ZYVOX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYVOX (ZYVOX).
Linezolid inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing the formation of the 70S initiation complex. It is a bacteriostatic agent against most susceptible organisms.
| Metabolism | Linezolid is primarily metabolized by oxidation of the morpholine ring to form two inactive metabolites: aminoethoxyacetic acid (major) and hydroxyethylglycine (minor). Metabolism is independent of cytochrome P450 (CYP) enzymes, mainly mediated by myeloperoxidase. |
| Excretion | Approximately 30% of a dose appears unchanged in urine within 24 hours, with 50% as oxidative metabolites; 10% is excreted fecally. Renal clearance accounts for ~40% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 4-5 hours in healthy adults, with no significant accumulation after multiple doses given twice daily. |
| Protein binding | Approximately 31% bound to serum proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution at steady state is approximately 0.5 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 100%, allowing for intravenous to oral switch. |
| Onset of Action | Intravenous: clinical response typically within 24-48 hours. Oral: similar onset due to high bioavailability. |
| Duration of Action | Antibacterial activity persists for the dosing interval (12 hours), supporting twice-daily dosing. Duration of therapy is typically 10-14 days depending on infection. |
| Molecular Weight | 337.35 |
600 mg IV or orally every 12 hours for 10-14 days; for uncomplicated skin infections, 400 mg orally every 12 hours.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for any degree of renal impairment; two primary metabolites may accumulate but are not clinically relevant. For patients on hemodialysis, administer after dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C), use with caution. |
| Pediatric use | For infections: <5 years: 10 mg/kg IV/orally every 8 hours; 5-11 years: 10 mg/kg IV/orally every 12 hours; ≥12 years: 600 mg IV/orally every 12 hours. Maximum 600 mg/dose. |
| Geriatric use | No specific dose adjustment based on age; monitor for myelosuppression, peripheral and optic neuropathy, and serotonin syndrome when coadministered with serotonergic agents. |
| 1st trimester | Animal studies have shown reproductive toxicity. There are no adequate and well-controlled studies in pregnant women. ZYVOX should be used during the first trimester only if the potential benefit justifies the potential risk to the fetus. |
| 2nd trimester | Safety data in the second trimester are limited. Use only if clearly needed and potential benefit outweighs risk. |
| 3rd trimester | Safety in third trimester not established. Maternal treatment near term may cause adverse effects in neonate (e.g., myelosuppression). Use only if benefit clearly outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for ZYVOX (ZYVOX).
| Placental transfer | Linezolid crosses the placenta in animal studies; likely in humans. Plasma concentrations in cord blood may approach maternal levels. |
| Breastfeeding | Linezolid is excreted in human milk. Caution should be exercised when ZYVOX is administered to a breastfeeding woman. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for the drug and any potential adverse effects on the breastfed child. |
■ FDA Black Box Warning
ZYVOX is not approved for the treatment of catheter-related bloodstream infections or catheter-site infections. ZYVOX has no activity against Gram-negative pathogens. If Gram-negative infection is documented or suspected, appropriate Gram-negative therapy should be initiated immediately.
| Serious Effects |
Known hypersensitivity to linezolid or any component of the formulationUncontrolled hypertensionPheochromocytomaCarcinoid syndromeThyrotoxicosisConcurrent use of MAOIs or within 2 weeks of MAOI therapyConcurrent use of serotonergic agents (unless urgent and under close monitoring) – contraindicated when there is a high risk for serotonin syndrome
| Precautions | Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) – monitor complete blood counts weekly, Peripheral and optic neuropathy – discontinue if symptoms occur, Lactic acidosis – monitor for unexplained acidosis, Serotonin syndrome – avoid concurrent use with serotonergic agents (e.g., SSRIs, SNRIs, MAOIs), Clostridioides difficile-associated diarrhea, Convulsions – use with caution in patients with seizure disorders, Hypertension – monitor blood pressure, especially with tyramine-rich foods |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, linezolid was not teratogenic in rats or rabbits at exposures up to 4 times the human exposure. However, linezolid crosses the placenta and can cause fetal harm due to inhibition of mitochondrial protein synthesis. Use in pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. |
| Fetal Monitoring | Monitor for signs of myelosuppression (e.g., anemia, leukopenia, thrombocytopenia) with weekly complete blood counts. Monitor blood pressure due to potential for hypertensive reactions, especially in patients with uncontrolled hypertension, pheochromocytoma, or those on serotonergic agents. Monitor for serotonin syndrome when coadministered with serotonergic drugs. Fetal monitoring not specifically required but standard prenatal care should be maintained. |
| Fertility Effects | In animal studies, linezolid did not impair fertility in male or female rats at doses up to 4 times the human exposure. However, effects on human fertility have not been studied. No specific data on reproductive toxicity in humans. |
| Avoid tyramine-rich foods: aged cheeses (cheddar, blue cheese), cured meats (salami, pepperoni), fermented soy products (tofu, miso), sauerkraut, tap beer, red wine, and yeast extracts (Marmite). |
| Clinical Pearls | Monitor for myelosuppression with weekly CBCs, especially with therapy >2 weeks; linezolid is a reversible non-selective MAO inhibitor, avoid concurrent serotonergic drugs to prevent serotonin syndrome; reserve for vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) infections when other options are limited. |
| Patient Advice | Take with or without food; avoid high-tyramine foods (aged cheese, cured meats, fermented products) to prevent hypertensive crisis. · Report any signs of bleeding, easy bruising, or infection (fever, sore throat) immediately. · Complete full course as prescribed; do not skip doses. · Avoid alcohol and over-the-counter decongestants without consulting your doctor. · Contact your doctor if you develop vision changes, severe headache, or diarrhea. |