Serotonin Toxicity Associated with Concomitant Use of Linezolid

Department of Pharmacy, Centre Hospitalier de Québec, Canada.
Annals of Pharmacotherapy (Impact Factor: 2.06). 06/2005; 39(5):956-61. DOI: 10.1345/aph.1E523
Source: PubMed


To report 2 cases of serotonin toxicity (ST) associated with concomitant use of linezolid and serotonergic drugs and review previously published case reports.
Case 1. A 38-year-old white female with cystic fibrosis treated with venlafaxine 300 mg/day for one year was prescribed linezolid 600 mg intravenously every 12 hours for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pulmonary infection. She displayed symptoms of ST 8 days after the introduction of linezolid. The venlafaxine dosage was decreased to 150 mg/day, and symptoms gradually abated over 36 hours. Case 2. A 37-year-old male with multiple myeloma received citalopram 40 mg/day and trazodone 150 mg/day for anxiety-related disorders. Linezolid treatment with 600 mg orally twice daily was instituted for MRSA cellulitis. The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment. Symptoms finally waned 5 days after linezolid treatment was stopped.
The symptoms observed in our patients were consistent with Sternbach's criteria for ST. A review of published case reports showed a short time to onset of symptoms following the introduction of linezolid, generally within 1-3 days. Also of note is the use of relatively high dosages of serotonergic drugs. Use of the Naranjo probability scale indicated a possible relationship between the use of linezolid and the occurrence of ST in both cases.
Clinicians should pay special attention to patients treated with serotonergic drugs, especially those receiving dosages in the higher end of the normal range who are prescribed linezolid, and consider tapering or reducing the dosage of serotonergic drugs for the duration of antibiotic therapy.

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    • "Concomitant use of MAOIs (including linezolid, furazolidone, and procarbazine) along with adrenergic/serotonergic antidepressants, St. John's wort, sibutramine, or opiate drugs that have SSRI-like properties (meperidine, tramadol, methadone, dextromethorphan, propoxyphene, and fentanyl) have been reported to precipitate dangerous SS.[1111213141516] Rarely, SS may also be precipitated by concomitant use of SSRIs with metoclopramide,[171819] sibutramine, fenfluramine or dexfenfluramine, lithium, dihydroergotamine, sumatriptan; but risk is severe when SSRIs and MAOIs are combined.[4] Linezolid has been reported to induce SS as an interaction with almost every category of antidepressant medications like imipramine,[20] amitriptyline,[2122] fluoxetine,[2324] citalopram,[32526] escitalopram,[25] paroxetine,[27] sertraline,[28] L-tryptophan (precursor of serotonin),[17] mirtazapine,[3] trazodone,[26] buspirone,[29] venlafaxine,[263031] and duloxetine.[32] "
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    ABSTRACT: Linezolid is a synthetic antimicrobial agent of the oxazolidinone class with weak, nonspecific inhibitor of monoamine oxidase enzymes. Concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine (>100 mg/day) may induce serotonin syndrome (SS). We present a case report of near-fatal adverse interaction between linezolid and escitalopram inducing SS in a 65-year-old woman with sepsis, under empirical antibiotic treatment. This report also summarizes the current relevant literature as identified via PubMed, EMBASE, and PsycINFO, supplemented with a manual search of cross references.
    Indian Journal of Psychological Medicine 10/2013; 35(4):413-6. DOI:10.4103/0253-7176.122245
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    • "The development of the serotonin syndrome has been reported as an interaction of linezolid plus almost every category of antidepressant medication. Interactions have been found with the selective serotonin reuptake inhibitors (SSRIs) as citalopram [29, 33–39], escitalopram [34], paroxetine [40], fluoxetine [41] [42], sertraline [43] [44] [45], with tryptophan , a precursor of serotonin [46], with noradrenaline and specific serotonergic agents (NaSSA) as mirtazapine [29], with serotonin 2 antagonist/reuptake inhibitor (SARI) as trazodone [36], the azapirone category anxiolytic buspirone "
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    ABSTRACT: We report a unique case of an adverse interaction between the oxazolidinone antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral arterial disease and sepsis, under empirical antibiotic treatment. We also summarize the current relevant literature as identified via PubMed, EMBASE, and PsycINFO as well as reference sections of selected articles.
    03/2013; 2013:617251. DOI:10.1155/2013/617251
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    • "Linezolid is a mild, reversible, inhibitor of monoamine oxidase and can potentially interact with serotonergic and adrenergic agents to cause serotonin syndrome (SS) and hypertension.166 There have been several case reports of SS in patients receiving linezolid with concomitant selective serotonin re-uptake inhibitors (SSRI)167,168 although no cases were reported in pre-marketing trials when linezolid was co-administered with several potentially interacting drugs.169 Some authors have proposed that linezolid should not be used in patients who have been receiving SSRIs until the SSRI has been discontinued for 2 weeks,167 however, a review of data from Phase III and IV CCTs showed the risk of SS in patients on linezolid was no different from the risk in patients on comparator drugs.170 "
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    ABSTRACT: Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs.
    Infection and Drug Resistance 06/2012; 5(1):87-102. DOI:10.2147/IDR.S25890
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