What is the ideal washout period when starting linezolid in patients who have been on bupropion (Wellbutrin)?

Washout Period When Starting Linezolid in Patients on Bupropion

A minimum washout period of 14 days is required when starting linezolid in patients who have been on bupropion due to the risk of serious drug interactions. 1

Mechanism of Interaction and Risks

• Linezolid is a reversible monoamine oxidase inhibitor (MAOI) that can interact with bupropion, potentially causing hypertensive reactions and serotonin syndrome 1
• The FDA label for bupropion specifically states that at least 14 days should elapse between discontinuation of bupropion and initiation of therapy with an MAOI such as linezolid 1
• Linezolid inhibits monoamine oxidases A and B, which can lead to dangerous interactions with drugs like bupropion that affect monoamine neurotransmitters 2

Clinical Decision Algorithm

1. Planned treatment (non-urgent situations):

   • Discontinue bupropion and wait a full 14 days before starting linezolid therapy 1
   • Monitor patient for withdrawal symptoms from bupropion discontinuation during this period 3

2. Urgent situations requiring immediate linezolid:

   • If urgent treatment with linezolid is required and acceptable alternatives are not available:
     • Stop bupropion immediately 1
     • Initiate close monitoring for hypertensive reactions and signs of serotonin syndrome 1, 4
     • Consider non-pharmacological interventions including hospitalization if psychiatric symptoms worsen 1

3. Post-linezolid considerations:

   • Bupropion therapy may be resumed 24 hours after the last dose of linezolid 1
   • When restarting bupropion, consider starting at a lower dose and titrating up as tolerated 3

Pharmacokinetic Considerations

• Bupropion has a biphasic elimination with an initial half-life of approximately 1.5 hours and a second phase half-life of approximately 14 hours 5
• Linezolid has an elimination half-life of 5-7 hours 2
• The 14-day washout period provides sufficient time for bupropion and its active metabolites to be eliminated from the body before introducing linezolid 1

Monitoring During Transition

• During the washout period, monitor patients for:
  • Withdrawal symptoms from bupropion discontinuation 3
  • Worsening of the underlying condition being treated with bupropion 3
  • Need for alternative psychiatric management during the transition period 1

Important Caveats and Pitfalls

• Despite the theoretical risk, a recent case series found only one definitive and two possible cases of serotonin syndrome among 194 encounters where linezolid was used concomitantly with medications that affect serotonin 4
• However, this does not negate the need for the recommended washout period, as severe reactions can occur even if relatively rare 1
• Do not attempt to overlap these medications or shorten the washout period, as this increases the risk of potentially life-threatening reactions 1

Special Populations

• Patients with renal or hepatic impairment may require longer washout periods due to altered drug metabolism and clearance 3, 1
• Elderly patients may also be more susceptible to adverse effects from this interaction and should be monitored more closely 2