Imipenem/cilastatin is indicated for the treatment of the following infections in adults and children 1 year of age
and above (see sections 4.4 and 5.1):
• complicated intra-abdominal infections
• severe pneumonia including hospital and ventilator-associated pneumonia
• intra- and post-partum infections
• complicated urinary tract infections
• complicated skin and soft-tissue infections
Imipenem/cilastatin 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.

Posology
The dose recommendations for Imipenem 500 mg/cilastatin 500 mg powder for solution for infusion represent
the quantity of imipenem/cilastatin to be administered.
The daily dose of imipenem/cilastatin should be based on the type and severity of infection, the pathogen(s)
isolated, the patient's renal function and body weight (see also section 4.4 and 5.1).

Adults and adolescents
For patients with normal renal function (creatinine clearance of > 70 ml/min/1.73 m2), the
recommended dose regimens are:
500 mg/500 mg every 6 hours OR
1000 mg/1000 mg every 8 hours OR every 6 hours

It is recommended that infections suspected or proven to be due to less susceptible bacterial species (such as
Pseudomonas aeruginosa) and very severe infections (e.g. in neutropenic patients with a fever) should be treated
with 1000 mg/1000 mg administered every 6 hours.
A reduction in dose is necessary when:
- creatinine clearance is ≤ 70 ml/min/l.73 m² (see Table 1) or
- body weight is < 70 kg. The proportionate dose for patients < 70 kg would be calculated using the following
formula:
(Actual body weight (kg) X standard dose)/70 (kg)
The maximum total daily dose should not exceed 4000 mg/4000 mg per day.

Renal impairment
To determine the reduced dose for adults with impaired renal function:

1. The total daily dose (i.e. 2000/2000, 3000/3000 or 4000/4000 mg) that would usually be applicable to patients
with normal renal function should be selected.

2. From table 1 the appropriate reduced dose regimen is selected according to the patient's creatinine clearance.
For infusion times see Method of administration.
Table 1: Reduced dose in adults with impaired renal function and body weight ≥ 70 kg*

* A further proportionate reduction in dose administered must be made for patients with a body weight < 70 kg.
The proportionate dose for patients < 70 kg would be calculated by dividing the patient's actual body weight (in
kg) by 70 kg multiplied by the respective dose recommended in Table 1.
** When the 500 mg/500 mg dose is used in patients with creatinine clearances of 6 to 20
ml/min/l.73 m², there may be an increased risk of seizures.

Patients with a creatinine clearance of ≤ 5 ml/min/1.73 m2

These patients should not receive Imipenem/cilastatin unless haemodialysis is instituted within 48 hours.

Patients on haemodialysis
When treating patients with creatinine clearances of ≤ 5 ml/min/1.73 m2 who are undergoing dialysis use the
dose recommendation for patients with creatinine clearances of 6 to 20 ml/min/1.73 m2 (see table 1).
Both imipenem and cilastatin are cleared from the circulation during haemodialysis. The patient should receive
imipenem/cilastatin after haemodialysis and at 12 hour intervals timed from the end of that haemodialysis
session. Dialysis patients, especially those with background central nervous system (CNS) disease, should be
carefully monitored; for patients on haemodialysis, imipenem/cilastatin is recommended only when the benefit
outweighs the potential risk of seizures (see section 4.4).

Currently there are inadequate data to recommend use of imipenem/cilastatin for patients on peritoneal dialysis.

Hepatic impairment
No dose adjustment is recommended in patients with impaired hepatic function (see section 5.2).

Elderly population
No dose adjustment is required for the elderly patients with normal renal function (see section 5.2).

Paediatric population ≥ 1 year of age
For paediatric patients ≥ 1 year of age, the recommended dose is 15/15 or 25/25 mg/kg/dose administered every
6 hours.

It is recommended that infections suspected or proven to be due to less susceptible bacterial species (such as
Pseudomonas aeruginosa) and very severe infections (e.g. in neutropenic patients with a fever) should be treated
with 25/25 mg/kg administered every 6 hours.

Paediatric population < 1 year of age
Clinical data are insufficient to recommend dosing for children less than 1 year of age

Paediatric population with renal impairment
Clinical data are insufficient to recommend dosing for paediatric patients with renal impairment (serum
creatinine > 2 mg/dl). See section 4.4.

