The non-steroidal anti-inflammatory drug celecoxib is metabolized by CYP2C91. Certain gene variants causing poor or intermediate CYP2C9 activity may increase risks of gastrointestinal (GI) bleeding with celecoxib and are therefore clinically actionable i.e. justify change of dose or use of another drug2. Risks of GI bleeding may be further increased by co-prescription of various other drugs.
To assess the prevalence of clinically actionable CYP2C9 genotypes and celecoxib use in older community-dwelling Australians and the prevalence of potential multifactorial drug-gene interactions involving co-prescription of drugs associated with GI bleeding.
Clinically actionable gene variants were identified from the Pharmacogenomics Knowledge Base, Clinical Pharmacogenetics Implementation Consortium and US Food and Drug Administration (FDA)2,3. Genotype data were obtained for 2121 community-dwelling older Australians aged 55 years and above from the Hunter Cohort Study using Affymetrix Kaiser Axiom arrays or imputed from 1000 Genomes and Hap Map Phase II European panels4.
Of the 2121 participants with genotype data, 250 (12%) had intermediate and 18 (~1%) had poor metabolising CYP2C9 genotypes i.e. almost 13% had at least one clinically actionable genotype increasing GI bleeding risk. Prevalence of celecoxib use in these two groups was 4.4% and 5.6% respectively. This represented 15% of the 79 participants on celecoxib for whom genotype data were available. Of the 137 participants on celecoxib, nearly half (56; 41%) were co-prescribed other drugs that may increase GI bleeding. Of the 38 participants on other drugs with genotype data available, 8 (21%) also had the intermediate metabolising genotype.
The results suggest that considerable numbers of people using the non-steroidal anti-inflammatory drug celecoxib are at risk of simple or multifactorial drug-gene interactions related to GI bleeding. There may be strong potential for prescribers to improve celecoxib safety by taking genotype and medication reviewing into account.