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ZYVOX 2MG/ML SOLUTION FOR INFUSION

Active substance(s): LINEZOLID / LINEZOLID / LINEZOLID

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Package leaflet: Information for the user

ZYVOX 2 mg/ml
solution for infusion

01‑59‑26‑0001_SUBM
FPO

Linezolid

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

1. What Zyvox is and what it is used for
2. What you need to know before you take Zyvox
3. How to take Zyvox
4. Possible side effects
5. How to store Zyvox
6. Contents of the pack and other information

1. What Zyvox is and what it is used for
Zyvox 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
Zyvox is suitable to treat your infection.

2. What you need to know before you are treated
with Zyvox
Do not take Zyvox:
• 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 Zyvox passes
into breast milk and could affect the baby.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Zyvox.
Zyvox 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 Zyvox
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 Zyvox. If this becomes severe or
persistent or you notice that your stool contains blood or
mucus, you should stop taking Zyvox 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 Zyvox
There is a risk that Zyvox 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 Zyvox must not be taken

if you are already taking these medicines or have taken them
recently (see also Section 2 above ‘Do not take Zyvox’).
• 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 Zyvox, 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.
Zyvox with food, drink and alcohol
• You can take Zyvox 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 Zyvox
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 Zyvox 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 Zyvox because it
passes into breast milk and could affect the baby.
Driving and using machines
Zyvox 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.
Zyvox contains
Glucose
Each 1 ml of Zyvox 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 Zyvox 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 Zyvox
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 Zyvox 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 Zyvox, your doctor should perform regular
blood tests to monitor your blood count.
Your doctor should monitor your eyesight if you take Zyvox for
more than 28 days.
Use in children and adolescents
Zyvox is not normally used to treat children and adolescents
(under 18 years old).

DETACH HERE

The following information is intended for healthcare
professionals only:

ZYVOX 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.
ZYVOX 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

Dosage and route
for twice daily
administration

Duration of
treatment

Nosocomial
pneumonia
600 mg twice daily
Community
acquired
10-14 Consecutive
pneumonia
Days
Complicated
skin and soft
600 mg twice daily
tissue infections
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, ZYVOX 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 post-marketing.
Where time of onset was known, most patients had received linezolid
therapy for more than 28 days. Most patients fully or partially recovered

following discontinuation of linezolid with or without treatment for their
anaemia.
Mortality imbalance in a clinical trial in patients with catheter-related Gram
positive bloodstream infections
Excess mortality was seen in patients treated with linezolid, relative to
vancomycin/dicloxacillin/oxacillin, in an open-label study in seriously
ill patients with intravascular catheter-related infections [78/363 (21.5%)
vs 58/363 (16.0%)]. The main factor influencing the mortality rate
was the Gram positive infection status at baseline. Mortality rates were
similar in patients with infections caused purely by Gram positive
organisms (odds ratio 0.96; 95% confidence interval: 0.58-1.59) but
were significantly higher (p=0.0162) in the linezolid arm in patients with
any other pathogen or no pathogen at baseline (odds ratio 2.48; 95%
confidence interval: 1.38-4.46). The greatest imbalance occurred during
treatment and within 7 days following discontinuation of study drug. More
patients in the linezolid arm acquired Gram negative pathogens during
the study and died from infection caused by Gram negative pathogens
and polymicrobial infections. Therefore, in complicated skin and soft
tissue infections linezolid should only be used in patients with known
or possible co-infection with Gram negative organisms if there are no
alternative treatment options available. In these circumstances treatment
against Gram negative organisms must be initiated concomitantly.
Antibiotic-associated diarrhoea and colitis
Antibiotic-associated diarrhoea and antibiotic-associated colitis,
including pseudomembranous colitis and Clostridium difficileassociated diarrhoea, has been reported in association with the use of
nearly all antibiotics including linezolid and may range in severity from
mild diarrhoea to fatal colitis. Therefore, it is important to consider this
diagnosis in patients who develop serious diarrhoea during or after the
use of linezolid. If antibiotic-associated diarrhoea or antibiotic-associated
colitis is suspected or confirmed, ongoing treatment with antibacterial
agents, including linezolid, should be discontinued and adequate
therapeutic measures should be initiated immediately. Drugs inhibiting
peristalsis are contraindicated in this situation.
Lactic acidosis
Lactic acidosis has been reported with the use of linezolid. Patients
who develop signs and symptoms of metabolic acidosis including
recurrent nausea or vomiting, abdominal pain, a low bicarbonate level,
or hyperventilation while receiving linezolid should receive immediate

medical attention. If lactic acidosis occurs, the benefits of continued
use of linezolid should be weighed against the potential risks.
Mitochondrial dysfunction
Linezolid inhibits mitochondrial protein synthesis. Adverse
events, such as lactic acidosis, anaemia and neuropathy (optic and
peripheral), may occur as a result of this inhibition; these events are
more common when the drug is used longer than 28 days.
Serotonin syndrome
Spontaneous reports of serotonin syndrome associated with the
co-administration of linezolid and serotonergic agents, including
antidepressants such as selective serotonin reuptake inhibitors (SSRIs)
have been reported. Co-administration of linezolid and serotonergic
agents is therefore contraindicated except where administration of
linezolid and concomitant serotonergic agents is essential. In those
cases patients should be closely observed for signs and symptoms
of serotonin syndrome such as cognitive dysfunction, hyperpyrexia,
hyperreflexia and incoordination. If signs or symptoms occur
physicians should consider discontinuing either one or both agents;
if the concomitant serotonergic agent is withdrawn, discontinuation
symptoms can occur.
Peripheral and optic neuropathy
Peripheral neuropathy, as well as optic neuropathy and optic neuritis
sometimes progressing to loss of vision, have been reported in
patients treated with Zyvox; 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 Zyvox for longer than the
recommended 28 days, their visual function should be regularly
monitored.
If peripheral or optic neuropathy occurs, the continued use of Zyvox
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
Zyvox. 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 or
without linezolid. No serotonin syndrome effects (confusion, delirium,
restlessness, tremors, blushing, diaphoresis and hyperpyrexia)