Method of administration
Imipenem 500 mg/cilastatin 500 mg powder for solution for infusion is to be reconstituted and further diluted
(see section 6.2, 6.3 and 6.6) prior to administration. Each dose of ≤ 500 mg/500 mg should be given by
intravenous infusion over 20 to 30 minutes. Each dose > 500 mg/500 mg should be infused over 40 to 60
minutes. In patients who develop nausea during the infusion, the rate of infusion may be slowed.

• Hypersensitivity to the active substances 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 beta-lactam antibacterial agent (e.g. penicillins or cephalosporins)

General
The selection of imipenem/cilastatin 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.

Hypersensitivity
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving
therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to
multiple allergens. Before initiating therapy with Imipenem 500 mg/cilastatin 500 mg powder for solution for
infusion, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems,
penicillins, cephalosporins, other beta-lactams and other allergens (see section 4.3). If an allergic reaction to
Imipenem/cilastatin 500 mg powder for solution for infusion occurs, discontinue the therapy immediately.
Serious anaphylactic reactions require immediate emergency treatment.

Hepatic
Hepatic function should be closely monitored during treatment with imipenem/cilastatin due to the risk of
hepatic toxicity (such as increase in transaminases, hepatic failure and fulminant hepatitis).

Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored
during treatment with imipenem/cilastatin. There is no dose adjustment necessary (see section 4.2).

Haematology
A positive direct or indirect Coombs test may develop during treatment with imipenem/cilastatin.

Antibacterial spectrum
The antibacterial spectrum of imipenem/cilastatin should be taken into account especially in lifethreatening
conditions before embarking on any empiric treatment. Furthermore, due to the limited susceptibility of specific
pathogens associated with e.g. bacterial skin and soft-tissue infections, to imipenem/cilastatin, caution should be
exercised. The use of imipenem/cilastatin is not suitable for treatment of these types of infections unless the
pathogen is already documented and known to be susceptible or there is a very high suspicion that the most
likely pathogen(s) would be suitable for treatment. Concomitant use of an appropriate anti-MRSA agent may be
indicated when MRSA infections are suspected or proven to be involved in the approved indications.
Concomitant use of an aminoglycoside may be indicated when Pseudomonas aeruginosa infections are suspected
or proven to be involved in the approved indications (see section 4.1).

Interaction with valproic acid
The concomitant use of imipenem/cilastatin and valproic acid/sodium valproate is not
recommended (see section 4.5).

Clostridium difficile
Antibiotic-associated colitis and pseudomembranous colitis have been reported with
imipenem/cilastatin and with nearly all other anti-bacterial agents and may range from mild to life-threatening in
severity. It is important to consider this diagnosis in patients who develop diarrhoea during or after the use of
imipenem/cilastatin (see section 4.8). Discontinuation of therapy with imipenem/cilastatin and the administration
of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis
should not be given.

Meningitis
Imipenem/cilastatin is not recommended for the therapy of meningitis.

Central nervous system
CNS adverse reactions such as myoclonic activity, confusional states, or seizures have been reported, especially
when recommended doses based on renal function and body weight were exceeded. These experiences have
been reported most commonly in patients with CNS disorders (e.g. brain lesions or history of seizures) and/or
compromised renal function in whom accumulation of the administered entities could occur. Hence close
adherence to recommended dose schedules is urged especially in these patients (see section 4.2). Anticonvulsant
therapy should be continued in patients with a known seizure disorder.

Special awareness should be made to neurological symptoms or convulsions in children with known risk factors
for seizures, or on concomitant treatment with medicinal products lowering the seizures threshold.

If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically and placed on
anticonvulsant therapy if not already instituted. If CNS symptoms continue, the dose of imipenem/cilastatin
should be decreased or discontinued.

Patients with creatinine clearances of ≤ 5 ml/min/1.73 m² should not receive imipenem/cilastatin unless
haemodialysis is instituted within 48 hours. For patients on haemodialysis, imipenem/cilastatin is recommended
only when the benefit outweighs the potential risk of seizures (see section 4.2).

