COUMADIN

What it is

COUMADIN contains warfarin sodium and is available in tablets of 1 mg, 3 mg or 5 mg.

Approved indications

— Prophylaxis and/or treatment of venous thrombosis and its extension and pulmonary embolism. — Prophylaxis and/or treatment of thromboembolic complications associated with atrial fibrillation. — Adjunct in the treatment of coronary occlusion. COUMADIN is not indicated in patients with lone atrial fibrillation who are less than 60 years of age with no risk factors such as previous thromboembolism, diabetes mellitus, hypertension, and an otherwise normal heart.

Dosing overview

Treatment with COUMADIN is highly individualised and dosage should be controlled by periodic determinations of International Normalised Ratio (INR) or other suitable coagulation tests according to the condition being treated, as COUMADIN is a narrow therapeutic range drug that may be affected by other drugs, dietary Vitamin K and genetic variations in CYP2C9 and VKORC1 enzymes. Target INR ranges vary by indication: 2.0 to 2.5 for prophylaxis of deep-vein thrombosis including high risk surgery; 2.0 to 3.0 for treatment of deep-vein thrombosis, pulmonary embolism, and atrial fibrillation; and 2.5 to 3.5 for recurrent deep-vein thrombosis and pulmonary embolism, arterial disease including myocardial infarction, arterial grafts, cardiac prosthetic valves and grafts. A commonly used regimen for initial dosing is 10 mg daily for 2 to 4 days, with daily dosage adjustments based on prothrombin time determinations. Most patients are satisfactorily maintained at a dose of 2 to 10 mg daily.

Key safety warnings

The most serious risks associated with anticoagulant therapy with warfarin sodium are haemorrhage in any tissue or organ and less frequently (< 0.1%), necrosis and/or gangrene of skin and other tissues. An INR of greater than 4.0 is associated with a higher risk of bleeding. There have been post-marketing reports of anticoagulant-related nephropathy (ARN) presenting as acute kidney injury, particularly in patients with altered glomerular integrity or with a history of kidney disease, possibly in relation to episodes of excessive anticoagulation and haematuria. Close monitoring including renal function evaluation is advised in patients with a supratherapeutic INR and haematuria. Anticoagulation therapy with warfarin may enhance the release of atheromatous plague emboli, thereby increasing the risk of complications from systemic cholesterol microembolisation, including the purple toes syndrome. Purple toes syndrome is characterised by a dark, purplish or mottled colour of the toes, usually occurring between 3 to 10 weeks, or later, after initiation of therapy with warfarin. Calciphylaxis is a rare syndrome of vascular calcification with cutaneous necrosis associated with high mortality, mainly observed in patients with end-stage renal disease on dialysis, though rare cases have been reported in patients receiving warfarin in the absence of renal disease.

Contraindications

COUMADIN is contraindicated in pregnancy, as the drug passes through the placental barrier and may cause fatal haemorrhage to the fetus in utero. Anticoagulation is also contraindicated in any localised or general physical condition or personal circumstances in which the hazard of haemorrhage might be greater than the potential clinical benefits of anticoagulation, including haemorrhagic tendencies or blood dyscrasias; recent or contemplated surgery of the central nervous system, eye, or traumatic surgery resulting in large open surfaces; bleeding tendencies associated with active ulceration or overt bleeding of the gastrointestinal, genitourinary or respiratory tracts, or cerebrovascular haemorrhage; threatened abortion, eclampsia and preeclampsia; and inadequate laboratory facilities or unsupervised senility, alcoholism, psychosis, or lack of patient cooperation.

PBS listing

COUMADIN tablets containing 1 mg, 2 mg and 5 mg of warfarin sodium are each listed on the PBS with unrestricted access. Ex-manufacturer prices are A$4.35 for the 1 mg tablet, A$4.53 for the 2 mg tablet, and A$5.00 for the 5 mg tablet.

Regulatory history

COUMADIN warfarin sodium tablets were first registered on the ARTG in 1991, with the 2 mg tablet listed on 9 September 1991, followed by the 1 mg and 5 mg tablets on 13 October 1992.