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Linezolid: MAOI Activity and Potential Drug Interactions

Key Words: Linezolid

TO THE EDITOR: Linezolid, a reversible, nonselective monoamine oxidase inhibitor (MAOI), is an antibacterial agent with a broad range of activity.¹ It belongs to a class of antibiotics that acts by inhibition of the initiation complex in bacterial translation systems.² Although of uncertain significance, linezolid's MAOI activity should be considered for potential drug interactions.

Linezolid has been evaluated in 2,046 patients across 7 Phase III trials. Most (85%) of the adverse events reported were mild to moderate. The only listed contraindication is a hypersensitivity to linezolid or to other product components.³ Given linezolid's MAOI properties, there is a potential for interaction with adrenergic and serotonergic agents.

According to Pharmacia (Medical Information communication; August 27, 2001), hypertension was reported during clinical trials in two patients who had received meperidine with concomitant linezolid; one patient had a history of hypertension. In addition, a Phase I study found a significant pressor response in normal adults receiving tyramine doses >100 mg with concomitant linezolid.

Pharmacia also reported that coadministration of linezolid and serotonergic agents was not associated with serotonin syndrome in Phase I, II, or III studies. During Phase III clinical trials, 52 linezolid-treated patients received a selective serotonin reuptake inhibitor, including fluoxetine, paroxetine, or sertraline (Medical Information communication; August 27, 2001).

We present two patients from our pediatric psychiatry consultation service who had potential drug interactions involving linezolid.

Case Report

M. is a 17-year-old boy with T-cell acute lymphoblastic leukemia who was admitted with fever and neutropenia. The child psychiatry department was consulted to evaluate him for depression and anxiety. He was started on lorazepam for anxiety. During his hospitalization, fever developed, with serum cultures positive for vancomycin-resistant enterococcus. Linezolid was added to his regimen. At this time, M. became increasingly despondent, and a psychiatry consultant was asked whether an antidepressant should be initiated. However, antidepressant treatment was deferred because of concerns regarding possible drug interactions in his tenuous medical state. Lorazepam was given more frequently during this acute phase of treatment, and he was followed closely by psychiatry personnel.

P. is a 7-year-old boy with attention-deficit/hyperactivity disorder and major depression who was admitted for upper-extremity osteomyelitis. At admission, his medications included venlafaxine. A trial of methylphenidate was initiated during his hospital stay, with moderate results. After 4 weeks of unsuccessful treatment of osteomyelitis, linezolid was added. During several days of concomitant administration of linezolid, venlafaxine, and methylphenidate, there were no alterations in vital signs or evidence of serotonin syndrome. However, questions about drug interactions were raised by our service. Low-dose venlafaxine was continued, but methylphenidate was replaced with guanfacine.

Discussion

Linezolid is a novel antibacterial agent with a broad range of activity, including against multi-drug-resistant bacteria. It possesses reversible, nonselective MAOI activity and therefore presents a potential risk of drug interactions with adrenergic and serotonergic agents. There are no known cases of serotonin syndrome or hypertensive crisis. However, as linezolid becomes increasingly used, knowledge of its MAOI activity and proper precautions may prevent adverse effects. Although this knowledge may be more applicable to consultation psychiatrists who treat medically compromised patients, outpatient providers may also confront this medication.

REFERENCES

1. Perry CM, Jarvis B: Linezolid: a review of its use in the management of serious gram-positive infections. Drugs 2001; 61:525-551[CrossRef][Medline]
2. Swaney SM, Aoki H, Ganoza MC, et al: The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria. Anti-microb Agents Chemother 1998; 42:3251-3255
3. Linezolid, in Physician's Desk Reference. Montvale, NJ, Medical Economics Company, 2001; pp. 2656-2660

This article has been cited by other articles:

				R. N Serio Acute Delirium Associated with Combined Diphenhydramine and Linezolid Use Ann. Pharmacother., January 1, 2004; 38(1): 62 - 65. [Abstract] [Full Text] [PDF]

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