MERONEM IV 1G

PACKAGE LEAFLET: INFORMATION FOR THE USER

Meronem IV 500 mg and 1 g

Powder for solution for injection or infusion
meropenem
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 Meronem is and what it is used for
2. What you need to know before you use Meronem
3. How to use Meronem
4. Possible

side effects
5. How to store Meronem
6. Contents of the pack and other information
1. What Meronem is and what it is used for
Meronem contains the active substance meropenem and
belongs to a group of medicines called carbapenem antibiotics.
It works by killing bacteria, which can cause serious infections.
Meronem is used to treat the following in adults and children
aged 3 months and older:
• Infection affecting the lungs (pneumonia)
• Lung and bronchial infections in patients suffering from
cystic fibrosis
• Complicated urinary tract infections
• Complicated infections in the abdomen
• Infections that you can catch during or after the delivery
• Complicated skin and soft tissues infections
• Acute bacterial infection of the brain (meningitis)
Meronem may be used in the management of neutropenic
patients with fever that is suspected to be due to a bacterial
infection.
Meronem may be used to treat bacterial infection of the blood which
might be associated with a type of infection mentioned above.
2. What you need to know before you use Meronem
Do not use Meronem if:
• you are allergic (hypersensitive) to meropenem or any of the
other ingredients of Meronem (listed in Section 6 Contents of
the pack and other information).

Medical Information Leaflet

Meronem

• you

are allergic (hypersensitive) to other antibiotics such as
penicillins, cephalosporins, or carbapenems as you may also
be allergic to meropenem.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Meronem if:
• you have health problems, such as liver or kidney problems.
• you have had severe diarrhoea after taking other antibiotics.
You may develop a positive test (Coombs test) which indicates
the presence of antibodies that may destroy red blood cells.
Your doctor will discuss this with you.
If you are not sure if any of the above applies to you, talk to
your doctor or nurse before using Meronem.
Other medicines and Meronem
Tell your doctor, pharmacist or nurse if you are taking, have
recently taken or might take any other medicines. This is
because Meronem can affect the way some medicines work
and some medicines can have an effect on Meronem.
In particular, tell your doctor, pharmacist or nurse if you are
taking any of the following medicines:
• Probenecid (used to treat gout).
• Valproic acid/sodium valproate/valpromide (used to treat
epilepsy). Meronem should not be used because it may
decrease the effect of sodium valproate.
• Oral anti-coagulant agent (used to treat or prevent blood clots).
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be
pregnant or planning to have a baby, ask your doctor or
pharmacist for advice before using this medicine. It is
preferable to avoid the use of meropenem during pregnancy.
Your doctor will decide whether you should use Meronem.
It is important that you tell your doctor if you are breast-feeding
or if you intend to breast-feed before receiving meropenem.
Small amounts of this medicine may pass into the breast milk.
Therefore, your doctor will decide whether you should use
Meronem while breast-feeding.
Driving and using machines
No studies on the effect on the ability to drive and use machines
have been performed.
Meronem has been associated with headache and tingling or
pricking skin (paraesthesia). Any of these side effects could
affect your ability to drive or operate machines.
Meronem may cause involuntary muscle movements which may cause
the person’s body to shake rapidly and uncontrollably (convulsions).
This is usually accompanied with a loss of consciousness. Do not
drive or use machines if you experience this side effect.
Meronem contains sodium
Meronem 500 mg: This medicinal product contains approximately
2 mEq of sodium per 500 mg dose which should be taken into
consideration by patients on a controlled sodium diet.

Meronem 1 g: This medicinal product contains approximately
4 mEq of sodium per 1 g dose which should be taken into
consideration by patients on a controlled sodium diet.
If you have a condition which requires you to monitor your
sodium intake please inform your doctor, pharmacist or nurse.

Adults and Adolescents

Infection

Infection

Dose to be administered
every 8 hours

Severe pneumonia including hospital and
ventilator-associated pneumonia.
Broncho-pulmonary infections in cystic fibrosis
Complicated urinary tract infections
Complicated intra-abdominal infections
Intra- and post-partum infections
Complicated skin and soft tissue infections
Acute bacterial meningitis
Management of febrile neutropenic patients

500 mg or 1 g

for Intravenous Administration
1. NAME OF THE MEDICINAL PRODUCT
Meronem IV
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Meronem IV 500 mg
Each vial contains meropenem trihydrate equivalent to 500 mg anhydrous
meropenem.
Meronem IV 1 g
Each vial contains meropenem trihydrate equivalent to 1 g anhydrous meropenem.
Excipients with known effect:
Each 500 mg vial contains 104 mg sodium carbonate which equates to
approximately 2 mEq of sodium (approximately 45 mg).
Each 1 g vial contains 208 mg sodium carbonate which equates to approximately
4 mEq of sodium (approximately 90 mg).
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Powder for solution for injection or infusion.
A white to light yellow powder.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Meronem is indicated for the treatment of the following infections in adults and
children aged 3 months and older (see sections 4.4 and 5.1):
•
Severe pneumonia, including hospital and ventilator-associated pneumonia.
•
Broncho-pulmonary infections in cystic fibrosis.
•
Complicated urinary tract infections.
•
Complicated intra-abdominal infections.
•
Intra- and post-partum infections.
Complicated skin and soft tissue infections.
•
•
Acute bacterial meningitis.
Meronem may be used in the management of neutropenic patients with fever that
is suspected to be due to a bacterial infection.
Treatment of patients with bacteraemia that occurs in association with, or is
suspected to be associated with, any of the infections listed above.
Consideration should be given to official guidance on the appropriate use of
antibacterial agents.
4.2 Posology and method of administration
Posology
The tables below provide general recommendations for dosing.
The dose of meropenem administered and the duration of treatment should take
into account the type of infection to be treated, including its severity, and the
clinical response.
A dose of up to 2 g three times daily in adults and adolescents and a dose of up to
40 mg/kg three times daily in children may be particularly appropriate when treating
some types of infections, such as infections due to less susceptible bacterial
species (e.g. Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.),
or very severe infections.
Additional considerations for dosing are needed when treating patients with renal
insufficiency (see further below).

