Is the concurrent use of Wellbutrin (bupropion) and Linezolid contraindicated?

Concurrent Use of Wellbutrin (Bupropion) and Linezolid is Contraindicated

The concurrent use of bupropion (Wellbutrin) and linezolid is contraindicated due to the increased risk of hypertensive reactions, as linezolid is a reversible monoamine oxidase inhibitor (MAOI). 1

Mechanism of Interaction

• Linezolid is classified as a reversible, nonselective monoamine oxidase inhibitor (MAOI) 2
• Bupropion is specifically contraindicated for use with reversible MAOIs such as linezolid according to FDA labeling 1
• The combination can increase the risk of hypertensive reactions and potentially serotonin syndrome 1, 3

FDA Guidance on This Interaction

• The FDA drug label for bupropion explicitly states: "Starting bupropion hydrochloride extended-release tablets (XL) in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated" 1
• For patients already on bupropion who urgently require linezolid treatment:
  • Bupropion should be stopped promptly if linezolid must be administered 1
  • The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first 1
  • Bupropion therapy may be resumed 24 hours after the last dose of linezolid 1

Clinical Considerations

• Linezolid can potentially cause serotonin syndrome when combined with serotonergic medications 4
• While some recent research suggests the absolute risk of serotonin syndrome with linezolid and certain antidepressants may be lower than previously thought 5, 6, the FDA contraindication remains in effect 1
• A 2022 study found the incidence of serotonin syndrome to be rare in patients receiving linezolid with concurrent antidepressants, but this study did not specifically focus on bupropion 5

Management Algorithm for Patients Requiring Both Medications

1. First-line approach: Avoid concurrent use of bupropion and linezolid 1

2. If linezolid is urgently needed in a patient on bupropion:

   • Stop bupropion before starting linezolid 1
   • Monitor the patient for 24 hours after the last dose of linezolid before resuming bupropion 1
   • Consider alternative antibiotics if clinically appropriate 1

3. If no acceptable alternatives to linezolid exist:

   • Perform a risk-benefit assessment 1
   • If benefits outweigh risks, discontinue bupropion before starting linezolid 1
   • Monitor closely for signs of hypertensive reactions and serotonin syndrome 3
   • Resume bupropion no sooner than 24 hours after the last linezolid dose 1

Warning Signs to Monitor

• Signs of serotonin syndrome include: mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia) 3
• Advanced symptoms may include fever, seizures, arrhythmias, and unconsciousness 3
• Treatment of serotonin syndrome requires hospital-based care with discontinuation of all serotonergic agents 3

Common Pitfalls

• Failing to recognize linezolid as a reversible MAOI 2
• Not stopping bupropion before administering linezolid in urgent situations 1
• Resuming bupropion too soon after linezolid discontinuation (should wait 24 hours) 1
• Overlooking the contraindication due to the relatively low reported incidence of adverse events in some studies 5, 6

Despite some recent research suggesting low incidence of serotonin syndrome with linezolid and certain antidepressants, the FDA contraindication remains clear and should be followed to ensure patient safety.