This table lists strong and moderate CYP450 2D6 inhibitors; there are no known clinically relevant inducers of CYP2D6.
Inhibitors of CYP2D6 metabolism listed above can alter serum concentrations of other drugs that are dependent on CYP2D6 liver enzymes for activation or elimination:
Codeine, tamoxifen, and tramadol are examples of drugs that require transformation by CYP2D6 to their active metabolite(s). The presence of CYP2D6 inhibitors can decrease efficacy of these drugs.
Amitriptyline, clozapine, desipramine, flecainide, haloperidol, nortriptyline, risperidone, and valbenazine are examples of drugs that are eliminated by CYP2D6 metabolism. The presence of CYP2D6 inhibitors can increase levels of these drugs.
The specific effect of CYP2D6 inhibition on CYP2D6 substrate blood levels varies widely among individual patients because of variability in CYP2D6 function (ie, genetic polymorphism). Poor, intermediate, extensive, and ultrarapid CYP2D6 function types have been well characterized.
These classifications are based upon US Food and Drug Administration (FDA) guidance.[1,2] Other sources may use a different classification system resulting in some agents being classified differently.
For additional information on CYP2D6 drug metabolism, refer to the UpToDate topic review of pharmacogenomics, section on CYP2D6 variants, and clinical topic reviews of the use of these agents and their drug interactions.
Specific drug interactions and management suggestions may be determined by using the Lexicomp drug interactions program included with UpToDate. Refer to UpToDate topics on specific agents and indications for further details.
CYP2D6: cytochrome P450 2D6. * Not available in United States.