3. How to use Meronem
Always use this medicine exactly as your doctor, pharmacist
or nurse has told you. Check with your doctor, pharmacist or
nurse if you are not sure.
Use in adults
• The dose depends on the type of infection that you have,
where the infection is in the body and how serious the
infection is. Your doctor will decide on the dose that you need.
• The dose for adults is usually between 500 mg (milligrams)
and 2 g (gram). You will usually receive a dose every
8 hours. However you may receive a dose less often if your
kidneys do not work very well.
Use in children and adolescents
• The
dose for children over 3 months old and up to 12 years of age
is decided using the age and weight of the child. The usual dose is
between 10 mg and 40 mg of Meronem for each kilogram (kg) that
the child weighs. A dose is usually given every 8 hours. Children
who weigh over 50 kg will be given an adult dose.
How to use Meronem
• Meronem will be given to you as an injection or infusion into
a large vein.
• Your doctor or nurse will normally give Meronem to you.
• However, some patients, parents and carers are trained
to give Meronem at home. Instructions for doing this are
provided in this leaflet (in the section called ‘Instructions
for giving Meronem to yourself or someone else at home’).
Always use Meronem exactly as your doctor has told you.
You should check with your doctor if you are not sure.
• Your injection should not be mixed with or added to solutions
that contain other medicines.
• The injection may take about 5 minutes or between 15 and
30 minutes. Your doctor will tell you how to give Meronem.
• You should normally have your injections at the same times
each day.
If you use more Meronem than you should
If you accidentally use more than your prescribed dose,
contact your doctor or nearest hospital straight away.
If you forget to use Meronem
If you miss an injection, you should have it as soon as possible.
However, if it is almost time for your next injection, skip the
missed injection. Do not have a double dose (two injections at
the same time) to make up for a forgotten dose.

Acute bacterial meningitis
Management of febrile neutropenic patients

Dose to be administered
every 8 hours
40 mg/kg
20 mg/kg

Children over 50 kg body weight
The adult dose should be administered.
There is no experience in children with renal impairment.

2g
500 mg or 1 g
500 mg or 1 g
500 mg or 1 g
500 mg or 1 g
2g
1g

Method of administration
Meropenem is usually given by intravenous infusion over approximately 15 to 30 minutes (see
sections 6.2, 6.3, and 6.6). Alternatively, meropenem doses of up to 20 mg/kg may be given
as an intravenous bolus over approximately 5 minutes. There are limited safety data available
to support the administration of a 40 mg/kg dose in children as an intravenous bolus injection.

Meropenem is usually given by intravenous infusion over approximately
15 to 30 minutes (see sections 6.2, 6.3 and 6.6).
Alternatively, doses up to 1 g can be given as an intravenous bolus injection over
approximately 5 minutes. There are limited safety data available to support the
administration of a 2 g dose in adults as an intravenous bolus injection.
Renal impairment
The dose for adults and adolescents should be adjusted when creatinine clearance
is less than 51 ml/min, as shown below. There are limited data to support the
administration of these dose adjustments for a unit dose of 2 g.
Frequency
Creatinine Dose
(based on “unit” dose range of 500 mg or 1 g or
clearance
2 g, see table above)
(ml/min)
26-50
one unit dose
every 12 hours
10-25

half of one unit dose

every 12 hours

<10

half of one unit dose

every 24 hours

Meropenem is cleared by haemodialysis and haemofiltration. The required dose
should be administered after completion of the haemodialysis cycle.
There are no established dose recommendations for patients receiving peritoneal
dialysis.
Hepatic impairment
No dose adjustment is necessary in patients with hepatic impairment (see section 4.4).
Dose in elderly patients
No dose adjustment is required for the elderly with normal renal function or
creatinine clearance values above 50 ml/min.
Paediatric population
Children under 3 months of age
The safety and efficacy of meropenem in children under 3 months of age have not
been established and the optimal dose regimen has not been identified. However,
limited pharmacokinetic data suggest that 20 mg/kg every 8 hours may be an
appropriate regimen (see section 5.2).
Children from 3 months to 11 years of age and up to 50 kg body weight
The recommended dose regimens are shown in the table below:
Infection
Dose to be administered
every 8 hours
Severe pneumonia including hospital and
10 or 20 mg/kg
ventilator-associated pneumonia
Broncho-pulmonary infections in cystic fibrosis
40 mg/kg
Complicated urinary tract infections
10 or 20 mg/kg
Complicated intra-abdominal infections
10 or 20 mg/kg
Complicated skin and soft tissue infections
10 or 20 mg/kg

