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What Is The Risk of Serotonin Syndrome With Linezolid (Zyvox) IDS 2023-11
What Is The Risk of Serotonin Syndrome With Linezolid (Zyvox) IDS 2023-11
Question
Answer
Linezolid (Zyvox) is an oxazolidinone antibiotic that works by inhibiting bacterial protein synthesis. It
can be used to treat infections caused by drug-resistant pathogens such as methicillin-resistant
Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The oral formulation of
linezolid has excellent bioavailability and the cost of linezolid has come down substantially in recent
years, making it a more appealing treatment option. However, linezolid has been seen by many
clinicians as an antibiotic with concerning toxicities, including thrombocytopenia, neuropathies, lactic
acidosis, and serotonin syndrome.
Linezolid can be a great drug for numerous infection types, but these toxicities combined with worries
about antibiotic resistance have made linezolid somewhat of a “double-edged sword.” But are the
downsides as concerning as we thought they may be when linezolid first came out? Let’s dig into one
potential toxicity: serotonin syndrome from linezolid.
St. John’s wort, cocaine, MDMA (also known as ecstasy), triptans, amphetamines and amphetamine-
derivatives.
The package insert for linezolid states “Patients taking serotonergic antidepressants should receive
linezolid only if no other therapies are available.“ However, post-marketing studies have shown the
theoretical risk of serotonin syndrome associated with linezolid appears much less likely than what
was originally thought. Let’s look at 4 recent publications:
Reflecting on the current literature, in many instances the risk of serotonin syndrome can be
considered minimal and make linezolid a valid option. This includes when concomitantly given with
medications like citalopram, escitalopram, methadone, trazodone and fentanyl.
While the more recent retrospective data are reassuring, special attention is certainly warranted for (1)
patients on multiple agents that can contribute to increased risk of serotonin syndrome as well as (2)
patients who have a history of serotonin syndrome. Fortunately, serotonin syndrome is reversible by
discontinuing the offending agent(s), but can become life-threatening so must not ignored if it does
develop and monitoring may be required when linezolid is prescribed.
READINGS/ RESOURCES
https://www.idstewardship.com/risk-serotonin-syndrome-linezolid-zyvox/ 2/3
11/8/23, 9:57 PM What Is The Risk Of Serotonin Syndrome With Linezolid (Zyvox)?
ANSWERED BY
Hunter O. Rondeau, Pharm.D. & Timothy P. Gauthier, Pharm.D., BCPS, BCIDP – November 2023
Q&A DISCLAIMER
The ID PharmD Q&A pages attempt to answer common pharmacy questions by providing the
perspective and opinion of a trained expert with knowledge relevant to the question. That noted, these
answers are not provided as all-inclusive comprehensive responses. This is not provided for direct
patient care purposes.
https://www.idstewardship.com/risk-serotonin-syndrome-linezolid-zyvox/ 3/3