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LINEZOLID 2 MG/ ML SOLUTION FOR INFUSION

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Package leaflet: Information for the user
Linezolid 2 mg/ml solution for infusion
Linezolid
Read all of this leaflet carefully before this medicine is given to you because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet:
1.
What Linezolid is and what it is used for
2.
What you need to know before you are treated with Linezolid
3.
How Linezolid is given
4.
Possible side effects
5.
How to store Linezolid
6.
Contents of the pack and other information
1.

What Linezolid is and what it is used for

Linezolid is an antibiotic of the oxazolidinones group that works by stopping the growth of certain
bacteria (germs) that cause infections. It is used to treat pneumonia and some infections in the skin or
under the skin. Your doctor will have decided if Linezolid is suitable to treat your infection.
2.

What you need to know before you are treated with Linezolid

You should not be treated with Linezolid:
 if you are allergic (hypersensitive) to linezolid or any of the other ingredients of this medicine.
 if you are taking or have taken within the last 2 weeks any medicines known as monoamine
oxidase inhibitors (MAOIs for example phenelzine, isocarboxazid, selegiline, moclobemide).
These medications may be used to treat depression or Parkinson’s disease.
 if you are breast-feeding. This is because Linezolid passes into breast milk and could affect the
baby.
Warnings and precautions
Linezolid may not be suitable for you if you answer yes to any of the following questions. In this case
tell your doctor as he/she will need to check your general health and your blood pressure before and
during your treatment or may decide that another treatment is better for you.
Ask your doctor if you are not sure whether these categories apply to you.
 Do you have high blood pressure, whether or not you are taking medicines for this?
 Have you been diagnosed with an overactive thyroid?
 Do you have a tumour of the adrenal glands (phaeochromocytoma) or carcinoid syndrome
(caused by tumours of the hormone system with symptoms of diarrhoea, flushing of the skin,
wheezing)?
 Do you suffer from manic depression, schizoaffective disorder, mental confusion or other mental
problems?
 Are you taking any of the following medicines?
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-decongestant, cold or flu remedies containing pseudoephedrine or phenylpropanolamine
-medicines used to treat asthma such as salbutamol, terbutaline, fenoterol
-antidepressants known as tricyclics or SSRIs (selective serotonin reuptake inhibitors) for
example amitriptyline, cipramil, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine,
imipramine, lofepramine, paroxetine, sertraline
-medicines used to treat migraine such as sumatriptan and zolmitriptan
-medicines used to treat sudden, severe allergic reactions such as adrenaline (epinephrine)
-medicines which increase your blood pressure, such as noradrenaline (norepinephrine),
dopamine and dobutamine
- used to treat moderate to severe pain, such as pethidine
- medicines used to treat anxiety disorders, such as buspirone
- an antibiotic called rifampicin
Take special care with Linezolid
Tell your doctor before you are treated with this medicine if you:
 bruise and bleed easily
 are anaemic (have low red blood cells)
 are prone to getting infections
 have a history of seizures
 have liver problems or kidney problems particularly if you are on dialysis
 have diarrhoea
Tell your doctor immediately if during treatment you suffer from:
 problems with your vision such as blurred vision, changes in colour vision, difficulty in seeing
detail or if your field of vision becomes restricted.
 loss of sensitivity in your arms or legs or a sensation of tingling or pricking in your arms or legs.
 you may develop diarrhoea while taking or after taking antibiotics, including Linezolid . If this
becomes severe or persistent or you notice that your stool contains blood or mucus, you should
stop taking Linezolid immediately and consult your doctor. In this situation, you should not take
medicines that stop or slow bowel movement.
 recurrent nausea or vomiting, abdominal pain or rapid breathing.
Other medicines and Linezolid
There is a risk that Linezolid may sometimes interact with certain other medicines to cause side
effects such as changes in blood pressure, temperature or heart rate.

Tell your doctor if you are taking or have taken within the last 2 weeks the following
medicines as Linezolid must not be taken if you are already taking these medicines or have taken
them recently. (See also Section 2 above ‘Do not take Linezolid’).


monoamine oxidase inhibitors ( MAOIs for example phenelzine, isocarboxazid, selegiline,
moclobemide). These may be used to treat depression or Parkinson’s disease.

Also tell your doctor if you are taking the following medicines. Your doctor may still decide to give
you Linezolid, but will need to check your general health and your blood pressure before and during
your treatment. In other cases, your doctor may decide that another treatment is better for you.




