of 2–3
Child: PO 0.1–0.3 mg/kg/day, adjust to maintain INR of 2–3
Pharmacogenetic Dosage Adjustment
Variations in CYP2C9 or VKORC1 may require dose adjustments (see package insert for tables)
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. Prescriber 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 10 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: Amikacin, ammonioum chloride, lactated Ringer’s, atropine, calcium chloride, calcium gluconate, ceftazidime, ceftriaxone, cephalothin, chloramphenicol, chlorothiazide, cyanocobalamine, epinephrine, ergonovine, erythromycin, kanamycin, methi - cillin, nitrofurantoin, oxacillin, penicillin, pentobarbital, phenobarbital, promethazine, sodium bicarbonate, succinyl chloride, tetracycline, vitamin B with C. Y-site: Aminophylline, cephalothin, dantrolene, diazepam, diazoxide, dobutamine, magnesium sulfate, phenytoin, promazine, SMZ/TMP, temocillin.
- 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, cotrimoxazole, 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, glutethimide, griseofulvin, LAXATIVES, mercaptopurine, ORAL CONTRACEPTIVES, rifampin, spironolactone, vitamin C, vitamin K.
Herbal: Boldo, capsicum, celery, coenzyme Q10, danshen, devil’s claw, dong quai, echinacea, evening primrose oil, fenugreek, feverfew, fish oil, garlic, ginger, ginkgo, glucosamine, 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 days. Peak: 0.5–3 days. Distribution: 97% protein bound; crosses placenta. Metabolism: In liver (CYP2C9). Elimination: In urine and bile. Half-Life: 0.5–3 days.
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| NURSING IMPLICATIONS WARFARIN SODIUM Coumadin Sodium, Warfilone |
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NURSING IMPLICATIONS
Black Box Warning
Warfarin has been associated with serious, sometimes fatal, bleeding events.
Assessment & Drug Effects
- Determine PT/INP prior to initiation of therapy and then daily until maintenance dosage is established.
- Obtain a COMPLETE 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).
- Dose is typically adjusted to maintain PT at 1½–2½ × the control (12–15 sec), or 15–35% of normal prothrombin activity, or an INR of 2–4 depending on diagnosis.
- 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.
- Montior lab tests: PT/INR prior to initiation of therapy and then daily until maintenance dosage is established. For maintenance dosage, PT/INR determinations at 1–4-wk intervals depending on patient’s response; periodic urinalyses, stool guaiac, and LFTs. Blood samples for PT/INR should be drawn at 12– 18 h after last dose (optimum).
Patient & Family Education
- Understand that bleeding can occur even though PT/INR are within therapeutic range. Stop drug and notify prescriber 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).
- Take drug at same time each day, and do NOT alter dose.
- 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.
- Avoid excess intake of alcohol.
- 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 prescriber or pharmacist.
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