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ZYVOX 2MG/ML SOLUTION FOR INFUSION

Active substance(s): LINEZOLID

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1. What Zyvox is and what it is used for

Package leaflet: Information for the user

ZYVOX 2 mg/ml

2014-0021050/1

solution for infusion



Linezolid

Read all of this leaflet carefully before this
medicine is given to you because it contains
important information for you.
Keep this leaflet. You may need to read it again.
– If you have any further questions, ask your doctor or
pharmacist.
– This medicine has been prescribed for you. Do not pass it
on to others. It may harm them, even if their symptoms are
the same as yours.
– If you get any side effects, talk to your doctor or pharmacist.
This includes any possible side effects not listed in this
leaflet. See section 4.

What is in this leaflet:
1. What Zyvox is and what it is used for
2. What you need to know before you are treated with Zyvox
3. How Zyvox is given
4. Possible side effects
5. How to store Zyvox
6. Contents of the pack and other information

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
You should not be treated with Zyvox:
• if you are allergic (hypersensitive) to linezolid or any of the
other ingredients of this medicine.
• if you are taking or have taken within the last 2 weeks
any medicines known as monoamine oxidase inhibitors
(MAOIs: for example phenelzine, isocarboxazid,
selegiline, moclobemide). These medications may be
used to treat depression or Parkinson’s disease.
• if you are breast-feeding. This is because Zyvox passes into
breast milk and could affect the baby.
Warnings and precautions
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?
• 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 Zyvox
Tell your doctor before you are treated with this medicine if you:
• bruise and bleed easily
• are anaemic (have low red blood cells)
• are prone to getting infections

• have a history of seizures
• have liver problems or kidney problems particularly if you
are on dialysis
• have diarrhoea
Tell your doctor immediately if during treatment you suffer
from:
• problems with your vision such as blurred vision, changes
in colour vision, difficulty in seeing detail or if your field of
vision becomes restricted.
• loss of sensitivity in your arms or legs or a sensation of
tingling or pricking in your arms or legs.
• you may develop diarrhoea while taking or after taking
antibiotics, including 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 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, cipramil, clomipramine,
dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine,
lofepramine, paroxetine, sertraline.
• Medicines used to treat migraine such as sumatriptan and
zolmitriptan.
• Medicines used to treat sudden, severe allergic reactions
such as adrenaline (epinephrine).
• Medicines which increase your blood pressure, such as
noradrenaline (norepinephrine), dopamine and dobutamine.
• Medicines used to treat moderate to severe pain, such as
pethidine.
• 
Medicines used to treat anxiety disorders, such as
buspirone.
• Medicines that stop blood clotting, such as warfarin.
Please tell your doctor or pharmacist if you are taking or have
recently taken any other medicines, including medicines
obtained without a prescription.
Zyvox with food and drink
• 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 or pharmacist 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, 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.
Important information about some of the ingredients in Zyvox
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.

DETACH HERE

A Guide for Hospital Staff

ZYVOX 2 mg/ml
solution for infusion


Linezolid

Infections

Dosage and route
for twice daily
administration
600 mg twice daily

Duration of
treatment

Nosocomial
10-14 Consecutive
pneumonia
Days
Community
acquired
pneumonia
Complicated skin
600 mg twice daily
and soft tissue
infections
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 patients: No dose adjustment is required.
Patients with renal insufficiency: No dose adjustment is required.
Patients with severe renal insufficiency (i.e. CLCR < 30 ml/min): No
dose adjustment is required. Due to the unknown clinical significance
of higher exposure (up to 10-fold) to the two primary metabolites of
linezolid in patients with severe renal insufficiency, linezolid should
be used with special caution in these patients and only when the
anticipated benefit is considered to outweigh the theoretical risk.

FPO

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 (E331), citric acid anhydrous (E330),
hydrochloric acid (E507) or sodium hydroxide (E524), water for injections.
Dosage and method of administration
Linezolid should only be initiated in a hospital environment and after
consultation with a relevant specialist such as a microbiologist or an
infectious diseases specialist.
Patients who commence treatment on the parenteral formulation may be
switched to either oral presentation when clinically indicated. In such
circumstances, no dose adjustment is required as linezolid has an oral
bioavailability of approximately 100 %.
The solution for infusion should be administered over a period of 30 to
120 minutes.
The recommended linezolid dosage should be administered IV or orally
twice daily.

