CLINICALLY SIGNIFICANT DRUG-INTERACTIONS WITH THE ORAL ANTICOAGULANTS

Oral anticoagulants were introduced in the late 1940s and remain widely used today. Indications include prevention of thrombosis associated with atrial fibrillation, structural cardiac diseases and following prosthetic valvular replacement. They have been used for both treatment and prophylaxis of deep venous thrombosis and in efforts to decrease the frequency and rate of second myocardial infarction. These compounds include the coumarin derivatives [dicoumarol (bishydroxycoumarin), phenprocoumon, nicoumalone (acenocoumarol)] and the indanedione derivatives (diphenadione, phenindione. anisindione) which, because of adverse reactions, are largely unavailable. The oral anticoagulants, and warfarin in particular, are highly interactive with other drugs. Mechanisms of those interactions include both pharmacokinetic and pharmacodynamic mechanisms and may result in either hyper- or hypoprothrombinaemia. Because their principal adverse reaction is haemorrhage, and interactions are widespread across many therapeutic specialties, it becomes imperative for the practising physician to be aware of the possibility of interaction whenever these agents are coadministered with other drugs.