Drug Interaction Between Ingrezza and Wellbutrin
Ingrezza (valbenazine) does not significantly increase Wellbutrin (bupropion) levels based on available evidence, as there is no documented pharmacokinetic interaction between these medications.
Lack of Direct Interaction Evidence
The available evidence does not demonstrate any clinically significant drug-drug interaction between valbenazine and bupropion:
Valbenazine is metabolized primarily through hydrolysis to its active metabolite and does not appear to significantly inhibit or induce the cytochrome P450 enzymes responsible for bupropion metabolism 1, 2, 3.
Bupropion is extensively metabolized by CYP2B6 to form hydroxybupropion, and by non-microsomal pathways to form threohydrobupropion and erythrohydrobupropion 4.
Valbenazine functions as a selective VMAT2 inhibitor and does not have documented effects on CYP2B6 or other enzymes involved in bupropion metabolism 2, 3.
Bupropion Metabolism Considerations
Understanding bupropion's metabolic profile is important when considering potential interactions:
Hydroxybupropion, the primary active metabolite formed by CYP2B6, reaches concentrations 4- to 7-fold higher at Cmax and approximately 10-fold greater AUC compared to the parent drug at steady state 4.
The half-life of bupropion is approximately 21 hours, with hydroxybupropion having a similar half-life of approximately 20 hours 4.
Bupropion itself is a CYP2D6 inhibitor, which is more relevant when considering what bupropion might affect rather than what affects bupropion 4.
Clinical Monitoring Recommendations
While no direct interaction exists, prudent clinical monitoring remains appropriate:
Monitor for changes in efficacy or side effects of either medication when initiating combination therapy, as individual patient responses can vary 5.
Be aware that bupropion can lower seizure threshold, with maximum doses not exceeding 450 mg per day for XL formulation or 400 mg per day for SR formulation 5, 6.
Valbenazine has been studied in patients receiving concomitant antipsychotic medications without significant drug interactions reported 1.
Practical Considerations for Combination Use
These medications may be used together when clinically indicated:
Patients with mood disorders and tardive dyskinesia may benefit from concurrent treatment with bupropion for depression and valbenazine for TD management 1.
In the KINECT 3 study, subjects with mood disorders receiving valbenazine were allowed stable concomitant medication regimens, demonstrating the feasibility of combination therapy 1.
Standard bupropion dosing (150 mg twice daily for SR or 300 mg once daily for XL) can be maintained when adding valbenazine 5.