Linezolid

Trade Names:Zyvox- Tablets 400 mg (sodium content is 1.95 mg per 400 mg tablet [0.1 mEq/tablet])- Tablets 600 mg (sodium content is 2.92 mg per 600 mg tablet [0.1 mEq/tablet])- Powder for oral suspension 100 mg per 5 mL (sodium content is 8.52 mg per 5 mL [0.4 mEq per 5 mL])- Injection 2 mg/mL (sodium content is 0.38 mg/mL [5 mEq per 300 mL bag, 3.3 mEq per 200 mL bag, 1.7 mEq per 100 mL bag])

Pharmacology

Prevents the formation of a functional 70S initiation complex, which is essential to the bacterial translation process.

Pharmacokinetics

Absorption

Rapidly and extensively absorbed. T _max is 1 to 2 h. Absolute bioavailability is about 100% (no dose adjustment needed from IV to oral). Food does not affect absorption; however, T _max is delayed from 1.5 to 2.2 h and C _max is decreased 17% when high-fat food is given.

Distribution

Readily distributed to well-perfused tissues; 31% protein bound. Vd at steady state is 40 to 50 L.

Metabolism

Primarily metabolized by oxidation of the morpholine ring. Metabolites are aminoethoxyacetic acid (A) and hydroxyethyl glycine (B) metabolite.

Elimination

About 65% nonrenal Cl. Approximately 30% of dose appears in urine (40% as metabolite B, 10% as metabolite A). Renal Cl is 40 mL/min.

Indications and Usage

Treatment of vancomycin-resistant Enterococcus faecium infections; treatment of nosocomial pneumonia, complicated and uncomplicated skin and skin structure infections, and community-acquired pneumonia caused by susceptible strains of specific organisms.

Contraindications

Standard considerations.

Dosage and Administration

No dosage adjustment is necessary when switching from IV to PO. Administer IV infusion over a period of 30 to 120 min.

PO or IV 600 mg every 12 h for 14 to 28 days.

PO or IV 10 mg/kg every 8 h for 14 to 28 days. Most preterm neonates younger than 7 days of age should start with 10 mg/kg every 12 h. A dose of 10 mg/kg every 8 h may be considered in neonates with a suboptimal response.

PO or IV 600 mg every 12 h for 10 to 14 days.

PO or IV 10 mg/kg every 8 h for 10 to 14 days. Most preterm neonates less than 7 days of age should start with 10 mg/kg every 12 h. A dose of 10 mg/kg every 8 h may be considered in neonates with a suboptimal response.

PO 400 mg every 12 h for 10 to 14 days.

PO 600 mg every 12 h for 10 to 14 days.

PO 10 mg/kg every 12 h for 10 to 14 days.

PO 10 mg/kg every 8 h for 10 to 14 days. Most preterm neonates younger than 7 days of age should start with 10 mg/kg every 12 h. A dose of 10 mg/kg every 8 h may be considered in neonates with a suboptimal response.

600 mg every 12 h.

General Advice

• Oral suspension contains phenylalanine. Do not administer oral suspension to patient with phenylketonuria without first discussing with health care provider.
• Administer tablets and oral suspension without regard to meals. Administer with food if GI upset occurs.
• Gently mix suspension by inverting bottle 3 to 5 times before each dose. Do not shake suspension. Measure and administer prescribed dose of suspension using dosing syringe, dosing spoon, or dosing cup.
• Suspension may be used in adults with swallowing problems.

• For administration by intermittent IV infusion only. Not for intradermal, subcutaneous, IM, continuous IV infusion, IV bolus, or intra-arterial administration.
• Keep infusion bag in protective overwrap until ready to administer.
• Do not administer if solution is cloudy, discolored, or contains particulate matter. Solution may exhibit a yellow color, which is normal and does not affect potency.
• Before administration, check IV bag for minute leaks by firmly squeezing bag. If leaks are detected, discard solution as sterility may be compromised.
• Do not use IV infusion bag in series connections nor add any other medications to infusion bag.
• If other drugs are being administered through same IV line, flush IV line before and after infusion of linezolid with dextrose 5% injection, sodium chloride 0.9% injection, or lactated Ringer's injection.

