Usage
Linezolid is an oxazolidinone-class antibiotic prescribed for the treatment of infections caused by susceptible Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and penicillin-resistant Streptococcus pneumoniae. It is indicated for nosocomial and community-acquired pneumonia, complicated and uncomplicated skin and soft tissue infections, and vancomycin-resistant enterococcal infections. Its pharmacological classification is antibiotic.
Linezolid inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S bacterial ribosome subunit, preventing formation of the 70S initiation complex, which is essential for bacterial translation and protein synthesis. This mechanism is unique, making it effective against bacteria resistant to other antibiotic classes.
Alternate Names
Linezolid is also known by the brand name Zyvox.
How It Works
Pharmacodynamics: Linezolid exerts its bactericidal effect by preventing the formation of the functional 70S ribosomal initiation complex, thereby inhibiting protein synthesis. It binds to a site on the bacterial 23S rRNA of the 50S subunit. This specific action differs from other protein synthesis inhibitors and contributes to its effectiveness against resistant strains.
Pharmacokinetics: Linezolid demonstrates 100% oral bioavailability, enabling oral and intravenous administration. It is metabolized non-enzymatically in the liver, primarily via oxidation, producing two inactive metabolites. Elimination occurs through both renal (30%) and hepatic (70%) pathways. The elimination half-life is approximately 4-6 hours in adults.
Mode of Action: Linezolid’s mechanism of action involves binding to the bacterial 23S rRNA of the 50S ribosomal subunit. This binding inhibits the formation of the 70S initiation complex, composed of the 30S and 50S subunits, effectively halting protein synthesis. It does not bind to mammalian ribosomes, contributing to its selective toxicity against bacterial cells.
Elimination Pathways: Linezolid is primarily eliminated through hepatic metabolism, with a smaller portion excreted renally. It is mostly cleared through non-renal mechanisms, thus dosage adjustments are not required in patients with renal impairment.
Dosage
Standard Dosage
Adults:
The standard adult dosage for most infections is 600 mg every 12 hours, administered orally or intravenously, for a duration of 10-28 days, depending on the infection type and severity.
Children:
- Neonates (<7 days old, <34 weeks gestation): 10 mg/kg every 12 hours increasing to 10mg/kg every 8 hours or earlier if the clinical response is suboptimal.
- Infants and Children (≥7 days old, <12 years): 10 mg/kg every 8 hours, not to exceed 600 mg per dose.
- Children (≥12 years): 600 mg every 12 hours.
Pediatric safety considerations include the potential for myelosuppression. Close monitoring of complete blood counts is essential.
Special Cases:
- Elderly Patients: No dose adjustment is generally required, however, careful monitoring for adverse events is recommended, particularly in those older than 85 years of age due to increased risk of overexposure.
- Patients with Renal Impairment: No dose adjustment is required. However, caution is advised for severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild to moderate impairment. Caution is advised for severe hepatic dysfunction.
- Patients with Comorbid Conditions: Caution is warranted in patients with diabetes, uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, thyrotoxicosis, or seizure disorders. Monitoring for potential drug interactions is crucial for patients taking sympathomimetics, vasopressors, or dopaminergic agents.
Clinical Use Cases:
Dosage recommendations in various clinical settings generally align with the standard adult and pediatric dosages. The route of administration (oral or IV) depends on the patient’s condition and ability to tolerate oral medication. There are no specific dosing recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments:
Dose adjustments are generally not necessary for renal or hepatic dysfunction. For prolonged use (over 28 days), monitor closely for myelosuppression and consider dose reduction or discontinuation.
Side Effects
Common Side Effects:
Diarrhea, headache, nausea, vomiting, taste perversion (metallic taste), rash, dizziness.
Rare but Serious Side Effects:
Myelosuppression (thrombocytopenia, anemia, leukopenia), serotonin syndrome, lactic acidosis, peripheral neuropathy, optic neuropathy, seizures, angioedema, Clostridium difficile-associated diarrhea, Stevens-Johnson syndrome.
