Imipenem Cilastatin-Vista powder for preparation of solution for infusions 0.5/0.5 g bottle No. 10

Instructions Imipenem Cilastatin-Vista powder for preparation of solution for infusions 0.5/0.5 g bottle No. 10

Composition

active ingredients:

1 vial contains imipenem monohydrate 530 mg, equivalent to 500 mg of imipenem, and cilastatin sodium 530 mg, equivalent to 500 mg of cilastatin;

excipient: sodium bicarbonate.

Dosage form

Powder for preparation of solution for infusions.

Main physicochemical properties: white to almost white or slightly yellowish powder.

Pharmacotherapeutic group

Antibacterials for systemic use, Carbapenems. Imipenem and enzyme inhibitor. ATX code J01D H51.

Pharmacological properties

Pharmacodynamics

Imipenem/Cilastatin-Vista consists of two components: imipenem, the first representative of a new class of b-lactam antibiotics - thienamycins, and cilastatin sodium, a special enzyme inhibitor that blocks the metabolism of imipenem in the kidneys and significantly increases the concentration of unchanged imipenem in the urinary tract. The weight ratio of imipenem and cilastatin sodium in the preparation is 1:1.

The thienamycin class of antibiotics, to which imipenem belongs, is characterized by a broader spectrum of potent bactericidal activity than that provided by any of the antibiotics studied.

Imipenem/Cilastatin-Vista is indicated for the treatment of mixed infections caused by susceptible strains of aerobic and anaerobic bacteria. Imipenem/Cilastatin-Vista has been shown to be effective in the treatment of many infections caused by aerobic and anaerobic Gram-positive and Gram-negative bacteria resistant to cephalosporins, including cefazolin, cefoperazone, cephalothin, cefoxitin, cefotaxime, moxalactam, cefamandole, ceftazidime and ceftriaxone. A large number of infections caused by pathogens resistant to aminoglycosides (gentamicin, amikacin, tobramycin) and/or penicillins (ampicillin, carbenicillin, penicillin-G, ticarcillin, piperacillin, azlocillin, mezlocillin) are also treatable with this combination.

Imipenem/Cilastatin-Vista is not indicated for the treatment of meningitis.

Imipenem/Cilastatin-Vista is a potent inhibitor of bacterial cell wall synthesis and has a bactericidal effect against a wide range of gram-positive and gram-negative, aerobic and anaerobic pathogenic microorganisms.

Imipenem/Cilastatin-Vista, together with the newer cephalosporins and penicillins, has a broad spectrum of activity against gram-negative species, but its distinguishing feature is its high activity against gram-positive species, which was previously observed only with narrow-spectrum b-lactam antibiotics. The spectrum of activity of the drug Imipenem/Cilastatin-Vista covers Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis and Bacteroides fragilis, a diverse and clinically problematic group of pathogens, usually resistant to other antibiotics.

Imipenem/Cilastatin-Vista is effective against a wide range of microorganisms, such as Pseudomonas aeruginosa, Serratia species, and Enterobacter, which are inherently resistant to most β-lactam antibiotics.

The antibacterial spectrum of imipenem/cilastatin is broader than that of any other currently known antibiotic and covers all clinically important pathogenic microorganisms. Microorganisms against which imipenem/cilastatin is usually effective in vitro include:

Gram-negative aerobic bacteria

Achromobacter species

Acinetobacter species (formerly Mima-Herellea)

Aeromonas hydrophila

Alcaligenes species

Bordetella bronchicanis

Bordetella bronchiseptica

Bordetella pertussis

Brucella melitensis

Burkholderia pseudomallei (formerly Pseudomonas pseudomallei)

Burkholderia stutzeri (formerly Pseudomonas stutzeri)

Campylobacter species

Capnocytophaga species

Citrobacter species

Citrobacter koseri (formerly Citrobacter diversus)

