Potential Serious Adverse Interactions Between Linezolid and Atomoxetine

Abstract

To the Editor:

L inezolid is an oxazolidinone antibiotic that is widely used in general hospitals. Originally discovered as a psychotropic agent with antidepressant effects through reversible nonselective inhibition of monoamine oxidase (MAO), it was also found to have antibiotic efficacy against drug-resistant gram-positive cocci. (Moellering 2003). MAO-A deaminates noradrenaline, adrenaline, and 5-hydroxytryptamine (serotonin). As linezolid is a competitive monoamine oxidase inhibitor (MAO-I), the potential exists for interactions with drugs that have effects on the serotonergic or noradrenergic systems, as well as tyramine, which is capable of releasing stored catecholamines (Stevens et al. 2004).There have been various published reports of serotonin syndrome occurring with co-administration of linezolid with serotonergic medications (Thomas et al. 2004, Lawrence et al. 2006).

The manufacturer of atomoxetine HCl lists co-administration with an MAO-I as a contraindication, and states that with other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an MAO-I. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity (Strattera package insert 2002).

Case Report

We recently encountered a case of a 10-year-old Caucasian female with history of cystic fibrosis (CF) and attention-deficit/hyperactivity disorder (ADHD) who had been admitted to the pediatric inpatient service with an acute exacerbation of CF. The patient had been taking atomoxetine 40 mg once daily as prescribed by her primary care physician, with good control of her ADHD symptoms. Based on the results of her sputum culture, the primary team decided to start linezolid but was alerted by the computer order entry system that is designed to detect and flag all potential drug interactions. Different treatment options for her ADHD and CF exacerbation were discussed and it was found that linezolid was the only antibiotic that the bacteria were sensitive to. Because of the potential for serious adverse events, atomoxetine was stopped and she was started on IV linezolid 310 mg every 8 hours, and successfully completed the course for 14 days. At the time of discharge she was advised to restart atomoxetine 14 days after the last dose of linezolid as per the manufacturer's guidelines (Strattera package insert 2002).

Discussion

Most clinicians associate MAO-Is with a group of antidepressant medications, but it is clear that there are other medications with this property (some others being furazolidone and Procarbazine). Furthermore, amphetamines and derivatives should also be used with caution in conjunction with MAO-Is because of concerns about exaggerated increase in blood pressure, thus limiting the options for ADHD treatment.

Although rare, serious interactions between linezolid and atomoxetine can occur and be lethal if unrecognized and untreated. This case illustrates the value of anticipating an eventual adverse event and the need to be proactive in minimizing possible dangerous interactions with a patient's other medications.

Footnotes

Disclosures

No competing financial interests exist.

References

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. Serotonin toxicity associated with the use of linezolid: A review of postmarketing data. Clin Infect Dis, 42:1578–1583. 2006.

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