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LINEZOLID PFIZER 2 MG/ML SOLUTION FOR INFUSION

Active substance(s): LINEZOLID

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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 side effects, talk to your doctor or pharmacist. This includesany 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 Pfizer 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 Pfizer

You should not be treated with Linezolid Pfizer:
 if you are allergic to linezolid or any of the other ingredients of this medicine (listed in
section 6).
 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?
Page 1 of 18





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?
-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 Pfizer
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 Pfizer
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 Pfizer’).


monoamine oxidase inhibitors ( MAOIs for example phenelzine, isocarboxazid,
selegiline, moclobemide). These may be used to treat depression or Parkinson’s
disease
Page 2 of 18

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.











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.
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 Pfizer 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, breast-feeding and fertility
The effect of Linezolid in pregnant women is not known. Therefore it should not be taken in
pregnancy unless advised by your doctor. If you are pregnant, think you may be pregnant or
are planning to have a baby, ask your doctor or pharmacist for advice before taking this
medicine.
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 Pfizer
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.
Page 3 of 18

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 Pfizer 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 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 Pfizer 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 Pfizer
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).
Page 4 of 18

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 (may affect up to 1 in 10 people):
 Fungal infections especially vaginal or oral “thrush”
 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 (may affect up to 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
Page 5 of 18

 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 (may affect up to 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 (Not known: frequency cannot be
estimated from the available data):
 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, pharmacist or nurse. 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 Pfizer

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton, bags and
overwrap after exp. The expiry date refers to the last day of that month.
Hospital Staff will make sure that Linezolid Pfizer 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.
After opening:

Page 6 of 18

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
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist
how to throw away medicines you no longer use. These measures will help protect the
environment.
6.

Contents of the pack and other information

What Linezolid Pfizer solution for infusion contains
-The active substance is linezolid. Each 1 ml of solution contains 2 mg linezolid. Each 300
ml infusion bag contains 600 mg linezolid.
-The other ingredients are glucose monohydrate (a type of sugar, see section 2), sodium citrate
(E331, see section 2), citric acid anhydrous (E330) and water for injections.
What Linezolid Pfizer 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 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 Ltd
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:
Austria 
France 
Germany 
Greece 
Ireland 
Italy 
Netherlands 
Portugal 
United Kingdom 

Linezolid Pfizer
Linezolid Pfizer 2mg/ml solution pour perfusion
Linezolid Pfizer 2mg/ml Infusionslösung
Linezolid Pfizer
Linezolid Pfizer 2mg/ml Solution for Infusion
Linezolid Pfizer
Linezolid Pfizer 2mg/ml oplossing voor infusie
Linezolid Pfizer
Linezolid Pfizer 2mg/ml Solution for Infusion

This leaflet was last revised in (12/2014)

Page 7 of 18

A Guide for Hospital Staff
Linezolid Pfizer 2mg/ 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 (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 Pfizer 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 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

Dosage and route for
twice daily administration
600 mg twice daily

Page 8 of 18

Duration of treatment
10-14 Consecutive Days

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
(Child-Pugh class A or B): No dose adjustment is required.
Patients with severe hepatic insufficiency (Child-Pugh class C): As linezolid is metabolised
by a non-enzymatic 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
Patients hypersensitive to linezolid or 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.
Page 9 of 18

• 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
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.

Page 10 of 18

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
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
Page 11 of 18

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.
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 drug-related 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.
Page 12 of 18

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 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 coadministered 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
syndrome-like 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.
Page 13 of 18

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
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, breast-feeding 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 allcausality 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.

Page 14 of 18

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

Infections and
infestations

Blood and the
lymphatic
system
disorders
Immune
system
disorders
Metabolism
and nutrition
disorders
Psychiatric
disorders
Nervous
system
disorders

Common
(≥1/100 to
<1/10)
candidiasis,
oral
candidiasis,
vaginal
candidiasis,
fungal
infections
anaemia*†

Uncommon
(≥1/1,000 to
<1/100)
vaginitis

Rare
(≥1/10,000 to
<1/1,000)

Very Rare
(<1/10,000
)

Frequency not
known (cannot
be estimated
from available
data)

antibioticassociated
colitis,
including
pseudomembr
anous colitis*

pancytopenia*
leucopenia*,
neutropenia,
thrombocytopenia*,
eosinophilia

myelosuppressio
n*, sideroblastic
anaemia*
anaphylaxis

hyponatraemia

lactic acidosis*

convulsions*,
hypoaesthesia,
paraesthesia

serotonin
syndrome**,
peripheral
neuropathy*

insomnia
headache, taste
perversion
(metallic
taste),
dizziness

Eye disorders

blurred vision*

Ear and
labyrinth
disorders
Cardiac
disorders
Vascular
disorders

tinnitus

hypertension

Gastrointestina diarrhoea,

arrhythmia
(tachycardia)
transient ischaemic
attacks, phlebitis,
thrombophlebitis
pancreatitis,
Page 15 of 18

changes in
visual field
defect*

superficial

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

System Organ
Class

l disorders

Hepato-biliary
disorders

Skin and
subcutaneous
tissue disorders

Renal and
urinary
disorders
Reproductive
system and
breast
disorders
General
disorders and
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)

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

gastritis, abdominal
distention, dry
mouth, glossitis,
loose stools,
stomatitis, tongue
discolouration or
disorder

tooth
discolouration

Very Rare
(<1/10,000
)

Frequency not
known (cannot
be estimated
from available
data)

increased total
bilirubin

urticaria,
dermatitis,
diaphoresis

increased BUN renal failure,
increased
creatinine, polyuria
vulvovaginal
disorder
fever, localised
pain

chills, fatigue,
injection site pain,
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.

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

Page 16 of 18

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

System Organ
Class

Common
(≥1/100 to
<1/10)

Haematology
Increased
neutrophils or
eosinophils.
Decreased
haemoglobin,
haematocrit or
red blood cell
count.
Increased or
decreased
platelet or
white blood
cell counts.

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)

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.
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
Page 17 of 18

should be used. Do not use these bags in series connections. Any unused solution must be
discarded. Do not reconnect partially used bags.
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 Pfizer 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
This leaflet was approved in
® is a Registered Trademark.
© Pharmacia Limited 2005.
ZY 8_0

Page 18 of 18

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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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