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LINEZOLID 2MG/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 you
start using 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.
• This medicine has been prescribed for you only.
Do not pass it on to others. It may harm them,
even if their signs of illness are the same as yours.
• 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:

1. What Linezolid is and what it is used for
2. What you need to know before you use Linezolid
3. How to use Linezolid
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 2 mg/ml solution for infusion is a
medicine containing an active substance
called linezolid. 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 use
Linezolid
Do not use Linezolid
• If you are allergic (hypersensitive) 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 may be used to treat
depression or Parkinson’s disease;
• If you are breast-feeding. This is because it 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
* 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

Talk to your doctor, pharmacist or nurse before
using Linezolid 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

A Guide for Hospital Staff

Linezolid 2 mg/ ml
solution for infusion

Tell your doctor or pharmacist if you are taking,
have recently taken or might take any other
medicines, including medicines obtained without
a prescription.

(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

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.

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
use Linezolid’).

Description

A clear colourless or yellowish polypropylene
infusion bag with one port or two ports in a
transparent foil laminate overwrap bag. The bag
holds 300 ml solution and is packaged in a box.
Box containing 1*, 2**, 5, 10, 20 or 25 infusion
bag(s).
Additionally, the following boxes may also be
supplied in hospital packs of:
*5, 10 or 20
**3, 6 or 10
Not all package sizes may be marketed.

• 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,
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.

Linezolid with food and drink

• You can use 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 this medicine 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 used 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 using this medicine.

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 and sodium
Glucose

Each 1 ml of Linezolid solution contains 0.38 mg
sodium (114 mg sodium in one bag).
To be taken into consideration by patients on a
controlled sodium diet.

3. How to use Linezolid
Always use this medicine exactly as your doctor or
pharmacist has told you. Check with your doctor or
pharmacist 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 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.
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 using linezolid, your doctor should
perform regular blood tests to monitor your
blood count.
Your doctor should monitor your eyesight if you
use linezolid for more than 28 days.

Special warnings and precautions for use

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.

Infections

Dosage and
route for
twice daily
administration

Duration of
treatment

Nosocomial
pneumonia

600 mg twice
daily

10 – 14
Consecutive
days

Complicated
skin and
soft tissue
infections

Sodium

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.

Recommended dosage and duration for adults:

Community
acquired
pneumonia

Each 1 ml of Linezolid solution contains 48 mg
glucose (14.4 g glucose in one bag).
This should be taken into account in patients with
diabetes mellitus.

Hypersensitive to linezolid or to any of the
excipients.

Breast-feeding should be discontinued prior to and
throughout administration.

The duration of treatment is dependent on the
pathogen, the site of infection and its severity, and
on the patient’s clinical response.

600 mg twice
daily

Paediatric population: 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: 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.

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.

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.

Packing Site/Printer Mylan
Institutional - FR
Supplier Code PR905314

Kingdom,
Client Market United
Ireland

Keyline/Drawing No. N/A
Barcode Info N/A

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.
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 48 mg (i.e.
14.4 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.
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).

PR905314

Colours

Glams Proof No. N/A

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.

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

SAP No. N/A

MA No. N/A

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.

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.

Affiliate Item Code 905314

Trackwise Proof No. 2

If peripheral or optic neuropathy occurs, the
continued use of linezolid should be weighed
against the potential risks.

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.

No. of colours

TrackWise PR No. 905314

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.

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.

Pharma Code N/A

Vendor Job No. 282770

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.

Component Type Leaflet

Superceded Affiliate Item Code 755045

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.

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.

Date: 14 Jul 2016

Description Linezolid 2 mg/ml all

Antibiotic-associated diarrhoea and colitis
Antibiotic-associated diarrhoea and antibioticassociated 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.

Contra-indications

The recommended linezolid dosage should be
administered IV or orally twice daily.

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.

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 is
as follows:

Driving and using machines

Severe hepatic impairment (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.

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.

Dosage and method of administration

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.

Hepatic impairment: Patients with mild to
moderate hepatic insufficiency (Child-Pugh class
A or B): No dose adjustment is required.

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.

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.

You should not breast-feed when using linezolid
because it passes into breast milk and could affect
the baby.

