Dosing and uses of Zyvox (linezolid)
Adult dosage forms and strengths
injectable solution
- 2mg/mL (100mL, 300mL infusion bags)
oral suspension
- 100mg/5mL
tablet
- 600mg
Vancomycin-Resistant Enterococcal Infections
600 mg PO/IV q12hr for 14-28 days
Complicated Skin & Skin Structure Infections
600 mg PO/IV q12hr for 10-14 days
Uncomplicated Skin & Skin Structure Infections
400-600 mg PO q12hr for 10-14 days
Community-Acquired Pneumonia (Including Concurrent Bacteremia)
600 mg PO/IV q12hr for 10-14 days
Nosocomial Pneumonia
600 mg PO/IV q12hr for 10-14 days
Methicillin-Resistant Staphylococcal Infections
600 mg PO/IV q12hr
Methicillin-Susceptible Staphylococcus Aureus
600 mg PO/IV q12hr for 10-14 days
Dosing Considerations
Monitor: CBC count qWeek
Pediatric dosage forms and strengths
injectable solution
- 2mg/mL (100mL, 300mL infusion bags)
oral suspension
- 100mg/5mL
tablet
- 600mg
Complicated Skin & Skin Structure Infections
<12 years: 10 mg/kg PO/IV q8hr for 10-14 days
≥12 years: 600 mg PO/IV q12hr for 10-14 days
Uncomplicated Skin & Skin Structure Infections
<5 years: 10 mg/kg PO q8hr for 10-14 days
5-12 years: 10 mg/kg PO q12hr for 10-14 days
>12 years: 600 mg PO q12hr for 10-14 days
Pneumonia
<12 years: 10 mg/kg PO/IV q8hr for 10-14 days
≥12 years: 600 mg PO/IV q12hr for 10-14 days
Vancomycin-Resistant Enterococcal Infections
<12 years: 10 mg/kg PO/IV q8hr for 14-28 days
≥12 years: 600 mg PO/IV q12hr for 14-28 days
Dosing Considerations
Monitor: CBC count qWeek
Zyvox (linezolid) adverse (side) effects
>10%
Pediatrics
- Diarrhea (7.8-10.8%)
1-10%
Headache (5.7-8.8%)
Diarrhea (8.2-8.3%)
Nausea (5.1-6.6%)
Vomiting (2-4.3%)
Dizziness (1.8-2.6%)
Rash (1.1-2.3%)
Vaginal moniliasis (1.1-1.8%)
Taste alteration (1-1.8%)
Oral moniliasis (0.5-1.7%)
Abnormal LFTs (0.4-1.6%)
Fungal infection (0.3-1.5%)
Localized abdominal pain (1.2-1.3%)
Tongue discoloration (0.3-1.3%)
Generalized abdominal pain (0.9-1.2%)
Pediatrics
- Vomiting (2.9-9.4%)
- Headache (0.9-6.5%)
- Anemia (5.6%)
- Thrombocytopenia (4.7%)
- Nausea (1.9-3.7%)
- Generalized abdominal pain (0.9-2.4%)
- Localized abdominal pain (0.5-2.4%)
- Loose stools (1.6-2.3%)
- Eosinophilia (0.4-1.9%)
- Pruritus, other than application site (0.8-1.4%)
- Vertigo (1.2%)
<1%
Lactic acidosis
Myelosuppression
Peripheral neuropathy
Disorder of optic nerve
Serotonin syndrome
Postmarketing Reports
Superficial tooth discoloration
Superficial tongue discoloration
Warnings
Contraindications
Hypersensitivity
Within 14 days of taking MAO inhibitor
Cautions
Use caution in patients with pheochromocytoma, concurrent apraclonidine, brimonidine, uncontrolled hypertension, thyrotoxicosis, carcinoid syndrome, diabetes mellitus, or seizure disorders
Use oral suspension with caution in phenylketonuria (contains phenylalanine)
Not approved for gram-negative bacteria or for catheter-related infections; clinical study showed higher mortality rate with linezolid than with other antibiotics for these conditions
Monitor for myelosuppression; consider discontinuation in patients who develop or have worsening myelosuppression
Evaluate for clostridium difficile if diarrhea occurs
Peripheral and optic neuropathy reported, especially in patients given extended courses of therapy >28 days
May cause hypoglycemia; monitor blood glucose levels
Lactic acidosis reported with use; immediately evaluate patients who develop recurrent unexplained acidosis with nausea and vomiting