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Decongestant cold or flu remedies containing pseudoephedrine or phenylpropanolamine.
Some medicines used to treat asthma such as salbutamol, terbutaline, fenoterol.
Certain antidepressants known as tricyclics or SSRIs (selective serotonin reuptake
inhibitors). There are many of these, including amitriptyline, cipramil, clomipramine,
dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine,
sertraline.
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Medicines used to treat migraine such as sumatriptan and zolmitriptan.
Medicines used to treat sudden, severe allergic reactions such as adrenaline (epinephrine).
Medicines which increase your blood pressure, such as noradrenaline (norepinephrine),
dopamine and dobutamine.
Medicines used to treat moderate to severe pain, such as pethidine.
Medicines used to treat anxiety disorders, such as buspirone.
Medicines that stop blood clotting, such as warfarin.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Linezolid with food and drink


You can take Linezolid either before, during or after a meal.



Avoid eating large amounts of mature cheese, yeast extracts, or soya bean extracts e.g. soy sauce
and drinking alcohol, especially draught beers and wine. This is because Linezolid may react
with a substance called tyramine which is naturally present in some foods. This interaction may
cause an increase in your blood pressure.



If you develop a throbbing headache after eating or drinking, tell your doctor or pharmacist
immediately.

Pregnancy and breast-feeding
The effect of Linezolid in pregnant women is not known. Therefore it should not be taken in
pregnancy unless advised by your doctor. Tell your doctor if you are pregnant, think you may be
pregnant or are trying to become pregnant.
You should not breast-feed when taking Linezolid because it passes into breast milk and could affect
the baby.
Driving and using machines
Linezolid may make you feel dizzy or experience problems with your vision. If this happens, do not
drive or operate any machinery. Remember that if you are unwell your ability to drive or operate
machinery may be affected.
Important information about some of the ingredients in Linezolid
Glucose
Each 1 ml of Linezolid solution contains 45.7 mg glucose (13.7 g glucose in one bag).
Please tell your doctor or nurse if you are diabetic.
Sodium
Each 1 ml of Linezolid solution contains 0.38 mg sodium (114 mg sodium in one bag).
Please tell your doctor or nurse if you are on a low sodium diet.
3.

How Linezolid is given

Adults
This medicine will be given to you through a drip (by infusion into a vein) by a doctor or healthcare
professional. The usual dose for adults (18 years and older) is 300 ml (600 mg linezolid) twice daily

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which is given directly into the blood stream (intravenously) by a drip over a period of 30 to 120
minutes.
If you are on kidney dialysis, you should be given Linezolid after dialysis treatment.
A course of treatment usually lasts 10 to 14 days, but can last up to 28 days. The safety and
effectiveness of this medicine have not been established for treatment periods longer than 28 days.
Your doctor will decide how long you should be treated.
While you are taking Linezolid, your doctor should perform regular blood tests to monitor your blood
count.
Your doctor should monitor your eyesight if you take Linezolid for more than 28 days.
Use in children
Linezolid is not normally used to treat children and adolescents (under 18 years old).
If you receive more Linezolid than you should
If you are concerned that you may have been given too much Linezolid, tell your doctor or a nurse at
once.
If you miss a dose of Linezolid
As you will be given this medicine under close supervision, it is very unlikely that you will miss a dose.
If you think that you have missed a dose of treatment, tell a doctor or nurse at once.
4.

Possible side effects

Like all medicines, Linezolid, can cause side effects, although not everybody gets them.
Tell your doctor, nurse or pharmacist immediately if you notice any of these side effects during
your treatment with Linezolid:






skin reactions such as red sore skin and flaking (dermatitis), rash, itching, or swelling,
particularly around the face and neck. This may be the sign of an allergic reaction and it may
be necessary for you to stop taking Linezolid.
problems with your vision such as blurred vision, changes in colour vision, difficulty in
seeing detail or if your field of vision becomes restricted.
severe diarrhoea containing blood and/or mucus (antibiotic associated colitis including
pseudomembranous colitis), which in rare circumstances may develop into complications that
are life-threatening.
recurrent nausea or vomiting, abdominal pain or rapid breathing.
fits or seizures have been reported with Linezolid . You should let your doctor know if you
experience agitation, confusion, delirium, rigidity, tremor, incoordination and seizure while
also taking antidepressants known as SSRI’s (see section 2).