Adults

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; as 10%
solution) for pH-adjustment or sodium hydroxide
(E524, as 10% solution) for pH-adjustment, water
for injections.

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).

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Sign-offs

v1/May 2015

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 CYP450induced drug interactions are expected with
linezolid.

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.

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.

Pregnancy
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.

System Organ Class

Fertility, pregnancy and lactation

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.

Linezolid should not be used during pregnancy
unless clearly necessary i.e. only if the potential
benefit outweighs the theoretical risk.

Common (≥1/100 to <1/10)

Breast-feeding
Animal data suggest that linezolid and its
metabolites may pass into breast milk and,
accordingly, breastfeeding should be discontinued
prior to and throughout administration.

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.

Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000)

Infections and infestations

Candidiasis, oral candidiasis,
vaginal candidiasis, fungal
infections

Vaginitis

Antibiotic-associated colitis,
including pseudomembranous
colitis*

Blood and the lymphatic
system disorders

Anaemia*†

Leucopenia*, neutropenia,
thrombocytopenia*, eosinophilia

Pancytopenia*

Use in children

Those most commonly reported were diarrhoea
(8.4 %), headache (6.5%), nausea (6.3%) and
vomiting (4.0%).

Linezolid is not normally used to treat children and
adolescents (under 18 years old).

If you use more Linezolid than you should

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.

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.

Additional adverse reactions reported from postmarketing experience are included in the table
with frequency category ‘Not known’, since the
actual frequency cannot be estimated from the
available data.

Very Rare
(<1/10,000)

Frequency not known
(cannot be estimated from
available data)

Myelosuppression*, sideroblastic
anaemia*

Immune system disorders

Anaphylaxis

Metabolism and nutrition
disorders
Psychiatric disorders

Insomnia

Nervous system disorders

Headache, taste perversion
(metallic taste), Dizziness

Eye disorders

Hyponatraemia

Lactic acidosis*

Convulsions*, hypoaesthesia,
paraesthesia

Serotonin syndrome**,
peripheral neuropathy*

Blurred vision*

Changes in visual field defect*

Ear and labyrinth disorders

Tinnitus

Cardiac disorders

Arrhythmia (tachycardia)

Vascular disorders

Hypertension

Transient ischaemic attacks,
phlebitis, thrombophlebitis

Gastrointestinal disorders

Diarrhoea, nausea, vomiting.
localised or general abdominal
pain, constipation, dyspepsia

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

Hepato-biliary disorders

Abnormal liver function test;
increased AST, ALT or alkaline
phosphatase

Increased total bilirubin

Skin and subcutaneous tissue
disorders

Pruritus, rash

Urticaria, dermatitis, diaphoresis

Renal and urinary disorders

Increased BUN

Renal failure, polyuria, increased
creatinine

Reproductive system and
breast disorders

Vulvovaginal disorder

General disorders and
administration site conditions

Fever, localised pain

Chills, fatigue, injection site pain,
increased thirst

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.

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

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
• 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)

Haematology
Increased neutrophils or
eosinophils. Decreased
haemoglobin, haematocrit or red
blood cell count. Increased or
decreased platelet or white blood
cell counts.
Haematology
Increased reticulocyte count.
Decreased neutrophils.
* See section Special warnings and precautions for use
** See sections Contra-indications 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.

Overdose

†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.

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.

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.

No specific antidote is known.
No cases of overdose have been reported. However,
the following information may prove useful:

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. No special
requirements for disposal. Any unused medicinal
product or waste material should be disposed of
in accordance with local requirements. 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.

In the absence of compatibility studies, this
medicinal product must not be mixed with other
medicinal products.

Shelf life

Before opening: 30 months
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.

Rare (may affect up to 1 in 1000 people)
• Restricted field of vision
• Superficial tooth discolouration, removable with
professional dental cleaning (manual descaling)

Special precautions for storage

Store in the original package (overwrap and carton)
in order to protect from light.

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)

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.

