Skip to Content

LINEZOLID 2 MG/ ML SOLUTION FOR INFUSION

View full screen / Print PDF » Download PDF ⇩

PDF Transcript

Package leaflet: Information for the user

Linezolid 2 mg/ml
solution for infusion


01‑59‑12‑028_subm
FPO

Read all of this leaflet carefully before you start taking this medicine
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,
pharmacist or nurse.
- If you get any side effects, talk to your doctor, pharmacist or
nurse. This includes any possible side effects not listed in this
leaflet. See section 4.
What is in this leaflet
Linezolid is and what it is used for
1. What

you need to know before you take Linezolid
2. What

to take Linezolid
3. How

4. Possible
side effects

to store Linezolid
5. How

of the pack and other information
6. Contents


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
Do not take Linezolid:
• 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
Talk to your doctor, pharmacist or nurse before taking Linezolid.
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?

Take special care with Linezolid
Tell your doctor before you take 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 or pharmacist if you are taking or have recently
taken any other medicines.

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.
• 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, citalopram, 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.
• An antibiotic called rifampicin.

Linezolid with food, drink and alcohol
• 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, pharmacist or nurse 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 or breast-feeding, 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.
Linezolid contains
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

to take Linezolid
Adults
Always take this medicine exactly as described in this leaflet or as
your doctor, pharmacist or nurse has told you. Check with your
doctor, pharmacist or nurse if you are not sure.
This medicine will be given to you through a drip (by infusion into
a vein) by a doctor or healthcare professional. The recommended
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 take Linezolid after your
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 and adolescents
Linezolid is not normally used to treat children and adolescents
(under 18 years old).

DETACH HERE

The following information is intended for
healthcare professionals only:

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 dihydrate (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
intravenously (I.V.) 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
Complicated skin
and soft tissue
infections

Dosage and route Duration of treatment
for twice daily
administration
600 mg twice
daily
10-14 Consecutive Days
600 mg twice
daily

Paediatric population: The safety and efficacy of linezolid in
children aged (< 18 years old) has not been established.
Currently available data are described in section 4.8,
5.1, and 5.2 of the SmPC but no recommendation on a
posology can be made.
Elderly: No dose adjustment is required.
Renal impairment: No dose adjustment is required.
Severe renal impairment (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).
Hepatic impairment: Patients with mild to moderate hepatic
insufficiency (Child-Pugh class A or B): No dose adjustment
is required.
Severe hepatic impairment (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 limited clinical data and
it is recommended that linezolid should be used in such
patients only when the anticipated benefit is considered to
outweigh the theoretical risk (see sections 4.4 and 5.2).
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 product.
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 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 (see section 4.6 of SmPC).
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 postmarketing. 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 catheterrelated 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
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 antibioticassociated 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. Coadministration 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.
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 of the SmPC).
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 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

If you use 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 forget to use 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. Do not take a
double dose to make up for a forgotten dose.

4. Possible side effects
Like all medicines, this medicine 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:
The serious side effects (with frequency in brackets) of Linezolid
are:
• Severe skin disorder (not known), swelling particularly around
the face and neck (not known), wheezing and/or difficulty
breathing (not known). This may be the sign of an allergic
reaction and it may be necessary for you to stop taking
Linezolid. Skin reactions such as red sore skin and flaking
(dermatitis) (uncommon), rash (common), itching (common).
• Problems with your vision such as blurred vision (uncommon),
changes in colour vision (not known), difficulty in seeing detail
(not known) or if your field of vision becomes restricted (rare).
• 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 (rare).
• Recurrent nausea or vomiting, abdominal pain or rapid
breathing (not known).

• Fits or seizures (uncommon) 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
SSRIs (see section 2) (not known).

• 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 (common).
• Changes in numbers of certain cells in the blood which may
affect your ability to fight infection (common) some signs of
infection include: any fever (common), sore throat (uncommon),
mouth ulcers (uncommon) and tiredness (uncommon).
• Inflammation of the pancreas (uncommon).