Paediatric use
Clinical data are insufficient to recommend the use of imipenem/cilastatin in children under 1
year of age or paediatric patients with impaired renal function (serum creatinine >2 mg/dl). See
also above under Central nervous system.
Imipenem 500 mg/cilastatin 500 mg powder for solution for infusion contains 36 mg of sodium
(1.57 mEq) which should be taken into consideration by patients on a controlled sodium diet.

Generalised seizures have been reported in patients who received ganciclovir and
imipenem/cilastatin. These medicinal products should not be used concomitantly unless the potential benefit
outweighs the risks.

Decreases in valproic acid levels that may fall below the therapeutic range have been reported when valproic
acid was co-administered with carbapenem agents. The lowered valproic acid levels can lead to inadequate
seizure control; therefore, concomitant use of imipenem and valproic acid/sodium valproate is not recommended
and alternative antibacterial or anti-convulsant therapies should be considered (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.

Concomitant administration of imipenem/cilastatin and probenecid resulted in minimal increases in the plasma
levels and plasma half-life of imipenem. The urinary recovery of active (nonmetabolised) imipenem decreased to
approximately 60% of the dose when imipenem/cilastatin was administered with probenecid. Concomitant
administration of imipenem/cilastatin and probenecid doubled the plasma level and half-life of cilastatin, but had
no effect on urine recovery of cilastatin.

Pregnancy
There are no adequate and well-controlled studies for the use of imipenem/cilastatin in pregnant women.

Studies in pregnant monkeys have shown reproductive toxicity (see section 5.3). The potential risk for humans is
unknown.

Imipenem/cilastatin should be used during pregnancy only if the potential benefit justifies the potential risk to
the foetus.

Breast-feeding
Imipenem and cilastatin are excreted into the mother’s milk in small quantities. Little absorption of either
compound occurs following oral administration. Therefore it is unlikely that the suckling infant will be exposed
to significant quantities. If the use of imipenem/cilastatin is deemed necessary, the benefit of breast feeding for
the child should be weighed against the possible risk for the child.

Fertility
There are no data available regarding potential effects of imipenem/cilastatin treatment on male or female
fertility.

No studies on the effects on the ability to drive and use machines have been performed. However, there are some
side effects (such as hallucination, dizziness, somnolence, and vertigo) associated with this product that may
affect some patients’ ability to drive or operate machinery (see section 4.8).

In clinical trials including 1,723 patients treated with imipenem/cilastatin intravenous the most frequently
reported systemic adverse reactions that were reported at least possibly related to therapy were nausea (2.0 %),
diarrhoea (1.8 %), vomiting (1.5 %), rash (0.9 %), fever (0.5 %), hypotension (0.4 %), seizures (0.4 %) (see
section 4.4), dizziness (0.3 %), pruritus (0.3 %), urticaria (0.2 %), somnolence (0.2 %). Similarly, the most
frequently reported local adverse reactions were phlebitis/thrombophlebitis (3.1 %), pain at the injection site (0.7
%), erythema at the injection site (0.4 %) and vein induration (0.2 %). Increases in serum transaminases and in
alkaline phosphatase are also commonly reported.

The following adverse reactions have been reported in clinical studies or during post-marketing experience.

All adverse reactions are listed under 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.

Paediatric (≥ 3 months of age)
In studies of 178 paediatric patients ≥3 months of age, the reported adverse reactions were consistent with those
reported for adults.

Symptoms of overdose that can occur are consistent with the adverse reaction profile; these may include
seizures, confusion, tremors, nausea, vomiting, hypotension, bradycardia. No specific information is available on
treatment of overdose with imipenem/cilastatin.

Imipenem-cilastatin sodium is haemodialyzable. However, usefulness of this procedure in the overdose setting is
unknown.

Pharmacotherapeutic group: Antibacterials for systemic use, carbapenems, ATC code: J01D H51

Mode of action
Imipenem 500 mg/cilastatin 500 mg powder for solution for infusion consists of two components: imipenem and
cilastatin sodium in a 1:1 ratio by weight.
Imipenem, also referred to as N-formimidoyl-thienamycin, is a semi-synthetic derivative of thienamycin, the
parent compound produced by the filamentous bacterium Streptomyces cattleya.

