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 using this
medicine because it contains important information for you.
- Keep this leaflet. You may need to read it again.
-  you have any further questions, ask your doctor, pharmacist
If
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.
-  you get any side effects, talk to your doctor, pharmacist or
If
nurse. This includes any possible side effects not listed in this
leaflet. See section 4.
What is in this leaflet
1.  hat Meronem is and what it is used for
W
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 belongs to a group of medicines called carbapenem
antibiotics. It works by killing bacteria, which can cause serious
infections.
• nfection affecting the lungs (pneumonia)
I
•  ung and bronchial infections in patients suffering from cystic
L
fibrosis
•  omplicated urinary tract infections
C
C
•  omplicated infections in the abdomen
I
• nfections 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.

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):
•  evere pneumonia, including hospital and ventilator-associated pneumonia.
S
•  roncho-pulmonary infections in cystic fibrosis.
B
•  omplicated urinary tract infections.
C
•  omplicated intra-abdominal infections.
C
• ntra- and post-partum infections.
I
•  omplicated skin and soft tissue infections.
C
•  cute bacterial meningitis.
A
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
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).
Adults and Adolescents
Infection
Severe pneumonia including hospital and
ventilator-associated pneumonia.
Broncho-pulmonary infections in cystic fibrosis

Dose to be administered
every 8 hours
500 mg or 1 g
2 g

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 Further
information).
• 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:
•  robenecid (used to treat gout).
P
• 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 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 breast-feeding.
Driving and using machines
No studies on the effect on the ability to drive and use machines
have been performed.

Infection
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

Dose to be administered
every 8 hours
500 mg or 1 g
500 mg or 1 g
500 mg or 1 g
500 mg or 1 g
2 g
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.
Creatinine
clearance
(ml/min)
26-50
10-25
<10

Dose
(based on “unit” dose range of 500 mg or
1 g or 2 g, see table above)
one unit dose
half of one unit dose
half of one unit dose

Frequency
every 12 hours
every 12 hours
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
Severe pneumonia including hospital and
ventilator-associated 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

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, pharmacist or nurse.
3. How to use Meronem

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.
If you stop using Meropenem
Do not stop having Meronem until your doctor tells you to.

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
•  he dose depends on the type of infection that you have,
T
where the infection is in the body and how serious the infection
is. Your doctor will decide on the dose that you need.
•  he dose for adults is usually between 500 mg (milligrams)
T
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
•  he dose for children over 3 months old and up to 12 years
T
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
•  eronem will be given to you as an injection or infusion into
M
a large vein.
•  our doctor or nurse will normally give Meronem to you.
Y
•  owever, some patients, parents and carers are trained
H
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.
Y
•  our injection should not be mixed with or added to solutions
that contain other medicines.
T
•  he injection may take about 5 minutes or between 15 and
30 minutes. Your doctor will tell you how to give Meronem.
•  ou should normally have your injections at the same times
Y
each day.

If you have any further questions on the use of this medicine,
ask your doctor, pharmacist or nurse.

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 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.
Resistance to penems of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter
spp. varies across the European Union. Prescribers are advised to take into account
the local prevalence of resistance in these bacteria to penems.
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/valpromide 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.

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 having Meronem
and see a doctor straight away. You may need urgent medical
treatment. The signs may include a sudden onset of:
•  evere rash, itching or hives on the skin.
S
•  welling of the face, lips, tongue or other parts of the body.
S
•  hortness of breath, wheezing or trouble breathing.
S
Damage to red blood cells (not known)
The signs include:
•  eing breathless when you do not expect it.
B
•  ed or brown urine.
R
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)
•  bdominal (stomach) pain.
A
F
•  eeling sick (nausea).
•  eing sick (vomiting).
B
• Diarrhoea.
• Headache.
•  kin rash, itchy skin.
S
•  ain and inflammation.
P
• ncreased numbers of platelets in your blood (shown in a
I
blood test).
•  hanges in blood tests, including tests that show how well
C
your liver is working.

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 coadministered 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 coadministration 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 postmarketing 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.

P037260
Uncommon (may affect up to 1 in 100 people)
•  hanges in your blood. These include reduced numbers of
C
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.
•  hanges in blood tests, including tests that show how well
C
your kidneys are working.
•  tingling feeling (pins and
A
needles).
• nfections of the mouth or
I
the vagina that are caused
by a fungus (thrush).