Long-Term Effects:
Peripheral neuropathy and optic neuritis (especially with courses over 28 days), prolonged myelosuppression.
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis), serotonin syndrome (high fever, confusion, muscle rigidity), lactic acidosis (muscle weakness, fatigue, rapid breathing), severe thrombocytopenia (easy bruising or bleeding).
Contraindications
Hypersensitivity to linezolid, concurrent use of MAO inhibitors or within two weeks of MAOI discontinuation.
Drug Interactions
Serotonergic drugs (SSRIs, SNRIs, tricyclic antidepressants, MAOIs), sympathomimetics (pseudoephedrine), vasopressors (epinephrine, norepinephrine), dopaminergic agents (dopamine, dobutamine), tyramine-rich foods. Linezolid may also interact with certain medications metabolized by CYP450 enzymes. Concomitant use with pethidine is generally avoided.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Animal studies have shown potential adverse effects. Use only if the potential benefit outweighs the risk to the fetus. Linezolid is excreted in breast milk. Breastfeeding is generally not recommended. Monitor the nursing infant for adverse effects.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
- Side Effects: Diarrhea, headache, nausea, myelosuppression, serotonin syndrome, peripheral/optic neuropathy.
- Contraindications: Hypersensitivity, concurrent MAOI use.
- Drug Interactions: Serotonergic drugs, sympathomimetics, vasopressors.
- Pregnancy & Breastfeeding: Category C; not recommended during breastfeeding.
- Dosage: Adults: 600 mg every 12 hours; Children: 10 mg/kg every 8 hours (under 12 years) or every 12 hours for those between 5 to 12 years old.
- Monitoring Parameters: Complete blood count (weekly), liver function tests, renal function tests, blood pressure.
Popular Combinations
No popular drug combinations are typically recommended for synergistic benefits. Linezolid is generally used as monotherapy.
Precautions
- General Precautions: Assess renal and hepatic function, monitor blood counts, monitor blood pressure.
- Specific Populations: Monitor pregnant women closely; breastfeeding is not recommended. Monitor pediatric and elderly patients for adverse reactions.
- Lifestyle Considerations: Counsel patients to avoid tyramine-rich foods. No restrictions on alcohol are explicitly stated in the reviewed data.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Linezolid?
A: Adults: 600 mg every 12 hours. Children (<12 years): 10 mg/kg every 8 hours. Children (≥12 years): 600 mg every 12 hours.
Q2: What are the most common side effects of Linezolid?
A: Diarrhea, headache, nausea, vomiting, and changes in taste perception.
A: Serotonin syndrome (high fever, confusion, muscle rigidity), myelosuppression (decreased blood cell counts), lactic acidosis (muscle weakness, fatigue), allergic reactions, and vision changes.
Q4: How does Linezolid work against bacterial infections?
A: It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing the formation of the 70S initiation complex, which is essential for bacterial translation.
Q5: Can Linezolid be used during pregnancy?
A: It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as Pregnancy Category C.
Q6: Is Linezolid safe to use while breastfeeding?
A: Linezolid is excreted in breast milk and might cause diarrhea and vomiting in infants. Breastfeeding is not generally recommended during Linezolid therapy.
Q7: What are the contraindications for using Linezolid?
A: Known hypersensitivity to Linezolid and concurrent use of MAO inhibitors. Patients with uncontrolled hypertension should be closely monitored for blood pressure elevations.
Q8: Does Linezolid interact with other medications?
A: Yes, it interacts with serotonergic drugs, sympathomimetics, vasopressors, and tyramine-containing foods.
Q9: Are there any specific monitoring parameters for patients on Linezolid?
A: Yes. Complete blood counts should be monitored weekly due to the risk of myelosuppression. Liver and renal function, as well as blood pressure, should also be monitored.
Q10: What is the maximum duration of treatment for Linezolid?
A: The maximum recommended duration is generally 28 days. Longer courses may be considered, but with increased monitoring for potential adverse effects like myelosuppression and peripheral neuropathy.
