Linezolid and Serotonergic Drug Interactions: A Retrospective Survey

Taylor, Jeremy; Wilson, John W.; Estes, Lynn L.

doi:10.1086/504809

Cited by 125 publications

(60 citation statements)

References 14 publications

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“…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%

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

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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

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Section: Figmentioning

confidence: 99%

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

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“…44 Medications with monoamine oxidase inhibitor activity such as linezolid may precipitate the syndrome when administered concurrently with a serotonergic agent. 45 Diagnosis requires recognition of symptoms that include mental status changes, autonomic instability (hyperthermia, heart rate and BP fluctuation, arrhythmias and diaphoresis), and neuromuscular abnormalities such as tremor, myoclonus, or hypertonicity. Symptoms of SS are usually noted to improve within 24 h after withdrawal of the offending agent(s).…”

Section: Antidepressantsmentioning

confidence: 99%

Toxicology in the Critical Care Unit

Alapat

Zimmerman

2008

Chest

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“…3 It has been noted that Boyer's criteria are more specific for serotonin toxicity than are Sternbach's criteria. 4 …”

Section: What Is the Serotonin Syndrome And How Is It Diagnosed?mentioning

confidence: 99%

“…7 Since linezolid was approved by the FDA for use, there have been 17 published case reports documenting the occurrence of symptoms of serotonin toxicity in patients receiving linezolid and SSRIs. Taylor and colleagues, 4 in a retrospective chart review of cases at the Mayo Clinic (Rochester, Minnesota), found an incidence of serotonin toxicity of 3% in patients taking SSRIs and linezolid. Table 4 lists the case reports found in the literature.…”

Section: What Is the Prevalence Of Linezolid-induced Serotonin Toxicity?mentioning

confidence: 99%