Bupropion and Linezolid Interaction

Mechanism and Guidelines

Linezolid, while primarily an antibiotic, has MAOI properties that can lead to potentially dangerous drug interactions, particularly with bupropion, which inhibits the reuptake of dopamine and norepinephrine 1
The British Thoracic Society guidelines explicitly state that linezolid should be avoided with other drugs that inhibit monoamine oxidases A or B, including bupropion 2

Patients with uncontrolled hypertension, phaeochromocytoma, carcinoid tumor, thyrotoxicosis, bipolar depression, schizophrenia, or acute confusional states are at higher risk for adverse reactions when taking bupropion and linezolid 2
The American Thoracic Society guidelines note that linezolid should generally not be administered to patients taking serotonergic agents, such as bupropion, due to potential for serious CNS reactions 1

The British Thoracic Society guidelines recommend avoiding the combination of bupropion and linezolid completely, due to the risk of hypertensive reactions and serotonin syndrome 2
The contraindication applies regardless of the indication for either medication, and caution is warranted due to the potential severity of adverse outcomes 1, 2

The combination of bupropion and linezolid can increase the risk of hypertensive reactions and potentially serotonin syndrome, as linezolid is a reversible monoamine oxidase inhibitor (MAOI) 3
Linezolid can potentially cause serotonin syndrome when combined with serotonergic medications, according to the American Academy of Child and Adolescent Psychiatry 4

Signs of serotonin syndrome include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity, such as hypertension and tachycardia, as reported by the Journal of the American Academy of Child and Adolescent Psychiatry 3
Advanced symptoms of serotonin syndrome may include fever, seizures, arrhythmias, and unconsciousness, requiring hospital-based care with discontinuation of all serotonergic agents, as recommended by the Journal of the American Academy of Child and Adolescent Psychiatry 3

Linezolid is a reversible, non‑selective monoamine oxidase (MAO) inhibitor; concomitant use with serotonergic agents (e.g., SSRIs, SNRIs) can precipitate serotonin syndrome or neuroleptic malignant syndrome‑like reactions, and the American Thoracic Society advises that linezolid generally should not be given to patients receiving these drugs. [5][6]

The American Thoracic Society recommends that, when clinically feasible, the antidepressant should be stopped before initiating linezolid therapy, especially if the planned duration of linezolid is short (≤ 28 days). This is the preferred first‑line approach. 5

Patients receiving linezolid should have a complete blood count (CBC) checked weekly to detect myelosuppression and undergo a neurological examination monthly to screen for peripheral neuropathy and optic neuritis, as highlighted by the American Thoracic Society. 5