WARFARIN SODIUM

Posology:

A baseline coagulation screen and liver function tests should be performed before initiating warfarin therapy.

Adults:

The typical induction dose is 10 mg daily for 2 days but this should be tailored to individual requirements. The daily maintenance dose is usually 3 to 9 mg taken at the same time each day. The exact maintenance dose depends on the prothrombin time, usually reported as the INR (international normalised ratio), or other appropriate coagulation tests.

Control tests should be made at regular intervals and the maintenance dose should be adjusted according to the results obtained. Once the maintenance dose is established, it is rarely necessary to alter it (see Section

The frequencies of the adverse reactions are classified as follows:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000), not known (cannot be estimated from the available data). 4) a MedDRA is a dictionary of medical terminology used by the MHRA to enter data into the Yellow Card database.

The dictionary is organized by system organ class Skin necrosis is a rare but serious side effect of warfarin. It occurs mainly in obese, female patients, usually within 3 to 10 days of starting therapy, and is associated with the use of high induction doses.

Patients with protein C or protein S deficiency are at particular risk. Initially, the lesions consist of painful, indurated, reddened areas, which progress through a stage of blood-filled blisters into well-demarcated blackened necrotic patches.

Areas of skin with underlying fatty tissue, such as breasts, flanks and buttocks are most often affected. Pain in a particular area of skin is a premonitory symptom, and withdrawal of the oral anticoagulant at this stage, reversal of its effects with vitamin k or fresh frozen plasma, and the use of heparin may limit the extent of tissue damage.

‘Purple toes’ which is a rare complication of warfarin therapy. Typically, the syndrome presents 3 to 8 weeks after initiation of warfarin therapy as a sometimes painful blue-tinged discoloration of the plantar aspects and sides of the toes.

Cholesterol emboli released from atheromatous plaques have been implicated as the cause. If the syndrome occurs, it is recommended that warfarin therapy be withdrawn, if possible, as the affected tissue may undergo ischaemic necrosis Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

4 Commencement of Therapy). In emergencies, anticoagulant therapy should be initiated with heparin and warfarin together. Concomitant therapy with heparin affects the results of control tests and should be discontinued for at least six hours before the first test is carried out.

Elderly:

As for adults, but dosage may need to be lowered. The elderly are generally more sensitive to the effects of warfarin and often require a smaller dose.

Paediatric population:

Dosage for children has not been established. Warfarin 1mg/ml Oral Suspension is not recommended for use in children.

Method of administration:

For oral administration only. 1. 4) Use within 48 hours postpartum. Warfarin is contraindicated in pregnancy. 5). 4). 4 Special warnings and precautions for use Most adverse events reported with warfarin are a result of over anticoagulation therefore it is important that the need for therapy is reviewed on a regular basis and therapy discontinued when no longer required.

Patients should be given a patient-held information booklet (‘warfarin card’) and informed of symptoms for which they should seek medical attention. Commencement of therapy If this preparation replaces or is replaced by another warfarin product, the patient should be monitored closely in the period immediately following the change.

Monitoring When warfarin is started using a standard dosing regimen the INR should be determined daily or on alternate days in the early days of treatment. Once the INR has stabilised in the target range the INR can be determined at longer intervals.

g. patients with severe hypertension, liver or renal disease. Patients for whom adherence may be difficult should be monitored more frequently. For patients with any impairments that may influence their ability to take the correct dosage safely, the assistance of a carer to administer the dose may be required.

Thrombophilia Patients with protein C deficiency are at risk of developing skin necrosis when starting warfarin treatment. In patients with protein C deficiency, therapy should be introduced without a loading dose of warfarin even if heparin is given.

Patients with protein S deficiency may also be at risk and it is advisable to introduce warfarin therapy slowly in these circumstances. Risk of haemorrhage The most frequently reported adverse effect of all oral anticoagulants is haemorrhage.

g. concomitant NSAID use, recent ischaemic stroke, bacterial endocarditis, previous gastrointestinal bleeding). 3. g. 5). Genetic factors: genetic polymorphisms in the cytochrome P450 CYP2C9 gene result in impaired metabolism of S-warfarin.

Affected individuals have an increased sensitivity to warfarin, manifesting as low dose requirements and an increased risk of bleeding. The variant alleles occur at a higher frequency in white populations than in other ethnic groups studies.

All patients treated with warfarin should have INR monitored regularly. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy. Patients should be instructed on measures to minimise risk of bleeding and to report immediately to physicians signs and symptoms of bleeding.

Checking the INR and reducing or omitting doses depending on INR level is essential, following consultation with anticoagulation services if necessary. If the INR is found to be too high, reduce dose or stop warfarin treatment; sometimes it will be necessary to reverse anticoagulation.

INR should be checked within 2–3 days to ensure that it is falling. Any concomitant anti-platelet drugs should be used with caution due to an increased risk of bleeding. Haemorrhage Haemorrhage can indicate an overdose of warfarin has been taken.

9. 9). Bleeding may occur at therapeutic INR values, in which case the possibility of an underlying condition that predisposes the haemorrhage should be investigated. Ischaemic stroke Anticoagulation following an ischaemic stroke increases the risk of secondary haemorrhage into the infarcted brain.

In patients with atrial fibrillation long term treatment with warfarin is beneficial, but the risk of early recurrent embolism is low and therefore a break in treatment after ischaemic stroke is justified. Warfarin treatment should be re-started 2–14 days following ischaemic stroke, depending on the size of the infarct and blood pressure.

In patients with large embolic strokes, or uncontrolled hypertension, warfarin treatment should be […]

1. 4) Use within 48 hours postpartum. Warfarin is contraindicated in pregnancy. 5). 4).