CLINICALLY SIGNIFICANT DRUG-INTERACTIONS WITH THE ORAL ANTICOAGULANTS

Oral anticoagulants were introduced in the late 1940s and remain widel y used today. Indications include prevention of thrombosis associated with atrial fibrillation, structural cardiac diseases and following pr osthetic valvular replacement. They have been used for both treatment and prophylaxis of deep venous thrombosis and in efforts to decrease t he frequency and rate of second myocardial infarction. These compounds include the coumarin derivatives [dicoumarol (bishydroxycoumarin), ph enprocoumon, nicoumalone (acenocoumarol)] and the indanedione derivati ves (diphenadione, phenindione. anisindione) which, because of adverse reactions, are largely unavailable. The oral anticoagulants, and warf arin in particular, are highly interactive with other drugs. Mechanism s of those interactions include both pharmacokinetic and pharmacodynam ic mechanisms and may result in either hyper- or hypoprothrombinaemia. Because their principal adverse reaction is haemorrhage, and interact ions are widespread across many therapeutic specialties, it becomes im perative for the practising physician to be aware of the possibility o f interaction whenever these agents are coadministered with other drug s.