Convulsions (uncommon).
• 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) (uncommon).
• “Ringing” in the ears (tinnitus) (uncommon).
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 (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


in sleeping
• Difficulty
• Increased

blood pressure
• Anaemia

(low red blood cell)
• Dizziness
• Localised

or general abdominal pain
• Constipation
• Indigestion
• Localised pain
Uncommon (may affect up to 1 in 100 people):
• Inflammation

of the vagina or genital area in women
• Sensations

such as tingling or feeling numb

• 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)
 need to urinate more often
• A
• Chills
• Feeling thirsty
• Increased sweating
• Changes

in proteins, salts or enzymes in the blood which
measure kidney or liver function
• Hyponatraemia

(low blood sodium levels)
• Kidney failure
in platelets
• Reduction

• Abdominal bloating
• Injection

site pain
• Increase

in creatinine
• Stomach pain
• Changes

in heart rate (e.g., increase rate)
Rare (may affect up to 1 in 1,000 people):
• 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):
• Alopecia

(hair loss)

of the blood cell count
• Decrease
• Weakness

and/or sensory changes
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
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 Solution is not used
after the “EXP” 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 and foil wrapping in order to protect from light
and out of the sight and reach of children until it is needed.
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.

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.

This leaflet was last revised in 09/2016
Ref: ddZY 9_0

6. Contents of the pack and other information
What Linezolid 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 dihydrate (E331, see section 2),
citric acid anhydrous (E330, see section 2), hydrochloric acid
(E507) or sodium hydroxide (E524) and water for injections.
What Linezolid 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.
The Marketing Authorisation Holder
Pfizer Limited
Ramsgate Road, Sandwich,
Kent, CT13 9NJ, United Kingdom
Manufacturer
The manufacturer is Fresenius Kabi Norge AS, Svinesundveien 80,
NO-1788, Halden, Norway.
This medicinal product is authorised in the Member States of the
EEA under the following names:
B
 elgium Linezolid Pfizer
F  inland Linezolid Pfizer
L  uxembourg Linezolid Pfizer
U
 nited Kingdom Linezolid

DETACH HERE

or without linezolid. No serotonin syndrome effects (confusion,
delirium, restlessness, tremors, blushing, diaphoresis and
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.
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
Pregnancy
There are limited 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.
Breast-feeding
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.
Fertility
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)

Infections and
infestations

candidiasis, oral candidiasis,
vaginal candidiasis, fungal
infections

Blood and the
lymphatic system
disorders

anaemia*†

Immune system
disorders
Metabolism and
nutrition disorders
Psychiatric disorders insomnia
Nervous system
headache, taste perversion
disorders
(metallic taste), dizziness
Eye disorders

Ear and labyrinth
disorders
Cardiac disorders
Vascular disorders
Gastrointestinal
disorders

Hepato-biliary
disorders

Uncommon
Rare
Very Rare Frequency not known
(≥1/1,000 to <1/100) (≥1/10,000 to <1/1,000) (<1/10,000) (cannot be estimated from
available data)
vaginitis
antibiotic-associated
colitis, including
pseudomembranous
colitis*
leucopenia*,
pancytopenia*
myelosuppression*,
neutropenia,
sideroblastic anaemia*
thrombocytopenia*,
eosinophilia
anaphylaxis
hyponatraemia

lactic acidosis*

convulsions*,
hypoaesthesia,
paraesthesia
blurred vision*

serotonin syndrome**,
peripheral neuropathy*
changes in visual field
defect*

tinnitus
arrhythmia
(tachycardia)
hypertension
transient ischaemic
attacks, phlebitis,
thrombophlebitis
diarrhoea, nausea, vomiting, pancreatitis, gastritis, superficial tooth
localised or general abdominal abdominal distention, discolouration
pain, constipation, dyspepsia dry mouth, glossitis,
loose stools,
stomatitis, tongue
discolouration or
disorder
abnormal liver function test;
increased total bilirubin
increased AST, ALT or alkaline
phosphatase

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

System Organ Class

Common
(≥1/100 to <1/10)

Skin and
pruritus, rash
subcutaneous tissue
disorders

Renal and urinary
increased BUN
disorders
Reproductive system
and breast disorders
General disorders and fever, localised pain
administration site
conditions
Investigations
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.

Uncommon
Rare
Very Rare Frequency not known
(≥1/1,000 to <1/100) (≥1/10,000 to <1/1,000) (<1/10,000) (cannot be estimated from
available data)
urticaria, dermatitis,
bullous disorders such
diaphoresis
as those described
as Stevens-Johnson
syndrome and toxic
epidermal necrolysis,
angioedema, alopecia
renal failure, increased
creatinine, polyuria
vulvovaginal disorder
chills, fatigue, injection
site pain, increased
thirst
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.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation
of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard
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
sulfamethoxazole / 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 7_1

01‑59‑12‑028_subm

Expand Transcript

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.

Hide