Numbness, tingling or blurred vision have been reported by patients who have been given Linezolid
for more than 28 days. If you experience difficulties with your vision you should consult your doctor
as soon as possible.
Other side effects include:
Common side effects (likely to occur in less than 1 in 10 people):
 Fungal infections especially vaginal or oral “thrush”
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Headache
Metallic taste in the mouth
Diarrhoea, nausea or vomiting
Changes in some blood test results including those measuring your kidney or liver function or
blood sugar levels
Unexplained bleeding or bruising, which may be due to changes in the numbers of certain cells in
the blood which may affect blood clotting or lead to anaemia
Difficulty in sleeping
Increased blood pressure
Anaemia (low red blood cell)
Changes in numbers of certain cells in the blood which may affect your ability to fight infection
Skin rash
Itching skin
Dizziness
Localised or general abdominal pain
Constipation
Indigestion
Localised pain
Fever

Uncommon side effects (likely to occur in less than 1 in 100 people):
 Inflammation of the vagina or genital area in women
 Sensations such as tingling or feeling numb
 Blurred vision
 “Ringing” in the ears (tinnitus)
 Inflammation of the veins
 Dry or sore mouth, swollen, sore, or discoloured tongue
 Pain at and around the place where the infusion (drip) was given
 Inflammation of the veins (including where the infusion (drip) was given)
 A need to urinate more often
 Chills
 Feeling tired or thirsty
 Inflammation of the pancreas
 Increased sweating
 Changes in proteins, salts or enzymes in the blood which measure kidney or liver function
 Convulsions
 Hyponatraemia (low blood sodium levels)
 Kidney failure
 Reduction in platelets
 Abdominal bloating
 Transient ischaemic attacks (temporary disturbance of blood flow to the brain causing short term
symptoms such as loss of vision, leg and arm weakness, slurring of speech and loss of
consciousness)
 Injection site pain
 Inflammation of the skin
 Increase in creatinine
 Stomach pain
 Changes in heart rate (e.g. increase rate)
Rare side effects (likely to occur in less than 1 in 1000 people):
 Restricted field of vision
 Superficial tooth discolouration, removable with professional dental cleaning (manual descaling)
The following side effects have also been reported (frequency not known):
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Serotonin syndrome (symptoms include fast heart rate, confusion, abnormal sweating,
hallucinations, involuntary movements chills and shivering)
Lactic acidosis (symptoms include recurrent nausea and vomiting, abdominal pain, rapid
breathing)
Severe skin disorders
Sideroblastic anaemia ( a type of anaemia (low red blood cells))Alopecia (hair loss)
Changes in colour vision or difficulty in seeing detail
Decrease of the blood count
Weakness and/or sensory changes

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects
not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on
the safety of this medicine.
5.

How to store Linezolid

Hospital Staff will make sure that Linezolid Solution is not used after the “Use by” date printed on
the bag and that it is given to you as soon as the seal is broken. They will also visually inspect the
solution prior to use and only clear solution, without particles will be used. They will also make sure
that the solution is kept correctly in its box andfoil wrapping in order to protect from light and out of
the sight and reach of children until it is needed.
6.

Contents of the pack and other information

What Linezolid solution for infusion contains
-The active substance is linezolid. Each 1 ml of solution contains 2 mg linezolid.
-The other ingredients are glucose monohydrate (a type of sugar), sodium citrate (E331), citric acid
anhydrous (E330), hydrochloric acid (E507) or sodium hydroxide (E524) and water for injections.
What Linezolid solution for infusion looks like and contents of the pack
Linezolid solution for infusion is presented as a clear solution in single infusion bags containing
300 ml (600 mg linezolid) of solution.
The bags are supplied in boxes of 1, 2, 5, 10, 20 or 25 bags.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer

The Marketing Authorisation Holder
Pfizer Limited
Ramsgate Road, Sandwich,
Kent, CT13 9NJ, United Kingdom
Manufacturer
The manufacturer is Fresenius Kabi Norge AS, Svinesundveien 80, N-1789 Berg I Ostfold, Halden,
Norway.
This medicinal product is authorised in the Member States of the EEA under the following names:
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Belgium

