What are the potential interactions between bupropion (antidepressant) and omeprazole (proton pump inhibitor)?

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Potential Interactions Between Bupropion and Omeprazole

There is no clinically significant interaction expected between bupropion and omeprazole that would affect morbidity or mortality outcomes. While both medications are metabolized through hepatic pathways, they primarily utilize different cytochrome P450 enzymes, minimizing the risk of meaningful drug interactions.

Metabolic Pathways and Potential Interaction

  • Bupropion is primarily metabolized by CYP2B6, while omeprazole is predominantly metabolized by CYP2C19 and to a lesser extent by CYP3A4 1, 2.
  • Omeprazole is a weak to moderate inhibitor of CYP2C19, but this does not significantly affect bupropion metabolism since bupropion relies primarily on CYP2B6 2.
  • In a study examining drug interactions with cenobamate, researchers found that omeprazole (as a CYP2C19 probe) and bupropion (as a CYP2B6 probe) have distinct metabolic pathways, supporting their compatibility 2.

Clinical Implications

  • Unlike interactions between omeprazole and clopidogrel (which share the CYP2C19 pathway), there is no evidence suggesting that omeprazole significantly alters bupropion's efficacy or safety profile 1.
  • Bupropion has been shown to inhibit CYP2D6, but this does not meaningfully impact omeprazole metabolism since omeprazole does not rely significantly on this pathway 1, 3.
  • The most clinically significant drug interactions with PPIs involve benzodiazepines, not antidepressants like bupropion 3.

Special Considerations

  • Both medications can be administered without dose adjustments or altered timing when used concomitantly 1.
  • Unlike some other antidepressants (particularly MAOIs), bupropion has a lower potential for serious drug interactions 4.
  • Patients with genetic variations in CYP2C19 (poor metabolizers) may theoretically experience slightly altered drug levels, but this has not been shown to be clinically significant for the bupropion-omeprazole combination 1.

Monitoring Recommendations

  • Routine monitoring of therapeutic efficacy for both medications is sufficient; no special monitoring is required specifically for this drug combination 1.
  • If a patient reports unexpected side effects or reduced efficacy of either medication, consider evaluating for other potential drug interactions or contributing factors 4.

Common Pitfalls to Avoid

  • Do not confuse this interaction profile with that of omeprazole and clopidogrel, which has documented clinical significance due to shared metabolic pathways 1.
  • Avoid assuming that all antidepressants have similar interaction profiles with PPIs; bupropion's unique metabolic pathway differentiates it from SSRIs and MAOIs 5, 4.
  • Do not unnecessarily separate administration times of these medications, as there is no evidence supporting the need for this practice 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Proton pump inhibitors and their drug interactions: an evidence-based approach.

European journal of gastroenterology & hepatology, 2001

Research

Systematic overview of drug interactions with antidepressant medications.

Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2006

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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