MERONEM IV 500MG

Active substance: MEROPENEM TRIHYDRATE

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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 taking this medicine.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or nurse.
- 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 any of the side effects gets serious, or if you notice any side effects
not listed in this leaflet, please tell your doctor or nurse.
In this leaflet:
1. What Meronem is and what it is used for
2. Before you use Meronem
3. How to use Meronem
4. Possible side effects
5. How to store Meronem
6. Further information
1. What Meronem is and what it is used for
Meronem belongs to a group of medicines called carbapenem antibiotics.
It works by killing bacteria, which can cause serious infections.
• 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.
2. 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 Further information).
• If you are allergic (hypersensitive) to other antibiotics such as
penicillins, cephalosporins, or carbapenems as you may also be
allergic to meropenem.
Take special care with Meronem
Check with your doctor before using Meronem:
• If you have health problems, such as liver or kidney problems.
• If you have had severe diarrhoea after taking other antibiotics.
Medical Information Leaflet

Meronem

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:
Each 500 mg vial contains 104 mg sodium carbonate which equates to approximately 2.0 mEq of
sodium (approximately 45 mg).
Each 1 g vial contains 208 mg sodium carbonate which equates to approximately 4.0 mEq of sodium
(approximately 90 mg).
For a 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 over 3 months
of age (see sections 4.4 and 5.1):
• Pneumonia, including community acquired pneumonia and nosocomial 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.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
4.2 Posology and method of administration
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
nosocomial infections due to Pseudomonas aeruginosa or Acinetobacter spp.
Additional considerations for dosing are needed when treating patients with renal insufficiency
(see further below).
Adults and Adolescents
Infection
Dose to be administered every 8 hours
Pneumonia including community-acquired
500 mg or 1 g
pneumonia and nosocomial pneumonia.
Broncho-pulmonary infections in cystic fibrosis 2 g

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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.
Using other medicines
Please tell your doctor if you are taking or have recently taken any
other medicines, including medicines obtained without a prescription
and herbal 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 or nurse if you are taking any of the
following medicines:
• Probenecid (used to treat gout).
• Sodium valproate (used to treat epilepsy). Meronem should not be
used because it may decrease the effect of sodium valproate.
Pregnancy and breast-feeding
It is important that you tell your doctor if you are pregnant or are
planning to become pregnant before receiving meropenem. It is
preferable to avoid the use of meropenem during pregnancy.
Your doctor will decide whether you should use meropenem.
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 and it may affect the baby.
Therefore, your doctor will decide whether you should use meropenem
while breastfeeding.
Ask your doctor for advice before taking any medicine.
Driving and using machines
No studies on the effect on the ability to drive and use machines have
been performed.
Important information about some of the ingredients of Meronem
Meronem contains sodium.
Meronem 500 mg: This medicinal product contains approximately
2.0 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 4.0 mEq
of sodium per 1.0 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 or nurse.

3. How to use Meronem
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.
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.
• 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 take a double dose (two injections at the same time) to make
up for a forgotten dose.
If you stop using Meropenem
Do not stop having Meronem until your doctor tells you to.
If you have any further questions on the use of this product, ask your
doctor or nurse.

4. Possible side effects
Like all medicines, Meronem can cause side effects, although not
everybody gets them.
The frequency of possible side effects listed below is defined using the
following convention:
• Very common (affects more than 1 user in 10).
• Common (affects 1 to 10 users in 100).
• Uncommon (affects 1 to 10 users in 1,000).
• Rare (affects 1 to 10 users in 10,000).
• Very rare (affects less than 1 user in 10,000).
• Not known (frequency cannot be estimated from the available data
but this is rare or very rare).
Severe allergic reactions
If you have a severe allergic reaction, stop having 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
• 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
• 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.

Complicated urinary tract infections
500 mg or 1 g
Complicated intra-abdominal infections
500 mg or 1 g
Intra- and post-partum infections
500 mg or 1 g
Complicated skin and soft tissue infections
500 mg or 1 g
Acute bacterial meningitis
2 g
Management of febrile neutropenic patients
1 g
Meropenem is usually given by intravenous infusion over approximately 15 to 30 minutes (see section
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 application of these dose adjustments
for a unit dose of 2 g.