Linezolid Pfizer

Finland

Linezolid Pfizer

Luxembourg

Linezolid Pfizer

United Kingdom Linezolid
This leaflet was last revised in 04/2014
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A Guide for Hospital Staff
Linezolid 2 mg/ ml solution for infusion
Linezolid
IMPORTANT: Refer to Summary of Product Characteristics before prescribing.
Linezolid is not active against infections caused by Gram negative pathogens. Specific therapy
against Gram negative organisms must be initiated concomitantly if co-infection with a Gram
negative pathogen is documented or suspected.
Description
Single use, ready-to-use, latex-free, multilayered polyolefine film infusion bags (Excel or Freeflex)
sealed inside a foil laminate overwrap. The bag holds 300 ml solution and is packaged in a box. Each
box contains 1, 2, 5, 10*, 20 or 25 infusion bags.
Note:
*Only boxes of 10 bags are currently marketed.
Linezolid 2 mg/ml Solution for Infusion contains linezolid 2 mg/ml in an isotonic, clear, colourless to
yellow solution. Other ingredients are: glucose monohydrate, sodium citrate (E331), citric acid
anhydrous (E330), hydrochloric acid (E507) or sodium hydroxide (E524), water for injections.
Dosage and method of administration
Linezolid should only be initiated in a hospital environment and after consultation with a relevant
specialist such as a microbiologist or an infectious diseases specialist.
Patients who commence treatment on the parenteral formulation may be switched to either oral
presentation when clinically indicated. In such circumstances, no dose adjustment is required as
linezolid has an oral bioavailability of approximately 100 %.
The solution for infusion should be administered over a period of 30 to 120 minutes.
The recommended linezolid dosage should be administered IV or orally twice daily.
Recommended dosage and duration for adults:
The duration of treatment is dependent on the pathogen, the site of infection and its severity, and on
the patient’s clinical response.
The following recommendations for duration of therapy reflect those used in the clinical trials.
Shorter treatment regimens may be suitable for some types of infection but have not been evaluated
in clinical trials.
The maximum treatment duration is 28 days. The safety and effectiveness of linezolid have not yet
been established for treatment periods longer than 28 days.
No increase in the recommended dosage or duration of treatment is required for infections associated
with concurrent bacteraemia. The dose recommendation for the solution for infusion and the
tablets/granules for oral suspension are identical and are as follows:
Infections
Nosocomial pneumonia
Community acquired
pneumonia
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Dosage and route for twice
daily administration
600 mg twice daily

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Duration of treatment
10-14 Consecutive Days

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Complicated skin and soft
tissue infections