Citrobacter freundii

Eikenella corrodens

Enterobacter species

Enterobacter aerogenes

Enterobacter agglomerans

Enterobacter cloacae

Escherichia coli

Gardnerella vaginalis

Haemophilus ducreyi

Haemophilus influenzae (including β-lactamase producing strains)

Haemophilus parainfluenzae

Hafnia alvei

Klebsiella species

Klebsiella oxytoca

Klebsiella ozaenae

Klebsiella pneumoniae

Moraxella species

Morganella morganii (formerly Proteus morganii)

Neisseria gonorrhoeae (including penicillinase-producing strains)

Neisseria meningitidis

Pasteurella species

Pasteurella multocida

Plesiomonas shigelloides

Proteus species

Proteus mirabilis

Proteus vulgaris

Types of Providencia

Providencia alcalifaciens

Providencia rettgeri (formerly Proteus rettgeri)

Providencia stuartii

Pseudomonas species*

Pseudomonas fluorescens

Pseudomonas putida

Pseudomonas aeruginosa

Salmonella species

Salmonella typhi

Serratia species

Serratia proteamaculans (formerly Serratia liquefaciens)

Serratia marcescens

Shigella species

Yersinia species (formerly Pasteurella)

Yersinia enterocolitica

Yersinia pseudotuberculosis

*Stenotrophomonas maltophilia (formerly Xanthomas maltophilia, formerly Pseudomonas maltophilia) and strains of Burkholderia cepacia (formerly Pseudomonas cepacia) are generally insensitive to Imipenem/Cilastatin-Vista.

Gram-positive aerobic bacteria

Bacillus species

Enterococcus faecalis

Erysipelothrix rhusiopathiae

Listeria monocytogenes

Nocardia species

Pediococcus species

Staphylococcus aureus (including penicillinase-producing strains)

Staphylococcus epidermidis (including penicillinase-producing strains)

Staphylococcus saprophyticus

Streptococcus agalactiae

Group C Streptococcus

Group G Streptococcus

Streptococcus pneumoniae

Streptococcus pyogenes

Viridans Streptococci (including α and γ-hemolytic strains)

Enterococcus faecium and some methicillin-resistant staphylococci are insensitive to Imipenem/Cilastatin-Vista.

Gram-negative anaerobic bacteria

Bacteroides species

Bacteroides distasonis

Bacteroides fragilis

Bacteroides ovalus

Bacteroides thelaiotaomicron

Bacteroides uniformis

Bacteroides vulgatus

Bilophila wadsworthia

Fusobacterium species

Fusobacterium necrophorum

Porphyromonas asaccharolytica (formerly Bacteroides asaccharolyticus)

Prevotella bivia (formerly Bacteroides bivius)

Prevotella disiens (formerly Bacteroides disiens)

Prevotella intermedia (formerly Bacteroides intermedius)

Prevotella melaninogenica (formerly Bacteroides melaninogenicus)

Veilonella spp.

Gram-positive anaerobic bacteria

Actinomyces species

Bifidobacterium species

Clostridium species

Clostridium perfringens

Eubacterium species

Lactoballus species

Mobiluncus species

Microaerophilic streptococcus

Peptococcus species

Peptostreptococcus species

Propionibacterium species (including P. acnes)

Others

Mycobacterium fortuitum

Mycobacterium smegmatis

In vitro studies indicate that imipenem acts synergistically with aminoglycosides against some isolates of Pseudomonas aeruginosa.

Pharmacokinetics

Imipenem: In healthy volunteers, intravenous infusion of 500 mg of Imipenem/Cilastatin-Vista over 20 minutes resulted in peak plasma levels of imipenem of 21 to 58 mcg/mL. The binding of imipenem to human serum proteins is approximately 20%.

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

Cilastatin is a specific inhibitor of the enzyme dehydropeptidase-I, it effectively inhibits the metabolism of imipenem, therefore, the concomitant use of imipenem and cilastatin allows achieving therapeutic antibacterial levels of imipenem in urine and plasma.

