Are there interactions between Bactrim (trimethoprim/sulfamethoxazole) and Nuplazid (pimavanserin), Nuedexta (dextromethorphan/quinidine), Lexapro (escitalopram), Lamictal (lamotrigine), Depakote (valproate), and Pregabalin?

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From the Guidelines

Bactrim (trimethoprim/sulfamethoxazole) may interact with the other medications listed, including Lexapro (escitalopram), Nuedexta (dextromethorphan/quinidine), Lamictal (lamotrigine), Depakote (valproate), Nuplazid (pimavanserin), and Pregabalin, potentially leading to increased risks of serotonin syndrome, lamotrigine toxicity, liver toxicity, blood disorders, QT interval prolongation, and other adverse effects. The potential interactions between Bactrim and the other medications listed are primarily related to the inhibition of metabolism, competition for elimination pathways, and effects on similar physiological systems.

  • Bactrim may increase the risk of serotonin syndrome when combined with Lexapro and Nuedexta, as it can inhibit the metabolism of these serotonergic medications, potentially leading to excessive serotonin levels 1.
  • Bactrim may increase blood levels of Lamictal by competing for the same elimination pathways, potentially causing lamotrigine toxicity 1.
  • When combined with Depakote, there's an increased risk of liver toxicity and blood disorders as both medications can affect liver function and blood cell production 1.
  • The interaction with Nuplazid is primarily related to QT interval prolongation, as both medications can extend this cardiac conduction period, potentially causing dangerous heart rhythm disturbances 1.
  • The interaction with Pregabalin appears to be minimal, but patients should still be monitored for increased side effects 1. Patients taking these combinations should be closely monitored for side effects, and dosage adjustments may be necessary. Always inform healthcare providers about all medications being taken to prevent potential adverse interactions.

From the Research

Interaction between Bactrim and Other Medications

There are potential interactions between Bactrim (trimethoprim/sulfamethoxazole) and other medications, including:

  • Nuplazid (pimavanserin): No direct evidence of interaction is available in the provided studies.
  • Nuedexta (dextromethorphan/quinidine): No direct evidence of interaction is available in the provided studies.
  • Lexapro (escitalopram): No direct evidence of interaction is available in the provided studies.
  • Lamictal (lamotrigine): No direct evidence of interaction is available in the provided studies.
  • Depakote (valproate): No direct evidence of interaction is available in the provided studies.
  • Pregabalin: No direct evidence of interaction is available in the provided studies.

General Information on Drug-Drug Interactions

  • Drug-drug interactions (DDIs) occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug, or when one drug adds to or diminishes the effect of another drug 2.
  • DDIs can cause adverse drug events (ADEs) and are associated with a significant burden on the healthcare system 2, 3.
  • Some common DDIs result from alterations in drug metabolism through interactions with cytochrome P450 enzymes and absorption through interactions with P-glycoproteins 2.
  • Other common DDIs occur because of additive effects, including combinations of drugs that increase the risk of seizures, prolong the QT interval, increase central nervous system depression, and increase the risk of serotonin syndrome 2.

Specific Interactions Involving Trimethoprim-Sulfamethoxazole

  • Trimethoprim-sulfamethoxazole has been reported to interact with other medications, including angiotensin-converting enzyme (ACE) inhibitors, which can increase the risk of hyperkalemia 4.
  • Trimethoprim-sulfamethoxazole has also been reported to interact with phenytoin, which can increase the risk of phenytoin toxicity 4.
  • However, these interactions may not be directly relevant to the medications listed in the question (Nuplazid, Nuedexta, Lexapro, Lamictal, Depakote, and Pregabalin) 5, 6, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Potentially harmful drug-drug interactions in the elderly: a review.

The American journal of geriatric pharmacotherapy, 2011

Research

Vancomycin, trimethoprim-sulfamethoxazole, and rifampin.

Infectious disease clinics of North America, 1995

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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