600 mg twice daily

Children: There are insufficient data on the pharmacokinetics, safety and efficacy of linezolid in
children and adolescents (< 18 years old) to establish dosage recommendations. Therefore, until
further data are available, use of linezolid in this age group is not recommended.
Elderly patients: No dose adjustment is required.
Patients with renal insufficiency: No dose adjustment is required.
Patients with severe renal insufficiency (i.e. CLCR < 30 ml/min): No dose adjustment is required.
Due to the unknown clinical significance of higher exposure (up to 10-fold) to the two primary
metabolites of linezolid in patients with severe renal insufficiency, linezolid should be used with
special caution in these patients and only when the anticipated benefit is considered to outweigh the
theoretical risk.
As approximately 30 % of a linezolid dose is removed during 3 hours of haemodialysis, Linezolid
should be given after dialysis in patients receiving such treatment. 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 insufficiency. Therefore, linezolid should be used with special
caution in patients with severe renal insufficiency who are undergoing dialysis, and only when the
anticipated benefit is considered to outweigh the theoretical risk.
To date, there is no experience of linezolid administration to patients undergoing continuous
ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal failure (other than
haemodialysis).
Patients with hepatic insufficiency: Patients with mild to moderate hepatic insufficiency (ChildPugh class A or B): No dose adjustment is required.
Patients with severe hepatic insufficiency (Child-Pugh class C): As linezolid is metabolised by a nonenzymatic process, impairment of hepatic function would not be expected to significantly alter its
metabolism and, therefore, no dose adjustment is recommended. However, there are no
pharmacokinetic data and limited clinical experience of Linezolid in patients with severe hepatic
insufficiency. Linezolid should be used with special caution in patients with severe hepatic
insufficiency and only when the anticipated benefit is considered to outweigh the theoretical risk.
Contraindications
Hypersensitivity to linezolid or to any of the excipients.
Linezolid should not be used in patients taking any medicinal product which inhibits monoamine
oxidases A or B (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks of
taking any such medicinal drug.
Unless there are facilities available for close observation and monitoring of blood pressure, linezolid
should not be administered to patients with the following underlying clinical conditions or on the
following types of concomitant medications:
• Patients with uncontrolled hypertension, phaeochromocytoma, carcinoid, thyrotoxicosis, bipolar
depression, schizoaffective disorder, acute confusional states.
• Patients taking any of the following medications: Serotonin re-uptake inhibitors, tricyclic
antidepressants, serotonin 5-HT1 receptor agonists (triptans), directly and indirectly acting
sympathomimetic agents (including the adrenergic bronchodilators, pseudoephedrine and
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phenylpropanolamine), vasopressive agents (e.g. adrenaline / epinephrine, noradrenaline /
norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), pethidine or buspirone.
Breast feeding should be discontinued prior to and throughout administration.
Special warnings and precautions for use
Myelosuppression
Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been
reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was
discontinued, the affected haematologic parameters have risen toward pretreatment levels. The risk
of these effects appears to be related to the duration of treatment. Elderly patients treated with
linezolid may be at greater risk of experiencing blood dyscrasias than younger patients.
Thrombocytopenia may occur more commonly in patients with severe renal insufficiency, whether or
not on dialysis. Therefore, close monitoring of blood counts is recommended in patients who: have
pre-existing anaemia, granulocytopenia or thrombocytopenia; are receiving concomitant medications
that may decrease haemoglobin levels, depress blood counts or adversely affect platelet count or
function; have severe renal insufficiency; receive more than 10-14 days of therapy. Linezolid should
be administered to such patients only when close monitoring of haemoglobin levels, blood counts and
platelet counts is possible.
If significant myelosuppression occurs during linezolid therapy, treatment should be stopped unless it
is considered absolutely necessary to continue therapy, in which case intensive monitoring of blood
counts and appropriate management strategies should be implemented.
In addition, it is recommended that complete blood counts (including haemoglobin levels, platelets,
and total and differentiated leucocyte counts) should be monitored weekly in patients who receive
linezolid regardless of baseline blood count.
In compassionate use studies, a higher incidence of serious anaemia was reported in patients
receiving linezolid for more than the maximum recommended duration of 28 days. These patients
more often required blood transfusion. Cases of anaemia requiring blood transfusion have also been
reported post marketing, with more cases occurring in patients who received linezolid therapy for
more than 28 days.
Cases of sideroblastic anaemia have been reported post-marketing. Where time of onset was known,
most patients had received linezolid therapy for more than 28 days. Most patients fully or partially
recovered following discontinuation of linezolid with or without treatment for their anaemia.
Mortality imbalance in a clinical trial in patients with catheter-related Gram positive bloodstream
infections
Excess mortality was seen in patients treated with linezolid, relative to
vancomycin/dicloxacillin/oxacillin, in an open-label study in seriously ill patients with intravascular
catheter-related infections [78/363 (21.5%) vs 58/363 (16.0%)]. The main factor influencing the
mortality rate was the Gram positive infection status at baseline. Mortality rates were similar in
patients with infections caused purely by Gram positive organisms (odds ratio 0.96; 95% confidence
interval: 0.58-1.59) but were significantly higher (p=0.0162) in the linezolid arm in patients with any
other pathogen or no pathogen at baseline (odds ratio 2.48; 95% confidence interval: 1.38-4.46). The
greatest imbalance occurred during treatment and within 7 days following discontinuation of study
drug. More patients in the linezolid arm acquired Gram negative pathogens during the study and died
from infection caused by Gram negative pathogens and polymicrobial infections. Therefore, in
complicated skin and soft tissue infections linezolid should only be used in patients with known or
possible co-infection with Gram negative organisms if there are no alternative treatment options
available. In these circumstances treatment against Gram negative organisms must be initiated
concomitantly.
Antibiotic-associated diarrhoea and colitis
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Pseudomembranous colitis has been reported with nearly all antibacterial agents, including linezolid.
Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent
to the administration of any antibacterial agent. In cases of suspected or verified antibiotic-associated
colitis, discontinuation of linezolid may be warranted. Appropriate management measures should be
instituted.
Antibiotic-associated diarrhoea and antibiotic-associated colitis, including pseudomembranous colitis
and Clostridium difficile-associated diarrhoea, has been reported in association with the use of nearly
all antibiotics including linezolid and may range in severity from mild diarrhoea to fatal colitis.
Therefore, it is important to consider this diagnosis in patients who develop serious diarrhoea during
or after the use of linezolid. If antibiotic-associated diarrhoea or antibiotic-associated colitis is
suspected or confirmed, ongoing treatment with antibacterial agents, including linezolid, should be
discontinued and adequate therapeutic measures should be initiated immediately. Drugs inhibiting
peristalsis are contraindicated in this situation.
Lactic acidosis
Lactic acidosis has been reported with the use of linezolid. Patients who develop signs and symptoms
of metabolic acidosis including recurrent nausea or vomiting, abdominal pain, a low bicarbonate
level, or hyperventilation while receiving linezolid should receive immediate medical attention. If
lactic acidosis occurs, the benefits of continued use of linezolid should be weighed against the
potential risks.
Mitochondrial dysfunction
Linezolid inhibits mitochondrial protein synthesis. Adverse events, such as lactic acidosis, anaemia
and neuropathy (optic and peripheral), may occur as a result of this inhibition; these events are more
common when the drug is used longer than 28 days.
Serotonin syndrome
Spontaneous reports of serotonin syndrome associated with the co-administration of linezolid and
serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs)
have been reported. Co-administration of linezolid and serotonergic agents is therefore
contraindicated except where administration of linezolid and concomitant serotonergic agents is
essential. In those cases patients should be closely observed for signs and symptoms of serotonin
syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or
symptoms occur physicians should consider discontinuing either one or both agents; if the
concomitant serotonergic agent is withdrawn, discontinuation symptoms can occur.
Peripheral and optic neuropathy
Peripheral neuropathy, as well as optic neuropathy and optic neuritis sometimes progressing to loss of
vision, have been reported in patients treated with Linezolid; these reports have primarily been in
patients treated for longer than the maximum recommended duration of 28 days.
All patients should be advised to report symptoms of visual impairment, such as changes in visual
acuity, changes in colour vision, blurred vision, or visual field defect. In such cases, prompt
evaluation is recommended with referral to an ophthalmologist as necessary. If any patients are taking
Linezolid for longer than the recommended 28 days, their visual function should be regularly
monitored.
If peripheral or optic neuropathy occurs, the continued use of Linezolid should be weighed against
the potential risks.
There may be an increased risk of neuropathies when linezolid is used in patients currently taking or
who have recently taken antimycobacterial medications for the treatment of tuberculosis.