The plasma half-life of imipenem was 1 hour. Approximately 70% of the administered antibiotic was recovered intact in the urine within 10 hours, and no further urinary excretion was observed. No accumulation of imipenem in plasma or urine was observed when Imipenem/Cilastatin-Vista was administered every 6 hours in patients with normal renal function. Concomitant administration of Imipenem/Cilastatin-Vista and probenecid resulted in minimal increases in plasma levels and half-life of imipenem.

Cilastatin. Peak plasma levels of cilastatin following a 20-minute intravenous infusion of 500 mg ranged from 21 to 55 μg/mL. The binding of cilastatin to human serum proteins is approximately 40%. The plasma elimination half-life of cilastatin is approximately 1 hour. Approximately 70-80% of a dose of cilastatin is excreted unchanged in the urine within 10 hours of administration. Thereafter, cilastatin was not detected in the urine. Approximately 10% was detected as the N-acetyl metabolite, which has a dehydropeptidase inhibitory activity comparable to that of the parent drug. Concomitant use of the drug and probenecid resulted in a doubling of the plasma levels and half-life of cilastatin, but had no effect on urinary recovery of cilastatin.

Kidney failure

Following a single intravenous dose of imipenem/cilastatin 250 mg/250 mg, the area under the concentration-time curve (AUC) for imipenem increased 1.1-, 1.9-, and 2.7-fold, respectively, in patients 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 compared to patients with normal renal function (CrCL >80 mL/min/1.73 m2), and the area under the concentration-time curve (AUC) for cilastatin increased 1.6-, 2-, and 6.2-fold, respectively, in patients with mild, moderate, and severe renal impairment compared to patients with normal renal function. After Following a single intravenous dose of imipenem/cilastatin 250 mg/250 mg administered 24 hours after hemodialysis, the area under the concentration-time curve (AUC) for imipenem and cilastatin was 3.7- and 16.4-fold higher, respectively, than in patients with normal renal function. Urinary excretion, renal clearance, and plasma clearance of imipenem and cilastatin decrease with decreasing renal function following intravenous administration of Imipenem/Cilastatin. Dose adjustment is necessary in patients with impaired renal function.

Liver failure

The pharmacokinetics of imipenem in patients with hepatic impairment have not been established. Due to the limited extent of hepatic metabolism of imipenem, hepatic impairment is not expected to affect its pharmacokinetics. Therefore, no dose adjustment is recommended for patients with hepatic impairment.

Children

The mean clearance and volume of distribution for imipenem were approximately 45% higher in children (3 months to 14 years of age) compared to adults. The area under the concentration-time curve (AUC) for imipenem following a dose of 15/15 mg/kg of imipenem/cilastatin in children was approximately 30% higher than the exposure in adults given a dose of 500 mg/500 mg. At the higher dose, the exposure following administration of 25/25 mg/kg of imipenem/cilastatin to children was 9% higher than the exposure in adults given a dose of 1000 mg/1000 mg.

In healthy elderly volunteers (aged 65 to 75 years with normal renal function for their age), the pharmacokinetics of a single intravenous dose of imipenem/cilastatin 500 mg/500 mg administered over 20 minutes were consistent with those expected in patients with mild renal impairment, for whom any dose adjustment is considered unnecessary. The mean plasma half-lives of imipenem and cilastatin were 91 ± 7 minutes and 69 ± 15 minutes, respectively. Multiple dosing had no effect on the pharmacokinetics of imipenem or cilastatin, and no accumulation of imipenem/cilastatin was observed.

Indication

Treatment of infections in adults and children aged 1 year and over caused by microorganisms sensitive to the drug:

intra-abdominal infections; lower respiratory tract infections (severe pneumonia, including hospital-acquired and ventilator-associated pneumonia); intranatal and postpartum infections; complicated genitourinary infections; complicated skin and soft tissue infections; bone and joint infections; septicemia; endocarditis.

The drug can be used in the treatment of patients with neutropenia accompanied by fever, the probable cause of which is a bacterial infection.

Treatment of patients with bacteremia associated or suspected to be associated with any of the above infections.

