Table 1 Examples of implementation of pharmacogenetics for the improvement of drug response and avoidance of adverse drug reactions
Drug | Marker and genetic variants | Treatment application | Drug effect and risks |
|---|---|---|---|
Tamoxifen | CYP2D6; PM alleles *3, *4,*5, *6 and *7 | Breast cancer | Prodrug that requires conversion into active metabolite (endoxifen); PM patients have a higher risk of developing recurrence than EM patients; CYP2D6 polymorphism explains 38 to 69% of variable plasma endoxifen levels |
Warfarin | CYP2C9; VKORC1 | Prevention of thrombo-embolic events; maintenance dose is critical (INR 2-3) | Increased risk of thrombo-embolic events at INR <2 to 3; increased risk of bleeding at INR >2 to 3; drug is the largest cause of AEs and hospital emergency room visits |
Clopidogrel | CYP2C19*2 | Cardiovascular medicine to prevent platelet aggregation | Increased risk of cardiovascular event; explains 12% of variability |
Abacavir | HLA-B*5701 | AIDS | 5% of patients develop hypersensitivity (fever, skin rash, gastro-intestinal symptoms, or eosinophilia); genotyping before therapy reduces incidence of hypersensitivity and is cost effective |
Flucloxacillin, amoxicillin-clavulanate | HLA-B*5701 | Bacterial infections; β-lactam antibiotics | 20% of DILI-related hospitalizations |
Simvastatin | OATP1B1*5 | Control of elevated cholesterol (hypercholesterolemia) | Increased risk of myopathy |
Cisplatin | TPMT, COMT | Chemotherapy | Permanent, bilateral hearing loss (grade 2-4) in 10 to 25% of adult patients and 41 to 61% of children |