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Convulsions
Convulsions have been reported to occur in patients when treated with Linezolid. In most of these
cases, a history of seizures or risk factors for seizures was reported. Patients should be advised to
inform their physician if they have a history of seizures.
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); however, at the
doses used for antibacterial therapy, it does not exert an anti-depressive effect. There are very limited
data from drug interaction studies and on the safety of linezolid when administered to patients with
underlying conditions and/or on concomitant medications which might put them at risk from MAO
inhibition. Therefore, linezolid is not recommended for use in these circumstances unless close
observation and monitoring of the recipient is possible.
Use with tyramine-rich foods
Patients should be advised against consuming large amounts of tyramine rich foods.
Superinfection
The effects of linezolid therapy on normal flora have not been evaluated in clinical trials.
The use of antibiotics may occasionally result in an overgrowth of non-susceptible organisms. For
example, approximately 3% of patients receiving the recommended linezolid doses experienced drugrelated candidiasis during clinical trials. Should superinfection occur during therapy, appropriate
measures should be taken.
Special populations
Linezolid should be used with special caution in patients with severe renal insufficiency and only
when the anticipated benefit is considered to outweigh the theoretical risk (see sections 4.2 and 5.2).
It is recommended that linezolid should be given to patients with severe hepatic insufficiency only
when the perceived benefit outweighs the theoretical risk.
Impairment of fertility
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.
Clinical trials
The safety and effectiveness of linezolid when administered for periods longer than 28 days have not
been established.
Controlled clinical trials did not include patients with diabetic foot lesions, decubitus or ischaemic
lesions, severe burns or gangrene. Therefore, experience in the use of linezolid in the treatment of
these conditions is limited.
Excipients
Each ml of the solution contains 45.7 mg (i.e. 13.7 g/300 ml) glucose. This should be taken into
account in patients with diabetes mellitus or other conditions associated with glucose intolerance.
Each ml of solution also contains 0.38 mg (114 mg/300 ml) sodium. The sodium content should be
taken into account in patients on a controlled sodium diet.
Interactions
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI). There are very
limited data from drug interaction studies and on the safety of linezolid when administered to patients
on concomitant medications that might put them at risk from MAO inhibition. Therefore, linezolid is
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not recommended for use in these circumstances unless close observation and monitoring of the
recipient is possible.
Potential interactions producing elevation of blood pressure
In normotensive healthy volunteers, linezolid enhanced the increases in blood pressure caused by
pseudoephedrine and phenylpropanolamine hydrochloride. Co-administration of linezolid with either
pseudoephedrine or phenylpropanolamine resulted in mean increases in systolic blood pressure of the
order of 30-40 mm Hg, compared with 11-15 mm Hg increases with linezolid alone, 14-18 mm Hg
with either pseudoephedrine or phenylpropanolamine alone and 8-11 mm Hg with placebo. Similar
studies in hypertensive subjects have not been conducted. It is recommended that doses of drugs with
a vasopressive action, including dopaminergic agents, should be carefully titrated to achieve the
desired response when co-administered with linezolid.
Potential serotonergic interactions
The potential drug-drug interaction with dextromethorphan was studied in healthy volunteers.
Subjects were administered dextromethorphan (two 20 mg doses given 4 hours apart) with or without
linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing,
diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and
dextromethorphan.
Post marketing experience: there has been one report of a patient experiencing serotonin syndromelike effects while taking linezolid and dextromethorphan which resolved on discontinuation of both
medications.
During clinical use of linezolid with serotonergic agents, including antidepressants such as selective
serotonin reuptake inhibitors (SSRIs), cases of serotonin syndrome have been reported. Therefore,
while co-administration is contraindicated, management of patients for whom treatment with
linezolid and serotonergic agents is essential, is described in special warnings and precautions for
use.
Use with tyramine-rich foods
No significant pressor response was observed in subjects receiving both linezolid and less than 100
mg tyramine. This suggests that it is only necessary to avoid ingesting excessive amounts of food and
beverages with a high tyramine content (e.g. mature cheese, yeast extracts, undistilled alcoholic
beverages and fermented soya bean products such as soy sauce).
Drugs metabolised by cytochrome P450
Linezolid is not detectably metabolised by the cytochrome P450 (CYP) enzyme system and it does
not inhibit any of the clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4).
Similarly, linezolid does not induce P450 isoenzymes in rats. Therefore, no CYP450-induced drug
interactions are expected with linezolid.
Rifampicin
The effect of rifampicin on the pharmacokinetics of linezolid was studied in sixteen healthy adult
male volunteers administered linezolid 600 mg twice daily for 2.5 days with and without rifampicin
600 mg once daily for 8 days. Rifampicin decreased the linezolid Cmax and AUC by a mean 21%
[90% CI, 15, 27] and a mean 32% [90% CI, 27, 37], respectively. The mechanism of this interaction
and its clinical significance are unknown.
Warfarin
When warfarin was added to linezolid therapy at steady-state, there was a 10% reduction in mean
maximum INR on co-administration with a 5% reduction in AUC INR. There are insufficient data
from patients who have received warfarin and linezolid to assess the clinical significance, if any, of
these findings.
Fertility, pregnancy and lactation
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There are no adequate data from the use of linezolid in pregnant women. Studies in animals have
shown reproductive toxicity. A potential risk for humans exists.
Linezolid should not be used during pregnancy unless clearly necessary i.e. only if the potential
benefit outweighs the theoretical risk.
Animal data suggest that linezolid and its metabolites may pass into breast milk and, accordingly,
breastfeeding should be discontinued prior to and throughout administration.
In animal studies, linezolid caused a reduction in fertility.
Effects on ability to drive and use machines
Patients should be warned about the potential for dizziness or symptoms of visual impairment whilst
receiving Linezolid and should be advised not to drive or operate machinery if any of these symptoms
occurs.
Undesirable effects
The table below provides a listing of adverse drug reactions with frequency based on all-causality
data from clinical studies that enrolled more than 2,000 adult patients who received the recommended
linezolid doses for up to 28 days. Those most commonly reported were diarrhoea (8.4%), headache
(6.5%), nausea (6.3%) and vomiting (4.0%).
The most commonly reported drug-related adverse events which led to discontinuation of treatment
were headache, diarrhoea, nausea and vomiting. About 3 % of patients discontinued treatment
because they experienced a drug-related adverse event.
Additional adverse reactions reported from post-marketing experience are included in the table with
frequency category ‘Not known’, since the actual frequency cannot be estimated from the available
data.
The following undesirable effects have been observed and reported during treatment with linezolid
with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon
(≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); Not known (cannot be
estimated from the available data)
System Organ
Class