Recommended dosage and duration for adults:
The duration of treatment is dependent on the pathogen, the site of
infection and its severity, and on the patient’s clinical response.
The following recommendations for duration of therapy reflect those used
in the clinical trials. Shorter treatment regimens may be suitable for some
types of infection but have not been evaluated in clinical trials.
The maximum treatment duration is 28 days. The safety and effectiveness
of linezolid have not yet been established for treatment periods longer
than 28 days.
No increase in the recommended dosage or duration of treatment is
required for infections associated with concurrent bacteraemia. The dose
recommendation for the solution for infusion and the tablets/granules for
oral suspension are identical and are as follows:

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).
Patients with hepatic insufficiency: Patients with mild to moderate
hepatic insufficiency (Child-Pugh class A or B): No dose adjustment is
required.
Patients with severe hepatic insufficiency (Child-Pugh class C): As
linezolid is metabolised by a non-enzymatic process, impairment of hepatic
function would not be expected to significantly alter its metabolism and,
therefore, no dose adjustment is recommended. However, there are no
pharmacokinetic data and limited clinical experience of ZYVOX in patients
with severe hepatic insufficiency. Linezolid should be used with special
caution in patients with severe hepatic insufficiency and only when the
anticipated benefit is considered to outweigh the theoretical risk.
Contraindications
Hypersensitivity to linezolid or to any of the excipients.
Linezolid should not be used in patients taking any medicinal product
which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid,
selegiline, moclobemide) or within two weeks of taking any such medicinal
drug.
Unless there are facilities available for close observation and monitoring
of blood pressure, linezolid should not be administered to patients with
the following underlying clinical conditions or on the following types of
concomitant medications:
• Patients with uncontrolled hypertension, phaeochromocytoma,
carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorder,
acute confusional states.
• Patients taking any of the following medications: Serotonin re-uptake
inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor

agonists (triptans), directly and indirectly acting sympathomimetic
agents (including the adrenergic bronchodilators, pseudoephedrine
and phenylpropanolamine), vasopressive agents (e.g. adrenaline /
epinephrine, noradrenaline / norepinephrine), dopaminergic agents
(e.g. dopamine, dobutamine), pethidine or buspirone.
Breast-feeding should be discontinued prior to and throughout
administration.
Special warnings and precautions for use
Myelosuppression
Myelosuppression (including anaemia, leucopenia, pancytopenia and
thrombocytopenia) has been reported in patients receiving linezolid. In
cases where the outcome is known, when linezolid was discontinued,
the affected haematologic parameters have risen toward pretreatment
levels. The risk of these effects appears to be related to the duration of
treatment. Elderly patients treated with linezolid may be at greater risk of
experiencing blood dyscrasias than younger patients. Thrombocytopenia
may occur more commonly in patients with severe renal insufficiency,
whether or not on dialysis. Therefore, close monitoring of blood
counts is recommended in patients who: have pre-existing anaemia,
granulocytopenia or thrombocytopenia; are receiving concomitant
medications that may decrease haemoglobin levels, depress blood
counts or adversely affect platelet count or function; have severe renal
insufficiency; receive more than 10-14 days of therapy. Linezolid
should be administered to such patients only when close monitoring of
haemoglobin levels, blood counts and platelet counts is possible.
If significant myelosuppression occurs during linezolid therapy, treatment
should be stopped unless it is considered absolutely necessary to
continue therapy, in which case intensive monitoring of blood counts and
appropriate management strategies should be implemented.
In addition, it is recommended that complete blood counts (including
haemoglobin levels, platelets, and total and differentiated leucocyte
counts) should be monitored weekly in patients who receive linezolid
regardless of baseline blood count.
In compassionate use studies, a higher incidence of serious anaemia
was reported in patients receiving linezolid for more than the maximum
recommended duration of 28 days. These patients more often required
blood transfusion. Cases of anaemia requiring blood transfusion have

