Poster Presentation Australian Society for Medical Research Annual Scientific Meeting 2016

Prevalence of drug-drug interactions, drug-gene interactions and multifactorial drug-gene interactions for cardiovascular drugs in a community cohort of older Australians (#111)

Mohitosh Biswas 1 , Nilofar Daneshi 1 , Thilani Hasanthi Dias 1 , Karen Mate 1 , Liz Holliday 2 3 , Stephen Hancock 2 3 , John Attia 2 3 , David Newby 2 , Karen Kerr 1 , Liz Milward 1
  1. University of Newcastle, Callaghan, NSW, Australia
  2. School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia
  3. Clinical Research Design, IT and Statistical Support (CReDITSS) Unit, Hunter Medical Research Institute, Newcastle, NSW, Australia

Introduction: The safety and efficacy of cardiovascular drugs can be affected by interactions involving other drugs or genetic factors, including multifactorial drug-gene interactions. Such interactions are important considerations for optimal treatment.1
Objectives: To investigate prevalence of drug-drug interactions, drug-gene interactions and multifactorial drug-gene interactions among older Australians taking the cardiovascular drugs clopidogrel, warfarin and  statins.
Methods: Co-prescription prevalence was obtained from self-reported medication data from the Hunter Community Study (HCS), an Australian population based cohort of individuals aged 55-85 years.2 Interacting drugs were identified from U.S. Food and Drug Administration (FDA), Monthly Index of Medical Specialties (MIMS), Australian Medicines Handbook (AMH) and other resource.3-6 Participants were genotyped using Affymetrix Kaiser Axiom arrays or imputation from HapMap 2 and 1000 Genome reference panels.
Results: Of 92 participants on clopidogrel, potential drug-drug interactions were identified in 84 participants (91.3%, 95% CI; 86%-97%) with 1.9 interactions on average per participant (1.9±0.9; 95% CI; 1.7-2.1). Of 116 participants on warfarin, potential drug-drug interactions were identified in 93 participants (80.2%, 95% CI; 73%-87%) with 3.0 interactions on average per participant (3.0±2.4; 95% CI; 2.6-3.5). Of 976 participants on statins, potential drug-drug interactions were identified in 303 participants (31.1%; 95% CI; 28%-34%) with 1.8 interactions on average per participant (1.8±1.2; 95% CI; 1.7-1.8). In total, 8.9% (95% CI; 7%-11%) of all participants co-prescribed interacting drugs were determined to be at risk of five or more interactions. Clinically actionable drug-gene interactions were found for 26% of participants taking cardiovascular drugs and for whom genotype data were available (95% CI; 21%-31%). Clinically actionable multifactorial drug-gene interactions were found in 14% of these participants (95% CI; 7%-21%) taking interacting drugs.
Conclusions: The findings suggest some proportion of older Australians are at serious risk of adverse cardiovascular events, providing evidence that analysing genetic status and drug-drug interactions may improve medication safety and effectiveness.

  1. 1. Westervelt P, et al (2014); Pharmacy and Therapeutics. 2014; 39 (9):630-637. 2. McEvoy M et al (2010) International Journal of Epidemiology 39:1452–1463 3. U.S.FDA (online), http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#4 Accessed 15/09/16 4. MIMS (online), https://www.mimsonline.com.au/Search/Search.aspx Accessed 16/09/16 5. AMH (online), http://amhonline.amh.net.au/ Accessed 17/09/16 6. Flockhart DA (2007), http://www.medicine.iupui.edu/clinpharm/ddis/clinical-table/ Accessed 18/09/16