Drugs List

Therapeutic Indications

Uses

Community acquired pneumonia
Complicated skin and soft tissue infections
Nosocomial pneumonia

Nosocomial pneumonia or community acquired pneumonia

Treatment of nosocomial pneumonia or community acquired pneumonia when known or suspected to be caused by susceptible Gram positive bacteria.

Microbiological tests and the prevalence of antibacterial resistance in Gram positive bacteria should be considered before linezolid treatment.

Combination therapy will be necessary if a concomitant Gram negative pathogen is documented or suspected.

Complicated skin and soft tissue infections

Treatment of complicated skin and soft tissue infections when known to be caused by susceptible Gram positive bacteria.

Linezolid is not effective against Gram negative pathogens. If co-infection with Gram negative pathogens is known or suspected, linezolid should only be used if no other alternative treatment options are appropriate. Treatment against Gram negative organisms must be initiated concurrently.

Contraindications

Within 2 weeks of discontinuing other MAOIs
Breastfeeding

Precautions and Warnings

Carcinoid
Children under 18 years
Predisposition to seizures
Anaemia
Bipolar disorder
Confusional states
Glucose-galactose malabsorption syndrome
Haemodialysis
Hepatic impairment
Hereditary fructose intolerance
History of agranulocytosis
History of seizures
Myelosuppression
Phaeochromocytoma
Phenylketonuria
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Schizoaffective disorder
Schizophrenia
Sucrase-isomaltase insufficiency
Thrombocytopenia
Thyrotoxicosis
Uncontrolled hypertension

Sodium content of formulation may be significant
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain fructose
Some formulations contain sucrose
Some formulations may contain alcohol
Assess risk/benefit of treatment if symptoms of peripheral neuropathy occur
If visual disturbances occur, perform ophthalmic evaluation
Monitor blood counts in anaemia, leukopenia and thrombocytopenia
Monitor closely patients receiving > 10-14 days of treatment
Monitor closely patients receiving myelosuppressive drugs
Monitor closely patients with pre-existing myelosuppression
Monitor for development of lactic acidosis
Monitor for signs of superinfection with non-susceptible organisms
Monitor full blood counts weekly
When used with SSRIs, risk of Serotonin syndrome
Advise patient to report new visual problems and symptoms
Consider pseudomembranous colitis if patient presents with diarrhoea
Discontinue if myelosuppression occurs
Not recommended for use longer than 4 weeks
Advise patient against consuming large amounts of tyramine rich foods

All patients receiving linezolid should have complete blood counts (including haemoglobin levels, platelets and total and differentiated leucocyte counts) monitored weekly regardless of baseline blood count.

Elderly patients may be at greater risk of experiencing blood dyscrasias than younger patients.

Thrombocytopenia may occur more commonly in patients with severe renal impairment, whether or not on dialysis.

Linezolid inhibits mitochondrial protein synthesis, which can cause lactic acidosis, anaemia and neuropathy. More commonly in treatments lasting longer than 28 days.

As approximately 30% of a linezolid dose is removed during 3 hours of haemodialysis, linezolid should be given after dialysis with extreme caution. The primary metabolites of linezolid are removed to some extent by haemodialysis, but the concentrations of these metabolites are still very considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal impairment.

Linezolid reversibly decreased fertility and induced abnormal sperm morphology in adult male rats at exposure levels approximately equal to those expected in humans. Possible effects of linezolid on the human male reproductive system are not known.

Patients should be advised against consuming large amounts of tyramine rich foods, such as mature cheese, yeast extracts, undistilled alcoholic drinks or fermented soya bean products.

Linezolid used in patients taking or taken antimycobacterial medications to treat tuberculosis, may show an increased risk of neuropathies.

Myelosuppression has been reported in patients receiving linezolid. The risk of these effects appears to be related to the duration of treatment.
If significant myelosuppression occurs, discontinue treatment unless it is considered absolutely necessary to continue therapy. If therapy is continued, intensive monitoring of blood counts and appropriate management strategies should be implemented.

