What are the potential adverse drug reactions (ADRs) of Zyvox (linezolid)?

Adverse Drug Reactions of Zyvox (Linezolid)

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

Common Adverse Reactions (>5% incidence)

The FDA-approved labeling identifies the most frequent adverse reactions 2, 3:

• Diarrhea (8.3% in adults, 7.8-10.8% in pediatrics) 2
• Headache (6.5% in adults) 2
• Nausea (6.2% in adults) 2
• Vomiting (3.7% in adults, higher in pediatrics at 6.4-9.4%) 2
• Anemia (particularly in pediatric patients at 5.6%) 2

These reactions are typically mild to moderate in intensity and of limited duration 4, 5.

Hematologic Toxicity (Critical Monitoring Required)

Myelosuppression represents the most significant early adverse effect and requires weekly complete blood count monitoring, especially beyond 2 weeks of therapy. 1, 4

Specific Hematologic Effects:

• Thrombocytopenia occurs in approximately 2.4% of patients, with reversibility upon discontinuation 4
• Anemia is particularly severe in patients with pre-existing anemia 6, 7
• Neutropenia can affect any cell line and may occur quickly after treatment initiation 1
• Dose-dependent effect: 600 mg daily causes adverse events in 46.7% versus 74.5% at 1200 mg daily 1

High-Risk Populations:

• Children <10 years of age are particularly susceptible to myelosuppression at the recommended dose of 10 mg/kg twice daily 1, 7
• Patients with pre-existing anemia face higher risk of severe anemia 6, 7
• Patients with severe renal impairment or moderate to severe hepatic impairment experience thrombocytopenia more frequently 3

Neurological Adverse Effects (Late-Onset, Potentially Irreversible)

Peripheral neuropathy and optic neuritis typically occur after 12-20 weeks of treatment and may be irreversible or only partially reversible. 1

Management Approach:

• Monthly visual acuity and color discrimination testing are required to monitor for optic neuritis 1
• Monthly screening for peripheral neuropathy symptoms is mandatory 1
• If optic neuritis occurs, linezolid may be restarted once vision normalizes, often at a reduced dose of 300 mg daily 1
• Prompt ophthalmologic evaluation is recommended if patients experience visual impairment symptoms 3

Metabolic Disturbances

Lactic Acidosis:

• Linezolid inhibits mitochondrial protein synthesis, causing hyperlactatemia and lactic acidosis with long-term use 1, 8
• Lactate levels should be monitored periodically during extended therapy 1
• Risk increases with concurrent use of stavudine or zidovudine 1
• Hemodialysis may be required for metabolic acidosis refractory to thiamine 8

Hypoglycemia:

• Postmarketing cases of symptomatic hypoglycemia reported in diabetic patients receiving insulin or oral hypoglycemic agents 3
• Periodic blood glucose monitoring recommended during extended therapy 8

Hyponatremia/SIADH:

• Monitor serum sodium levels regularly in patients at risk 3

Serious Drug Interactions and Contraindications

Linezolid is absolutely contraindicated with MAO inhibitors or serotonergic agents due to risk of serotonin syndrome and serious CNS reactions. 1

Absolute Contraindications:

• Concurrent use with MAO inhibitors or serotonergic agents 1, 3
• Uncontrolled hypertension 1
• Pheochromocytoma 1
• Thyrotoxicosis 1

Dietary Restrictions:

• Tyramine-rich foods must be avoided during treatment due to linezolid's weak, reversible MAO inhibitor properties 1, 4, 9

Additional Adverse Reactions

• Gastrointestinal: Constipation (2.2%), oral moniliasis, vaginal moniliasis 2
• Dermatologic: Rash (2.0%), pruritus, tongue discoloration 2
• Cardiovascular: Hypertension (monitor blood pressure) 3
• Hepatic: Abnormal liver function tests (1.3%) 2
• Infectious: Clostridioides difficile-associated diarrhea (evaluate if diarrhea occurs) 3
• Pancreatic: Pancreatitis (rare, reported with extended therapy) 10, 8

Critical Monitoring Algorithm

First 2 Months:

• Weekly complete blood counts to detect early myelosuppression 1, 4
• Monitor for infection if WBC drops to 2000-3000/mm³ or ANC drops to 1000-1500/mm³ 1
• Consider hematology consultation if WBC drops below 2000/mm³ or ANC drops below 1000/mm³ 1

After 2 Months (if stable):

• Monthly complete blood counts 1
• Monthly visual acuity and color discrimination testing 1
• Monthly peripheral neuropathy screening 1
• Periodic lactate monitoring during extended therapy 1

Dose Adjustment Strategy:

• Consider dose reduction from 600 mg to 300 mg once daily if serious adverse effects develop 1
• Over half of tuberculosis patients required dose reduction to 300 mg due to myelosuppression or neurotoxicity 7
• Discontinue if worsening myelosuppression occurs despite dose reduction 3

Pediatric-Specific Considerations

• Mortality was 6.0% in linezolid-treated hospitalized pediatric patients versus 3.0% with vancomycin, though causality could not be established given severe underlying illness 2
• Most common pediatric adverse events: fever (14.1%), diarrhea (10.8%), vomiting (9.4%), and anemia (5.6%) 2
• Thrombocytopenia occurred in 4.7% of pediatric patients 2