Imipenem exerts its bactericidal activity by inhibiting bacterial cell wall synthesis in Grampositive and Gramnegative
bacteria through binding to penicillin-binding proteins (PBPs).

Cilastatin sodium is a competitive, reversible and specific inhibitor of dehydropeptidase-I, the renal enzyme
which metabolizes and inactivates imipenem. It is devoid of intrinsic antibacterial activity and does not affect the
antibacterial activity of imipenem.

Pharmacokinetic/Pharmacodynamic (PK/PD) relationship
Similar to other beta-lactam antibacterial agents, the time that imipenem concentrations exceed the MIC
(T>MIC) has been shown to best correlate with efficacy.

Mechanism of resistance
Resistance to imipenem may be due to the following:
• Decreased permeability of the outer membrane of Gram-negative bacteria (due to diminished production of
porins)
• Imipenem may be actively removed from the cell with an efflux pump.
• Reduced affinity of PBPs to imipenem
• Imipenem is stable to hydrolysis by most beta-lactamases, including penicillinases and
cephalosporinases produced by gram-positive and gram-negative bacteria, with the exception of relatively rare
carbapenem hydrolysing beta-lactamases. Species resistant to other carbapenems do generally express coresistance
to imipenem. There is no target-based cross resistance between imipenem and agents of the quinolone,
aminoglycoside, macrolide and tetracycline classes.

Breakpoints
EUCAST MIC breakpoints for imipenem to separate susceptible (S) pathogens from resistant (R) pathogens are
as follows (v 1,1 2010-04-27):
• Enterobacteriaceae ¹: S ≤2 mg/l, R >8 mg/l
• Pseudomonas spp. ²: S ≤4 mg/l, R >8 mg/l
• Acinetobacter spp.: S ≤2 mg/l, R >8 mg/l
• Staphylococcus spp. ³: Inferred from cefoxitin susceptibility
• Enterococcus spp.: S ≤4 mg/l, R >8 mg/l
• Streptococcus A, B, C, G: The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and
G is inferred from the penicillin susceptibility.
• Streptococcus pneumoniae ⁴: S ≤2 mg/l, R >2 mg/l
• Other streptococci ⁴: S ≤2 mg/l, R >2 mg/l
• Haemophilus influenzae 4: S ≤2 mg/l, R >2 mg/l
• Moraxalla catarrhalis ⁴: S ≤2 mg/l, R >2 mg/l
• Neisseria gonorrhoeae: There is insufficient evidence that Neisseria gonorrhoeae is a good target for therapy
with imipenem.
• Gram-positive anaerobes: S ≤2 mg/l, R >8 mg/l
• Gram-negative anaerobes: S ≤2 mg/l, R >8 mg/l
• Non-species related breakpoints ⁵: S ≤2 mg/l, R >8 mg/l

¹ Proteus and Morganella species are considered poor targets for imipenem.
² The breakpoints for Pseudomonas relate to high dose frequent therapy (1g every 6 hours).
³ Susceptibility of staphylococci to carbapenems is inferred from the cefoxitin susceptibility.
⁴ Strains 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 must be sent to a reference laboratory. Until there is evidence regarding clinical response
for confirmed isolates with MIC above the current resistant breakpoint they should be reported resistant.
⁵ Non-species related breakpoint have been determined mainly on the basis of PK/PD data and are independent
of MIC distributions of specific species. They are for use only for species not mentioned in the overview of
species-related breakpoints or footnotes.

Susceptibility
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.

* All methicillin-resistant staphylococci are resistant to imipenem/cilastatin.
** EUCAST non-species related breakpoint is used.

Imipenem
Plasma concentrations
In normal volunteers, intravenous infusion of imipenem/cilastatin over 20 minutes resulted in peak plasma levels
of imipenem ranging from 12 to 20 μg/ml for the 250 mg/250 mg dose, from 21 to 58 μg/ml for the 500 mg/500
mg dose, and from 41 to 83 μg/ml for the 1000 mg/1000 mg dose. The mean peak plasma levels of imipenem
following the 250 mg/250 mg, 500 mg/500 mg, and 1000 mg /1000 mg doses were 17, 39, and 66 μg/ml,
respectively. At these doses, plasma levels of imipenem decline to below 1 μg/ml or less in four to six hours.