also been reported post marketing, with more cases occurring in patients
who received linezolid therapy for more than 28 days.
Cases of sideroblastic anaemia have been reported post-marketing. Where
time of onset was known, most patients had received linezolid therapy for
more than 28 days. Most patients fully or partially recovered following
discontinuation of linezolid with or without treatment for their anaemia.
Mortality imbalance in a clinical trial in patients with catheter-related Gram
positive bloodstream infections
Excess mortality was seen in patients treated with linezolid, relative to
vancomycin/dicloxacillin/oxacillin, in an open-label study in seriously ill
patients with intravascular catheter-related infections [78/363 (21.5%) vs
58/363 (16.0%)]. The main factor influencing the mortality rate was the
Gram positive infection status at baseline. Mortality rates were similar in
patients with infections caused purely by Gram positive organisms (odds
ratio 0.96; 95% confidence interval: 0.58-1.59) but were significantly
higher (p=0.0162) in the linezolid arm in patients with any other pathogen
or no pathogen at baseline (odds ratio 2.48; 95% confidence interval:
1.38-4.46). The greatest imbalance occurred during treatment and within
7 days following discontinuation of study drug. More patients in the
linezolid arm acquired Gram negative pathogens during the study and
died from infection caused by Gram negative pathogens and polymicrobial
infections. Therefore, in complicated skin and soft tissue infections
linezolid should only be used in patients with known or possible
co-infection with Gram negative organisms if there are no alternative
treatment options available. In these circumstances treatment against Gram
negative organisms must be initiated concomitantly.
Antibiotic-associated diarrhoea and colitis
Pseudomembranous colitis has been reported with nearly all antibacterial
agents, including linezolid. Therefore, it is important to consider this
diagnosis in patients who present with diarrhoea subsequent to the
administration of any antibacterial agent. In cases of suspected or verified
antibiotic-associated colitis, discontinuation of linezolid may be warranted.
Appropriate management measures should be instituted.
Antibiotic-associated diarrhoea and antibiotic-associated colitis, including
pseudomembranous colitis and Clostridium difficile-associated diarrhoea,
has been reported in association with the use of nearly all antibiotics
including linezolid and may range in severity from mild diarrhoea to fatal
colitis. Therefore, it is important to consider this diagnosis in patients

who develop serious diarrhoea during or after the use of linezolid.
If antibiotic-associated diarrhoea or antibiotic-associated colitis is
suspected or confirmed, ongoing treatment with antibacterial agents,
including linezolid, should be discontinued and adequate therapeutic
measures should be initiated immediately. Drugs inhibiting peristalsis are
contraindicated in this situation.
Lactic acidosis
Lactic acidosis has been reported with the use of linezolid. Patients
who develop signs and symptoms of metabolic acidosis including
recurrent nausea or vomiting, abdominal pain, a low bicarbonate level,
or hyperventilation while receiving linezolid should receive immediate
medical attention. If lactic acidosis occurs, the benefits of continued use
of linezolid should be weighed against the potential risks.
Mitochondrial dysfunction
Linezolid inhibits mitochondrial protein synthesis. Adverse events, such
as lactic acidosis, anaemia and neuropathy (optic and peripheral), may
occur as a result of this inhibition; these events are more common when
the drug is used longer than 28 days.
Serotonin syndrome
Spontaneous reports of serotonin syndrome associated with the
co-administration of linezolid and serotonergic agents, including
antidepressants such as selective serotonin reuptake inhibitors (SSRIs)
have been reported. Co-administration of linezolid and serotonergic
agents is therefore contraindicated except where administration of
linezolid and concomitant serotonergic agents is essential. In those cases
patients should be closely observed for signs and symptoms of serotonin
syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and
incoordination. If signs or symptoms occur physicians should consider
discontinuing either one or both agents; if the concomitant serotonergic
agent is withdrawn, discontinuation symptoms can occur.
Peripheral and optic neuropathy
Peripheral neuropathy, as well as optic neuropathy and optic neuritis
sometimes progressing to loss of vision, have been reported in patients
treated with 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).

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

3. How Zyvox is given
Adults
This medicine will be given to you through a drip (by infusion into
a vein) by a doctor or healthcare professional. The usual dose for
adults (18 years and older) is 300 ml (600 mg linezolid) twice daily
which is given directly into the blood stream (intravenously) by a
drip over a period of 30 to 120 minutes.
If you are on kidney dialysis, you should be given Zyvox 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 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
Zyvox is not normally used to treat children and adolescents
(under 18 years old).
If you receive 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 miss a dose of 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.

4. Possible side effects
Like all medicines, Zyvox 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:
• 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 Zyvox.
• 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 Zyvox. You should
let your doctor know if you experience agitation, confusion,
delirium, rigidity, tremor, incoordination and seizure while also
taking antidepressants known as SSRI’s (see section 2).
Numbness, tingling or blurred vision have been reported by
patients who have been given 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 side effects (likely to occur in less than 1 in
10 people):
• Fungal infections especially vaginal or oral “thrush”
• Headache
• Metallic taste in the mouth
• Diarrhoea, nausea or vomiting
• Changes in some blood test results including those
measuring your kidney or liver function or blood sugar levels

