Linezolid and Serotonin Syndrome

Quinn, Davin K.; Stern, Theodore A.

doi:10.4088/pcc.09r00853

Cited by 54 publications

(47 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A retrospective review of 20 comparator-controlled linezolid clinical trials involving Ͼ10,000 participants identified approximately 2.8-fold higher, but not significantly different, incidence of serotonin toxicity for linezolid-treated versus comparator-treated patients (40). A number of drugs with potential (alone or in combination) for linezolid interaction leading to serotonin syndrome, including certain tricyclic antidepressants, serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and opioids, have been identified (13,(41)(42)(43).…”

Section: Figmentioning

confidence: 99%

“…Postmarketing reports identified rare episodes of serotonin toxicity, resulting from high intrasynaptic concentrations of serotonin and serotonin receptor 2A overstimulation in the central nervous system (13). Serotonin syndrome is remarkable in its severity and potentially fatal outcome, and it occurs independent of duration of treatment (14).…”

mentioning

confidence: 99%

“…MAO inhibitors, when taken in combination with vasoconstrictors, such as pseudoephedrine, or high dietary tyramine can cause sudden blood pressure elevations that may lead to hypertensive crises. Combination with serotonergic agents may lead to rare, but potentially life-threatening, serotonin syndrome (13,14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

In Vitro , In Vivo , and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

Flanagan

Bartizal

Minassian

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bTedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drugfood interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC 50 ) for tedizolid was 8.7 M for MAO-A and 5.7 M for MAO-B and 46.0 and 2.1 M, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a >30-mmHg increase in systolic blood pressure (TYR 30 ) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR 30 /tedizolid phosphate TYR 30 ) was 1.33; a ratio of >2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials .gov as NCT01539473 (tyramine interaction study conducted at

show abstract

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

In Vitro , In Vivo , and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

Flanagan

Bartizal

Minassian

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…We purposefully made the entry criteria for vancomycin Ն2 days to avoid matching linezolid patients to patients who received vancomycin for only Ͻ24 h; there was a considerable number of "one-time" orders for vancomycin over the study period. We selected to include patients who received at least 1 day of linezolid treatment, since ST after the receipt of one dose of linezolid has been reported (20). Matching criteria were (i) location at the start of therapy (intensive care unit [ICU] or non-ICU), (ii) admission hospital within VISN-2 (Albany, Bath, Buffalo, Canandaigua, or Syracuse, NY), (iii) length of stay (LOS) prior to initiation of therapy Ϯ 7 days, (iv) age (Ͻ50, 50 to 70, or Ͼ70 years), and (v) baseline platelet counts (Յ100,000 or Ͼ100,000 cells/mm 3 ).…”

Section: Methodsmentioning

confidence: 99%

Comparative Evaluation of Serotonin Toxicity among Veterans Affairs Patients Receiving Linezolid and Vancomycin

Lodise

Patel

Rivera

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

. Matching criteria included VISN-2 hospital, hospital ward, prior hospital length of stay, age, and baseline platelet counts. The patients' electronic medical records were evaluated for symptoms consistent with ST and the Hunter serotonin toxicity criteria (HSTC) using an intensive, natural word search algorithm. The study included 251 matched pairs. Demographics and comorbidities were similar between groups. Over half of the study population received at least one concurrent medication with serotonergic activity. Receipt of agents with serotonergic activity was more pronounced in the vancomycin group, and the higher frequency was due to concomitant antihistamine and antiemetic use. Antidepressant use, including selective serotonin reuptake inhibitors (SSRIs), was similar between groups. No patients in either group were found to meet the criteria using the word search algorithm for ST. Fewer linezolid patients than vancomycin patients met the HSTC overall (3.2% versus 8.8%) and when stratified by receipt of a concurrent serotonergic agent (4.3% versus 12.4%). Of the patients meeting the HSTC, most had past or present comorbidities that may have contributed to or overlapped the HSTC. This study of hospitalized patients revealed comparably low frequencies of adverse events potentially related to ST among patients who received linezolid or vancomycin.

show abstract

“…Despite diverse presentations, serotonin toxicity is classically described as a triad including mental status changes, autonomic hyperactivity, and neuromuscular abnormalities (Quinn and Stern 2009;Boyer and Shannon 2005). The impact of this toxicity can range in intensity from mild/nearly imperceptible to lethal.…”

Section: Serotonin Syndromementioning

confidence: 99%

Psychiatric Emergencies

Lynn¹,

Valentine²

2014

Psychopharmacology in Oncology and Palliative Care

View full text Add to dashboard Cite

The complexity of oncology and supportive care is such that psychotropic drugs are themselves potential causes of urgent or emergent clinical problems. Polypharmacy and medication interactions increase the risk of drug-related emergencies. Serotonin syndrome is characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities varying from mild to life-threatening. Use of standardized diagnostic criteria can be helpful. Neuroleptic malignant syndrome presents with muscle rigidity, mental status changes, autonomic instability, and hyperpyrexia. Treatment of both syndromes is focused on removal of the precipitating agents and supportive interventions. Psychotropic drugs that are well tolerated in healthy persons are potentially dangerous in high acuity and end stage disease settings. Overdose and intoxication with psychotropic drugs are usually accidental or idiosyncratic in oncology and supportive care though the medications might be used in suicide attempts. Benzodiazepine intoxication risks hypotension, decreased respiratory drive, and exacerbation of delirium. Antipsychotic drugs may cause or exacerbate anticholinergic delirium. Typical and second generation antipsychotics may cause or exacerbate dangerous cardiac conduction delays including torsades de pointes. Antidepressants, frequently involved in suicides, are variably toxic or lethal between classes. Tricyclic antidepressants and monoamine oxidase inhibitors are particularly dangerous. In all cases of psychotropic drug intoxication or overdose treatment involve withdrawal of offending agents and support of affected organ systems. Emergencies related to psychotropic drugs are

show abstract

Linezolid and Serotonin Syndrome

Cited by 54 publications

References 23 publications

In Vitro , In Vivo , and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

In Vitro , In Vivo , and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

Comparative Evaluation of Serotonin Toxicity among Veterans Affairs Patients Receiving Linezolid and Vancomycin

Psychiatric Emergencies

Contact Info

Product

Resources

About