What are the side effects of linezolid?

Linezolid Side Effects

Linezolid causes significant hematologic toxicity (thrombocytopenia, anemia, neutropenia), neurological complications (peripheral neuropathy and optic neuritis), and metabolic disturbances (lactic acidosis), with myelosuppression occurring early in treatment and neurotoxicity typically manifesting after 12-20 weeks. 1

Hematologic Toxicity

Myelosuppression Profile

• All cell lines can be affected, with thrombocytopenia being most common, followed by anemia and neutropenia 1, 2
• Hematological toxicity can occur quickly after starting treatment, particularly within the first two weeks 3, 2
• Dose-dependent effect: 600 mg daily causes adverse events in 46.7% of patients versus 74.5% at 1200 mg daily 3, 2
• Risk factors include: elevated trough concentrations (>8 mg/L), renal impairment, low body weight, severe liver dysfunction, and pre-existing anemia 4, 5

Monitoring Requirements

• Weekly complete blood counts are mandatory for patients receiving linezolid longer than 2 weeks 1, 2
• Monthly monitoring is recommended for pediatric MDR-TB patients 2
• Discontinue linezolid if myelosuppression develops or worsens 1
• Counts typically rise toward pretreatment levels after discontinuation 1

Neurological Toxicity

Peripheral Neuropathy and Optic Neuritis

• These serious adverse effects typically occur after 12-20 weeks of treatment 3, 2
• May be irreversible or only partially reversible 2
• Monthly visual acuity and color discrimination testing are recommended 2
• Monthly screening for peripheral neuropathy symptoms is required 2
• If optic neuritis occurs, linezolid may be restarted once vision normalizes, often at a reduced dose of 300 mg daily 2

Metabolic and Mitochondrial Toxicity

Lactic Acidosis and Hyperlactatemia

• Linezolid inhibits mitochondrial protein synthesis, causing hyperlactatemia and lactic acidosis with long-term use 3, 2
• Lactate levels should be monitored periodically during extended therapy 2, 6
• Risk increases with concurrent use of stavudine or zidovudine 2
• If venous lactate is abnormal, obtain arterial blood gas 2

Hypoglycemia (Rare)

• Extremely rare but documented adverse effect, occurring in both diabetic and non-diabetic patients 7, 6
• Periodic blood glucose monitoring should be considered during extended therapy 6

Gastrointestinal Effects

• Diarrhea, nausea, and vomiting are common, typically mild to moderate in intensity 8, 4
• Clostridium difficile-associated diarrhea (CDAD) can occur and must be considered in all patients presenting with diarrhea following linezolid use 1

Drug Interactions and Contraindications

Absolute Contraindications

• Concurrent use with MAO inhibitors or serotonergic agents due to risk of serotonin syndrome 2
• Uncontrolled hypertension, pheochromocytoma, or thyrotoxicosis 2

Dietary Restrictions

• Tyramine-rich foods should be avoided during treatment 2
• Linezolid is a weak, reversible monoamine oxidase inhibitor 8

Special Populations

Pediatric Considerations

• Children <10 years of age are particularly susceptible to myelosuppression at the recommended dose of 10 mg/kg twice daily 3, 2, 5
• Adverse effects are more common in children, including diarrhea, loose stools, and vomiting 8

Patients with Pre-existing Anemia

• Pre-existing anemia is a major risk factor for developing severe linezolid-induced anemia 5
• Standard dosing (600 mg daily) should be used with strict clinical monitoring 5

Dosing Strategy to Minimize Toxicity

• 600 mg once daily is significantly safer than 1200 mg daily without compromising efficacy 3, 2, 5
• Reducing to 300 mg once daily may be considered if serious adverse effects develop 2
• Therapeutic drug monitoring is emphasized to reduce adverse events, with toxicity associated with trough levels >2.0 mg/L 3, 2

Critical Clinical Caveat

Linezolid has no activity against Gram-negative pathogens and should not be used for catheter-related bloodstream infections or when Gram-negative pathogens are documented or suspected 1. An imbalance in mortality was observed in patients with mixed or Gram-negative infections treated with linezolid 1.