Common
(≥1/100 to
<1/10)

Uncommon
(≥1/1,000 to <1/100)

Infections and
infestations

candidiasis, oral vaginitis
candidiasis,
vaginal
candidiasis,
fungal infections

Blood and the
lymphatic
system disorders

anaemia*†

Immune system
disorders
Metabolism and
nutrition
disorders
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leucopenia*,
neutropenia,
thrombocytopenia*,
eosinophilia

Rare
(≥1/10,000 to
<1/1,000)
antibioticassociated
colitis,
including
pseudomembra
nous colitis*
pancytopenia*

Very Rare
(<1/10,000)

Frequency not
known (cannot
be estimated
from available
data)

myelosuppression
*, sideroblastic
anaemia*
anaphylaxis

hyponatraemia

Ref: ddZY 4_2

lactic acidosis*

PFLEET: 2014-5207 (2013-3466)

System Organ
Class

Psychiatric
disorders
Nervous system
disorders

Common
(≥1/100 to
<1/10)

Uncommon
(≥1/1,000 to <1/100)

Rare
(≥1/10,000 to
<1/1,000)

Very Rare
(<1/10,000)

Frequency not
known (cannot
be estimated
from available
data)

insomnia
headache, taste
perversion
(metallic taste),
dizziness

convulsions*,
hypoaesthesia,
paraesthesia

Eye disorders

blurred vision*

Ear and
labyrinth
disorders
Cardiac
disorders
Vascular
disorders

tinnitus

Gastrointestinal
disorders

Hepato-biliary
disorders

Skin and
subcutaneous
tissue disorders

Renal and
urinary
disorders
Reproductive
system and
breast disorders
General
disorders and
Page 15 of 17

hypertension
diarrhoea,
nausea,
vomiting,
localised or
general
abdominal pain,
constipation,
dyspepsia
abnormal liver
function test;
increased AST,
ALT or alkaline
phosphatase
pruritus, rash