Contraindication

Hypersensitivity to any of the components of the drug, other carbapenem drugs, acute manifestations of hypersensitivity (e.g. anaphylactic reactions, severe skin reactions) to other ß-lactam antibiotics (e.g. penicillin or cephalosporins).

Interaction with other medicinal products and other types of interactions

Generalized seizures have been reported in patients receiving ganciclovir with intravenous imipenem/cilastatin. These drugs should be used together only if the expected benefit outweighs the potential risk.

Decreased plasma valproic acid levels have been reported when co-administered with carbapenems, and in some cases sudden convulsions have been reported. Therefore, concomitant use of imipenem and valproic acid/sodium valproate is not recommended. Alternative antibacterial or anticonvulsant therapy should also be considered (see section 4.4).

Oral anticoagulants.

Concomitant use of antibiotics with warfarin may increase its anticoagulant effects. There have been many reports of increased anticoagulant effects of oral anticoagulants, including warfarin, in patients receiving concomitant antibiotics. The risk may vary depending on the type of infection, age, and general status of the patient, making it difficult to assess the role of the antibiotic in increasing the international normalized ratio (INR). Frequent monitoring of the international normalized ratio (INR) is recommended during and after concomitant use of antibiotics with oral anticoagulants.

Concomitant use of imipenem/cilastatin and probenecid resulted in minimal increases in imipenem plasma concentrations and imipenem plasma half-life. Urinary excretion of active (unmetabolized) imipenem was reduced to approximately 60% of the dose when administered with probenecid. Concomitant use of probenecid doubled cilastatin plasma levels and the half-life of cilastatin, but had no effect on urinary excretion of cilastatin.

Application features

General recommendations.

When choosing imipenem/cilastatin as a treatment for each individual case, the appropriateness of using carbapenems should be considered in light of the severity of the infection, the prevalence of resistance to other acceptable antibacterial agents, and the possibility of carbapenem-resistant bacteria.

Hypersensitivity.

There is some clinical and laboratory evidence that suggests a partial cross-allergenicity of Imipenem/Cilastatin-Vista with other β-lactam antibiotics, penicillins and cephalosporins. Severe reactions (including anaphylaxis) have been reported with most β-lactam antibiotics. Such reactions are most likely to occur in individuals with a history of hypersensitivity to multiple allergens. Before initiating therapy with the drug, the patient's history should be carefully examined for hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other β-lactam antibiotics and other allergens (see section "Contraindications"). If an allergic reaction develops during the use of the drug, the drug should be discontinued and appropriate measures taken. Serious anaphylactic reactions require emergency therapy.

Liver functions.

Liver function should be closely monitored during treatment with imipenem/cilastatin due to the risk of liver toxicity (increased transaminase levels, hepatic failure and fulminant hepatitis).

Patients with pre-existing liver disease should have liver function monitored during treatment with imipenem/cilastatin. No dose adjustment is necessary.

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

Antibacterial spectrum.

The antibacterial spectrum of imipenem/cilastatin should be considered before any empiric treatment, especially in life-threatening conditions. In addition, caution should be exercised because of the limited susceptibility of certain pathogens (e.g. associated with bacterial skin and soft tissue infections) to imipenem/cilastatin. The use of imipenem/cilastatin is appropriate for the treatment of these types of infections when the specific pathogen has already been documented and is known to be susceptible or when there are very good reasons to believe that the most likely pathogen(s) is/are susceptible to such treatment. Concomitant use of this agent against methicillin-resistant Staphylococcus aureus (MRSA) may be indicated when MRSA infections are suspected or proven in approved indications. Concomitant use of an aminoglycoside may be indicated when Pseudomonas aeruginosa infections are suspected or proven in approved indications.

