Patients that carry variants associated with elevated drug metabolism (ultra-fast metabolizers) can benefit from higher doses in order to achieve therapeutic effects. On the other hand, patients that carry variants resulting in poor drug metabolism are at risk for toxicity and more than twice as likely to display adverse drug effects3. For example, three different CYP2C19 variants correlate to a reduced ability to metabolize antiplatelet agent clopidogrel and carriers are at increased risk for adverse cardiovascular events3. A recent study focused on one of the three variants (CYP2C19*2) and showed carriers exhibited a 2 fold greater risk of a cardiovascular ischemic event or death during a 1-year follow up period9. In response to mounting evidence, the FDA now recommends prescribers consider alternative treatment options for patients in the poor metabolizer category.
A higher incidence of toxicity for poor metabolizers has also been reported with a number of antidepressants, including desipramine, venlafaxine, amitriptyline and haloperidol. In addition, specific CYP2D6 polymorphisms can inhibit the analgesic effects of pro-drug opioid medication such as codeine, tramadol and oxycodone3. Conversely, ultra-fast metabolizers can experience life-threatening toxicity with the same opioids.