Vraylar (Cariprazine) and CYP2D6 Inhibition
No, Vraylar (cariprazine) does not inhibit CYP2D6 at clinically relevant levels. According to the FDA drug label, cariprazine and its major active metabolites are weak inhibitors of CYP2D6 in vitro 1.
Pharmacokinetic Profile of Cariprazine
- Cariprazine is extensively metabolized primarily by CYP3A4 and to a lesser extent by CYP2D6 1, 2
- The drug produces two major active metabolites: desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR) 1
- In vitro studies show that cariprazine and its major active metabolites were weak inhibitors of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 1
- The FDA label specifically states that based on in vitro studies, Vraylar is unlikely to cause clinically significant pharmacokinetic drug interactions with substrates of CYP2D6 1
CYP2D6 Inhibition Potential
- Unlike some other psychotropic medications such as paroxetine and fluoxetine which are potent CYP2D6 inhibitors (Ki values of 0.15 μM and 0.60 μM respectively), cariprazine demonstrates only weak inhibitory effects on CYP2D6 3
- CYP2D6 inhibitors are not expected to significantly influence the pharmacokinetics of cariprazine, DCAR, or DDCAR 1
- This is supported by observations in CYP2D6 poor metabolizers, where CYP2D6 poor metabolizer status does not have clinically relevant effects on the pharmacokinetics of cariprazine or its metabolites 1
Clinical Implications
- Unlike some medications that strongly inhibit CYP2D6 (such as paroxetine), cariprazine is unlikely to cause significant drug interactions with medications metabolized by CYP2D6 1, 3
- This pharmacokinetic profile may be advantageous when prescribing for patients on multiple medications that are CYP2D6 substrates 2
- When considering drug interactions with cariprazine, the focus should be on CYP3A4 inhibitors or inducers rather than CYP2D6 interactions 4
- Co-administration with moderate CYP3A4 inhibitors like erythromycin increases total cariprazine exposure by approximately 40-50%, which may require dose adjustment or monitoring 4
Important Considerations
- While cariprazine itself is not a significant CYP2D6 inhibitor, it is partially metabolized by CYP2D6 (as a secondary pathway to CYP3A4) 1, 2
- The pharmacokinetics of cariprazine are not substantially affected by CYP2D6 phenotypes, making pharmacogenetic testing for CYP2D6 unnecessary for optimizing cariprazine therapy 4
- When prescribing cariprazine, the primary drug interaction concern should be with strong or moderate CYP3A4 inhibitors, which can significantly increase cariprazine exposure 1, 4
In summary, Vraylar (cariprazine) is not a clinically significant inhibitor of CYP2D6 and is unlikely to cause drug interactions through this mechanism, making it potentially advantageous in patients taking multiple medications that are CYP2D6 substrates.