What is the interaction between Linezolid and Bupropion (Wellbutrin)?

From the Guidelines

Linezolid and Wellbutrin should not be taken together due to the risk of developing serotonin syndrome, a potentially life-threatening condition. Linezolid is an antibiotic that also functions as a monoamine oxidase inhibitor (MAOI), while Wellbutrin affects serotonin and dopamine levels in the brain. When combined, these medications can cause dangerous increases in serotonin levels, leading to symptoms such as agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or coma. This is supported by the most recent evidence from 1, which highlights the contraindication of concomitant use of an MAO inhibitor, such as linezolid, with other medications.

Key Considerations

• The risk of serotonin syndrome is a major concern when combining Linezolid and Wellbutrin, as it can be life-threatening.
• Linezolid's MAOI properties and Wellbutrin's effects on serotonin and dopamine levels in the brain contribute to this risk.
• Alternative options to Linezolid should be considered for patients taking Wellbutrin, as suggested by 1.
• If Linezolid is necessary, Wellbutrin should be discontinued at least 14 days before starting Linezolid therapy, and at least 24 hours should pass before resuming Wellbutrin after completing Linezolid treatment.

Clinical Implications

The interaction between Linezolid and Wellbutrin is based on their pharmacological properties and effects on neurotransmitter systems in the brain, as noted in 1. Therefore, it is crucial to prioritize caution and avoid concomitant use of these medications to minimize the risk of serotonin syndrome and ensure patient safety. If a patient is currently taking Wellbutrin and requires an antibiotic, consulting a healthcare provider for alternative options to Linezolid is essential, as emphasized by 1.

From the FDA Drug Label

Do not start bupropion hydrochloride extended-release tablets (XL) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (XL) may require urgent treatment with linezolid or intravenous methylene blue If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (XL) should be stopped promptly, and linezolid or intravenous methylene blue can be administered.

The use of linezolid and bupropion (Wellbutrin) together is contraindicated due to the increased risk of hypertensive reactions.

• If a patient is already taking bupropion, it should be stopped before starting linezolid.
• If a patient requires urgent treatment with linezolid while taking bupropion, the bupropion should be stopped promptly and the patient monitored for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first 2.
• Bupropion therapy may be resumed 24 hours after the last dose of linezolid.

From the Research

Linezolid and Serotonin Syndrome

• Linezolid is an antibiotic that can interact with certain medications, including antidepressants, to increase the risk of serotonin syndrome 3, 4, 5, 6, 7.
• Serotonin syndrome is a rare but life-threatening condition that can cause symptoms such as hyperthermia, mental status changes, autonomic hyperactivity, and neuromuscular abnormalities 3.

Interaction with Antidepressants

• Studies have investigated the risk of serotonin syndrome when linezolid is used in combination with antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) 4, 5.
• One study found that the incidence of serotonin syndrome was low and did not differ significantly between patients who received linezolid alone and those who received linezolid with an SSRI or SNRI 5.
• Another study found that concurrent use of antidepressants did not significantly increase the risk of serotonin syndrome in patients receiving linezolid 4.

Specific Interactions

• There is limited information available on the specific interaction between linezolid and Wellbutrin (bupropion), an antidepressant that can also increase the risk of serotonin syndrome.
• However, studies have investigated the interaction between linezolid and other medications that can increase serotonin levels, such as methadone and buprenorphine 7.
• These studies suggest that the risk of serotonin toxicity is low when linezolid is used in combination with these medications, but further study is needed to fully understand the risks 7.

Clinical Implications

• Clinicians should be aware of the potential risk of serotonin syndrome when using linezolid in combination with other medications that can increase serotonin levels, including antidepressants 3, 4, 5, 6, 7.
• Patients who receive linezolid should be monitored closely for signs and symptoms of serotonin syndrome, and the medication should be discontinued if symptoms occur 3, 6.