Warfarin is the most commonly used, orally administered coumarin anticoagulant in the United Kingdom. Indications for this medicine include the prophylaxis of embolisation in atrial fibrillation and prophylaxis / treatment of pulmonary embolism.

This agent is the preferred choice of coumarin due to its potency, duration of action and predictable bioavailability.

On delivery via the oral route, Warfarin is rapidly absorbed into the systemic circulation and becomes highly bound to circulating plasm proteins (i.e. 99% bound).

Warfarin works by preventing clotting factors within the bloodstream interacting with calcium (i.e. cross-linking) and consequently associating with nearby biomembrane structures. Here, there is a functional reduction of Vitamin K that in turn guards against clot formation.

Due to the way in which Warfarin works, there is a delay with the anticoagulant effect. Hence, if anticoagulant cover is needed rapidly then alternative agents (i.e. Heparins) need to be prescribed.

The daily dose of Warfarin varies depending on the patient and the condition being treated. Typically, the range of Warfarin is 3mg - 9mg daily for maintenance and the advice is to take the medicine at the same time each day (i.e. maintains relatively stable plasma levels over time).

The International Normalised Ratio (INR) is used to monitor the efficacy of Warfarin. The value of the INR is dependent on the condition being managed and reference ranges are available for inspection in the BNF to support prescribing practice. The higher the value of the INR results in an increased chance of bleeding, and vice-versa. For example, INR levels of above 4.9 are considered dangerous and increase the risk of a patient bleeding.

Warfarin is metabolised by the liver via the cytochrome P450 system. This agent has a long half-life (i.e. the time taken for the concentration of the drug to decrease to half of what is was). The half-life of Warfarin is said to be 40 hours on average. As such, it takes about 1 week to reach steady state concentrations once initiated, which explains the point above regarding the need for cover with alternative agents (i.e. Heparins).

A key aspect for consideration with Warfarin is the potential for drug-drug interactions. In this case, the Prescribing Clinician and Pharmacist involved in patient care must thoroughly check for interactions in the BNF. Scope also exists for drug-food interactions in this case. As a result of these issues, a drive has taken place to develop alternative anticoagulants that are essentially safer for clinical application; this family of drugs is often referred to as DOACs (i.e. Apixaban). Here, monitoring requirements are much lower as compared to Warfarin and the potential for interactions is much reduced.

As anticipated, the major adverse effect of Warfarin is unexpected bleeding and this may present in the case of ulcers / tumours for instance. The risk of haemorrhage is mitigated with close attention to the INR level. In this case, frequent visits to the clinic are required for accurate readings. Naturally, with the advent of DOACs, the costs associated with monitoring have reduced (i.e. reduced clinic time).

Reversal of Warfarin induced bleeding is achieved with Phytomenadione (i.e. Vitamin K1). The dosing schedule of this agent is dependent on the situation at hand (i.e. if the bleeding is major or minor) and as such reference to the BNF is always recommended.

In terms of patient counselling, consideration should be given to aspects such as:

Eat a regular, healthy, well-balanced diet
Avoid drinking excessive amounts of alcohol over a short period of time
The effect of Warfarin can be opposed if large amounts of dark, green vegetables are consumed. Examples include broccoli, cabbage and spinach
Avoid cranberry and grapefruit juice whilst taking Warfarin