For instructions on reconstitution of the medicinal product before administration,
see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to any other carbapenem antibacterial agent.
Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any
other type of beta-lactam antibacterial agent (e.g. penicillins or cephalosporins).
4.4 Special warnings and precautions for use
The selection of meropenem to treat an individual patient should take into account
the appropriateness of using a carbapenem antibacterial agent based on factors
such as severity of the infection, the prevalence of resistance to other suitable
antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.
Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. resistance
Resistance to penems of Enterobacteriaceae, Pseudomonas aeruginosa and
Acinetobacter spp. varies across the European Union. Prescribers are advised to
take into account the local prevalence of resistance in these bacteria to penems.
Hypersensitivity reactions
As with all beta-lactam antibiotics, serious and occasionally fatal hypersensitivity
reactions have been reported (see sections 4.3 and 4.8).
Patients who have a history of hypersensitivity to carbapenems, penicillins or other
beta-lactam antibiotics may also be hypersensitive to meropenem. Before initiating
therapy with meropenem, careful inquiry should be made concerning previous
hypersensitivity reactions to beta-lactam antibiotics.
If a severe allergic reaction occurs, the medicinal product should be discontinued
and appropriate measures taken.
Antibiotic-associated colitis
Antibiotic-associated colitis and pseudomembranous colitis have been reported with
nearly all anti-bacterial agents, including meropenem, and may range in severity
from mild to life threatening. Therefore, it is important to consider this diagnosis in
patients who present with diarrhoea during or subsequent to the administration of
meropenem (see section 4.8). Discontinuation of therapy with meropenem and the
administration of specific treatment for Clostridium difficile should be considered.
Medicinal products that inhibit peristalsis should not be given.
Seizures
Seizures have infrequently been reported during treatment with carbapenems,
including meropenem (see section 4.8).
Hepatic function monitoring
Hepatic function should be closely monitored during treatment with meropenem due
to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis)
(see section 4.8).
Use in patients with liver disease: patients with pre-existing liver disorders should
have liver function monitored during treatment with meropenem. There is no dose
adjustment necessary (see section 4.2).
Direct antiglobulin test (Coombs test) seroconversion
A positive direct or indirect Coombs test may develop during treatment with meropenem.

If you stop using Meronem
Do not stop having Meronem until your doctor tells you to.
If you have any further questions on the use of this medicine,
ask your doctor, pharmacist or nurse.
4. Possible side effects
Like all medicines, this medicine can cause side effects,
although not everybody gets them.
Severe allergic reactions
If you have a severe allergic reaction, stop using Meronem
and see a doctor straight away. You may need urgent
medical treatment. The signs may include a sudden onset of:
• Severe rash, itching or hives on the skin.
• Swelling of the face, lips, tongue or other parts of the body.
• Shortness of breath, wheezing or trouble breathing.
Damage to red blood cells (not known)
The signs include:
• Being breathless when you do not expect it.
• Red or brown urine.
If you notice any of the above, see a doctor straight away.
Other possible side effects:
Common (may affect up to 1 in 10 people)
• Abdominal (stomach) pain.
• Feeling sick (nausea).
• Being sick (vomiting).
• Diarrhoea.
• Headache.
• Skin rash, itchy skin.
• Pain and inflammation.
• Increased numbers of platelets in your blood (shown in a
blood test).
• Changes in blood tests, including tests that show how well
your liver is working.
Uncommon (may affect up to 1 in 100 people)
• Changes in your blood. These include reduced numbers of
platelets (which may make you bruise more easily), increased
numbers of some white blood cells, decreased numbers of
other white cells and increased amounts of a substance called
‘bilirubin’. Your doctor may do blood tests from time to time.
• Changes in blood tests, including tests that show how well
your kidneys are working.
• A tingling feeling (pins and needles).
• Infections of the mouth or the vagina that are caused by a
fungus (thrush).
• Inflammation of the bowel with diarrhoea.
• Sore veins where Meronem is injected.
• Other changes in your blood. The symptoms include frequent
infections, high temperature and sore throat. Your doctor may
do blood tests from time to time.

Concomitant use with valproic acid/sodium valproate/valpromide
The concomitant use of meropenem and valproic acid/sodium valproate/valpromide
is not recommended (see section 4.5).
Meronem contains sodium.
Meronem 500 mg: This medicinal product contains approximately 2 mEq of sodium
per 500 mg dose which should be taken into consideration by patients on a
controlled sodium diet.
Meronem 1 g: This medicinal product contains approximately 4 mEq of sodium per 1 g
dose which should be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
No specific medicinal product interaction studies other than probenecid were conducted.
Probenecid competes with meropenem for active tubular secretion and thus inhibits
the renal excretion of meropenem with the effect of increasing the elimination
half-life and plasma concentration of meropenem. Caution is required if probenecid
is co-administered with meropenem.
The potential effect of meropenem on the protein binding of other medicinal products
or metabolism has not been studied. However, the protein binding is so low that no
interactions with other compounds would be expected on the basis of this mechanism.
Decreases in blood levels of valproic acid have been reported when it is co-administered
with carbapenem agents resulting in a 60-100% decrease in valproic acid levels in about
two days. Due to the rapid onset and the extent of the decrease, co-administration of
valproic acid/sodium valproate/valpromide with carbapenem agents is not considered to
be manageable and therefore should be avoided (see section 4.4).
Oral anti-coagulants

Simultaneous administration of antibiotics with warfarin may augment its anti-coagulant
effects. There have been many reports of increases in the anti-coagulant effects
of orally administered anti-coagulant agents, including warfarin in patients who are
concomitantly receiving antibacterial agents. The risk may vary with the underlying
infection, age and general status of the patient so that the contribution of the antibiotic
to the increase in INR (international normalised ratio) is difficult to assess. It is
recommended that the INR should be monitored frequently during and shortly after
co-administration of antibiotics with an oral anti-coagulant agent.

