Warfarin sodium

Warfarin sodium

[1 tablet 10 cents]

ADMINISTRATION ROUTES:

  • PO, NG

BRAND NAMES:

  • Coumadin, Marevan

ICU INDICATIONS:

  1. Anticoagulation for prophylaxis and/or treatment of venous thrombosis, pulmonary embolism, thromboembolism associated with atrial fibrillation or prosthetic valve insertion.

PRESENTATION AND ADMINISTRATION:

  • PO: Coumadin 1mg (beige), 2mg (lavender) and 5mg (green) tablets; Marevan 1mg (brown), 3mg (blue) and 5mg (pink) tablets
  • DOSAGE: The dosage is individualised according to the patientʼs sensitivity to the drug as indicated by their INR. Most patients are satisfactorily maintained with a dose of 2 to 10mg daily. Several studies have shown that a loading regimen of 5mg/5mg/5mg produces a therapeutic INR by day 4 to 5 as rapidly as higher dosed regimens but with a reduced risk of bleeding complications. In patients after cardiac surgery, a loading regimen of 2.5mg for the first 2 days with the third dose adjusted only if the INR was <1.5 or >3.0 has been shown to reduce excessive anticoagulation; this is the recommended dosing schedule in these patients
  • Recommended INR ranges:
    DVT and PE: 2.0-3.0
    Atrial fibrillation: 2.0-3.0
    Bioprosthetic heart valves: 2.0-3.0
    Mechanical heart valves: 2.5-3.5
  • An INR greater than 4.0 appears to provide no additional therapeutic benefit in most patients & is associated with a higher risk of bleeding. Duration of therapy is individualised and in general should be continued until the danger of thrombosis & embolism has passed.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose as in normal renal function. Active metabolites may accumulate in renal failure. Not dialysed.

DOSAGE IN PAEDIATRICS:

  • Day 1: 0.2mg/kg single dose
    Day 2: 0.2mg/kg single dose providing INR<1.3
    Day 3 & onwards: 0.05-0.2mg/kg single dose titrated to INR

CLINICAL PHARMACOLOGY:

  • Warfarin sodium acts by inhibiting the synthesis of vitamin K dependent clotting factors which include Factors II, VII, IX and X, and the anticoagulant proteins C and S.
  • Therapeutic warfarin doses decrease the total amount of the active form of each vitamin K dependent factor made by the liver by approximately 30-50%. An anticoagulant effect generally occurs within 24 hours after drug administration, however peak anticoagulant effect may be delayed by 72-96 hours. The duration of action of a single dose of warfarin is 2-5 days.
  • Warfarin may potentiate a more hypercoagulable state in the first 24-48 hours due to the more rapid depletion of the anticoagulant proteins C & S when compared to the clotting factors with longer half-lives. As such, any concomitant anticoagulant therapy such as Heparin or Enoxaparin should be continued until the desired therapeutic INR is reached. This initial pro-coagulant effect is increased with the use of higher loading doses.
  • Warfarin may increase the aPTT test even in the absence of heparin. Heparin therapy may also affect the INR.
  • Anticoagulants have no direct effect on established thrombus but prevent further extension of the formed clot.

CONTRAINDICATIONS:

  • Any condition in which the hazard of haemorrhage is greater than the potential clinical benefits of anticoagulation, such as:
  1. Pregnancy, threatened abortion, eclampsia and pre-eclampsia
  2. Haemorrhagic tendencies or blood dyscrasias
  3. Severe-to-moderate hepatic or renal insufficiency
  4. Recent or contemplated surgery of the CNS, eye or traumatic surgery resulting in large open surfaces
  5. Bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal/genitourinary or respiratory tracts, cerebrovascular haemorrhage, cerebral aneurysms, dissecting aorta, pericarditis and pericardial effusions, bacterial endocarditis
  6. Inadequate laboratory facilities
  7. Unsupervised senility, alcoholism, psychosis or lack of patient co-operation
  8. Spinal puncture
  9. Malignant hypertension
  10. Known or suspected deficiency in protein C
  11. Known hypersensitivity to warfarin

WARNINGS:

  • Risk of haemorrhage in any tissue or organ related to level of intensity & duration of anticoagulant therapy.
  • Necrosis & gangrene of skin and other tissues is seen less frequently (<0.1%) and usually appears within a few days of the start of therapy.
  • Therapy in each patient is highly individualised and regular INR monitoring is required due to the narrow therapeutic index of warfarin which may be easily affected by other drugs and dietary vitamin K.

PRECAUTIONS

  • General: Patients of 60 years or older appear to exhibit a greater than expected INR response to the anticoagulant effects of warfarin for reasons unknown. An increased INR response may also be seen with cancer, congestive heart failure, hyperthermia, hyperthyroidism and in patients with a poor nutritional state. A decreased INR response may be seen with oedema, hyperlipidaemia and hypothyroidism
  • Laboratory Tests: Therapeutic effect is monitored by regular measurement of the INR
  • Drug/Laboratory Test Interactions: None

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Drugs that may cause an increased INR include:
    Alcohol, allopurinol, amiodarone, aspirin, azithromycin, cephazolin, ceftriaxone, chloramphenicol, chloral hydrate, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, fluconazole, fluoxetine, glucagon, heparin, ibuprofen, indomethacin, influenza flu vaccine, itraconazole, ketorolac, methyldopa, metronidazole, naproxen, neomycin, omeprazole, paracetamol, paroxetine, penicillin G (intravenous), phenytoin, prednisone, propranolol, quinine, ranitidine, simvastatin, tamoxifen, tetracycline, thyroid drugs, tramadol, valproate
  • Drugs that may cause a decreased INR include:
    Alcohol, atorvastatin, azathioprine, carbamazepine, chloral hydrate, clozapine, cortisone, haloperidol, phenobarbitone, prednisone, rifampicin, spironolactone, sucralfate, vitamin C (high dose), vitamin K

ADVERSE REACTIONS

  • Nervous system: Headache, dizziness. Haemorrhagic complications may present as headache, paralysis, paraesthesia or altered consciousness & need to be excluded.
  • Cardiovascular: None described
  • Digestive: Nausea, vomiting, diarrhoea, flatulence, bloating
  • Skin: Necrosis, bullous eruptions, urticaria, pruritus, alopecia

Critical Care Drug Manual

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