Serotonergic and Adrenergic Drug Interactions Associated with Linezolid: A Critical Review and Practical Management Approach

Abstract

OBJECTIVE To describe the evidence for serotonergic and adrenergic drug interactions with linezolid and discuss clinical management strategies. DATA SOURCES A literature search of PubMed (1947–November 2012), MEDLINE (1946–November 2012), EMBASE (1974–November 2012), and International Pharmaceutical Abstracts (1970–November 2012) was conducted using the terms linezolid, drug interaction, serotonin syndrome, serotonin toxicity, sympathomimetic, serotonergic agents, and adrenergic agents. Citations of retrieved articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION English-language articles describing coadministration of serotonergic or adrenergic agents with linezolid to humans were included. Studies published only in abstract form were excluded. DATA SYNTHESIS One prospective study, 6 retrospective studies, and 24 case reports were identified describing a serotonergic or adrenergic drug interaction. Incidence of serotonin syndrome in patients on linezolid and serotonergic agents ranged between 0.24% and 4%. Serotonergic agents determined to have probable (according to the Horn Drug Interaction Probability Scale) linezolid interactions in case reports included meperidine, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, and venlafaxine. Serotonergic agent dose and duration of coadministration with linezolid did not appear to influence the occurrence of serotonin syndrome. Adrenergic medication coadministration was associated with a possible drug interaction as determined by the Horn Drug Interaction Probability Scale but did not appear to result in clinically significant drug interactions with linezolid. CONCLUSIONS Linezolid-associated serotonergic drug interactions occur more commonly than adrenergic interactions. Serotonergic interactions considered probable according to the Horn Drug Interaction Probability Scale do not appear to correlate with drug dosage; time of onset ranges from <1 to 20 days, and effect resolves in <1 to 5 days after discontinuation of offending agents. If coadministration of linezolid and a serotonergic agent cannot be avoided, clinicians should be aware of the symptoms and management of serotonergic toxicity; close monitoring is recommended and additional serotonergic agents should not be used. While adrenergic drug interactions with linezolid are less common in clinical practice, monitoring for signs of hypertension remains important.