Paediatric population
Interaction studies have only been performed in adults.
4.6 Pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of meropenem in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to
reproductive toxicity (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of meropenem during
pregnancy.
Breast-feeding
Small amounts of meropenem have been reported to be excreted in human milk.
Meropenem should not be used in breast-feeding women unless the potential
benefit for the mother justifies the potential risk to the baby.
4.7 Effects on ability to drive and use machines
No studies on the effect on the ability to drive and use machines have been performed.
However, when driving or operating machines, it should be taken into account that
headache, paraesthesia and convulsions have been reported for meropenem.
4.8 Undesirable effects
Summary of the safety profile
In a review of 4,872 patients with 5,026 meropenem treatment exposures,
meropenem-related adverse reactions most frequently reported were diarrhoea
(2.3%), rash (1.4%), nausea/vomiting (1.4%) and injection site inflammation (1.1%).
The most commonly reported meropenem-related laboratory adverse events were
thrombocytosis (1.6%) and increased hepatic enzymes (1.5-4.3%).

2017-0004797/1
• Sudden

onset of a severe rash or blistering or
peeling skin. This may be associated with a high fever and
joint pains.
Rare (may affect up to 1 in 1,000 people)
• Fits (convulsions).
Frequency not known (cannot be estimated from available data)
• Serious

hypersensitivity reactions involving fever, skin rash,
and changes in the blood tests that check how the liver is
working (increased levels
of liver enzymes) and an
increase in a type of white
blood cell (eosinophilia)
and enlarged lymph nodes.
These may be signs of a multi-organ sensitivity disorder
known as DRESS syndrome.
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 at: www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance, Earlsfort Terrace,
IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.
Website: www.hpra.ie; e-mail: [email protected].

5. How to store Meronem
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 container. The expiry date refers to the last day of that month.
Do not store above 30°C.
Injection
After reconstitution: The reconstituted solutions for intravenous
injection should be used immediately. The time interval between
the beginning of reconstitution and the end of intravenous
injection should not exceed:
• 3 hours when stored at up to 25°C;
• 12 hours when stored under refrigerated conditions (2-8°C).
Infusion
After reconstitution: The reconstituted solutions for intravenous
infusion should be used immediately. The time interval
between the beginning of reconstitution and the end of
intravenous infusion should not exceed:
• 3 hours when stored at up to 25°C when Meronem is
dissolved in sodium chloride;
Please turn over→

Tabulated risk of adverse reactions
In the table below all adverse reactions are listed by system organ class and
frequency: 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). Within each frequency grouping,
undesirable effects are presented in order of decreasing seriousness.
Table 1
System Organ Class

Frequency

Infections and infestations Uncommon
Blood and lymphatic
Common
system disorders
Uncommon
Immune system disorders

Uncommon

Nervous system disorders Common
Uncommon
Rare
Gastrointestinal disorders Common
Uncommon
Hepatobiliary disorders
Common

Skin and subcutaneous
tissue disorders

Uncommon
Common
Uncommon
Not known

Event
oral and vaginal candidiasis
thrombocythaemia
eosinophilia, thrombocytopenia, leucopenia,
neutropenia, agranulocytosis, haemolytic
anaemia
angioedema, anaphylaxis
(see sections 4.3 and 4.4)
headache
paraesthesiae
convulsions (see section 4.4)
diarrhoea, vomiting, nausea, abdominal pain
antibiotic-associated colitis (see section 4.4)
transaminases increased, blood alkaline
phosphatase increased, blood lactate
dehydrogenase increased.
blood bilirubin increased
rash, pruritus
urticaria, toxic epidermal necrolysis, Stevens
Johnson syndrome, erythema multiforme.
Drug Reaction with Eosinophilia and
Systemic Symptoms (DRESS Syndrome)
blood creatinine increased, blood urea
increased
inflammation, pain
thrombophlebitis, pain at the injection site

Renal and urinary
Uncommon
disorders
General disorders and
Common
administration site
Uncommon
conditions
Paediatric population
Meronem is licensed for children over 3 months of age. There is no evidence of an
increased risk of any adverse drug reaction in children based on the limited available
data. All reports received were consistent with events observed in the adult population.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse
reactions via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse
reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL -Dublin 2;
Tel: +353 1 6764971; Fax: +353 16762517. Website: www.hpra.ie;
E-mail:[email protected].
4.9 Overdose
Relative overdose may be possible in patients with renal impairment if the dose is not
adjusted as described in section 4.2. Limited post-marketing experience indicates that
if adverse reactions occur following overdose, they are consistent with the adverse
reaction profile described in section 4.8, are generally mild in severity and resolve on
withdrawal or dose reduction. Symptomatic treatments should be considered.
In individuals with normal renal function, rapid renal elimination will occur.
Haemodialysis will remove meropenem and its metabolite.

