General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
war-fa-rin


Trade Name(s)

  • Coumadin
  • Jantoven

Pregnancy Category
Category X

Ther. Class.
anticoagulants

Pharm. Class.
coumarins

Indications

  • Prophylaxis and treatment of:
    • Venous thrombosis,
    • Pulmonary embolism,
    • Atrial fibrillation with embolization.
  • Management of myocardial infarction:
    • Decreases risk of death,
    • Decreases risk of subsequent MI,
    • Decreases risk of future thromboembolic events.
  • Prevention of thrombus formation and embolization after prosthetic valve placement.

Action

Interferes with hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X).

Therapeutic Effect(s):

Prevention of thromboembolic events.

Pharmacokinetics

Absorption: Well absorbed from the GI tract after oral administration.

Distribution: Crosses the placenta but does not enter breast milk.

Protein Binding: 99%.

Metabolism and Excretion: Metabolized by the liver.

Half-life: 42 hr.

TIME/ACTION PROFILE (effects on coagulation tests)

† At a constant dose
‡ After discontinuation

ROUTEONSETPEAKDURATION
PO, IV36–72 hr5–7 days†2–5 days‡

Contraindication/Precautions

Contraindicated in:

  • Uncontrolled bleeding;
  • Open wounds;
  • Active ulcer disease;
  • Recent brain, eye, or spinal cord injury or surgery;
  • Severe liver or kidney disease;
  • Uncontrolled hypertension;
  • OB: Crosses placenta and may cause fatal hemorrhage in the fetus. May also cause congenital malformation.

Use Cautiously in:

  • Malignancy;
  • Patients with history of ulcer or liver disease;
  • History of poor compliance;
  • Women with childbearing potential;
  • Asian patients or those who carry the CYP2C9*2 allele and/or the CYP2C9*3 allele, or with the VKORC1 AA genotype (↑ risk of bleeding with standard dosing; lower initial doses should be considered);
  • Pedi: Has been used safely but may require more frequent PT/INR assessments;
  • Geri: Due to greater than expected anticoagulant response, initiate and maintain at lower doses.

Adverse Reactions/Side Effects

GI: cramps, nausea

Derm: dermal necrosis

Hemat: BLEEDING

Misc: fever

* CAPITALS indicate life-threatening.
Italics indicate most frequent.

Interactions

Drug-Drug

Drug-Natural Products:

Drug-Food:

Ingestion of large quantities of foods high in vitamin K content (see list in food sources for specific nutrients) may antagonize the anticoagulant effect of warfarin.

Route/Dosage

PO: IV: (Adults) 2–5 mg/day for 2–4 days; then adjust daily dose by results of INR. Initiate therapy with lower doses in geriatric or debilitated patients or in Asian patients or those with CYP2C9*2 and/or CYP2C9*3 alleles or VKORC1 AA genotype.

PO: IV: (Children >1 mo): Initial loading dose– 0.2 mg/kg (maximum dose: 10 mg) for 2–4 days then adjust daily dose by results of INR, use 0.1 mg/kg if liver dysfunction is present. Maintenance dose range– 0.05–0.34 mg/kg/day.

Availability (generic available)

Tablets: 1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10 mg

Cost:

Generic: 1 mg $10.83/100, 2 mg $10.83/100, 2.5 mg $10.83/100, 3 mg $10.83/100, 4 mg $10.83/100, 5 mg $8.52/100, 6 mg $10.64/100, 7.5 mg $10.83/100, 10 mg $10.83/100

Powder for injection: 5 mg/vial

Assessment

  • Assess for signs of bleeding and hemorrhage (bleeding gums; nosebleed; unusual bruising; tarry, black stools; hematuria; fall in hematocrit or BP; guaiac-positive stools, urine, or nasogastric aspirate).
  • Assess for evidence of additional or increased thrombosis. Symptoms depend on area of involvement.
  • Geri: Patients over 60 yr exhibit greater than expected PT/INR response. Monitor for side effects at lower therapeutic ranges.
  • Pedi: Achieving and maintaining therapeutic PT/INR ranges may be more difficult in pediatric patients. Assess PT/INR levels more frequently.