Date: 14 Jul 2016

Description Linezolid 2 mg/ml all
Component Type Leaflet

Pharma Code N/A

No. of colours

Affiliate Item Code 905314

SAP No. N/A

Colours

Superceded Affiliate Item Code 755045
TrackWise PR No. 905314
MA No. N/A
Packing Site/Printer Mylan
Institutional - FR
Supplier Code PR905314

Vendor Job No. 282770
Trackwise Proof No. 2
Glams Proof No. N/A
Kingdom,
Client Market United
Ireland

Keyline/Drawing No. N/A
Barcode Info N/A

1

IRELAND

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
• 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 cells)
• 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

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

Time: 09:35
Page Count

2/2

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Dimensions 440 x 480 mm

UK

Like all medicines this medicine can cause sideeffects, although not everybody gets them.

Other side effects include:

Superficial tooth discolouration

If you get any side effects, talk to your doctor or,
pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report
side effects directly via the national reporting
system:
The Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.

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.

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

Reporting of side effects

4. Possible side effects

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).

The following undesirable effects have been
observed and reported during treatment with
linezolid with the following frequencies: 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)

• Changes in colour vision or difficulty in seeing
detail
• Decrease of the blood cell count
• Weakness and/or sensory changes

Body Text Size 9 pt
Min Text Size used 9 pt

Sign-offs

v1/May 2015

HPRA, Pharmacovigilance, Earlsfort Terrace, IRL –
Dublin 2
Tel: +353 1 6764971; Fax: +353 1 6762517;
Website: www.hpra.ie; E-mail: medsafety@hpra.ie
By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store Linezolid
As you will be given this medicine under close
medical supervision, Hospital Staff will comply with
the following advices:
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 bag after EXP. The first two
digits indicate the month and the last four digits
indicate the year. The expiry date refers to the last
day of that month. Use the medicine as soon as the
seal is broken.
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.
Store in the original package (overwrap and carton)
in order to protect from light.
Do not use this medicine if you notice that the
solution is not clear and contains particles.
Do not throw away any medicines via wastewater
or household waste. Ask your pharmacist how to
throw away medicines that you no longer use.
These measures will help protect the environment.

6. Contents of the pack and other
information
What Linezolid contains

• The active substance is linezolid. Each 1ml 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; as 10%
solution) for pH-adjustment or sodium hydroxide
(E524; as 10% solution) for pH-adjustment and
water for injections.

What Linezolid looks like and contents of
the pack
Linezolid is presented as a clear, colourless to
yellow solution in single infusion bags containing
300 ml (600 mg linezolid) of solution.
Each box contains 1, 2, 5, 10, 20 or 25 infusion
bag(s). Additionally, hospital packaging of 3, 5, 6,
10 or 20 boxes containing either 1 or 2 infusion
bag(s) are available.
Not all package sizes may be marketed.

Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation Holder
UK: Mylan,
Ireland: Generics [UK] Ltd
Potters Bar, Hertfordshire EN6 1TL, United Kingdom
Manufacturer(s)
Synthon BV, Microweg 22, 6545 CM, Nijmegen,
The Netherlands
Synthon Hispania SL, C/ Castelló no1,
Pol. Las Salinas, Sant Boi de Llobregat,
08830 Barcelona, Spain
Mylan S.A.S., 117 Allée des Parcs, 69800 Saint-Priest,
France
This medicinal product is authorised in the
Member States of the EEA under the following
names:
Belgium
Linezolid Mylan 2 mg/ml
oplossing voor infusie
Czech Republic Linezolid Mylan 2mg/ml,
infuzní roztok
Germany
Linezolid Mylan 2 mg/ml,
Infusionslösung
Denmark
Linezolid Mylan
Spain
Linezolido Mylan 2 mg/ml,
solución para persusión
Finland
Linezolid Mylan
France
Linézolide Mylan 2 mg/ml,
solution pour perfusion
Ireland
Linezolid 2 mg/ml solution for
infusion
Italy
Linezolid Mylan
Norway
Linezolid Mylan
Portugal
Linezolida Mylan
Sweden
Linezolid Mylan
Slovakia
Linezolid Mylan 2 mg/ml,
infúzny roztok
United Kingdom Linezolid 2 mg/ml solution for
infusion
This leaflet was last revised in 05/2016 

905314
PR905314

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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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