• Unexplained bleeding or bruising, which may be due to
changes in the numbers of certain cells in the blood which
may affect blood clotting or lead to anaemia
• Difficulty in sleeping
• Increased blood pressure
• Anaemia (low red blood cell)
• Changes in numbers of certain cells in the blood which may
affect your ability to fight infection
• Skin rash
• Itching skin
• Dizziness
• Localised or general abdominal pain
• Constipation
• Indigestion
• Localised pain
• Fever
Uncommon side effects (likely to occur in less than 1 in 100
people):
• Inflammation of the vagina or genital area in women
• Sensations such as tingling or feeling numb
• Blurred vision
• “Ringing” in the ears (tinnitus)
• Inflammation of the veins
• Dry or sore mouth, swollen, sore, or discoloured tongue
• Pain at and around the place where the infusion (drip) was
given
• Inflammation of the veins (including where the infusion (drip)
was given)
• A need to urinate more often
• Chills
• Feeling tired or thirsty
• Inflammation of the pancreas

• Increased sweating
• Changes in proteins, salts or enzymes in the blood which
measure kidney or liver function
• Convulsions
• Hyponatraemia (low blood sodium levels)
• Kidney failure
• Reduction in platelets
• Abdominal bloating
• Transient ischaemic attacks (temporary disturbance of
blood flow to the brain causing short term symptoms such
as loss of vision, leg and arm weakness, slurring of speech
and loss of consciousness)
• Injection site pain
• Inflammation of the skin
• Increase in creatinine
• Stomach pain
• Changes in heart rate (e.g. increase rate)
Rare side effects (likely to occur in less than 1 in 1000
people):
• Restricted field of vision
• Superficial tooth discolouration, removable with professional
dental cleaning (manual descaling)
The following side effects have also been reported
(frequency not known):
• Serotonin syndrome (symptoms include fast heart rate,
confusion, abnormal sweating, hallucinations, involuntary
movements chills and shivering)
• Lactic acidosis (symptoms include recurrent nausea and
vomiting, abdominal pain, rapid breathing)
• Severe skin disorders
• Sideroblastic anaemia (a type of anaemia (low red blood
cells))

• Alopecia (hair loss)
• Changes in colour vision or difficulty in seeing detail
• Decrease of the blood cell count
• Weakness and/or sensory changes
If any of the side effects gets serious, or if you notice any
side effects not listed in this leaflet, please tell your doctor or
pharmacist.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet. You
can also report side effects directly via the Yellow Card Scheme
at: www.mhra.gov.uk/yellowcard. By reporting side effects you
can help provide more information on the safety of this medicine.

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

6. Contents of the pack and other
information
What Zyvox solution for infusion 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) 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 (600 mg linezolid) of solution.
The bags are supplied in boxes of 1, 2, 5, 10, 20 or 25 bags.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
The Marketing Authorisation Holder is Pfizer Limited, Sandwich,
Kent, CT13 9NJ, UK and the manufacturer is Fresenius Kabi Norge
AS, Svinesundveien 80, N-1789 Berg I Ostfold, Halden, Norway.
Company contact address: Medical Information Department, Pfizer
Limited, Walton Oaks, Dorking Road, Tadworth, Surrey KT20 7NS.
Telephone: 01304 616 161.
This medicinal product is authorised in the Member States of the
EEA under the following names:
AustriaZyvoxid
BelgiumZyvoxid
CyprusZyvoxid
Czech Republic
Zyvoxid
DenmarkZyvoxid
EstoniaZyvoxid
FinlandZyvoxid
FranceZyvoxid
GermanyZyvoxid
GreeceZyvoxid
IcelandZyvoxid
IrelandZyvox
ItalyZyvoxid

LatviaZyvoxid
LithuaniaZyvoxid
LuxembourgZyvoxid
MaltaZyvox
NetherlandsZyvoxid
NorwayZyvoxid
PolandZyvoxid
PortugalZyvoxid
SlovakiaZyvoxid
SloveniaZyvoxid
SpainZyvoxid
SwedenZyvoxid
United Kingdom
Zyvox

This leaflet was last revised in 11/2014.
Ref: ZY 15_0

DETACH HERE

recommended that doses of drugs with a vasopressive action, including
dopaminergic agents, should be carefully titrated to achieve the desired
response when co-administered with linezolid.
Potential serotonergic interactions
The potential drug-drug interaction with dextromethorphan was studied
in healthy volunteers. Subjects were administered dextromethorphan (two
20 mg doses given 4 hours apart) with or without linezolid. No serotonin
syndrome effects (confusion, delirium, restlessness, tremors, blushing,
diaphoresis, hyperpyrexia) have been observed in normal subjects
receiving linezolid and dextromethorphan.
Post marketing experience: there has been one report of a patient
experiencing serotonin 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 no adequate data from the use of linezolid in pregnant women.
Studies in animals have shown reproductive toxicity. A potential risk for
humans exists.
Linezolid should not be used during pregnancy unless clearly necessary
i.e. only if the potential benefit outweighs the theoretical risk.
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.