Lab Test Considerations:

Monitor PT, INR and other clotting factors frequently during therapy. Therapeutic PT ranges 1.3–1.5 times greater than control; however, the INR, a standardized system that provides a common basis for communicating and interpreting PT results, is usually referenced. Normal INR (not on anticoagulants) is 0.8–1.2. An INR of 2.5–3.5 is recommended for patients at very high risk of embolization (for example, patients with mitral valve replacement and ventricular hypertrophy). Lower levels are acceptable when risk is lower. Heparin may affect the PT/INR; draw blood for PT/INR in patients receiving both heparin and warfarin at least 5 hr after the IV bolus dose, 4 hr after cessation of IV infusion, or 24 hr after subcut heparin injection. Asian patients and those who carry the CYP2C9*2 allele and/or the CYP2C9*3 allele, or those with VKORC1 AA genotype may require more frequent monitoring and lower doses.

  • Monitor hepatic function and CBC before and periodically throughout therapy.
  • Monitor stool and urine for occult blood before and periodically during therapy.

Toxicity Overdose:

Withholding 1 or more doses of warfarin is usually sufficient if INR is excessively elevated or if minor bleeding occurs. If overdose occurs or anticoagulation needs to be immediately reversed, the antidote is vitamin K (phytonadione, AquaMEPHYTON). Administration of whole blood or plasma also may be required in severe bleeding because of the delayed onset of vitamin K.

Potential Diagnoses

Implementation

  • High Alert: Medication errors involving anticoagulants have resulted in serious harm or death from internal or intracranial bleeding. Before administering, evaluate recent INR or PT results and have second practitioner independently check original order.
  • Do not confuse Coumadin (warfarin) with Avandia (rosiglitazone) or Cardura (doxazosin). Do not confuse Jantoven (warfarin) with Janumet (sitagliptin/metformin) or Januvia (sitagliptin).
  • Because of the large number of medications capable of significantly altering warfarin's effects, careful monitoring is recommended when new agents are started or other agents are discontinued. Interactive potential should be evaluated for all new medications (Rx, OTC, and natural products).
  • PO: Administer medication at same time each day. Medication requires 3–5 days to reach effective levels; usually begun while patient is still on heparin.
    • Do not interchange brands; potencies may not be equivalent.

IV Administration

  • Direct IV: Reconstitute each 5-mg vial with 2.7 mL of sterile water for injection. Reconstituted solution is stable for 4 hr at room temperature. Diluent: No further dilution needed before administration. Concentration: 2 mg/mL.
  • Rate: Administer over 1–2 min.
  • Y-Site Compatibility
    • amikacin
    • ascorbic acid
    • bivalrudin
    • cefazolin
    • ceftriaxone
    • dopamine
    • epinephrine
    • heparin
    • lidocaine
    • morphine
    • nitroglycerin
    • oxytocin
    • potassium chloride
    • ranitidine
  • Y-Site Incompatibility
    • aminophylline
    • ceftazidime
    • ciprofloxacin
    • dobutamine
    • esmolol
    • gentamicin
    • labetalol
    • promazine

Patient/Family Teaching

  • Instruct patient to take medication as directed. Take missed doses as soon as remembered that day; do not double doses. Inform health care professional of missed doses at time of checkup or lab tests. Inform patients that anticoagulant effect may persist for 2–5 days following discontinuation. Advise patient to read Medication Guide before starting therapy and with each Rx refill.
  • Review foods high in vitamin K (see food sources for specific nutrients). Patient should have consistent limited intake of these foods, as vitamin K is the antidote for warfarin, and alternating intake of these foods will cause PT levels to fluctuate. Advise patient to avoid cranberry juice or products during therapy.
  • Caution patient to avoid IM injections and activities leading to injury. Instruct patient to use a soft toothbrush, not to floss, and to shave with an electric razor during warfarin therapy. Advise patient that venipunctures and injection sites require application of pressure to prevent bleeding or hematoma formation.
  • Advise patient to report any symptoms of unusual bleeding or bruising (bleeding gums; nosebleed; black, tarry stools; hematuria; excessive menstrual flow) and pain, color, or temperature change to any area of your body to health care professional immediately.Patients with a deficiency in protein C and/or S mediated anticoagulant response may be at greater risk for tissue necrosis.
  • Instruct patient not to drink alcohol or take other Rx, OTC, or herbal products, especially those containing aspirin or NSAIDs, or to start or stop any new medications during warfarin therapy without advice of health care professional.
  • Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Instruct patient to carry identification describing medication regimen at all times and to inform all health care personnel caring for patient on anticoagulant therapy before lab tests, treatment, or surgery.
  • Emphasize the importance of frequent lab tests to monitor coagulation factors.

Evaluation/Desired Outcomes

Prolonged PT (1.3–2.0 times the control; may vary with indication) or INR of 2–4.5 without signs of hemorrhage.