• 24
hours when stored under refrigerated conditions (2-8°C)
when Meronem is dissolved in sodium chloride;
• when Meronem is dissolved in dextrose the solution should
be used immediately.
From a microbiological point of view, unless the method of
opening/reconstitution/dilution precludes the risk of microbiological
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 freeze the reconstituted solution.
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 to protect the
environment.
6. Contents of the pack and other information
What Meronem contains
The active substance is meropenem trihydrate equivalent to
500 mg anhydrous meropenem.
The active substance is meropenem trihydrate equivalent to 1 g
anhydrous meropenem.
The other ingredient is anhydrous sodium carbonate.
What Meronem looks like and contents of the pack
• Meronem is a white to light yellow powder for solution for
injection or infusion in a vial. Pack sizes of 1 or 10 vials.
Marketing Authorisation Holder and Manufacturer
The Marketing Authorisations for Meronem are held by:
UK:
Pfizer Limited,
Ramsgate Road,
Sandwich,
Kent ,
CT13 9NJ,
United Kingdom
IE:
Pfizer Healthcare Ireland,
9 Riverwalk, National Digital Park,
Citywest Business Campus,
Dublin 24,
Ireland
Meronem is manufactured by AstraZeneca UK Ltd, Silk Road
Business Park, Macclesfield, Cheshire SK10 2NA, UK.
This medicinal product is authorised in the Member States
of the EEA under the following names:
Austria:
Optinem
Belgium:
Meronem IV
Cyprus:
MERONEM
Czech Republic: MERONEM

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterials for systemic use, carbapenems
ATC code: J01DH02
Mechanism of action
Meropenem exerts its bactericidal activity by inhibiting bacterial cell wall synthesis in
Gram-positive and Gram-negative bacteria through binding to penicillin-binding proteins
(PBPs).
Pharmacokinetic/Pharmacodynamic (PK/PD) relationship
Similar to other beta-lactam antibacterial agents, the time that meropenem concentrations
exceed the MIC (T>MIC) has been shown to best correlate with efficacy. In preclinical
models meropenem demonstrated activity when plasma concentrations exceeded the MIC
of the infecting organisms for approximately 40% of the dosing interval. This target has not
been established clinically.
Mechanism of resistance
Bacterial resistance to meropenem may result from: (1) decreased permeability of the outer
membrane of Gram-negative bacteria (due to diminished production of porins) (2) reduced
affinity of the target PBPs (3) increased expression of efflux pump components, and
(4) production of beta-lactamases that can hydrolyse carbapenems.
Localised clusters of infections due to carbapenem-resistant bacteria have been reported
in the European Union.
There is no target-based cross-resistance between meropenem and agents of the
quinolone, aminoglycoside, macrolide and tetracycline classes. However, bacteria may
exhibit resistance to more than one class of antibacterial agents when the mechanism
involved include impermeability and/or an efflux pump(s).
Breakpoints
European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints
for MIC testing are presented below.
EUCAST clinical MIC breakpoints for meropenem (2013-02-11, v 3.1)
Organism
Susceptible (S) Resistant (R)
(mg/l)
(mg/l)
≤2
>8
Enterobacteriaceae
≤2
>8
Pseudomonas spp.
≤2
>8
Acinetobacter spp.
note 6
note 6
Streptococcus groups A, B, C and G
≤2
>2
Streptococcus pneumoniae1
≤2
>2
Viridans group streptococci2
--Enterococcus spp.
note 3
note 3
Staphylococcus spp.
≤2
>2
Haemophilus influenzae1, 2 and Moraxella catarrhalis2
≤ 0.25
> 0.25
Neisseria meningitidis2,4
≤2
>8
Gram-positive anaerobes except Clostridium difficile
Gram-negative anaerobes
≤2
>8
≤ 0.25
> 0.25
Listeria monocytogenes
Non-species related breakpoints5
≤2
>8
1
2

3
4

Meropenem breakpoints for Streptococcus pneumoniae and Haemophilus influenzae
in meningitis are 0.25 mg/l (Susceptible) and 1 mg/l (Resistant).
Isolates with MIC values above the susceptible breakpoint are very rare or not yet
reported. The identification and antimicrobial susceptibility tests on any such isolate
must be repeated and if the result is confirmed the isolate sent to a reference
laboratory. Until there is evidence regarding clinical response for confirmed isolates
with MIC values above the current resistant breakpoint they should be reported
resistant.
Susceptibility of staphylococci to carbapenems is inferred from the cefoxitin susceptibility.
Breakpoints relate to meningitis only.

Denmark:
Estonia:
Finland:
France:
Germany:
Greece:
Iceland:
Ireland:
Italy:
Luxembourg:
Netherlands:
Norway:
Poland:
Portugal:
Romania:
Spain:
Sweden:
United Kingdom:

MERONEM
Meronem
Meronem
MERONEM
Meronem
Meronem
Meronem
Meronem IV
MERREM
Meronem IV
Meronem i.v.
Meronem
Meronem
Meronem
Meronem i.v.
Meronem I.V.
Meronem
Meronem IV

