What are the adverse drug reactions (ADRs) associated with Zyvox (linezolid)?

Adverse Drug Reactions of Zyvox (Linezolid)

Most Common Adverse Effects

The most frequently reported adverse drug reactions with linezolid are gastrointestinal disturbances (diarrhea 8.3%, nausea 6.2%, vomiting 3.7%), headache (6.5%), and insomnia (2.5%), with 85% of adverse events being mild to moderate in intensity. 1

Gastrointestinal Effects

• Diarrhea occurs in 2.8% to 11.0% of patients across studies 1
• Nausea affects 3.4% to 9.6% of patients 1
• Vomiting is reported in 3.7% of patients 1
• Constipation (2.2%), dyspepsia, and localized abdominal pain are also documented 1
• Clostridium difficile-related complications are uncommon 2

Neurological Effects

• Headache occurs in 0.5% to 11.3% of patients 1
• Dizziness affects 2.0% of patients 1
• Insomnia is reported in 2.5% of patients 1

Other Common Effects

• Oral and vaginal moniliasis 1
• Rash (2.0%) 1
• Fever (1.6%) 1
• Tongue discoloration 1
• Taste alteration (1.8% in uncomplicated skin infections) 1

Serious Hematologic Toxicity

Linezolid causes significant myelosuppression including thrombocytopenia, anemia, and neutropenia, which can occur rapidly after treatment initiation and requires weekly complete blood count monitoring, especially for treatment durations exceeding 2 weeks. 3

Thrombocytopenia

• Reversible thrombocytopenia occurred in 2.4% of linezolid-treated patients versus 1.5% with comparators (P = 0.066) 2
• Risk increases with treatment duration ≥2 weeks 2
• More common at doses >600 mg/day 3

Anemia and Neutropenia

• Severe anemia is particularly common in patients with pre-existing anemia 3, 4
• Neutropenia can affect any cell line and may occur quickly after starting treatment 3
• Children <10 years of age are particularly susceptible to myelosuppression at the recommended dose of 10 mg/kg twice daily 3

Monitoring Requirements

• Weekly complete blood counts are mandatory for the first 2 months, then monthly if stable 3
• If WBC drops to 2000-3000/mm³ OR ANC drops to 1000-1500/mm³: monitor daily for infection; counts should recover spontaneously after discontinuation 3
• If WBC drops below 2000/mm³ OR ANC drops below 1000/mm³: consider hematology consultation and monitor daily for infection 3

Serious Neurological Toxicity

Peripheral neuropathy and optic neuritis are potentially irreversible adverse effects that typically manifest after 12-20 weeks of treatment and may only be partially reversible even after drug discontinuation. 3

Peripheral Neuropathy

• Occurs after 12-20 weeks of treatment 3
• May be irreversible or only partially reversible 3
• Monthly screening for peripheral neuropathy symptoms is required 3

Optic Neuritis

• Typically occurs after 12-20 weeks of treatment 3
• May be irreversible or only partially reversible 3
• Monthly visual acuity and color discrimination testing are recommended 3
• If optic neuritis occurs, linezolid may be restarted once vision normalizes, often at a reduced dose of 300 mg daily 3

Metabolic and Mitochondrial Toxicity

Linezolid inhibits mitochondrial protein synthesis, leading to hyperlactatemia and lactic acidosis with long-term use, requiring periodic lactate monitoring. 3

Lactic Acidosis

• Results from mitochondrial protein synthesis inhibition 3
• Risk increases with concurrent use of stavudine or zidovudine 3
• Obtain arterial blood gas if venous lactate is abnormal 3
• Sodium bicarbonate therapy is not recommended for pH ≥7.15 3

Hypoglycemia

• Case reports document hypoglycemia with extended duration therapy 5
• Periodic monitoring of blood glucose is suggested for extended therapy 5

Pancreatitis

• Rare but documented with extended duration therapy 5

Serious Drug Interactions and Contraindications

Linezolid is a reversible monoamine oxidase inhibitor and must not be co-administered with serotonergic agents or MAO inhibitors due to risk of life-threatening serotonin syndrome. 3, 6

Serotonin Syndrome

• Occurs with concurrent selective serotonin reuptake inhibitors (26 of 43 patients in postmarketing reports) 6
• Can lead to serious CNS reactions including neuroleptic malignant syndrome-like reactions 3
• 13 of 29 reported cases required intervention to prevent permanent impairment or hospitalization 6
• Absolute contraindication to concurrent use with MAO inhibitors or serotonergic agents 3

Other Contraindications

• Uncontrolled hypertension 3
• Pheochromocytoma 3
• Thyrotoxicosis 3
• Tyramine-rich foods should be avoided during treatment 3

Dose-Dependent Toxicity

Reducing the daily dose from 1,200 mg to 600 mg per day is associated with significantly fewer adverse events (46.7% vs 74.5%) without compromising effectiveness. 3

• The 600 mg daily dose is significantly safer than 1,200 mg daily 3
• Reducing to 300 mg once daily may be considered if serious adverse effects develop 3
• Therapeutic drug monitoring is emphasized to reduce adverse events, with toxicity associated with trough levels >2.0 mg/L 3, 7

Pediatric-Specific Considerations

In hospitalized pediatric patients (birth through 11 years), mortality was 6.0% in the linezolid arm versus 3.0% in the vancomycin arm, though causality could not be established given severe underlying illness. 1

• Children <10 years are particularly susceptible to myelosuppression at recommended doses 3
• 83-99% of adverse events in pediatric trials were mild to moderate 1
• Diarrhea, loose stools, and vomiting are the most common adverse effects in children 2

Drug Discontinuation Rates

Drug-related adverse events leading to discontinuation occurred in 2.1-3.5% of patients, most commonly due to nausea, headache, diarrhea, and vomiting. 1