Patients should be advised to report any visual impairment. If any changes occur, the patient should be evaluated immediately and referred to an ophthalmologist if necessary. In patients taking linezolid for longer than the recommended 28 days, their visual function should be monitored.

Sideroblastic anaemia has been reported in patients who had been treated with linezolid for more than 28 days. Most patients fully or partially recovered following discontinuation of linezolid.

CSM Warnings

Severe optic neuropathy may occur rarely if linezolid if treatment lasts longer than 28 days.

The CHM recommends that:

Patients should report any symptoms of visual impairment (including blurred vision, visual field defect, changes in visual acuity and colour vision) immediately;

Patients experiencing new visual symptoms (regardless of treatment duration) should be evaluated promptly and referred to an ophthalmologist if necessary;

Visual function should be monitored regularly if treatment is required for longer than 28 days.

Pregnancy and Lactation

Pregnancy

Use linezolid with caution in pregnancy.

At the time of writing there is limited data from the use of linezolid in pregnant women. It is not known if linezolid crosses the placenta, but the molecular weight is low enough that transfer to the foetus should be expected.

Studies in animals have shown reproductive toxicity and a potential risk for humans exists.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Linezolid is contraindicated during breastfeeding.

The molecular weight is low enough that excretion of linezolid should be expected. The effects of this on the breastfed infant are unknown. Limited data indicate that the maximum dose an infant would receive through breast milk would be much lower than the standard infant dose.

Its is suggested that if linezolid is required by the mother, breastfeeding can be continued but the infant should be monitored for possible effects on the gastrointestinal tract.

Animal data suggest that linezolid and its metabolites may pass into breast milk; it is excreted in the milk of lactating rats. Levels observed were higher than in the maternal plasma.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Abnormal serum sodium levels
Alopecia
Anaemia
Anaphylaxis
Angioedema
Arrhythmias
Blood glucose disturbances
Blurred vision
Bullous reactions
Candidiasis
Changes in blood chemistry
Chills
Colour vision deficiencies
Constipation
Convulsions
Creatine kinase increased
Creatine phosphokinase increased
Decrease in haemoglobin and haematocrit
Decrease in plasma calcium
Decreased serum albumin
Decreased total serum protein
Dermatitis
Diaphoresis
Diarrhoea/loose stools
Dizziness
Dry mouth
Dyspepsia
Elevated amylase levels
Elevated serum lipase
Eosinophilia
Fatigue
Fever
Fluctuating serum potassium levels
Fungal infection
Gastritis
Glossitis
Headache
Hypertension
Hypoaesthesia
Increase in alkaline phosphatase
Increase in blood urea nitrogen
Increase in lactate dehydrogenase
Increase in plasma calcium
Increase in serum ALT/AST
Increased platelet count
Increased thirst
Increases in eosinophils
Insomnia
Lactic acidosis
Leucopenia
Local pain
Loss of vision
Metallic taste
Myelosuppression
Nausea
Neutropenia
Optic neuritis
Optic neuropathy
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Phlebitis
Polyuria
Pruritus
Pseudomembranous colitis
Raised neutrophil count
Rash
Reduced neutrophil count
Reduced platelet count
Renal failure
Reticulocytosis
Serotonin syndrome
Serum bilirubin increased
Serum creatinine increased
Sideroblastic anaemia
Stevens-Johnson syndrome
Stomatitis
Superficial tooth discolouration
Taste disturbances
Thrombocytopenia
Thrombophlebitis
Tinnitus
Tongue discolouration
Toxic epidermal necrolysis
Transient ischaemic attack
Urticaria
Vaginitis
Visual field defects
Vomiting
Vulvovaginal disorders
White blood cell count decreased
White blood cell count raised

Presentation

Granules for oral suspension containing linezolid 100mg/5ml.

Film coated tablets containing 600mg linezolid.

Drugs List

Therapeutic Indications

Uses

Community acquired pneumonia
Complicated skin and soft tissue infections
Nosocomial pneumonia

Nosocomial pneumonia or community acquired pneumonia

Treatment of nosocomial pneumonia or community acquired pneumonia when known or suspected to be caused by susceptible Gram positive bacteria.