arrhythmia
(tachycardia)
transient ischaemic
attacks, phlebitis,
thrombophlebitis
pancreatitis, gastritis,
abdominal distention,
dry mouth, glossitis,
loose stools,
stomatitis, tongue
discolouration or
disorder

changes in
visual field
defect*

serotonin
syndrome**,
peripheral
neuropathy*
optic neuropathy*,
optic neuritis*,
loss of vision*,
changes in visual
acuity*, changes
in colour vision*

superficial
tooth
discolouration

increased total
bilirubin

urticaria, dermatitis,
diaphoresis

increased BUN

renal failure,
increased creatinine,
polyuria
vulvovaginal
disorder

fever, localised
pain

bullous disorders
such as those
described as
Stevens-Johnson
syndrome and
toxic epidermal
necrolysis,
angioedema,
alopecia

chills, fatigue,
injection site pain,
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System Organ
Class

administration
site conditions
Investigations

Common
(≥1/100 to
<1/10)

Uncommon
(≥1/1,000 to <1/100)

Rare
(≥1/10,000 to
<1/1,000)

Very Rare
(<1/10,000)

Frequency not
known (cannot
be estimated
from available
data)

increased thirst
Chemistry
Increased LDH,
creatine kinase,
lipase, amylase
or non fasting
glucose.
Decreased total
protein,
albumin, sodium
or calcium.
Increased or
decreased
potassium or
bicarbonate.
Haematology
Increased
neutrophils or
eosinophils.
Decreased
haemoglobin,
haematocrit or
red blood cell
count. Increased
or decreased
platelet or white
blood cell
counts.

Chemistry
Increased sodium or
calcium. Decreased
non fasting glucose.
Increased or
decreased chloride.

Haematology
Increased
reticulocyte count.
Decreased
neutrophils.

* See section Special warnings and precautions for use
** See sections Contraindications and Interactions
† See below
The following adverse reactions to linezolid were considered to be serious in rare cases: localised
abdominal pain, transient ischaemic attacks and hypertension.
† In controlled clinical trials where linezolid was administered for up to 28 days, 2.0% of the patients
reported anaemia. In a compassionate use program of patients with life-threatening infections and
underlying co-morbidities, the percentage of patients who developed anaemia when receiving
linezolid for ≤28 days was 2.5% (33/1326) as compared with 12.3% (53/430) when treated for > 28
days. The proportion of cases reporting drug-related serious anaemia and requiring blood transfusion
was 9% (3/33) in patients treated for ≤ 28 days and 15% (8/53) in those treated for >28 days.
Paediatric population
Safety data from clinical studies based on more than 500 paediatric patients (from birth to 17 years)
do not indicate that the safety profile of linezolid for paediatric patients differs from that for adult
patients.

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Overdose
No specific antidote is known.
No cases of overdose have been reported. However, the following information may prove useful:
Supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of
a linezolid dose is removed during 3 hours of haemodialysis, but no data are available for the removal
of linezolid by peritoneal dialysis or haemoperfusion.
Instructions for use and handling
For single use only. Remove overwrap only when ready to use, then check for minute leaks by
squeezing the bag firmly. If the bag leaks, do not use as sterility may be impaired. The solution
should be visually inspected prior to use and only clear solutions, without particles should be used.
Do not use these bags in series connections. Any unused solution must be discarded. Do not
reconnect partially used bags.
Linezolid Solution for Infusion is compatible with the following solutions: 5 % glucose intravenous
infusion, 0.9 % sodium chloride intravenous infusion, Ringer-lactate solution for injection
(Hartmann’s solution for injection).
Incompatibilities
Additives should not be introduced into this solution. If linezolid is to be given concomitantly with
other drugs, each drug should be given separately in accordance with its own directions for use.
Similarly, if the same intravenous line is to be used for sequential infusion of several drugs, the line
should be flushed prior to and following linezolid administration with a compatible infusion solution.
Linezolid Solution for Infusion is known to be physically incompatible with the following
compounds: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate,
erythromycin lactobionate, phenytoin sodium and sulphamethoxazole / trimethoprim. Additionally, it
is chemically incompatible with ceftriaxone sodium.
Shelf life
Before opening: 3 years
After opening: From a microbiological point of view, unless the method of opening precludes the risk
of microbial contamination, the product should be used immediately. If not used immediately, in-use
storage times and conditions are the responsibility of the user.
Special precautions for storage
Store in the original package (overwrap and carton) until ready to use, in order to protect from light.
For further information please contact the Medical Information at Pfizer:
Pfizer Limited, Walton Oaks, Dorking Road, Walton-on-the-Hill, Surrey, KT20 7NS, UK
Tel: 01304 616 161
Fax: 01737 332507
Ref; ddZY 4_2

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Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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