Linezolid


Generic Medicine Info
Indications and Dosage
Intravenous
Vancomycin-resistant Enterococcus faecium
Adult: 600 mg 12 hourly via infusion over 30-120 minutes for 14-28 days.
Child: Pre-term neonates <7 days (gestational age <34 weeks) Initially, 10 mg/kg 12 hourly, may consider to increase to 10 mg/kg 8 hourly if with sub-optimal clinical response; 7 days to 11 years 10 mg/kg 8 hourly; ≥12 years Same as adult dose. All doses are given via infusion over 30-120 minutes. Treatment duration: 14-28 days. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Intravenous
Community-acquired pneumonia, Complicated skin and skin structure infections, Nosocomial pneumonia
Adult: 600 mg 12 hourly via infusion over 30-120 minutes for 10-14 days.
Child: Pre-term neonates <7 days (gestational age <34 weeks) Initially, 10 mg/kg 12 hourly, may consider to increase to 10 mg/kg 8 hourly if with sub-optimal clinical response; 7 days to 11 years 10 mg/kg 8 hourly; ≥12 years Same as adult dose. All doses are given via infusion over 30-120 minutes. Treatment duration: 10-14 days. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Oral
Vancomycin-resistant Enterococcus faecium
Adult: 600 mg 12 hourly for 14-28 days.
Child: Pre-term neonates <7 days (gestational age <34 weeks) Initially, 10 mg/kg 12 hourly, may consider to increase to 10 mg/kg 8 hourly if with sub-optimal clinical response; 7 days to 11 years 10 mg/kg 8 hourly; ≥12 years Same as adult dose. Treatment duration: 14-28 days. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Oral
Community-acquired pneumonia, Complicated skin and skin structure infections, Nosocomial pneumonia
Adult: 600 mg 12 hourly for 10-14 days.
Child: Pre-term neonates <7 days (gestational age <34 weeks) Initially, 10 mg/kg 12 hourly, may consider to increase to 10 mg/kg 8 hourly if with sub-optimal clinical response; 7 days to 11 years 10 mg/kg 8 hourly; ≥12 years Same as adult dose. Treatment duration: 10-14 days. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).

