• Two CYP genes, CYP2D6 and CYP2C19, influence the rate of amitriptyline metabolism. Gene testing can show whether amitriptyline metabolism is going to be slower than standard, meaning a reduced dose may be appropriate. If testing indicates metabolism will be enhanced, then a higher than standard dose or an alternative drug may be necessary.⁸
• Codeine is a prodrug metabolized by CYP2D6 to morphine. CYP2D6 has many variants categorised into poor metabolisers (PM), intermediate metabolisers (IM), extensive/normal function metabolisers (EM), and ultra-rapid metabolisers (UM).¹

This has several implications – prescribing codeine for PM and IM genotypes may mean individuals experience less analgesia from codeine. Meanwhile, UM patients may be at higher risk of opioid-related adverse effects. This may be fatal, so codeine is contraindicated for analgesia following tonsillectomy in children with obstructive sleep apnoea, and also for anyone known to be a UM genotype.^1,16

• Warfarin’s elimination is influenced by cytochrome P450 genes in the liver (CYP2C9 for S-warfarin; CYP1A2 and CYP3A4 for R-warfarin). However, its anticoagulant activity stems from it interfering with vitamin K epoxide reductase, an enzyme involved in the blood clotting process. This enzyme is coded for by the VKORC1 gene.^17,18

However, genetics are not the only factor in the body’s response to warfarin– age and body mass also play a role, meaning there is no pharmacogenetic test as yet to determine what the correct dose of warfarin should be for an individual.