Superinfection may develop
Serotonin syndrome
- Avoid coadministration with serotonergic psychiatric drugs (eg, SSRIs, SNRIs, TCAs, MAOIs) unless indicated for life-threatening or urgent infections (eg, vancomycin-resistant enterococcal infections, nosocomial pneumonia, complicated skin and skin structure infections such as methicillin-resistant S aureus), due to increased risk of serotonin syndrome; linezolid may increase serotonin CNS levels by MAO-A inhibition
- If linezolid must be administered to a patient currently taking a serotonergic drug, stop serotonergic drug immediately and monitor for CNS toxicity; serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring (5 weeks if fluoxetine was taken), whichever comes first; serotonergic psychiatric medications should be stopped at least 2 weeks in advance of linezolid therapy; fluoxetine should be stopped at least 5 weeks in advance due to longer half-life
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zyvox (linezolid)
Mechanism of action
Binds to bacterial 23S rRNA of the 50S subunit to prevent protein translation; also elicits nonselective MAO inhibition
Absorption
Rapid and extensive
Bioavailability: 100%
Peak plasma time: 1-2 hr
Distribution
Protein bound: 31%
Vd: 40-50 L
Metabolism
Hepatic via oxidation of the morpholine ring, resulting in 2 inactive metabolites (aminoethoxyacetic acid, hydroxyethyl glycine); does not involve CYp
Elimination
Half-life: 4-5 hr (adults); 1.5-3hr
Clearance: Nonrenal (65% of total clearance)
Excretion: Urine (80% of administered dose [30% unchanged, 50% metabolites]); feces (9% [metabolites])
Administration
IV Incompatibilities
Additive: Kanamycin, phenytoin, ceftriaxone, erythromycin lactobionate, TMP-SMX
Syringe: Ampicillin
Y-site: Ampho B, chlorpromazine, diazepam, pentamidine, phenytoin
IV Compatibilities
Additive: Aztreonam, cefazolin, ceftazidime, ciprofloxacin, gentamicin, levofloxacin, ofloxacin, piperacillin, tobramycin
Y-site: Acyclovir, alfentanil, amikacin, aminophylline, ampicillin, aztreonam, bretylium, buprenorphine, butorphanol, Ca-gluconate, cefazolin, cefoperazone, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dexamethasone Na-phosphate, dexmetedomidine, digoxin, diphenhydramine, dobutamine, dopamine, doxorubicin, doxycycline, droperidol, enalaprilat, esmolol, etoposide PO4, famotidine, fenoldopam, fluconazole, fluorouracil, furosemide, ganciclovir, gemcitabine, gentamycin, granisetron, haloperidol, heparin, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, ifosfamide, imipenem-cilastatin, labetalol, leucovorin, lidocaine, lorazepam, magnesium sulfate, mannitol, meperidine, meropenem, mesna, methotrexate, methylprednisolone, metoclopramide, metronidazole, midazolam, minocycline, mitoxantrone, morphine sulfate, nalbuphine, nicardipine, naloxone, nitroglycerin, ofloxacin, ondansetron, paclitaxel, pentobarbital, piperacillin, KCl, prochlorperazine, promethazine, propranolol, ranitidine, remifentanil, Na-bicarbonate, sufentanil, theophylline, ticarcillin, tobramycin, vancomycin, vecuronium, verapamil, vincristine, zidovudine
IV Preparation
Injection is supplied as a single-use, ready-to-use infusion bag; inspect for particulate matter and minute leaks in bag
Infusion should be administered over 30-120 min
Use reconstituted suspension within 21 days
Storage
Store at 25°C (77°F)
Protect from light
Keep infusion bags in overwrap until ready to use
Protect infusion bags from freezing