Distribution
The binding of imipenem to human serum proteins is approximately 20 %.

Biotransformation and elimination
When administered alone, imipenem is metabolized in the kidneys by dehydropeptidase-I. Individual urinary
recoveries ranged from 5 to 40 %, with an average recovery of 15-20 % in several studies.

Cilastatin is a specific inhibitor of dehydropeptidase-I enzyme and effectively inhibits metabolism of imipenem
so that concomitant administration of imipenem and cilastatin allows therapeutic antibacterial levels of
imipenem to be attained in both urine and plasma.

The plasma half-life of imipenem was one hour. Approximately 70 % of the administered
antibiotic was recovered intact in the urine within ten hours, and no further urinary excretion of imipenem was
detectable. Urine concentrations of imipenem exceeded 10 μg/ml for up to eight hours after a 500 mg/500 mg
dose of imipenem/cilastatin. The remainder of the administered dose was recovered in the urine as antibacterially
inactive metabolites, and faecal elimination of imipenem was essentially nil.

No accumulation of imipenem in plasma or urine has been observed with regimens of imipenem/cilastatin,
administered as frequently as every six hours, in patients with normal renal function.

Cilastatin

Plasma concentrations
Peak plasma levels of cilastatin, following a 20 minute intravenous infusion of
imipenem/cilastatin, ranged from 21 to 26 μg/ml for the 250 mg/250 mg dose, from 21 to 55 μg/ml for the 500
mg/500 mg dose and from 56 to 88 μg/ml for the 1000 mg/1000 mg dose. The mean peak plasma levels of
cilastatin following the 250 mg/250 mg, 500 mg/500 mg, and 1000 mg/1000 mg doses were 22, 42, and 72 μg/ml respectively.

Distribution
The binding of cilastatin to human serum proteins is approximately 40 %.

Biotransformation and elimination
The plasma half-life of cilastatin is approximately one hour. Approximately 70-80% of the dose of cilastatin was
recovered unchanged in the urine as cilastatin within 10 hours of administration of imipenem/cilastatin. No
further cilastatin appeared in the urine thereafter. Approximately 10% was found as the N-acetyl metabolite,
which has inhibitory activity against dehydropeptidase comparable to that of cilastatin. Activity of
dehydropeptidase-I in the kidney returned to normal levels shortly after the elimination of cilastatin from the
blood stream.

 

Renal insufficiency
Following a single 250 mg/250 mg intravenous dose of imipenem/cilastatin, the area under the curve (AUCs) for
imipenem increased 1.1-fold, 1.9-fold, and 2.7-fold in subjects with mild (Creatinine Clearance (CrCL) 50-80
ml/min/1.73 m2), moderate (CrCL 30-<50 ml/min/1.73 m2), and severe (CrCL <30 ml/min/1.73 m2) renal
impairment, respectively, compared to subjects with normal renal function (CrCL >80 ml/min/1.73 m2), and
AUCs for cilastatin increased 1.6-fold, 2.0-fold, and 6.2-fold in subjects with mild, moderate, and severe renal
impairment, respectively, compared to subjects with normal renal function. Following a single 250 mg/250 mg
intravenous dose of imipenem/cilastatin given 24 hours after haemodialysis, AUCs for imipenem and cilastatin
were 3.7-fold and 16.4-fold higher, respectively, as compared to subjects with normal renal function. Urinary
recovery, renal clearance and plasma clearance of imipenem and cilastatin decrease with decreasing renal
function following intravenous administration of imipenem/cilastatin. Dose adjustment is necessary for patients
with impaired renal function (see section 4.2).
 

Hepatic insufficiency
The pharmacokinetics of imipenem in patients with hepatic insufficiency have not been
established. Due to the limited extent of hepatic metabolism of imipenem, its pharmacokinetics are not expected
to be affected by hepatic impairment. Therefore, no dose adjustment is recommended in patients with hepatic
impairment (see section 4.2).
 