Advice/medical education
Antibiotics are used to treat infections caused by bacteria.
They have no effect against infections caused by viruses.
Sometimes an infection caused by bacteria does not respond
to a course of an antibiotic. One of the commonest reasons
for this to occur is because the bacteria causing the infection
are resistant to the antibiotic that is being taken. This means
that they can survive and even multiply despite the antibiotic.
Bacteria can become resistant to antibiotics for many reasons.
Using antibiotics carefully can help to reduce the chance of
bacteria becoming resistant to them.
When your doctor prescribes a course of an antibiotic it is
intended to treat only your current illness. Paying attention
to the following advice will help prevent the emergence of
resistant bacteria that could stop the antibiotic working.
1. It is very important that you take the antibiotic at the
right dose, at the right times and for the right number of
days. Read the instructions on the label and if you do
not understand anything ask your doctor or pharmacist to
explain.
2. You should not take an antibiotic unless it has been
prescribed specifically for you and you should use it only to
treat the infection for which it was prescribed.
3. You should not take antibiotics that have been prescribed
for other people even if they had an infection that was
similar to yours.
4. You should not give antibiotics that were prescribed for you
to other people.
5. If
you have any antibiotic left over when you have taken
the course as directed by your doctor you should take the
remainder to a pharmacy for appropriate disposal.


Non-species related breakpoints have been determined using PK/PD data and
are independent of MIC distributions of specific species. They are for use only for
organisms that do not have specific breakpoints. Non species related breakpoints are
based on the following dosages: EUCAST breakpoints apply to meropenem 1000 mg
x 3 daily administered intravenously over 30 minutes as the lowest dose. 2 g x 3 daily
was taken into consideration for severe infections and in setting the I/R breakpoint.
6
The beta-lactam susceptibility of streptococcus groups A, B, C and G is inferred from
the penicillin susceptibility.
-- = Susceptibility testing not recommended as the species is a poor target for therapy
with the drug.
Isolates may be reported as R without prior testing.
5

The prevalence of acquired resistance may vary geographically and with time for selected
species and local information on resistance is desirable, particularly when treating severe
infections. As necessary, expert advice should be sought when the local prevalence of
resistance is such that the utility of the agent in at least some types of infections is questionable.
The following table of pathogens listed is derived from clinical experience and therapeutic
guidelines.
Commonly susceptible species
Gram-positive aerobes
Enterococcus faecalis$
Staphylococcus aureus (methicillin-susceptible)£
Staphylococcus species (methicillin-susceptible) including Staphylococcus epidermidis
Streptococcus agalactiae (Group B)
Streptococcus milleri group (S. anginosus, S. constellatus, and S. intermedius)
Streptococcus pneumoniae
Streptococcus pyogenes (Group A)
Gram-negative aerobes
Citrobacter freundii
Citrobacter koseri
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Morganella morganii
Neisseria meningitides
Proteus mirabilis
Proteus vulgaris
Serratia marcescens
Gram-positive anaerobes
Clostridium perfringens
Peptoniphilus asaccharolyticus
Peptostreptococcus species (including P. micros, P anaerobius, P. magnus)
Gram-negative anaerobes
Bacteroides caccae
Bacteroides fragilis group
Prevotella bivia
Prevotella disiens
Species for which acquired resistance may be a problem
Gram-positive aerobes
Enterococcus faecium$†
Gram-negative aerobes
Acinetobacter species
Burkholderia cepacia
Pseudomonas aeruginosa
Inherently resistant organisms
Gram-negative aerobes
Stenotrophomonas maltophilia
Legionella species

This leaflet was last revised in:
UK 06/2017
IE 09/2017
Ref: MR 1_0
The following information is intended for medical or
healthcare professionals only:
Instructions for giving Meronem to yourself or someone
else at home
Some patients, parents and carers are trained to give Meronem
at home.
Warning – You should only give this medicine to yourself
or someone else at home after a doctor or nurse has
trained you.
How to prepare this medicine
• The

medicine must be mixed with another liquid
(the diluent). Your doctor will tell you how much of the
diluent to use.
• Use the medicine straight after preparing it. Do not freeze it.
1. Wash your hands and dry them very well. Prepare a clean
working area.
2. Remove the Meronem bottle (vial) from the packaging.
Check the vial and the expiry date. Check that the vial is
intact and has not been damaged.
3. Remove the coloured cap and clean the grey rubber
stopper with an alcohol wipe. Allow the rubber stopper to
dry.
4. Connect a new sterile needle to a new sterile syringe,
without touching the ends.
5. Draw up the recommended amount of sterile ‘Water for
Injections’ into the syringe. The amount of liquid that you
need is shown in the table below:
Dose of Meronem
500 mg (milligrams)
1 g (gram)
1.5 g
2g

Amount of ‘Water for Injections’
needed for dilution
10 ml (millilitres)
20 ml
30 ml
40 ml

Please note: If your prescribed dose of Meronem is more
than 1 g, you will need to use more than 1 vial
of Meronem. You can then draw the liquid in
the vials into the one syringe.
6. Put the needle of the syringe through the centre of the grey
rubber stopper and inject the recommended amount of
Water for Injections into the vial or vials of Meronem.

