Probiotics and Drug Interactions with Lisdexamfetamine and Brexpiprazole
Probiotics do not have clinically significant pharmacokinetic or pharmacodynamic interactions with lisdexamfetamine (Vyvanse) or brexpiprazole (Rexulti), and can be safely co-administered in immunocompetent adult patients.
Mechanism of Potential Interactions
The theoretical concern with probiotic-drug interactions centers on gut microbiota's ability to influence drug metabolism through several mechanisms 1, 2:
- Enzymatic modification: Gut bacteria contain enzymes capable of oxidation, hydrolysis, and conjugation reactions that could theoretically alter drug bioavailability 2
- Transporter regulation: Probiotics may up- or down-regulate intestinal epithelial transporters affecting drug absorption 2
- pH alterations: Probiotics lower intestinal pH, which could theoretically affect drug solubility and absorption 3
Why These Specific Medications Are Not Affected
Lisdexamfetamine is a prodrug that undergoes hydrolysis primarily in red blood cells (not the gut) to convert to active dextroamphetamine, making it largely independent of gut microbiota metabolism 1.
Brexpiprazole is metabolized primarily by hepatic CYP3A4 and CYP2D6 enzymes 4, 5. While gut microbiota can influence some drug metabolism, there is no evidence that probiotics significantly affect these specific cytochrome P450 pathways or brexpiprazole's pharmacokinetics 1, 2.
Practical Administration Guidelines
- Timing separation is unnecessary for these medications, unlike with antibiotics where a 2-hour separation is recommended 3
- Standard probiotic dosing of 10⁹-10¹⁰ CFU/day can be used without adjustment 6
- Continue both medications without modification to dosing schedules 3
Safety Considerations
The primary safety concern with probiotics relates to patient immune status, not drug interactions 6, 3:
- Contraindicated in: Immunocompromised patients, critically ill patients, those with central venous catheters due to risk of bacteremia or fungemia 6, 7, 3
- Generally safe in: Immunocompetent adults with psychiatric conditions taking stimulants or antipsychotics 3
- Common side effects: Bloating and flatulence, which are not medication interactions but rather direct probiotic effects 3
Clinical Monitoring
No specific monitoring for drug interactions is required when combining probiotics with these psychiatric medications 1, 3. Standard monitoring for the underlying psychiatric condition and medication efficacy should continue unchanged 4, 5.
Evidence Limitations
While literature on probiotic-drug interactions is emerging, there are no reported cases or studies demonstrating clinically significant interactions between probiotics and either lisdexamfetamine or brexpiprazole 1, 2. The absence of evidence combined with the distinct metabolic pathways of these medications supports their safe co-administration 1, 2.