From the FDA Drug Label
Cariprazine is extensively metabolized by CYP3A4 and, to a lesser extent, by CYP2D6 to DCAR and DDCAR CYP3A4 inhibitors ... increased total cariprazine Cmax and AUC0-24h by approximately 100% CYP3A4 inducers ... the net effect is unclear CYP2D6 inhibitors are not expected to influence pharmacokinetics of cariprazine, DCAR, or DDCAR Cariprazine and its major active metabolites did not induce CYP1A2 and CYP3A4 enzymes and were weak inhibitors of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 in vitro
Vraylar CYP450 Interactions:
- CYP3A4: Inhibitors increase exposure of cariprazine and its major active metabolite, DDCAR. Inducers have an unclear effect.
- CYP2D6: Inhibitors are not expected to influence pharmacokinetics of cariprazine, DCAR, or DDCAR.
- Other CYP enzymes: Cariprazine and its major active metabolites are weak inhibitors of CYP1A2, CYP2C9, and CYP2E1 in vitro. Based on the information provided, CYP3A4 inhibitors require a reduction in VRAYLAR dosage 1 1.
From the Research
Vraylar (cariprazine) is primarily metabolized by CYP3A4, and its dose should be adjusted when co-administered with strong CYP3A4 inhibitors or inducers to minimize potential drug interactions and optimize therapeutic outcomes.
Key Considerations
- Vraylar is susceptible to significant drug interactions with CYP3A4 inhibitors and inducers due to its primary metabolism by CYP3A4 2.
- Strong CYP3A4 inhibitors like ketoconazole, itraconazole, and clarithromycin can increase Vraylar concentrations, potentially leading to increased side effects.
- Conversely, strong CYP3A4 inducers such as rifampin, carbamazepine, and phenytoin can decrease Vraylar levels, potentially reducing its effectiveness.
- Vraylar itself is not a significant inhibitor or inducer of major CYP450 enzymes, so it is unlikely to affect the metabolism of other medications 3.
- However, cariprazine has active metabolites with long half-lives, which means drug interactions can persist for weeks after discontinuation 4.
- Patients with hepatic impairment may have altered Vraylar metabolism, requiring dose adjustments.
- Regular monitoring for side effects is recommended when Vraylar is used with other medications that affect or are affected by the CYP450 system.
Clinical Implications
- When co-administering Vraylar with strong CYP3A4 inhibitors, the dose should be reduced by half to minimize the risk of increased side effects 2.
- Conversely, when co-administering Vraylar with strong CYP3A4 inducers, the dose may need to be increased to maintain therapeutic effectiveness.
- Clinicians should be aware of the potential for drug interactions with Vraylar and monitor patients closely for adverse effects or reduced efficacy.
- The unique pharmacokinetic profile of cariprazine, including the formation of two clinically significant metabolites, should be considered when evaluating potential drug interactions 5.