Table 1.
Commonly used drugs in primary care with available pharmacogenomics guidelines.
| Class | Drug | Gene | Actionable Result | Guideline Availability | Therapeutic Recommendations 1 | |
|---|---|---|---|---|---|---|
| DPWG | CPIC | |||||
| Lipid lowering agents | Atorvastatin | SLCO1B1 | rs4145096 (521T > C) carriers | √ | - | AD |
| Simvastatin | SLCO1B1 | √ | √ | LD, AD, M | ||
| Antidepressants | Citalopram | CYP2C19 | PM, UM | √ | √ | LD (PM), AD (PM, UM) |
| Sertraline | CYP2C19 | PM, UM | √ | √ | LD (PM), AD (PM, UM) | |
| Amitriptyline |
CYP2C19
CYP2D6 |
PM, RM, UM IM, PM, UM |
- √ |
√ √ |
LD (PM), AD (PM, RM, UM) LD (IM, PM), AD (PM, UM) |
|
| Analgesics | Codeine | CYP2D6 | IM, PM, UM | √ | √ | AD (UM, PM), M (IM) |
| Tramadol | CYP2D6 | IM, PM, UM | √ | - | AD (IM, PM, UM), ID (IM, PM), LD (UM) |
|
| Anti-platelet | Clopidogrel | CYP2C19 | IM, PM | √ | √ | AD |
| Anticoagulant | Warfarin |
VKORC1 CYP2C9 CYP2C region |
VKORC1 c.-1639G > A *2, *3, *5, *6, *8, *11 rs12777823 |
√ √ |
√ √ √ |
LD 2 LD 2 LD |
| Anticonvulsant | Carbamazepine |
HLA-B
HLA-A |
HLA-B*15:02 detected HLA-A*31:01 detected |
- - |
√ √ |
AD, M AD, M |
| Antibiotic | Flucloxacillin | HLA-B | HLA-B*57:01 detected | √ | - | AD, M |
| Contraception | Oestrogen-containing contraceptives | F5 | rs6025 (p.R534Q) carriers | √ | - | AD |
| Xanthine oxidase inhibitor | Allopurinol | HLA-B | HLA-B*58:01 detected | - | √ | AD |
1 = Where a drug-gene pair has guidance available from both CPIC and DPWG, the CPIC recommendations are detailed here. 2 = VKORC1 -1639G > A and CYP2C9 alleles are often combined together into an algorithm, alongside clinical variables, to guide initial warfarin dosing. Please note that CYP2C9 *1/*2 does not lead to recommended warfarin dose changes unless the VKORC1 -1639A allele is also present, and VKORC1 -1639GA does not lead to a dose change unless a CYP2C9 reduction-of-function allele is also present [9]. AD = alternative drug; CPIC = Clinical Pharmacogenetics Implementation Consortium; DPWG = Dutch Pharmacogenetics Working Group; LD = lower dose; ID = increase dose; M = consider additional monitoring (e.g., routine CK surveillance for simvastatin); PM = poor metaboliser; UM = ultra-rapid metaboliser; √ = guideline available; - = no guideline available.