Microbiological tests and the prevalence of antibacterial resistance in Gram positive bacteria should be considered before linezolid treatment.

Combination therapy will be necessary if a concomitant Gram negative pathogen is documented or suspected.

Complicated skin and soft tissue infections

Treatment of complicated skin and soft tissue infections when known to be caused by susceptible Gram positive bacteria.

Linezolid is not effective against Gram negative pathogens. If co-infection with Gram negative pathogens is known or suspected, linezolid should only be used if no other alternative treatment options are appropriate. Treatment against Gram negative organisms must be initiated concurrently.

Dosage

Therapy with linezolid should only be initiated in a hospital environment and after consultation with a relevant specialist.

Adults

Children

Neonates

Additional Dosage Information

Contraindications

Within 2 weeks of discontinuing other MAOIs
Breastfeeding

Precautions and Warnings

Carcinoid
Children under 18 years
Predisposition to seizures
Anaemia
Bipolar disorder
Confusional states
Glucose-galactose malabsorption syndrome
Haemodialysis
Hepatic impairment
Hereditary fructose intolerance
History of agranulocytosis
History of seizures
Myelosuppression
Phaeochromocytoma
Phenylketonuria
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Schizoaffective disorder
Schizophrenia
Sucrase-isomaltase insufficiency
Thrombocytopenia
Thyrotoxicosis
Uncontrolled hypertension

Sodium content of formulation may be significant
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain fructose
Some formulations contain sucrose
Some formulations may contain alcohol
Assess risk/benefit of treatment if symptoms of peripheral neuropathy occur
If visual disturbances occur, perform ophthalmic evaluation
Monitor blood counts in anaemia, leukopenia and thrombocytopenia
Monitor closely patients receiving > 10-14 days of treatment
Monitor closely patients receiving myelosuppressive drugs
Monitor closely patients with pre-existing myelosuppression
Monitor for development of lactic acidosis
Monitor for signs of superinfection with non-susceptible organisms
Monitor full blood counts weekly
When used with SSRIs, risk of Serotonin syndrome
Advise patient to report new visual problems and symptoms
Consider pseudomembranous colitis if patient presents with diarrhoea
Discontinue if myelosuppression occurs
Not recommended for use longer than 4 weeks
Advise patient against consuming large amounts of tyramine rich foods

All patients receiving linezolid should have complete blood counts (including haemoglobin levels, platelets and total and differentiated leucocyte counts) monitored weekly regardless of baseline blood count.

Elderly patients may be at greater risk of experiencing blood dyscrasias than younger patients.

Thrombocytopenia may occur more commonly in patients with severe renal impairment, whether or not on dialysis.

Linezolid inhibits mitochondrial protein synthesis, which can cause lactic acidosis, anaemia and neuropathy. More commonly in treatments lasting longer than 28 days.

As approximately 30% of a linezolid dose is removed during 3 hours of haemodialysis, linezolid should be given after dialysis with extreme caution. The primary metabolites of linezolid are removed to some extent by haemodialysis, but the concentrations of these metabolites are still very considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal impairment.

Linezolid reversibly decreased fertility and induced abnormal sperm morphology in adult male rats at exposure levels approximately equal to those expected in humans. Possible effects of linezolid on the human male reproductive system are not known.

Patients should be advised against consuming large amounts of tyramine rich foods, such as mature cheese, yeast extracts, undistilled alcoholic drinks or fermented soya bean products.

Linezolid used in patients taking or taken antimycobacterial medications to treat tuberculosis, may show an increased risk of neuropathies.

Myelosuppression has been reported in patients receiving linezolid. The risk of these effects appears to be related to the duration of treatment.
If significant myelosuppression occurs, discontinue treatment unless it is considered absolutely necessary to continue therapy. If therapy is continued, intensive monitoring of blood counts and appropriate management strategies should be implemented.

