MAREVAN

What it is

MAREVAN is a warfarin sodium tablet available in strengths of 1 mg, 3 mg and 5 mg.

Approved indications

— Prophylaxis and treatment of venous thrombosis and its extension and pulmonary embolism. — Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation. — Adjunctive treatment of coronary occlusion. MAREVAN 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 or hypertension and an otherwise normal heart.

Dosing overview

Treatment with MAREVAN is highly individualised and must be controlled by periodic determinations of International Normalised Ratio (INR) or other suitable coagulation tests, as the drug is a narrow therapeutic range agent that may be affected by other drugs, dietary vitamin K and genetic variations. A commonly used regimen for initial dosing is 10 mg per day for 2 to 4 days, with daily adjustments based on prothrombin time results. Most patients are satisfactorily maintained at a dose of 2 to 10 mg daily. An INR greater than 4.0 is associated with a higher risk of bleeding.

Key safety warnings

The most serious risks associated with anticoagulant therapy with MAREVAN are haemorrhage in any tissue or organ and, less frequently (< 0.1%), necrosis and/or gangrene of skin and other tissues. The risk of haemorrhage is related to the level of intensity and duration of anticoagulant therapy, and haemorrhage and necrosis have in some cases resulted in death or permanent disability. Necrosis appears to be associated with local thrombosis and usually appears within a few days of starting anticoagulant therapy, and in severe cases has required debridement or amputation of the affected tissue, limb, breast or penis. Warfarin therapy should be discontinued when warfarin is suspected to be the cause of developing necrosis and heparin therapy may be considered for anticoagulation. Anticoagulant-related nephropathy presenting as acute kidney injury has been reported following anticoagulant use, with acute kidney injury potentially occurring in patients with altered glomerular integrity or history of kidney disease, possibly in relation to episodes of excessive anticoagulation and haematuria. Anticoagulation therapy with MAREVAN may enhance the release of atheromatous plaque emboli, thereby increasing the risk of complications from systemic cholesterol microembolisation including purple toes syndrome, and discontinuation of warfarin is recommended when such phenomena are observed. 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, though it is reported to be reversible, some cases progress to gangrene or necrosis which may require debridement or amputation. Calciphylaxis is a rare syndrome of vascular calcification with cutaneous necrosis associated with high mortality, mainly observed in patients with end-stage renal disease but also reported in patients receiving warfarin; when diagnosed, appropriate supportive treatment should be started and discontinuation of warfarin should be considered.

Contraindications

Anticoagulation is 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, cerebrovascular haemorrhage, cerebral or aortic aneurysms, pericarditis and pericardial effusions, and bacterial endocarditis. MAREVAN is contraindicated in pregnancy, as the drug passes through the placental barrier and may cause fatal haemorrhage to the fetus in utero.

PBS listing

MAREVAN warfarin sodium 3 mg tablet is listed on the PBS as one item with unrestricted access at an ex-manufacturer price of A$4.59.

Regulatory history

MAREVAN warfarin sodium tablets (1 mg, 3 mg and 5 mg) were first registered on the ARTG on 13 August 1991.