Children over 50 kg body weight
The adult dose should be administered.
There is no experience in children with renal impairment.
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.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to any other carbapenem antibacterial agent.
Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of
betalactam 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.
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 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 have infrequently been reported during treatment with carbapenems, including meropenem
(see section 4.8).
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).
A positive direct or indirect Coombs test may develop during treatment with meropenem.
The concomitant use of meropenem and valproic acid/sodium valproate is not recommended
(see section 4.5).
Meronem contains sodium.
Meronem 500 mg: This medicinal product contains approximately 2.0 mEq of sodium per 500 mg dose
which should be taken into consideration by patients on a controlled sodium diet.
Meronem 1.0 g: This medicinal product contains approximately 4.0 mEq of sodium per 1.0 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 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.
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.
Lactation
It is unknown whether meropenem is excreted in human milk. Meropenem is detectable at very low
concentrations in animal breast milk. A decision must be made whether to discontinue breast-feeding or
to discontinue/abstain from meropenem therapy taking into account the benefit of therapy for the woman.
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.
4.8 Undesirable effects
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 %).
Adverse reactions listed in the table with a frequency of “not known” were not observed in the
2,367 patients who were included in pre-authorisation clinical studies with intravenous and
intramuscular meropenem but have been reported during the post-marketing period.
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) and not known (cannot be estimated from the available data). Within each
frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Creatinine clearance (ml/min)

Dose
Frequency
(based on “unit” dose range of 500 mg
or 1 g or 2 g, see table above)
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
Pneumonia including community-acquired
pneumonia and nosocomial pneumonia
Broncho-pulmonary infections in cystic fibrosis
Complicated urinary tract infections
Complicated intra-abdominal infections
Complicated skin and soft tissue infections
Acute bacterial meningitis
Management of febrile neutropenic patients

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

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Table 1
System Organ Class
Infections and infestations
Blood and lymphatic
system disorders
Immune system disorders

Frequency
Uncommon
Common
Uncommon
Not known
Not known

Event
oral and vaginal candidiasis
thrombocythaemia
eosinophilia, thrombocytopenia, leucopenia, neutropenia
agranulocytosis, haemolytic anaemia
angioedema, anaphylaxis (see sections 4.3 and 4.4)

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• 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).
Rare
• Fits (convulsions).
Other possible side effects of unknown frequency
• 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.
• Sudden onset of a severe rash or blistering or peeling skin. This
may be associated with a high fever and joint pains.
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 nurse.
5. How to store Meronem
Keep out of the reach and sight of children.
Do not use Meronem 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 controlled room temperature (15-25°C).

Nervous system disorders Common
Uncommon
Rare
Gastrointestinal disorders Common
Not known
Hepatobiliary disorders
Common
Skin and subcutaneous
tissue disorders

Uncommon
Common
Uncommon
Not known

Renal and urinary disorders
General disorders and
administration site
conditions

Uncommon
Common
Uncommon
Not known

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, pruritis
urticaria
toxic epidermal necrolysis, Stevens Johnson syndrome,
erythema multiforme.
blood creatinine increased, blood urea increased
inflammation, pain
thrombophlebitis
pain at the injection site

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.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterials for systemic use, carbapenems
ATC code: J01DH02
Mode 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 antibacterials agents when the mechanism involved include impermeability and/or
an efflux pump(s).

