To the Editor: The recent article by Miller and colleagues regarding adverse drug events (ADEs) in general practice highlights the high frequency and considerable morbidity associated with ADEs in the general community.1 The authors identified recognised side effects, drug sensitivity, and allergy as responsible for most ADEs.

The contribution of the patient’s genotype to drug response, via altered metabolism or responsiveness to pharmaceuticals, is increasingly recognised as potentially responsible for a significant proportion of ADEs.

The science of determination of the genetic contribution to an individual’s response to drug action is referred to as pharmacogenomics,2 and represents a potentially beneficial diagnostic tool to aid in the prevention of ADEs.

Treatment with warfarin, one of the most frequently prescribed drugs in Australia, has been estimated to account for up to15.1% of all severe ADEs, manifest as minor and major bleeding.3

We have recently determined the presence, frequency and laboratory sequelae of genetic variants (single nucleotide polymorphisms) in two genes responsible for the metabolism (cytochrome P450 2C9 [CYP2C9]) and potency (vitamin K epoxide reductase complex, subunit 1 [VKORC1]) of warfarin4 in an Australian population. In our study of 120 patients in an anticoagulation clinic, the frequencies of allelic variants of the CYP2C9 and VKORC1 genes responsible for altered warfarin activity were 31%5 and 59% (unpublished data), respectively, in keeping with previously published studies.4 Detection of these variants was associated with increased induction international normalised ratio (INR) readings compared with controls, and reduced overall warfarin requirements.6 These findings support previous studies,7 and suggest that genotype determination may be of benefit in identification of patients with increased sensitivity to empiric induction phase warfarin dosing schedules. This may allow for a reduction of induction doses of warfarin, decreasing the risk of excessive INR and bleeding sequelae, commonly observed with induction of warfarin treatment. Furthermore these benefits may aid in reduced time to stabilisation.

Additional cost–benefit analysis8,9 will enable determination of the economic viability of genotype determination as an adjunct to management of warfarin dosing.

The high population frequency of genetic variants associated with warfarin response emphasises the significant contribution genetic factors can play in patient reaction to drugs and highlights their involvement as potential causes of ADEs.