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linezolid (Zyvox)

Indications: - bacterial infections due to susceptible organisms - resistant gram positive organisms - vancomycin-resistant enterococci - methicillin-resistant Staphylococcus aureus - pneumonia due to resistant organism(s) - community-acquired pneumonia - nosocomial pneumonia - complicated skin infections & skin structure infections - diabetic foot ulcer infections without osteomyelitis [7] - osteomyelitis - empiric treatment for fever of unknown origin [9] Contraindications: Caution: 1) uncontrolled hypertension 2) pheochromocytoma 3) carcinoid syndrome 4) untreated hyperthyroidism Dosage: 1) IV or oral dosing 2) 600 mg every 12 hours 3) infuse IV over 30-120 minutes Infusion: 200 mg (100 mL); 400 mg (200 mL); 600 mg (300 mL) Suspension: 20 mg/mL (150 mL), contains 20 mg of phenylalanine per tsp Tabs: 400 mg, 600 mg Dosage adjustment in renal failure: no special recommendations Pharmacokinetics: 1) bioavailability 100% 2) rapid absorption 3) protein binding 31% 4) volume of distribution 40-50 L 5) hepatic oxidation NOT involving cyt P450 a) morpholine ring is oxidized b) 2 inactive metabolites 1] aminoethoxyacetic acid 2] hydroxyethyl glycine 6) elimination 1/2life is 4-6 hours 7) 30% eliminated unchanged in the urine Monitor: - complete blood count (CBC) weekly: - neutrophil count for neutropenia - platelet count for thrombocytopenia [7] - eye exam if treatment for >= 3 months Adverse effects: 1) gastrointestinal a) diarrhea (most common), constipation b) nausea/vomiting c) tongue discoloration, oral moniliasis d) localized abdominal pain, pancreatitis e) dyspepsia 2) central nervous system -> headache, insomnia, dizziness, fever 3) dermatologic -> rash, pruritus 4) hematologic - reversible myelosuppression (after 2 weeks) - anemia, leukopenia, neutropenia, thrombocytopenia (10%) 5) cardiovascular: hypertension 6) genitourinary: vaginal moniliasis 7) hepatic: increased serum transaminases 8) renal: increased serum creatinine 9) fungal infections 10) Clostridium difficile infections 11) neuropathy after 4 weeks - optic neuropathy - decreased vision & color vision, visual field defects 12) lactic acidosis (type B) [7,8] - interferes with mitochondrial respiration [7] Drug interactions: 1) linezolid has mild monoamine oxidase (MAO) inhibitor properties & may interact with other MAO inhibitors 2) concurrent use with serotoninergic agents may result in serotonin syndrome a) selective serotonin re-uptake inhibitors (SSRIs) b) serotonin-norepinephrine re-uptake inhibitors (SNRIs) c) serotonin agonists 3) uncertain interactions a) tricyclic antidepressants (TCA) b) venlaxafine c) buspirone d) meperidine e) dextromethorphan f) lithium 4) avoid food (i.e. cheeses) & beverages (i.e. red wine) containing tyramine (hypertensive crisis) Mechanism of action: 1) inhibits bacterial protein synthesis by binding to bacterial 23S ribosomal RNA of the 50S subunit 2) this prevents formation of a functional 70S initiation complex 3) bacteriostatic against Enterococcus & Staphylococcus 4) bacteriocidal against most strains of Streptococcus Notes: Available for compasionate use (11/99) (800) 836-3535, Pharmacia & Upjohn

Interactions

drug interactions

General

oxazolidinone antibiotic

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 4-5 HOURS protein-binding 31% elimination by hemodialysis + <30%>

Database Correlations

PUBCHEM correlations

References

  1. The Prescriber's Letter, vol 6 #11, Nov 1999
  2. The Prescriber's Letter, vol 7 #5, May 2000
  3. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  4. Sanford Guide to antimicrobial therapy 2001
  5. Department of Veterans Affairs, VA National Formulary
  6. FDA Medwatch - 07/26/2011 Zyvox (linezolid): Drug Safety Communication - Serious CNS Reactions Possible When Given to Patients Taking Certain Psychiatric Medications http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm265479.htm
  7. Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
  8. Velez JC, Janech MG. A case of lactic acidosis induced by linezolid. Nat Rev Nephrol. 2010 Apr;6(4):236-42 PMID: 20348931
  9. Deprecated Reference