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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:
• 6 hours when stored at controlled room temperature (15-25°C)
when Meronem is dissolved in sodium chloride;
• 24 hours when stored at 2-8°C when Meronem is dissolved in
sodium chloride. In this case, the prepared solution should be used
within 2 hours after it has left the refrigerator;
• 1 hour when Meronem is dissolved in glucose (dextrose).
Do not freeze the reconstituted solution.
Medicines should not be disposed of via wastewater or household
waste. Ask your pharmacist how to dispose of medicines no longer
required. These measures will help to protect the environment.
6. Further information
What Meronem contains
Each vial contains meropenem trihydrate equivalent to 500 mg
anhydrous meropenem.
Each vial contains 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 AstraZeneca
UK Ltd, 600 Capability Green, Luton, LU1 3LU, UK.
Meronem is manufactured by Corden Pharma S.p.A., Viale dell’
Industria, 3, 20040 Caponago, Italy.
Breakpoints
European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints for MIC
testing are presented below.
EUCAST clinical MIC breakpoints for meropenem (2009-06-05, v 3.1)
Organism
Susceptible (S) Resistant (R)
(mg/l)
(mg/l)
Enterobacteriaceae
≤2
>8
Pseudomonas
≤2
>8
Acinetobacter
≤2
>8
Streptococcus groups A, B, C, G
≤2
>2
Streptococcus pneumoniae1
≤2
>2
Other streptococci
2
2
Enterococcus
--Staphylococcus2
note 3
note 3
Haemophilus influenzae1 and Moraxella catarrhalis
≤2
>2
Neisseria meningitidis2,4
≤ 0.25
> 0.25
Gram-positive anaerobes
≤2
>8
Gram-negative anaerobes
≤2
>8
≤2
>8
Non-species related breakpoints5
1
 Meropenem breakpoints for Streptococcus pneumoniae and Haemophilus influenzae in meningitis
are 0.25/1 mg/L.
2
 Strains with MIC values above the S/I breakpoint are 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 above the current resistant breakpoint (in italics) they should be reported as resistant.
3
 Susceptibility of staphylococci to meropenem is inferred from the methicillin susceptibility.
4
 Meropenem breakpoints in Neisseria meningitidis relates to meningitis only.
5
 Non-species related breakpoints have been determined mainly from PK/PD data and are independent
of the MIC distributions of specific species. They are for use for species not mentioned in the table
and footnotes.
-- = Susceptibility testing not recommended as the species is a poor target for therapy with the
medicinal product.
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)

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This medicinal product is authorised in the Member States of the
EEA under the following names:
Austria:
Optinem
Belgium:
Meronem IV
Bulgaria:
Meronem
Cyprus:
MERONEM
Czech Republic:
MERONEM
Denmark:
MERONEM
Estonia:
Meronem
Finland:
Meronem
France:
MERONEM
Germany:
Meronem
Greece:
Meronem
Hungary:
Meronem
Iceland:
Meronem
Ireland:
Meronem IV
Italy:
MERREM
Latvia:
Meronem
Lithuania:
Meronem IV
Luxembourg:
Meronem IV
Malta:
Meronem IV
Netherlands:
Meronem i.v.
Norway:
Meronem
Poland:
Meronem
Portugal:
Meronem
Romania:
Meronem i.v.
Slovak Republic:
Meronem 500mg i.v.
Slovenia:
Meronem
Spain:
Meronem I.V.
Sweden:
Meronem
United Kingdom:
Meronem IV

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Product name
Reference number
Meronem IV 500 mg 17901/0029
Meronem IV 1 g
17901/0030
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Gram-negative aerobes
Citrobacter freudii
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
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.
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

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.
This leaflet was last updated in April 2011
© AstraZeneca 2011
Meronem is a trade mark of the AstraZeneca group of companies.
INF 10 0021
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.

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.
Metabolism
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 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.
Paediatrics
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.

Warning – You should only give this medicine to yourself or
someone else at home after a doctor or nurse has trained you.
• 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.
How to prepare this medicine
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)

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

1 g (gram)
1.5 g
2 g

20 ml
30 ml
40 ml

I
f 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.
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.

Please note:

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 that 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 increased evidence of abortions at 500 mg/kg in a preliminary study in monkeys.
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 Meronem 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 controlled room temperature (15-25°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 Meronem in either 0.9% sodium
chloride solution for infusion or 5% glucose (dextrose) solution for infusion to a final concentration of
1 to 20 mg/ml.

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.

Chemical and physical in-use stability for a prepared solution for infusion using 0.9% sodium chloride
solution has been demonstrated for 6 hours at controlled room temperature (15-25°C) or 24 hours
at 2-8°C. The prepared solution should, if refrigerated, be used within 2 hours after it has left the
refrigerator. 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 Meronem in 5% glucose (dextrose) solution should be used immediately,
i.e. within one hour following reconstitution.
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
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% glucose 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
AstraZeneca UK Ltd
600 Capability Green
Luton
LU1 3LU
United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
Meronem IV 500 mg
PL 17901/0029
Meronem IV 1 g
PL 17901/0030
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
09 February 2009
10. DATE OF REVISION OF THE TEXT
April 2011
INF 10 0021

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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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