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Avoiding problems when prescribing warfarin

Professor Hugh McGavock continues his series by looking at the common problems with the anticoagulant

Professor Hugh McGavock continues his series by looking at the common problems with the anticoagulant

Warfarin is a particularly effective drug in the prevention of deep vein thrombosis (DVT), pulmonary embolism, and embolisation in atrial fibrillation and some prosthetic heart valves. It is also used during haemodialysis and to prevent myocardial infarction in patients with unstable angina.

No better drug for the purpose has been developed in the past 70 years. It was discovered and marketed by the Wisconsin Alumni Research Foundation as a result of its research into haemorrhagic disease in cattle, hence its name – ‘WARF' plus ‘arin', the last letters of coumarin, its chemical group.

Its initial use was as rat poison. If you think of this every time you prescribe warfarin or co-prescribe it with another drug, you may avoid it becoming a human poison. As in rats, its main function is as a potent vitamin K antagonist, producing progressive, dose-related anticoagulation.

As all GPs and warfarin clinic nurses know, for a given patient there is only a small difference between the clinically effective dose and the toxic dose. The maintenance dose must be determined for each patient by INR estimation, made at the same time of day on each occasion and monitored regularly.

Every year, patients die as a result of being dispensed warfarin 5mg tablets instead of the intended 0.5mg – in hospitals as well as in primary care.

Prescribers who are aware of this possibility could regularly remind patients of their tablet colours – for example, one blue tablet (3mg) and one white tablet (0.5mg) daily. This reminder should be delivered verbally, written on the anticoagulation card and recorded in the patient's record.

This simple ploy is doubly important if a carer is administering the drug. This includes staff in residential and nursing homes, where the drug administrator may not have nursing qualifications.

41230741However, the major cause of warfarin-related haemorrhage is its interaction with other drugs. In each case in the table left, the interacting drug potentiates warfarin. For example, the anti-coagulation effect of warfarin is added to that of an NSAID, which may have been bought over the counter. If the NSAID has caused a peptic ulcer, any gastrointestinal bleeding is likely to be severe and difficult to stop, because of the degree of anticoagulation caused by the warfarin.

The drug interactions in the table were identified as important in a long-term care setting in the US. The culprits are much the same in most countries' residential – and secondary – care sectors.

Harmful combinations

Every prescriber should memorise this short list ‘NSAID – MACRO – QUINO – PHENO – AMIO'. Remember, these are only the most common combinations that cause serious harm (see box left). The full picture can be found in appendix 1 of the BNF, on the page of interactions with the coumarins. If in any doubt, consult your BNF before issuing an ‘add-on' prescription to any patient who is on a maintenance dose of warfarin.

Most UK pharmacists have high-grade drug interaction software and have the detailed pharmacological knowledge to use it effectively. They should warn you and the patient if they detect a significant risk that for some reason you, or your own software, have overlooked. But, since the dispensing pharmacist – under the

NHS – is not usually provided with a full medication list, or even a diagnostic summary sheet, this excellent source of safety assurance may fail.

Warfarin is one of the drugs in which absorption from the intestine is significantly enhanced by consuming grapefruit juice, grapefruit or bitter oranges within 24 hours of the dose. Ask yourself how many apparently poorly controlled ‘anticoagulees' are drinking grapefruit juice. The family doctor and anticoagulation clinic nurse must warn them regularly and firmly to avoid this foodstuff.

Professor Hugh McGavock is visiting professor of prescribing science at the University of Ulster and course organiser of GP continuing clinical education at the Northern Ireland Medical and Dental Training Agency

This is an extract from Pitfalls in Prescribing and How to Avoid Them. Pulse readers can buy the book at the specially discounted price of £15.00 plus P&P (usual price £18.99 plus P&P) directly from Radcliffe Publishing. To claim the discount enter the discount code PPLSE9 at the checkout. Alternatively, please order via 01235 528820 quoting the same code. Offer ends 28 August 2009.

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