Storage/Stability

Store tablets and reconstituted suspension at controlled room temperature (59° to 86°F). Protect from light. Keep bottles tightly closed. Discard any unused suspension after 21 days.

Store IV infusion bags at controlled room temperature (59° to 86°F). Protect infusion bags from freezing and light.

Drug Interactions

Effects may be enhanced by linezolid.

Possible increased risk of serotonin syndrome.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (7%); insomnia, convulsions (3%); dizziness (2%); vertigo (1%); neuropathy (postmarketing).

Dermatologic

Rash (7%); skin disorder (2%).

EENT

Pharyngitis (3%).

GI

Diarrhea (11%); vomiting (9%); nausea (6%); generalized and localized abdominal pain, GI bleeding, loose stools, constipation, altered taste (2%); tongue discoloration, oral moniliasis (1%).

Genitourinary

Vaginal moniliasis (2%).

Hematologic

Anemia (6%); thrombocytopenia (5%); thrombocythemia (3%); eosinophilia (1%); leukopenia, pancytopenia (postmarketing).

Lab Tests

Abnormal LFTs (1%).

Metabolic

Hypokalemia (3%); generalized edema (2%); lactic acidosis (postmarketing).

Respiratory

Upper respiratory tract infection (4%); pneumonia, dyspnea (3%); cough, apnea (2%).

Miscellaneous

Fever (14%); sepsis (8%); trauma, injection site reactions (3%); fungal infections, localized pain (2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

See dosing recommendations.

Lactic acidosis

May occur.

Myelosuppression

Because myelosuppression has been reported, monitor CBC weekly in patients receiving linezolid.

Pseudomembranous colitis

Consider pseudomembranous colitis in patients who develop diarrhea.

Patient Information

• Review dosing schedule and prescribed length of therapy with patient. Advise patient that dose and duration of therapy are dependent on site and cause of infection and response to treatment.
• Advise patient or caregiver that injection is used when infection is severe and needs immediate treatment with large doses of antibiotic, or if oral therapy is not feasible. Advise patient or caregiver that injection will be prepared by a health care professional, administered in a health care setting, and oral therapy will be started as soon as possible.
• Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
• Advise patient or caregiver to gently mix suspension by inverting bottle 3 to 5 times before measuring dose, then measure and administer prescribed dose using a dosing syringe, dosing spoon, or dosing cup.
• Reinforce the need to take exactly as prescribed and complete entire course of therapy, even if symptoms of infection have disappeared. Caution patient or caregiver that skipping doses or not completing the full course of therapy may cause the infection to worsen and increase the possibility that the bacteria will become resistant to the antibiotic and may cause infections that will not be treatable in the future.
• Instruct patient to avoid foods and beverages with high tyramine content. Review common foods known to have high tyramine content (eg, aged cheeses, soy sauce, fermented or air-dried meats, sauerkraut, tap beers, red wines).
• Advise patient that diarrhea, headache, and nausea are most common adverse reactions and to inform health care provider if they occur and are intolerable.
• Advise patient to discontinue therapy and contact health care provider immediately if skin rash, hives, itching, general body discomfort, muscle aches, unexplained rapid breathing or shortness of breath, progressive drowsiness, or generalized stomach distress occurs.
• Advise patient to report signs of superinfection to health care provider: black, furry tongue, white patches in mouth, foul-smelling stools, vaginal itching or discharge.
• Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and not treat at home even if diarrhea starts after stopping the antibiotic.
• Caution patient not to take any OTC cold products containing decongestants (eg, pseudoephedrine) unless advised by health care provider.

Copyright © 2009 Wolters Kluwer Health.