Patients should be advised to report any visual impairment. If any changes occur, the patient should be evaluated immediately and referred to an ophthalmologist if necessary. In patients taking linezolid for longer than the recommended 28 days, their visual function should be monitored.

Sideroblastic anaemia has been reported in patients who had been treated with linezolid for more than 28 days. Most patients fully or partially recovered following discontinuation of linezolid.

CSM Warnings

Severe optic neuropathy may occur rarely if linezolid if treatment lasts longer than 28 days.

The CHM recommends that:

Patients should report any symptoms of visual impairment (including blurred vision, visual field defect, changes in visual acuity and colour vision) immediately;

Patients experiencing new visual symptoms (regardless of treatment duration) should be evaluated promptly and referred to an ophthalmologist if necessary;

Visual function should be monitored regularly if treatment is required for longer than 28 days.

Pregnancy and Lactation

Pregnancy

Use linezolid with caution in pregnancy.

At the time of writing there is limited data from the use of linezolid in pregnant women. It is not known if linezolid crosses the placenta, but the molecular weight is low enough that transfer to the foetus should be expected.

Studies in animals have shown reproductive toxicity and a potential risk for humans exists.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Linezolid is contraindicated during breastfeeding.

The molecular weight is low enough that excretion of linezolid should be expected. The effects of this on the breastfed infant are unknown. Limited data indicate that the maximum dose an infant would receive through breast milk would be much lower than the standard infant dose.

Its is suggested that if linezolid is required by the mother, breastfeeding can be continued but the infant should be monitored for possible effects on the gastrointestinal tract.

Animal data suggest that linezolid and its metabolites may pass into breast milk; it is excreted in the milk of lactating rats. Levels observed were higher than in the maternal plasma.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Abnormal serum sodium levels
Alopecia
Anaemia
Anaphylaxis
Angioedema
Arrhythmias
Blood glucose disturbances
Blurred vision
Bullous reactions
Candidiasis
Changes in blood chemistry
Chills
Colour vision deficiencies
Constipation
Convulsions
Creatine kinase increased
Creatine phosphokinase increased
Decrease in haemoglobin and haematocrit
Decrease in plasma calcium
Decreased serum albumin
Decreased total serum protein
Dermatitis
Diaphoresis
Diarrhoea/loose stools
Dizziness
Dry mouth
Dyspepsia
Elevated amylase levels
Elevated serum lipase
Eosinophilia
Fatigue
Fever
Fluctuating serum potassium levels
Fungal infection
Gastritis
Glossitis
Headache
Hypertension
Hypoaesthesia
Increase in alkaline phosphatase
Increase in blood urea nitrogen
Increase in lactate dehydrogenase
Increase in plasma calcium
Increase in serum ALT/AST
Increased platelet count
Increased thirst
Increases in eosinophils
Insomnia
Lactic acidosis
Leucopenia
Local pain
Loss of vision
Metallic taste
Myelosuppression
Nausea
Neutropenia
Optic neuritis
Optic neuropathy
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Phlebitis
Polyuria
Pruritus
Pseudomembranous colitis
Raised neutrophil count
Rash
Reduced neutrophil count
Reduced platelet count
Renal failure
Reticulocytosis
Serotonin syndrome
Serum bilirubin increased
Serum creatinine increased
Sideroblastic anaemia
Stevens-Johnson syndrome
Stomatitis
Superficial tooth discolouration
Taste disturbances
Thrombocytopenia
Thrombophlebitis
Tinnitus
Tongue discolouration
Toxic epidermal necrolysis
Transient ischaemic attack
Urticaria
Vaginitis
Visual field defects
Vomiting
Vulvovaginal disorders
White blood cell count decreased
White blood cell count raised

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2018.

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mother's Milk, 14th edition (2011) Hale, T.W. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Zyvox 600mg film-coated tablets, Pharmacia Ltd. Revised Septemeber 2018.

Summary of Product Characteristics: Zyvox 100mg/5ml granules for oral suspension, Pharmacia Ltd. Revised March 2019.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19 January 2018.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Linezolid Last revised: 23th March 2010
Last accessed: 19 January 2018.