Oxazolidinone (2nd-line antituberculosis agent; MAO inhibitor)
Linezolid is an antibiotic used to treat serious infections, including those caused by resistant bacteria (such as methicillin-resistant Staphylococcus aureus, MRSA). It is taken orally or intravenously. It is an MAO inhibitor, so it has important food and medication restrictions.
Also known as: Zyvox
Rifampin lowers Linezolid levels — risk of losing TB treatment efficacy.
Rifampicin increases linezolid clearance and reduces its exposure by about 30%, even though linezolid is not significantly CYP-metabolised; the clinical relevance is debated, but the failure risk is higher in severe infections (e.g. endocarditis, resistant staphylococcal pneumonia). Monitor the clinical response and consider an alternative (e.g. vancomycin, daptomycin) when the combination is discouraged by the context.
Linezolid + rifampicin: rifampicin lowers linezolid levels (~30%), with possible loss of efficacy. Monitor the clinical response.
Induction of enzymes and transporters that eliminate Linezolid.
Clinical TB response.
Persistent fever, positive sputum smear.
Consider therapeutic drug monitoring or regimen adjustment; watch the response.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=374af2a7-d994-40bd-a86a-cd9038d0b72c ; approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b
High risk of serotonin syndrome: Linezolid is an MAO inhibitor and with Fluoxetine serotonin accumulates — it can be dangerous.
Linezolid is a reversible, non-selective monoamine oxidase inhibitor and fluoxetine blocks serotonin reuptake: the combined effect can cause severe serotonin syndrome — agitation, tremor, hyperthermia, rigidity, hyperreflexia and diarrhoea, and in severe cases seizures, rhabdomyolysis and death. The approved labels of linezolid and fluoxetine warn of this risk. The combination should be avoided whenever possible; if clinically indispensable, use the lowest effective dose, closely monitor for serotonergic symptoms and discontinue immediately if signs appear.
Linezolid (MAO inhibitor) + SSRI: risk of potentially fatal serotonin syndrome. Avoid; if unavoidable, close monitoring of serotonergic symptoms.
MAO inhibition (linezolid) and serotonin reuptake inhibition (fluoxetine), with long fluoxetine half-life.
Watch for serotonergic signs.
Confusion, agitation, hyperthermia, tremor, rigidity, autonomic instability.
Avoid the combination; wait at least 2 weeks after stopping one of them.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=374af2a7-d994-40bd-a86a-cd9038d0b72c ; approved Fluoxetine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09fb3100-1e06-4cdc-8016-7e4f5d097490
High risk of serotonin syndrome between Linezolid and Sertraline (an SSRI).
Sertraline increases synaptic serotonin by blocking reuptake and linezolid inhibits monoamine oxidase: the combination of the two actions can precipitate severe serotonin syndrome (agitation, tremor, hyperthermia, rigidity, hyperreflexia) with risk of death. The approved linezolid label warns of the increased risk with serotonergic drugs, including SSRIs. Whenever possible, choose an alternative antibiotic; if the combination is unavoidable, use the lowest effective dose, monitor for serotonergic symptoms and discontinue immediately if they occur.
Linezolid (MAO inhibitor) + SSRI: risk of potentially fatal serotonin syndrome. Avoid; if unavoidable, close monitoring and immediate discontinuation if symptoms occur.
MAO inhibition (linezolid) and serotonin reuptake inhibition.
Signs of serotonin syndrome.
Agitation, tremor, hyperthermia, rigidity, myoclonus.
Avoid; washout of at least 14 days between drugs.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=374af2a7-d994-40bd-a86a-cd9038d0b72c ; approved Sertraline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61835f25-bfe4-49ac-9dbf-3d6387866e78
High risk of serotonin syndrome and seizures with Linezolid and Tramadol.
Tramadol increases synaptic serotonin (reuptake blockade) and lowers the seizure threshold; linezolid inhibits monoamine oxidase. The combination can precipitate serotonin syndrome and seizures, both potentially severe; the approved tramadol label contraindicates use with MAO inhibitors (linezolid acts as one). Avoid the combination whenever possible; if clinically indispensable, use the lowest effective dose, monitor serotonergic and neurological symptoms and discontinue at any warning sign.
Linezolid (MAO inhibitor) + tramadol: risk of serotonin syndrome and seizures. Avoid the combination; monitor serotonergic and neurological symptoms.
MAO inhibition (linezolid) plus tramadol serotonergic action and low seizure threshold.
Serotonergic and neurological signs.
Seizures, confusion, hyperthermia, myoclonus.
Avoid; choose an alternative analgesic (e.g. paracetamol or a non-serotonergic opioid).
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=374af2a7-d994-40bd-a86a-cd9038d0b72c ; approved Tramadol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=552955e6-2bb3-8755-e063-6394a90ab21c
Beer and wine contain tyramine and should be avoided during linezolid treatment.
Avoid beer, wine and fermented drinks during treatment.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90dd8c13-c428-4472-91e5-5b1fcdc4fce3
Linezolid inhibits monoamine oxidase (MAO-A); tyramine-rich foods (aged cheese, cured meats, red wine, sauerkraut, broad beans) can trigger a hypertensive crisis.
Avoid tyramine-rich foods during and up to 2 weeks after treatment.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90dd8c13-c428-4472-91e5-5b1fcdc4fce3
Linezolid causes myelosuppression (anaemia, leucopenia, thrombocytopenia), especially with prolonged courses or in patients with prior marrow depression.
Monitor the blood count weekly in courses longer than 2 weeks.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90dd8c13-c428-4472-91e5-5b1fcdc4fce3
Linezolid inhibits monoamine oxidase and can cause significant blood pressure increases in patients with uncontrolled hypertension.
Use with caution and monitor blood pressure during treatment.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90dd8c13-c428-4472-91e5-5b1fcdc4fce3
Human data are limited; linezolid should be used in pregnancy only if the benefit justifies the risk.
Use only if no safer alternative exists.
Excreted into breast milk; avoid while breastfeeding or use with caution.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Linezolid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90dd8c13-c428-4472-91e5-5b1fcdc4fce3
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bacteriostatic oxazolidinone that inhibits bacterial protein synthesis, active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, streptococci and vancomycin-resistant enterococci (VRE).
Linezolid binds to the bacterial 50S ribosomal subunit (P site), preventing the formation of the 70S initiation complex — blocking protein synthesis at a step earlier than macrolides and aminoglycosides. This distinct mechanism explains the lack of cross-resistance with other classes.
Linezolid is extensively absorbed after oral dosing, with an absolute bioavailability of ~100% and peak plasma concentrations 1–2 hours after dosing. Food delays the peak (1.5 → 2.2 hours) and decreases Cmax ~17%, without changing total exposure. Plasma protein binding is ~31% and the steady-state volume of distribution is 40–50 L.
Linezolid is metabolised primarily by oxidation of the morpholine ring, producing two inactive metabolites (metabolite A, aminoethoxyacetic acid, and metabolite B, hydroxyethyl glycine). CYP450 metabolism is minimal; nonrenal clearance accounts for ~65% of total clearance.
The elimination half-life is ~4.3–5.4 hours (5.2 hours for 400 mg; 4.26–5.4 hours for 600 mg). At steady state, ~30% of the dose appears in urine as linezolid, 40% as metabolite B and 10% as metabolite A; virtually none appears unchanged in faeces.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