If you take more Zyvox than you should
If you are concerned that you may have been given too much
Zyvox, tell your doctor or a nurse at once.
If you forget to use Zyvox
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 Zyvox:
The serious side effects (with frequency in brackets) of Zyvox
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 Zyvox. 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).

• R
 ecurrent nausea or vomiting, abdominal pain or rapid
breathing (not known).
• Fits or seizures (uncommon) have been reported
with Zyvox. 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 Zyvox 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”
 eadache
• H
• Metallic taste in the mouth

• D
 iarrhoea, nausea or vomiting
• Changes in some blood test results including those
measuring your kidney or liver function or blood sugar levels
• Difficulty in sleeping
• 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)
• A need to urinate more often
• 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
• Reduction in platelets
• 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)
• Decrease of the blood cell count
• 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 (see details
below). By reporting side effects you can help provide more
information on the safety of this medicine.
United Kingdom
Yellow Card Scheme website:
www.mhra.gov.uk/yellowcard
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal

5. How to store Zyvox
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 Zyvox 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.

6. Contents of the pack and other
information
What Zyvox 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 Zyvox looks like and contents of the pack
Zyvox 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, Sandwich, Kent, CT13 9NJ, UK

Manufacturer
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:
Austria
Zyvoxid Latvia
Zyvoxid
Belgium
Zyvoxid Lithuania
Zyvoxid
Cyprus
Zyvoxid Luxembourg
Zyvoxid
Czech Republic
Zyvoxid Malta
Zyvox
Denmark
Zyvoxid Netherlands
Zyvoxid
Estonia
Zyvoxid Norway
Zyvoxid
Finland
Zyvoxid Poland
Zyvoxid
France
Zyvoxid Portugal
Zyvoxid
Germany
Zyvoxid Slovakia
Zyvoxid
Greece
Zyvoxid Slovenia
Zyvoxid
Iceland
Zyvoxid Spain
Zyvoxid
Ireland
Zyvox
Sweden
Zyvoxid
Italy
Zyvoxid United Kingdom
Zyvox

This leaflet was last revised in 09/2016
Ref: ZY 18_0

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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
Immune system
disorders
Metabolism and
nutrition disorders
Psychiatric
disorders
Nervous system
disorders
Eye disorders

anaemia*



Hepato-biliary
disorders

vaginitis

leucopenia*, neutropenia,
thrombocytopenia*,
eosinophilia

antibiotic-associated
colitis, including
pseudomembranous
colitis*
pancytopenia*

Very Rare
(<1/10,000)

Frequency not
known (cannot be
estimated from
available data)

myelosuppression*,
sideroblastic anaemia*

hyponatraemia

lactic acidosis*

convulsions*,
hypoaesthesia, paraesthesia
blurred vision*
changes in visual field
defect*

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

insomnia
headache, taste perversion (metallic
taste), dizziness

tinnitus

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

System Organ
Class
Skin and
subcutaneous
tissue disorders

anaphylaxis

Ear and labyrinth
disorders
Cardiac disorders
Vascular disorders hypertension
Gastrointestinal
disorders

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

Common
(≥1/100 to <1/10)
pruritus, rash

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

Very Rare
(<1/10,000)

Frequency not
known (cannot be
estimated from
available data)
bullous disorders such
as those described
as Stevens-Johnson
syndrome and toxic
epidermal necrolysis,
angioedema, alopecia

renal failure, increased
Renal and urinary increased BUN
creatinine, polyuria
disorders
vulvovaginal disorder
Reproductive
system and breast
disorders
chills, fatigue, injection site
General disorders fever, localised pain
pain, increased thirst
and administration
site conditions
Chemistry
Chemistry
Investigations
Increased LDH, creatine kinase, lipase, Increased sodium or
amylase or non fasting glucose.
calcium. Decreased non
Decreased total protein, albumin,
fasting glucose. Increased
sodium or calcium. Increased or
or decreased chloride.
decreased potassium or bicarbonate.
Haematology
Haematology
Increased neutrophils or eosinophils. Increased reticulocyte count.
Decreased haemoglobin, haematocrit Decreased neutrophils.
or red blood cell count. Increased
or decreased platelet or white blood
cell counts.
* 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.

drugs, the line should be flushed prior to and following linezolid
administration with a compatible infusion solution.
ZYVOX 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.

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

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.

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.

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: ZY 16_1

Reporting of suspected adverse reactions

Overdose

Instructions for use and handling

Shelf life

Special precautions for storage

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.
ZYVOX 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

01‑59‑26‑0001_SUBM

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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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