Managing Psychotropic Drugs with Efavirenz

Efavirenz is in the non-nucleoside reverse transcriptase inhibitor categoryof HIV antiretroviral medicines. It is an in vivo inducer of theCYP3A4 isoenzyme within the cytochrome P450 (CYP450) system,and an in vitro inhibitor of the system’s CYP2C9/2C19, 3A4 and 2B6isoenzymes; as a result, concentrations of psychotropic drugs can beincreased or decreased depending on the specific enzyme pathwayinvolved in their metabolism. CYP3A4 is responsible for metabolizingmany benzodiazepines and other psychotropics, as well as selectiveserotonin reuptake inhibitors and tricyclic antidepressants. As aninducer of CYP3A4, efavirenz can increase the rate at which theseagents are metabolized, resulting in administered psychotropic druglevels that are below their therapeutic thresholds. Conversely,efavirenz is an inhibitor of CYP2B6, which metabolizes agents such asbupropion; consequently, bupropion levels in the blood can increase.Given the existing conflicting data, the clinician may find it impracticalto use an evidence-based approach when concomitantly prescribingefavirenz and psychotropic drugs to their HIV patients. Instead, itmay be preferable to use a more pragmatic approach that applies knowledgeof the most current pharmacological and pharmacokinetic data forpsychotropics and non-nucleoside reverse transcriptase inhibitors,which may help better predict their potential interactions