linezolid (Zyvox)
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Indications
- bacterial infections due to susceptible organisms
- resistant gram positive organisms
- vancomycin-resistant enterococci
- methicillin-resistant Staphylococcus aureus
- pneumonia due to resistant organism(s)
- complicated skin infections & skin structure infections
- diabetic foot ulcer infections without osteomyelitis[7]
- osteomyelitis
- empiric treatment for fever of unknown origin[9]
Contraindications
Caution:
- uncontrolled hypertension
- pheochromocytoma
- carcinoid syndrome
- untreated hyperthyroidism
Dosage
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
- bioavailability 100%
- rapid absorption
- protein binding 31%
- volume of distribution 40-50 L
- hepatic oxidation NOT involving cyt P450
- morpholine ring is oxidized
- 2 inactive metabolites
- aminoethoxyacetic acid
- hydroxyethyl glycine
- elimination 1/2life is 4-6 hours
- 30% eliminated unchanged in the urine
elimination via liver
elimination via kidney
1/2life = 4-5 hours
protein binding = 31 %
elimination by hemodialysis = +
Monitor
- complete blood count (CBC) weekly:
- eye exam if treatment for >= 3 months
Adverse effects
- gastrointestinal
- diarrhea (most common), constipation
- nausea/vomiting
- tongue discoloration, oral moniliasis
- localized abdominal pain, pancreatitis
- dyspepsia
- central nervous system
- dermatologic
- hematologic
- reversible myelosuppression (after 2 weeks)
- anemia, leukopenia, neutropenia, thrombocytopenia (10%)
- reversible myelosuppression (after 2 weeks)
- cardiovascular: hypertension
- genitourinary: vaginal moniliasis
- hepatic: increased serum transaminases
- renal: increased serum creatinine
- fungal infections
- Clostridium difficile infections
- neuropathy after 4 weeks
- optic neuropathy
- decreased vision & color vision, visual field defects
- optic neuropathy
- lactic acidosis (type B)[7][8]
- interferes with mitochondrial respiration[7]
Drug interactions
- linezolid has mild monoamine oxidase (MAO) inhibitor properties & may interact with other MAO inhibitors
- concurrent use with serotoninergic agents may result in serotonin syndrome
- selective serotonin re-uptake inhibitors (SSRIs)
- serotonin-norepinephrine re-uptake inhibitors (SNRIs)
- serotonin agonists
- uncertain interactions
- avoid food (i.e. cheeses) & beverages (i.e. red wine) containing tyramine (hypertensive crisis)
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) of linezolid with SNRIs
- drug interaction(s) of linezolid with SSRIs
- drug interaction(s) of linezolid with serotonin agonists
- drug interaction(s) of antibiotics with warfarin
Mechanism of action
- inhibits bacterial protein synthesis by binding to bacterial 23S ribosomal RNA of the 50S subunit
- this prevents formation of a functional 70S initiation complex
- bacteriostatic against Enterococcus & Staphylococcus
- bacteriocidal against most strains of Streptococcus
Notes
Available for compasionate use (11/99) (800) 836-3535, Pharmacia & Upjohn
More general terms
References
- ↑ The Prescriber's Letter, vol 6 #11, Nov 1999
- ↑ The Prescriber's Letter, vol 7 #5, May 2000
- ↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ Sanford Guide to antimicrobial therapy 2001
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ 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
- ↑ 7.0 7.1 7.2 7.3 7.4 Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
- ↑ 8.0 8.1 Velez JC, Janech MG. A case of lactic acidosis induced by linezolid. Nat Rev Nephrol. 2010 Apr;6(4):236-42 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20348931
- ↑ 9.0 9.1 Deprecated Reference