Other micro-organisms
Chlamydophila pneumoniae
Chlamydophila psittaci
Coxiella burnetii
Mycoplasma pneumoniae
Species that show natural intermediate susceptibility
All methicillin-resistant staphylococci are resistant to meropenem
†
Resistance rate ≥ 50% in one or more EU countries.
Glanders and melioidosis: Use of meropenem in humans is based on in vitro B.mallei and
B. pseudomallei susceptibility data and on limited human data. Treating physicians should
refer to national and/or international consensus documents regarding the treatment of
glanders and melioidosis.
$
£

5.2 Pharmacokinetic properties
In healthy subjects the mean plasma half-life is approximately 1 hour; the mean volume
of distribution is approximately 0.25 l/kg (11-27 l) and the mean clearance is 287 ml/min at
250 mg falling to 205 ml/min at 2 g. Doses of 500, 1000 and 2000 mg doses infused over
30 minutes give mean Cmax values of approximately 23, 49 and 115 μg/ml respectively,
corresponding AUC values were 39.3, 62.3 and 153 μg.h/ml. After infusion over
5 minutes Cmax values are 52 and 112 μg/ml after 500 and 1000 mg doses respectively.
When multiple doses are administered 8-hourly to subjects with normal renal function,
accumulation of meropenem does not occur.
A study of 12 patients administered meropenem 1000 mg 8 hourly post-surgically for
intra-abdominal infections showed a comparable Cmax and half-life to normal subjects but
a greater volume of distribution 27 l.
Distribution
The average plasma protein binding of meropenem was approximately 2% and
was independent of concentration. After rapid administration (5 minutes or less) the
pharmacokinetics are biexponential but this is much less evident after 30 minutes infusion.
Meropenem has been shown to penetrate well into several body fluids and tissues:
including lung, bronchial secretions, bile, cerebrospinal fluid, gynaecological tissues, skin,
fascia, muscle, and peritoneal exudates.
Biotransformation
Meropenem is metabolised by hydrolysis of the beta-lactam ring generating a
microbiologically inactive metabolite. In vitro meropenem shows reduced susceptibility to
hydrolysis by human dehydropeptidase-I (DHP-I) compared to imipenem and there is no
requirement to co-administer a DHP-I inhibitor.
Elimination
Meropenem is primarily excreted unchanged by the kidneys; approximately 70% (50 –75%)
of the dose is excreted unchanged within 12 hours. A further 28% is recovered as the
microbiologically inactive metabolite. Faecal elimination represents only approximately
2% of the dose. The measured renal clearance and the effect of probenecid show that
meropenem undergoes both filtration and tubular secretion.
Renal insufficiency
Renal impairment results in higher plasma AUC and longer half-life for meropenem. There
were AUC increases of 2.4 fold in patients with moderate impairment (CrCL 33-74 ml/min),
5 fold in severe impairment (CrCL 4-23 ml/min) and 10 fold in haemodialysis patients
(CrCL <2 ml/min) when compared to healthy subjects (CrCL >80 ml/min). The AUC of
the microbiologically inactive ring opened metabolite was also considerably increased
in patients with renal impairment. Dose adjustment is recommended for patients with
moderate and severe renal impairment (see section 4.2).
Meropenem is cleared by haemodialysis with clearance during haemodialysis being
approximately 4 times higher than in anuric patients.
Hepatic insufficiency
A study in patients with alcoholic cirrhosis shows no effect of liver disease on the
pharmacokinetics of meropenem after repeated doses.
Adult patients
Pharmacokinetic studies performed in patients have not shown significant pharmacokinetic
differences versus healthy subjects with equivalent renal function. A population model

7. Remove

the needle from the vial and shake the vial well
for about 5 seconds, or until all the powder has dissolved.
Clean the grey rubber stopper once more with a new
alcohol wipe and allow the rubber stopper to dry.
8. With the plunger of the syringe pushed fully into the
syringe, put the needle back through the grey rubber
stopper. You must then hold both the syringe and the vial
and turn the vial upside down.
9. Keeping the end of the needle in the liquid, pull back the
plunger and draw all the liquid in the vial into the syringe.
10. Remove the needle and syringe from the vial and throw the
empty vial away in a safe place.
11. Hold the syringe upright, with the needle pointing upwards.
Tap the syringe so that any bubbles in the liquid rise to the
top of the syringe.
12. Remove any air in the syringe by gently pushing the
plunger until all the air has gone.
13. If you are using Meronem at home, dispose of any needles
and infusion lines that you have used in an appropriate
way. If your doctor decides to stop your treatment, dispose
of any unused Meronem in an appropriate way.
Giving the injection
You can either give this medicine through a short cannula or
venflon, or through a port or central line.
Giving Meronem through a short cannula or venflon
1. Remove the needle from the syringe and throw the needle
away carefully in your sharps bin.
2. Wipe the end of the short cannula or venflon with an
alcohol wipe and allow it to dry. Open the cap on your
cannula and connect the syringe.
3. Slowly push the plunger of the syringe to give the antibiotic
steadily over about 5 minutes.
4. Once you have finished giving the antibiotic and the
syringe is empty, remove the syringe and use a flush as
recommended by your doctor or nurse.
5. Close the cap of your cannula and carefully throw the
syringe away in your sharps bin.
Giving Meronem through a port or central line
1. Remove the cap on the port or line, clean the end of the
line with an alcohol wipe and allow it to dry.
2. Connect the syringe and slowly push the plunger on the
syringe to give the antibiotic steadily over about 5 minutes.
3. Once you have finished giving the antibiotic, remove the
syringe and use a flush as recommended by your doctor or
nurse.
4. Place a new clean cap on your central line and carefully
throw the syringe away in your sharps bin.