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

anaemia*†

insomnia
headache, taste perversion (metallic
taste), dizziness

Eye disorders

Ear and labyrinth
disorders
Cardiac disorders
Vascular disorders hypertension
Gastrointestinal
disorders

Hepato-biliary
disorders

Uncommon
(≥1/1,000 to <1/100)

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

lactic acidosis*

convulsions*,
hypoaesthesia,
paraesthesia
blurred vision*

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

tinnitus

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

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

System Organ Class

Common
(≥1/100 to <1/10)

Uncommon
(≥1/1,000 to <1/100)

pruritus, rash
Skin and
subcutaneous tissue
disorders

urticaria, dermatitis,
diaphoresis

Renal and urinary increased BUN
disorders
Reproductive
system and breast
disorders
General disorders fever, localised pain
and administration
site conditions
Chemistry
Investigations
Increased LDH, creatine kinase, lipase,
amylase or non fasting glucose.
Decreased total protein, albumin,
sodium or calcium. Increased or
decreased potassium or bicarbonate.
Haematology
Increased neutrophils or eosinophils.
Decreased haemoglobin, haematocrit
or red blood cell count. Increased or
decreased platelet or white blood cell
counts.

renal failure, increased
creatinine, polyuria
vulvovaginal disorder

Rare
(≥1/10,000 to
<1/1,000)

Very Rare Frequency not known
(<1/10,000) (cannot be estimated
from available data)
bullous disorders such
as those described
as Stevens-Johnson
syndrome and toxic
epidermal necrolysis,
angioedema, alopecia

chills, fatigue, injection site
pain, increased thirst
Chemistry
Increased sodium or
calcium. Decreased non
fasting glucose. Increased
or decreased chloride.
Haematology
Increased reticulocyte
count.
Decreased neutrophils.

* See section Special warnings and precautions for use
** See sections Contraindications and Interactions
† See below
The following adverse reactions to linezolid were considered to be serious in rare cases: localised abdominal pain, transient ischaemic attacks and
hypertension.
† In controlled clinical trials where linezolid was administered for up to 28 days, 2.0% of the patients reported anaemia. In a compassionate use program
of patients with life-threatening infections and underlying co-morbidities, the percentage of patients who developed anaemia when receiving linezolid
for ≤28 days was 2.5% (33/1326) as compared with 12.3% (53/430) when treated for > 28 days. The proportion of cases reporting drug-related serious
anaemia and requiring blood transfusion was 9% (3/33) in patients treated for ≤ 28 days and 15% (8/53) in those treated for >28 days.

Paediatric population
Safety data from clinical studies based on more than 500 paediatric patients
(from birth to 17 years) do not indicate that the safety profile of linezolid for
paediatric patients differs from that for adult patients.
Overdose
No specific antidote is known.
No cases of overdose have been reported. However, the following
information may prove useful:
Supportive care is advised together with maintenance of glomerular
filtration. Approximately 30% of a linezolid dose is removed during 3 hours
of haemodialysis, but no data are available for the removal of linezolid by
peritoneal dialysis or haemoperfusion.
Instructions for use and handling
For single use only. Remove overwrap only when ready to use, then check
for minute leaks by squeezing the bag firmly. If the bag leaks, do not use
as sterility may be impaired. The solution should be visually inspected
prior to use and only clear solutions, without particles should be used. Do
not use these bags in series connections. Any unused solution must be
discarded. 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 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 sulphamethoxazole / trimethoprim. Additionally, it is
chemically incompatible with ceftriaxone sodium.

Shelf life
Before opening: 3 years
After opening: From a microbiological point of view, unless the method of
opening precludes the risk of microbial contamination, the product should
be used immediately. If not used immediately, in-use storage times and
conditions are the responsibility of the user.
Special precautions for storage
Store in the original package (overwrap and carton) until ready to use, in
order to protect from light.
For further information please contact the Medical Information at Pfizer:
Pfizer Limited, Walton Oaks, Dorking Road, Walton-on-the-Hill, Surrey,
KT20 7NS, UK
Tel: 01304 616 161
Fax: 01737 332507
Ref: ZY 15_0

2014-0021050/1

09 Oct 2014

2 of 2

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)

11:16

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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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