DangerousContraindicated
5-HTP
5-HTP can increase serotonergic tone and is unsafe with Linezolid's monoamine oxidase inhibitory activity.
Recommendation: Avoid 5-HTP while taking Linezolid.
Linezolid
Prescription ·Strong evidence ·Reviewed May 2026
Linezolid is a synthetic oxazolidinone antibiotic used to treat serious infections caused by resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). It has excellent oral bioavailability that approaches that of the intravenous form, allowing seamless IV-to-oral transition. Because it is a reversible, nonselective monoamine oxidase (MAO) inhibitor, it carries clinically important serotonergic and tyramine-related interaction risks.
What it's good for
What to watch for
- Diarrhea, nausea, and vomiting
- Headache
- Reversible myelosuppression including thrombocytopenia and anemia, especially with courses longer than 14 days
- Known hypersensitivity to linezolid or any product component1,2
- Concurrent use with or within 2 weeks of monoamine oxidase inhibitors (for example phenelzine, isocarboxazid)2
The bottom line
Evidence rating strong. Most-documented uses: nosocomial and community-acquired pneumonia caused by susceptible gram-positive organisms, complicated and uncomplicated skin and soft-tissue infections including mrsa, vancomycin-resistant enterococcus faecium infections. 3 sources indexed (2006–2020), with 4 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Linezolid inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit near its interface with the 30S subunit. This binding prevents formation of the functional 70S initiation complex, blocking translation at an early step that is distinct from other protein-synthesis inhibitors, which limits cross-resistance. The drug is generally bacteriostatic against staphylococci and enterococci and bactericidal against most streptococci. Separately, linezolid is a weak, reversible, nonselective inhibitor of monoamine oxidase, which underlies its serotonergic and tyramine interaction profile.1,2
Class
Oxazolidinone antibiotic
Dosing
Dosing & protocol.
Common range
600 mg orally or intravenously every 12 hours for most adult infections; 400 mg every 12 hours for uncomplicated skin and soft-tissue infections. Typical course is 10 to 14 days, or up to 28 days for VRE infections.
Recommended form
Oral tablet, oral suspension, or intravenous infusion; oral and IV doses are equivalent due to near-complete bioavailability
Oral linezolid is rapidly and almost completely absorbed (bioavailability approximately 100 percent) and can be taken with or without food. A high-fat meal slightly delays the time to peak concentration but does not meaningfully reduce overall absorption, so dose timing relative to meals is not critical. Patients should avoid large quantities of tyramine-rich foods because of the MAO-inhibitory activity.3
Safety
Full safety detail.
Side effects
- Diarrhea, nausea, and vomiting
- Headache
- Reversible myelosuppression including thrombocytopenia and anemia, especially with courses longer than 14 days
- Peripheral and optic neuropathy with prolonged use
- Lactic acidosis
- Serotonin syndrome when combined with serotonergic agents
- Clostridioides difficile-associated diarrhea
- Hypoglycemia in patients on insulin or oral hypoglycemics
Contraindications
- Known hypersensitivity to linezolid or any product component1,2
- Concurrent use with or within 2 weeks of monoamine oxidase inhibitors (for example phenelzine, isocarboxazid)2
- Uncontrolled hypertension, pheochromocytoma, or carcinoid syndrome unless closely monitored
- Concurrent use with serotonergic agents such as SSRIs, SNRIs, TCAs, triptans, or meperidine unless benefit outweighs risk and the patient is monitored2
- Concurrent use with sympathomimetic, vasopressive, or dopaminergic agents unless closely monitored2
Interactions
Interaction records.
DangerousContraindicated
L-Tryptophan
L-Tryptophan can increase serotonergic tone and is unsafe with Linezolid's monoamine oxidase inhibitory activity.
Recommendation: Avoid L-Tryptophan while taking Linezolid.
DangerousContraindicated
St. John's Wort
St. John's Wort can increase serotonergic tone and is unsafe with Linezolid's monoamine oxidase inhibitory activity.
Recommendation: Avoid St. John's Wort while taking Linezolid.
ModerateCaution
Vitamin B6
Vitamin B6 (pyridoxine) is the cofactor for aromatic L-amino acid decarboxylase, the enzyme that converts 5-HTP to serotonin and L-DOPA to dopamine. While vitamin B6 alone does not cause serotonin syndrome, high-dose supplementation may theoretically enhance conversion of serotonin precursors and is most relevant when other serotonergic agents are present. Separately, prolonged high-dose pyridoxine carries its own risk of sensory peripheral neuropathy, which can overlap with linezolid's known dose- and duration-dependent peripheral neuropathy.
Recommendation: Routine dietary or low-dose B6 is not a concern. Avoid high-dose pyridoxine supplements during prolonged linezolid therapy, both to avoid compounding peripheral neuropathy risk and because B6 facilitates serotonin synthesis if precursors are present. Report new numbness, tingling, or burning in the hands or feet to a clinician.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Randomized controlled trials
1- 1Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled StudyNeeds reviewNo linkWunderink RG, Niederman MS, Kollef MH, et al. · Clinical Infectious Diseases · 2012
Linezolid achieved a higher clinical cure rate than vancomycin in patients with MRSA nosocomial pneumonia while maintaining a comparable safety profile.
Reviews & position papers
1- 2Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing DataNeeds reviewNo linkLawrence KR, Adra M, Gillman PK · Clinical Infectious Diseases · 2006
Coadministration of linezolid with serotonergic agents, particularly SSRIs, was associated with reports of serotonin syndrome, supporting cautious or avoided concurrent use.
Reference material
1- 3Zyvox (linezolid) US Prescribing InformationNeeds reviewNo linkPfizer Inc. · FDA Label · 2020
Oral linezolid is approximately 100 percent bioavailable, so oral and intravenous doses are interchangeable without dose adjustment.
Keep exploring
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Linezolid in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.