Oral
Uncomplicated skin and skin structure infections
Adult: 400 mg 12 hourly for 10-14 days.
Child: <5 years 10 mg/kg 8 hourly; 5-11 years 10 mg/kg 12 hourly; ≥12 years 600 mg 12 hourly. Treatment duration: 10-14 days. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Administration
May be taken with or without food.
Reconstitution
Oral susp: Loosen the granules by gently tapping the bottle. Reconstitute by adding 123 mL of water in 2 equal portions to make a final concentration of 100 mg/5 mL. Vigorously shake the bottle in between each addition of water to obtain a uniform susp. Prior to administration, invert the bottle gently to mix; do not shake.
Incompatibility
Intravenous:
Physically incompatible in a simulated Y-site administration with diazepam, chlorpromazine hydrochloride, amphotericin B, pentamidine isethionate, erythromycin lactobionate, phenytoin Na, and trimethoprim-sulfamethoxazole. Chemically incompatible with ceftriaxone Na.
Contraindications
Hypersensitivity. Unless facilities are available for close observation and monitoring of blood pressure, avoid linezolid use in patients with uncontrolled hypertension, thyrotoxicosis, phaeochromocytoma, bipolar depression, acute confusional states, or schizoaffective disorder, and/or in patients taking directly and indirectly acting sympathomimetic agents (including adrenergic bronchodilators, pseudoephedrine, and phenylpropanolamine), vasopressive agents (e.g. epinephrine, norepinephrine), and dopaminergic drugs (e.g. dopamine, dobutamine). Unless patients are closely observed for signs and symptoms of serotonin syndrome, linezolid must not be given to those with carcinoid syndrome, and/or patients taking SSRIs, TCAs, serotonin 5-HT1 receptor agonists (triptans), pethidine, bupropion, or buspirone. Concomitant use or within 2 weeks of discontinuing MAOIs.
Special Precautions
Patient with a history of seizures; diabetes mellitus, liver cirrhosis. Not indicated for the treatment of Gram-negative infections and catheter-related systemic infections. If a concomitant Gram-negative pathogen is documented or suspected, specific Gram-negative treatment must be initiated immediately. Severe renal impairment (CrCl <30 mL/min), including those undergoing haemodialysis; severe hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Myelosuppression, including anaemia, thrombocytopenia, pancytopenia, and leucopenia; peripheral neuropathy and optic neuropathy and neuritis, particularly in patients treated for >28 days; convulsions, lactic acidosis, hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH); symptomatic hypoglycaemia, particularly in patients with diabetes mellitus receiving insulin or oral hypoglycaemic agents; fungal or bacterial superinfection (prolonged use).
Blood and lymphatic system disorders: Eosinophilia, sideroblastic anaemia.
Cardiac disorders: Tachycardia.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Blurred vision, changes in visual acuity or colour vision, loss of vision.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, abdominal pain, constipation, dyspepsia, abdominal distention, stomatitis, gastritis, pancreatitis, dry mouth, glossitis, tongue discolouration, taste perversion (metallic taste). Rarely, superficial tooth discolouration.
General disorders and administration site conditions: Fever, localised pain, chills, fatigue, increased thirst, inj site pain.
Immune system disorders: Anaphylaxis.
Infections and infestations: Candidiasis, fungal infections.
Investigations: Increased ALT, AST, alkaline phosphatase, total bilirubin, BUN, serum creatinine, lactate dehydrogenase, creatine kinase, serum lipase, amylase, and non-fasting glucose; decreased total protein, albumin, and Ca levels; increased or decreased K or bicarbonate levels.
Nervous system disorders: Headache, dizziness, hypoaesthesia, paraesthesia.
Psychiatric disorders: Insomnia.
Renal and urinary disorders: Renal failure, polyuria.
Reproductive system and breast disorders: Vaginitis, vulvovaginal disorder.
Skin and subcutaneous tissue disorders: Rash, pruritus, dermatitis, diaphoresis, urticaria, bullous disorders (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, alopecia.
Potentially Fatal: Clostridioides difficile-associated diarrhoea (CDAD), pseudomembranous colitis; serotonin syndrome.
IV/Parenteral/PO: C
Patient Counseling Information
This drug may cause dizziness or visual impairment, if affected, do not drive or operate machinery.
Monitoring Parameters
Perform culture and sensitivity tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Obtain CBC weekly; closely monitor blood counts in patients at risk of bleeding, with pre-existing myelosuppression or renal impairment, those receiving >2 weeks of therapy or concomitant agents that cause bone marrow suppression. Monitor blood pressure; serum Na levels regularly in patients taking diuretics, at risk of hyponatraemia and/or SIADH, and in the elderly. Perform visual function tests in patients on prolonged therapy or with vision changes. Closely monitor for signs and symptoms of serotonin syndrome and neuropathic adverse effects (e.g. peripheral neuropathy, optic neuritis); signs of bone marrow suppression in patients with renal impairment.
Drug Interactions
May enhance the hypoglycaemic effect of antidiabetic agents. Plasma concentration may be decreased by rifampicin.
Potentially Fatal: Increased risk of serotonin syndrome with MAOIs and other serotonergic agents such as SSRIs (e.g. citalopram, fluoxetine, fluvoxamine, paroxetine), serotonin norepinephrine reuptake inhibitors (SNRIs), TCAs, serotonin 5-HT1 receptor agonists (triptans), pethidine, buspirone, and bupropion. May enhance the elevated blood pressure caused by pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dopamine, and dobutamine.
Food Interaction
Avoid consuming large amounts of tyramine-rich foods or beverages (e.g. aged or matured cheese, air-dried or cured meats, fava or broad bean pods, yeast extracts, sauerkraut, soy sauce, red wine, tap or draft beers), and foods rich in dopamine, tyrosine, tryptophan, phenylalanine, or caffeine as these may cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome). May increase the risk of serotonin syndrome with St. John's wort.
Action
Description: Linezolid is an oxazolidinone antibacterial agent that selectively inhibits the bacterial protein synthesis by binding to the 23S ribosomal ribonucleic acid (RNA) of the 50S subunit of the bacteria, thereby preventing the formation of a functional 70S initiation complex essential for the bacterial translation process. It is active against Gram-positive bacteria only and has no clinical activity against Gram-negative bacteria.
Pharmacokinetics:
Absorption: Rapidly and extensively absorbed. Bioavailability: Approx 100% (oral). Time to peak plasma concentration: 1-2 hours (oral).
Distribution: Readily distributes into well-perfused tissues, and into CSF. Enters breast milk. Volume of distribution: 0.65 L/kg. Plasma protein binding: 31%.
Metabolism: Metabolised in the liver mainly via oxidation of the morpholine ring into 2 inactive metabolites, aminoethoxyacetic acid and hydroxyethyl glycine.
Excretion: Via urine (approx 30% as linezolid; approx 50% as metabolites); faeces (approx 9% as metabolites). Elimination half-life: Approx 5-7 hours.
Chemical Structure

Chemical Structure Image
Linezolid

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 441401, Linezolid. https://pubchem.ncbi.nlm.nih.gov/compound/441401. Accessed July 26, 2022.

Storage
Tab: Store below 30°C. Protect from light. Oral susp: Store at 25°C. Protect from light and moisture. After reconstitution, store at room temperature and use within 21 days. Solution for infusion: Store at 25°C. Do not freeze. Keep infusion bags in the overwrap until ready to use to protect from light.
MIMS Class
Other Antibiotics
ATC Classification
J01XX08 - linezolid ; Belongs to the class of other antibacterials. Used in the systemic treatment of infections.
References
Anon. Linezolid. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/06/2022.

Anon. Linezolid. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/06/2022.

Buckingham R (ed). Linezolid. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/06/2022.

Joint Formulary Committee. Linezolid. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/06/2022.

Linezolid 100 mg/5 mL Granules for Oral Suspension (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2022.

Linezolid 2 mg/mL Solution for Infusion (Baxter Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2022.

Linezolid 600 mg Film-coated Tablets (Bristol Laboratories Ltd). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2022.

Pfizer New Zealand Limited. Zyvox 600 mg Film Coated Tablets; Zyvox 20 mg/mL Granules for Oral Suspension; Zyvox 2 mg/mL Solution for Infusion data sheet 14 April 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 02/06/2022.

Zyvox (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/06/2022.

Zyvox Injection, Solution; Zyvox Granule for Suspension; Zyvox Tablet, Film Coated (Pharmacia & Upjohn Company LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/06/2022.

Disclaimer: This information is independently developed by MIMS based on Linezolid from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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