linezolid

Inhibits bacterial protein synthesis at the level of the 23S ribosome of the 50S subunit.

Therapeutic effects:

Bactericidal action against streptococci; bacteriostatic action against enterococci and staphylococci.

Spectrum:

Active against gram-positive pathogens, including:
- Staphylococcus aureus (methicillin-susceptible and methicillin-resistant),
- Streptococcus agalactiae,
- Streptococcus pneumoniae,
- Streptococcus pyogenes,
- Enterococcus faecium.

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly and extensively (100%) absorbed following oral administration. IV administration results in complete bioavailability.

Distribution: Readily distributes to well-perfused tissues.

Metabolism/Excretion: 65% metabolized, mostly by the liver; 30% excreted unchanged by the kidneys.

Half-Life: 6.4 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1–2 hr	12 hr
IV	rapid	end of infusion	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Phenylketonuria (suspension contains phenylalanine);
Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, or concurrent use of sympathomimetic agents, vasopressors, or dopaminergic agents (↑ risk of hypertensive response);
Concurrent or recent (<2 wk) use of MAO inhibitors (↑ risk of hypertensive response);
Carcinoid syndrome or concurrent use of SSRIs, SNRIs, TCAs, triptans, opioids, bupropion, or buspirone (↑ risk of serotonin syndrome).

Use Cautiously in:

Thrombocytopenia, concurrent use of antiplatelet agents or bleeding diathesis (platelet counts should be monitored more frequently);
Diabetes (↑ risk of hypoglycemia);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adv. Reactions/Side Effects ⬆ ⬇

CV: headache, insomnia

Derm: toxic epidermal necrolysis

EENT: teeth discoloration, tongue discoloration

Endo: hypoglycemia, syndrome of inappropriate diuretic hormone (SIADH) secretion

F and E: hyponatremia, lactic acidosis

GI: ↑liver enzymes, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, nausea, vomiting

Hemat: anemia, leukopenia, thrombocytopenia

MS: RHABDOMYOLYSIS

Neuro: dysgeusia, optic neuropathy, peripheral neuropathy

Misc: SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

↑risk of hypertensive crisis with MAO inhibitors, sympathomimetics (e.g., pseudoephedrine), vasopressors (e.g., epinephrine, norepinephrine), and dopaminergic agents (e.g., dopamine, dobutamine); concurrent or recent use should be avoided.
↑risk of serotonin syndrome with SSRIs, SNRIs, TCAs, triptans, opioids, bupropion, or buspirone; avoid concurrent use.
Rifampin, carbamazepine, phenytoin, and phenobarbital may ↓ levels.
Concurrent use with oral hypoglycemics or insulin may ↑ risk of hypoglycemia

Because of MAO inhibitory properties, consumption of large amounts of foods or beverages containing tyramine should be avoided (↑ risk of pressor response; see Food Sources for Specific Nutrients).

Route/Dosage ⬆ ⬇

Vancomycin-Resistant Enterococcus faecium Infections

PO IV (Adults ): 600 mg every 12 hr for 14–28 days.
PO IV (Children ≤11 yr): In the first wk of life, preterm neonates may initially receive 10 mg/kg every 12 hr.

Pneumonia or Complicated Skin/Skin Structure Infections

PO IV (Adults ): 600 mg every 12 hr for 10–14 days.
PO IV (Children ≤11 yr): 10 mg/kg every 8 hr for 10–14 days (in the first wk of life, preterm neonates may initially receive 10 mg/kg every 12 hr).

Uncomplicated Skin/Skin Structure Infections

PO (Adults ): 400 mg every 12 hr for 10–14 days.
PO IV (Children 5–11 yr): 10 mg/kg every 12 hr for 10–14 days.
PO IV (Children <5 yr): 10 mg/kg every 8 hr for 10–14 days (in the first wk of life, preterm neonates may initially receive 10 mg/kg every 12 hr).

Availability ⬆ ⬇

(Generic available)

Tablets: 600 mg
Oral suspension: orange flavored: 100 mg/5 mL (each 5 mL contains phenylalanine 20 mg)
Premixed infusion: 200 mg/100 mL; 600 mg/300 mL

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool) at beginning of and during therapy.
Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before obtaining these specimens.
May cause lactic acidosis. Notify health care professional if recurrent nausea and vomiting, unexplained acidosis, or low bicarbonate levels occur.
Monitor visual function in patients receiving linezolid for ≥3 mo or who report visual symptoms (changes in acuity or color vision, blurred vision, visual field defect) regardless of length of therapy. If optic neuropathy occurs, therapy should be reconsidered.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Monitor patient taking serotonergic drugs for signs of serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes, extreme agitation progressing to delirium and coma) for 2 wk (5 wk if fluoxetine was taken) or until 24 hr after the last dose of linezolid, whichever comes first.
Monitor for rhabdomyolysis (elevated CK). If rhabdomyolysis occurs,discontinue linezolid and initiate appropriate treatment.

Lab Test Considerations:

May cause myelosuppression. Monitor CBC and platelet count weekly, especially in patients at risk for ↑ bleeding, having pre-existing bone marrow suppression, having severe renal impairment or moderate/severe hepatic impairment, receiving concurrent medications that may cause myelosuppression, or requiring >2 wk of therapy. Consider discontinuing therapy if bone marrow suppression occurs or worsens.
- May cause ↑ AST, ALT, LDH, alkaline phosphatase, and BUN.
- May cause hypoglycemia requiring ↓ in dose of antidiabetic agent or discontinuation of linezolid.
- Monitor serum sodium levels regularly in older adults, patients taking diuretics, and other patients at risk of hyponatremia and/or SIADH. If signs and symptoms of hyponatremia and/or SIADH (confusion, somnolence, generalized weakness, respiratory failure, death) occur, discontinue linezolid, and institute supportive measures.

Implementation ⬆ ⬇

Do not confuse Zyvox with Zovirax.
Dose adjustment is not necessary when switching from IV to oral dose.
PO: May be administered with or without food.
- Before using oral solution, gently invert 3–5 times to mix; do not shake. Store at room temperature; use within 21 days of constitution.

IV Administration:

Intermittent Infusion: Diluent: Premixed infusions are already diluted and ready to use. Solution is yellowish in color, which may intensify over time without affecting its potency.Concentration: 2 mg/mL. Do not use in series connections.
Rate: Infuse over 30–120 min. Flush line before and after infusion.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of linezolid to patient.
Instruct patients taking oral linezolid to take as directed for full course of therapy, even if feeling better. Take missed doses as soon as remembered unless almost time for next dose; do not double dose.
Instruct patient to avoid large quantities of foods or beverages containing tyramine (see Food Sources for Specific Nutrients). May cause hypertensive response.
Instruct patient to notify health care professional if they have a history of hypertension, seizures, or diabetes.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially cold remedies, decongestants, or antidepressants.
Instruct patient to notify health care professional if changes in vision occur or immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.
Advise patient to notify health care professional if they experience signs of rhabdomyolysis (muscle pain or weakness, dark urine).
Advise patient to notify health care professional promptly if signs and symptoms of SIADH (confusion, somnolence, generalized weakness, respiratory failure). May be fatal.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise lactating women to monitor breastfed infant for diarrhea and vomiting. May reversibly impair fertility in male patients.
Advise patient to notify health care professional if no improvement is seen in a few days.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