developed from data in 79 patients with intra-abdominal infection or pneumonia, showed
a dependence of the central volume on weight and the clearance on creatinine clearance
and age.
Paediatric population
The pharmacokinetics in infants and children with infection at doses of 10, 20 and 40 mg/kg
showed Cmax values approximating to those in adults following 500, 1000 and 2000 mg doses,
respectively. Comparison showed consistent pharmacokinetics between the doses and half-lives
similar to those observed in adults in all but the youngest subjects (<6 months t1/2 1.6 hours). The
mean meropenem clearance values were 5.8 ml/min/kg (6-12 years), 6.2 ml/min/kg (2-5 years),
5.3 ml/min/kg (6-23 months) and 4.3 ml/min/kg (2-5 months). Approximately 60% of the dose is
excreted in urine over 12 hours as meropenem with a further 12% as metabolite. Meropenem
concentrations in the CSF of children with meningitis are approximately 20% of concurrent plasma
levels although there is significant inter-individual variability.
The pharmacokinetics of meropenem in neonates requiring anti-infective treatment showed
greater clearance in neonates with higher chronological or gestational age with an overall
average half-life of 2.9 hours. Monte Carlo simulation based on a population PK model
showed that a dose regimen of 20 mg/kg 8 hourly achieved 60%T>MIC for P. aeruginosa
in 95% of pre-term and 91% of full term neonates.
Elderly
Pharmacokinetic studies in healthy elderly subjects (65-80 years) have shown a reduction in
plasma clearance, which correlated with age-associated reduction in creatinine clearance,
and a smaller reduction in non-renal clearance. No dose adjustment is required in elderly
patients, except in cases of moderate to severe renal impairment (see section 4.2).
5.3 Preclinical safety data
Animal studies indicate that meropenem is well tolerated by the kidney. Histological
evidence of renal tubular damage was seen in mice and dogs only at doses of
2000 mg/kg and above after a single administration and above and in monkeys at
500 mg/kg in a 7-day study.
Meropenem is generally well tolerated by the central nervous system. Effects were seen in
acute toxicity studies in rodent at doses exceeding 1000 mg/kg.
The IV LD50 of meropenem in rodents is greater than 2000 mg/kg.
In repeat dose studies of up to 6 months duration only minor effects were seen including a
decrease in red cell parameters in dogs.
There was no evidence of mutagenic potential in a conventional test battery and no
evidence of reproductive toxicity including teratogenic potential in studies in rats up to
750 mg/kg and in monkeys up to 360 mg/kg.
There was no evidence of increased sensitivity to meropenem in juveniles compared to
adult animals. The intravenous formulation was well tolerated in animal studies.
The sole metabolite of meropenem had a similar profile of toxicity in animal studies.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Meronem 500 mg: anhydrous sodium carbonate
Meronem 1 g: anhydrous sodium carbonate
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those
mentioned in section 6.6.
6.3 Shelf life
4 years
After reconstitution:
Intravenous bolus injection administration
A solution for bolus injection is prepared by dissolving the drug product in water for
injection to a final concentration of 50 mg/ml. Chemical and physical in-use stability for a
prepared solution for bolus injection has been demonstrated for 3 hours at up to 25°C or
12 hours under refrigerated conditions (2-8°C).
From a microbiological point of view, unless the method of opening/reconstitution/
dilution precludes the risk of microbiological contamination, the product should be used
immediately.

If not used immediately in-use storage times and conditions are the responsibility of the
user.
Intravenous infusion administration
A solution for infusion is prepared by dissolving the drug product in either 0.9% sodium
chloride solution for infusion or 5% dextrose solution for infusion to a final concentration of
1 to 20 mg/ml. Chemical and physical in-use stability for a prepared solution for infusion
using 0.9% sodium chloride solution has been demonstrated for 3 hours at up to 25°C or
24 hours under refrigerated conditions (2-8°C).
From a microbiological point of view, unless the method of opening/reconstitution/
dilution precludes the risk of microbiological contamination, the product should be used
immediately.
If not used immediately in-use storage times and conditions are the responsibility of the user.
Reconstituted solution of the product in 5% dextrose solution should be used immediately.
The constituted solutions should not be frozen.
6.4 Special precautions for storage
Do not store above 30°C.
Do not freeze the reconstituted solution.
6.5 Nature and contents of container
Meronem 500 mg
674 mg powder in a 20 ml Type 1 glass vial with stopper (grey halobutilic rubber with an
aluminium cap)
Meronem 1 g
1348 mg powder in a 30 ml Type 1 glass vial with stopper (grey halobutilic rubber with an
aluminium cap)
The medicinal product is supplied in pack sizes of 1 or 10 vials.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Injection
Meropenem to be used for bolus intravenous injection should be constituted with sterile
water for injection.
Infusion
For intravenous infusion meropenem vials may be directly constituted with 0.9% sodium
chloride or 5% dextrose solutions for infusion.
Each vial is for single use only.
Standard aseptic techniques should be used for solution preparation and administration.
The solution should be shaken before use.
Any unused product or waste material should be disposed of in accordance with local
requirements.
7.
MARKETING AUTHORISATION HOLDER
UK:
Pfizer Limited,
Ramsgate Road,
Sandwich,
Kent,
CT13 9NJ,
United Kingdom
IE:
Pfizer Healthcare Ireland,
9 Riverwalk, National Digital Park,
Citywest Business Campus,
Dublin 24,
Ireland
8. MARKETING AUTHORISATION NUMBER(S)
Meronem IV 500 mg
PL 00057/1535, PA 0822/190/001
Meronem IV 1 g
PL 00057/1536, PA 0822/190/002
Ref: MR 1_0