Rare (may affect up to 1 in 1,000 people)
• Fits (convulsions).
Other possible side effects of unknown frequency
(frequency cannot be estimated from available data)
• nflammation of the bowel with diarrhoea.
I
•  ore veins where Meronem is injected.
S
•  ther changes in your blood. The symptoms include frequent
O
infections, high temperature and sore throat. Your doctor may
do blood tests from time to time.
•  udden onset of a severe rash or blistering or peeling skin.
S
This may be associated with a high fever and joint pains.
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 via the Yellow
Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side
effects you can help provide more information on the safety of
this medicine.
5. How to store 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 controlled
room temperature (15-25°C).

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

Frequency
Uncommon
Common
Uncommon

Immune system disorders

Not known
Not known

Nervous system disorders Common
Uncommon
Rare
Gastrointestinal disorders Common
Not known
Hepatobiliary disorders
Common

Skin and subcutaneous
tissue disorders

Renal and urinary
disorders
General disorders and
administration site
conditions

Uncommon
Common
Uncommon
Not known
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, pruritis
urticaria
toxic epidermal necrolysis, Stevens Johnson
syndrome, erythema multiforme.
blood creatinine increased, blood urea
increased
inflammation, pain
thrombophlebitis
pain at the injection site

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.
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.

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:
•   hours when stored at controlled room temperature
6
(15-25°C) when Meronem is dissolved in sodium chloride;
•  4 hours when stored at 2-8°C when Meronem is dissolved
2
in sodium chloride. In this case, the prepared solution should
be used within 2 hours after it has left the refrigerator;
•   hour when Meronem is dissolved in glucose (dextrose).
1
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. Each vial contains 500 mg
anhydrous meropenem as meropenem trihydrate.
The active substance is meropenem. Each vial contains 1 g
anhydrous meropenem as meropenem trihydrate.
The other ingredient is anhydrous sodium carbonate.
What Meronem looks like and contents of the pack
M
•  eronem 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 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
Bulgaria: Meronem
Cyprus: MERONEM
Czech Republic: MERONEM
Denmark: MERONEM

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).
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
>8
≤2
Pseudomonas spp.
≤2
>8
Acinetobacter spp.
note 6
note 6
Streptococcus groups A, B, C and G
≤2
>2
Streptococcus pneumoniae 1
≤2
>2
Viridans group streptococci2
--Enterococcus spp.
note 3
note 3
Staphylococcus spp.
≤2
>2
Haemophilus influenzae 1, 2 and Moraxella catarrhalis 2
≤ 0.25
> 0.25
Neisseria meningitidis 2,4
≤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

Meropenem breakpoints for Streptococcus pneumoniae and Haemophilus
influenzae in meningitis are 0.25 mg/l (Susceptible) and 1 mg/l (Resistant).
2

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.
3

Susceptibility of staphylococci to carbapenems is inferred from the cefoxitin
susceptibility.
4

Breakpoints relate to meningitis only.
5

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.
-- =  usceptibility testing not recommended as the species is a poor target for therapy
S
with the drug.
Isolates may be reported as R without prior testing.
1

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

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. t is very important that you take the antibiotic at the
I
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.  ou should not take an antibiotic unless it has been
Y
prescribed specifically for you and you should use it only to
treat the infection for which it was prescribed.
3.  ou should not take antibiotics that have been prescribed
Y
for other people even if they had an infection that was
similar to yours.
4.  ou should not give antibiotics that were prescribed for you
Y
to other people.
5. f you have any antibiotic left over when you have taken
I
the course as directed by your doctor you should take the
remainder to a pharmacy for appropriate disposal.

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
T
•  he medicine must be mixed with another liquid (the diluent).
Your doctor will tell you how much of the diluent to use.
•  se the medicine straight after preparing it. Do not freeze it.
U
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
Amount of ‘Water for Injections’
needed for dilution
500 mg (milligrams) 10 ml (millilitres)
1 g (gram)
20 ml
1.5 g
30 ml
2 g
40 ml

To listen to or request a copy of this
leaflet in Braille, large print or audio
please call, free of charge:
0800 198 5000 (UK only)
Please be ready to give the following
information:
Reference number
Product name
17901/0029
Meronem IV 500 mg
17901/0030
Meronem IV 1 g
This is a service provided by the Royal
National Institute of Blind People.

This leaflet was last revised in April 2014
© AstraZeneca 2014
Meronem is a trade mark of the AstraZeneca group of
companies.
INF 14 0012
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.

Please note:  your prescribed dose of Meronem is more
If
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.
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.

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 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.

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.
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.
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.

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.

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.
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
Leaflet updated: April 2014
INF 14 0012

Expand view ⇕

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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