What are the contraindications for linezolid (oxazolidinone antibiotic)?

Contraindications for Linezolid

Linezolid is absolutely contraindicated in patients with known hypersensitivity to the drug, those taking MAO inhibitors or serotonergic agents, patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and those with bipolar depression, schizophrenia, acute confusional states, or who are breastfeeding. 1, 2

Absolute Contraindications

Hypersensitivity

• Known hypersensitivity to linezolid or any product components is an absolute contraindication 1

Psychiatric Conditions

• Bipolar depression, schizophrenia, or acute confusional states are absolute contraindications due to linezolid's MAO inhibitor properties 2

Drug Interactions - MAO Inhibitors and Serotonergic Agents

• Concurrent use with MAO inhibitors (phenelzine, isocarboxazid) or within two weeks of discontinuing such agents is absolutely contraindicated 1, 2
• Serotonergic agents including SSRIs, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, and buspirone are contraindicated unless patients can be carefully observed for serotonin syndrome 1, 2
• The risk of serious CNS reactions including serotonin syndrome makes these combinations particularly dangerous 2

Cardiovascular and Endocrine Conditions

• Uncontrolled hypertension is an absolute contraindication unless blood pressure can be monitored 1, 2
• Pheochromocytoma is contraindicated due to risk of hypertensive crisis 1, 2
• Thyrotoxicosis is contraindicated due to increased risk of adverse reactions 1, 2

Sympathomimetic and Vasopressor Agents

• Unless blood pressure monitoring is available, linezolid should not be used with directly or indirectly acting sympathomimetic agents (pseudoephedrine), vasopressive agents (epinephrine, norepinephrine), or dopaminergic agents (dopamine, dobutamine) 1

Breastfeeding

• Breastfeeding is an absolute contraindication to linezolid use 2

Carcinoid Syndrome

• Patients with carcinoid syndrome should not receive linezolid unless carefully observed for serotonin syndrome 1

Relative Contraindications Requiring Enhanced Caution

Pregnancy

• Linezolid should be used with caution in pregnancy, requiring careful risk-benefit assessment 2

Neurological Conditions

• Patients with epilepsy or history of seizures require enhanced monitoring, as linezolid increases the risk of convulsions 2

Renal Impairment

• Use with caution in patients with renal impairment, as metabolites may accumulate 2
• In severe renal impairment requiring hemodialysis, exposure to metabolites increases 7-8 fold 3

Hepatic Impairment

• Use with caution in patients with liver disease, with close monitoring recommended 2

Pre-existing Anemia

• Pre-existing anemia is a major risk factor for developing severe linezolid-induced anemia, though not an absolute contraindication if the drug is essential 4, 5
• Strict clinical monitoring is mandatory when linezolid must be used in anemic patients 4

Pediatric Considerations

• Children under 10 years of age are particularly susceptible to myelosuppression at standard dosing (10 mg/kg twice daily) 2, 4

Important Dietary Restriction

• Tyramine-rich foods should be avoided during treatment due to linezolid's MAO inhibitor properties 2, 1
• Large amounts of tyramine-containing foods can precipitate hypertensive crisis 2

Critical Clinical Pitfall

The most commonly overlooked contraindication in general medical and surgical settings is the interaction with SSRIs and other serotonergic agents, as linezolid functions as an MAOI "in disguise" 6. Practitioners unfamiliar with MAOI complications may unwittingly precipitate hypertensive crisis or serotonin syndrome when prescribing linezolid to patients on antidepressants 6.