Linezolid-Bupropion Interaction as Possible Etiology of Severe Intermittent Intraoperative Hypertension?

Abstract

Linezolid is a valuable drug that is finding increased use in the hospitalized surgical patient for the treatment of infections resulting from resistant, gram-positive organisms. Along with its known efficacy as an antibacterial agent, linezolid is a mild, reversible monoamine oxidase inhibitor.1Reviews on the subject of its monoamine oxidase inhibitor-like profile have expressed caution about the use of linezolid in the clinical setting, specifically when combined with sympathomimetic agents,2but there have been few, if any, reported clinical examples of a significant interaction. Recently, however, we observed unexpected intraoperative hemodynamic lability, as well as severe intermittent hypertension, in a psychiatric patient maintained on bupropion who was subsequently placed on linezolid for treatment of an infected vascular graft. We raise the concern that we have seen one of the first examples in the perioperative setting of a potentially dangerous interaction between linezolid and bupropion.The patient was a 57-yr-old male status post axillary-femoral bypass graft who presented to the emergency room with evidence of a graft infection and was admitted for antibiotics. After a trial of several antibiotics, he was placed on linezolid for treatment of resistant, gram-positive organisms. As an outpatient, he had been stably maintained on bupropion for long-standing depression; this drug was continued throughout his hospital course. After about 24 h of linezolid therapy, the patient was taken to the operating room for graft removal, where he underwent a propofol/succinylcholine induction with standard doses and a maintenance anesthetic of 1.5% isoflurane and fentanyl 250 μg. His intraoperative course was notable for several episodes of severe hypertension (as high as 260/145 mmHg), despite an otherwise stable anesthetic. The unexpected hemodynamic lability was severe enough to result in an unplanned admission to the intensive care unit, where the patient had an unremarkable postoperative course.The possibility of a significant drug interaction between linezolid and bupropion was suspected immediately and is supported by a careful analysis of the underlying pharmacologic mechanisms. Bupropion is an antidepressant that, in concert with its primary metabolite hydroxybupropion, acts as a norepinephrine reuptake inhibitor as well as a mild dopamine reuptake inhibitor.3Both norepinephrine and dopamine are monoamine compounds metabolized by monoamine oxidase. The use of bupropion with older, more traditional monoamine oxidase inhibitor drugs (such as phenelzine and tranylcypromine) has long been contraindicated in standard psychiatric practice because of the risk of a hypertensive crisis.3The older monoamine oxidase inhibitors do differ from linezolid in that they are strong, irreversible inhibitors of monoamine oxidase. As linezolid is a weak, reversible monoamine oxidase inhibitor, it had not been appreciated that coadministration with bupropion might cause a similar hypertensive state.However, linezolid clearly resembles the stronger monoamine oxidase inhibitors in its capacity to interact adversely with certain drugs. Combining the older monoamine oxidase inhibitors with serotonergically active drugs, such as selective serotonin inhibitors,4,5meperidine,6and dextromethorphan,7may lead to a severe central serotonin syndrome.8Similarly, linezolid has been implicated in producing a central serotonin syndrome when combined with either paroxetine9or citalopram10(both selective serotonin reuptake inhibitors). Furthermore, it is known that sympathomimetic agents, when administered in combination with the traditional monoamine oxidase inhibitors, may produce severe hypertensive events.11Again, linezolid mimics the interaction profile of the stronger monoamine oxidase inhibitors by producing statistically significant increases in blood pressure when combined with pseudoephedrine and phenylpropanolamine.12Based on this information, it is not surprising that linezolid acts like a more traditional monoamine oxidase inhibitor when combined with bupropion, especially in the context of the well-known physiologic stimulation and adrenergic stress of surgery.13It is hoped that this letter will alert clinicians to the monoamine oxidase inhibitor-like profile of linezolid and prevent the combination of linezolid with agents that enhance the function of any of the monamines (serotonin, norepinephrine, epinephrine, and dopamine).* University of Maryland Medical System and Baltimore Veterans Administration Hospital. sandson.marcucci@comcast.net