Paediatric patients
The average clearance (CL) and volume of distribution (Vdss) for imipenem were approximately 45% higher in
paediatric patients (3 months to 14 years) as compared to adults. The AUC for imipenem following
administration of 15/15 mg/kg per body weight of imipenem/cilastatin to paediatric patients was approximately
30% higher than the exposure in adults receiving a 500 mg/500 mg dose. At the higher dose, the exposure
following administration of 25/25 mg/kg imipenem/cilastatin to children was 9% higher as compared to the
exposure in adults receiving a 1000 mg/1000 mg dose.
 

Elderly
In healthy elderly volunteers (65 to 75 years of age with normal renal function for their age), the
pharmacokinetics of a single dose of imipenem/cilastatin 500 mg/500 mg administered intravenously over 20
minutes were consistent with those expected in subjects with slight renal impairment for which no dose
alteration is considered necessary. The mean plasma half-lives of imipenem and cilastatin were 91 ± 7.0 minutes
and 69 ± 15 minutes, respectively. Multiple dosing has no effect on the pharmacokinetics of either imipenem or
cilastatin, and no accumulation of imipenem/cilastatin was observed (see section 4.2).

Non-clinical data reveal no special hazard for humans based on repeated dose toxicity and genotoxicity studies.

Animal studies showed that the toxicity produced by imipenem, as a single entity, was limited to the kidney. Coadministration
of cilastatin with imipenem in a 1:1 ratio prevented the nephrotoxic effects of imipenem in rabbits
and monkeys. Available evidence suggests that cilastatin prevents the nephrotoxicity by preventing entry of
imipenem into the tubular cells.

A teratology study in pregnant cynomolgus monkeys given imipenem-cilastatin sodium at doses of 40/40
mg/kg/day (bolus intravenous injection) resulted in maternal toxicity including emesis, inappetence, body weight
loss, diarrhoea, abortion, and death in some cases. When doses of imipenem-cilastatin sodium (approximately
100/100 mg/kg/day or approximately 3 times the usual recommended daily human intravenous dose) were
administered to pregnant cynomolgus monkeys at an intravenous infusion rate which mimics human clinical use,
there was minimal maternal intolerance (occasional emesis), no maternal deaths, no evidence of teratogenicity,
but an increase in embryonic loss relative to control groups (see section 4.6).

Long term studies in animals have not been performed to evaluate carcinogenic potential of imipenem/cilastatin.

Sodium hydrogen carbonate

This medicinal product is chemically incompatible with lactate and should not be reconstituted with diluents
containing lactate. However, it can be administered into an I.V. system through which a lactate solution is being infused.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

2 years After reconstitution: Do not freeze the reconstituted solution. Reconstituted/diluted solutions should be used immediately. The time interval between the beginning of reconstitution and the end of intravenous infusion should not exceed 4 hours.

Keep the vials in the outer carton in order to protect from light.
Do not store above 30 °C.
For storage conditions of the reconstituted medicinal product, see section 6.3.

Neutral, type I clear glass vial of 20 ml nominal capacity, closed with grey butyl rubber stopper 20 mm and
covered with aluminium flip-off green plastic cap

The medicinal product is supplied in packs of 5 vials.

Each vial is for single use only.
 

Reconstitution:
Contents of each vial must be transferred to 100 ml of an appropriate infusion solution (see section 6.2 and 6.3):
0.9% sodium chloride. In exceptional circumstances where 0.9% sodium chloride cannot be used for clinical
reasons 5% glucose may be used instead.

A suggested procedure is to add approximately 10 ml of the appropriate infusion solution to the vial. Shake well
and transfer the resulting mixture to the infusion solution container.

CAUTION: THE MIXTURE IS NOT FOR DIRECT INFUSION.

Repeat with an additional 10 ml of infusion solution to ensure complete transfer of vial contents to the infusion
solution. The resulting mixture should be agitated until clear.

The concentration of the reconstituted solution following the above procedure is approximately 5 mg/ml for both
imipenem and cilastatin.

The reconstituted solution should be inspected visually for particulate matter and discoloration prior to
administration. The reconstituted solution is clear and free of particles.

pH range: 5.5 – 8.5

Any unused product or waste material should be disposed of in accordance with local
requirements.