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

Clostridium difficile

Pseudomembranous colitis has been reported as a complication of nearly all antibiotics; its severity can range from mild to life-threatening. Therefore, antibiotics should be used with caution in patients with a history of gastrointestinal disease, especially colitis. It is important to be aware of the possibility of pseudomembranous colitis when a patient develops diarrhea during or after antibiotic treatment. Discontinuation of imipenem/cilastatin therapy and specific treatment for Clostridium difficile should be considered. Drugs that inhibit peristalsis should not be given.

Meningitis.

The drug is not recommended for the treatment of meningitis.

Kidney failure.

In patients with renal impairment, imipenem/cilastatin accumulates. If the dose is not reduced according to renal function, central nervous system adverse reactions may occur (see Dosage and Administration and below).

Central nervous system (CNS).

As with other β-lactam antibiotics, CNS side effects such as myoclonus, confusion or convulsions have been reported with Imipenem/Cilastatin-Vista, especially when the recommended doses are exceeded, which were determined depending on renal function and body weight. Usually, such disorders were observed in patients with CNS damage (brain injury or history of seizures) and/or in patients with impaired renal function, in whom cumulation of the drug in the body is possible. In this regard, especially for such patients, it is extremely important to strictly adhere to the recommended doses and treatment regimen. Anticonvulsant therapy should be continued in patients with a history of seizures.

Particular attention should be paid to neurological symptoms or seizures in children with known risk factors for seizures or who are receiving concomitant medication to reduce seizure intensity.

If focal tremor, myoclonus, or seizures occur during treatment with the drug, patients should undergo a neurological examination and prescribe anticonvulsant therapy, if it has not been prescribed before. If symptoms of CNS disorders persist, the dose of Imipenem/Cilastatin-Vista should be reduced or the drug should be discontinued.

Imipenem/Cilastatin-Vista is not indicated for the treatment of patients with creatinine clearance ≤ 5 ml/min/1.73 m2, unless hemodialysis is to be performed within 48 hours. For patients on hemodialysis, Imipenem/Cilastatin-Vista is recommended only when the positive results of treatment outweigh the potential risk of seizures.

Excipients.

The drug contains 37.6 mg of sodium (1.6 mg-eq.), which should be taken into account when using it in patients on a controlled sodium (salt-free) diet.

Ability to influence reaction speed when driving vehicles or other mechanisms

Studies on the effect of the drug on the ability to drive and use machines have not been conducted. However, some side effects, such as hallucinations, drowsiness, dizziness, vertigo, associated with the use of the drug, may affect the ability of patients to drive or operate machinery.

Use during pregnancy or breastfeeding

Pregnancy.

Adequate and well-controlled studies of the use of the drug in pregnant women have not been conducted.

Reproductive toxicity was observed in studies in pregnant monkeys. The potential risk to humans is unknown. Imipenem/Cilastatin-Vista should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the fetus.

Imipenem and cilastatin are excreted in small amounts in breast milk. If necessary, the benefit of breastfeeding for the child should be weighed against the potential risk associated with the use of the drug for the child.

Method of administration and doses

The dosage recommendations for Imipenem/Cilastatin-Vista relate to the amount of imipenem/cilastatin that will be used.

The daily dose of Imipenem/Cilastatin-Vista is determined taking into account the severity of the infection, the type of pathogen(s) isolated; it is divided into several equal administrations, in equal doses, taking into account the state of renal function and body weight.

Adults and adolescents

Dosage for patients with normal renal function (creatinine clearance ≥ 90 ml/min):

500 mg/500 mg every 6 hours or 1000 mg/1000 mg every 8 hours or every 6 hours.

For the treatment of infections known or suspected to be caused by less susceptible species of bacteria (such as Pseudomonas aeruginosa) and severe infections (e.g. in neutropenic patients with fever), a dose of 1000 mg/1000 mg every 6 hours is recommended.

The dose should be reduced for patients with creatinine clearance < 90 mL/min (see Table 1).

The maximum daily dose should not exceed 4000 mg/4000 mg per day.

Adult patients with renal impairment

To determine a reduced dose for adult patients with renal impairment, it is necessary to:

Determine the total daily dose (i.e. 2000/2000, 3000/3000 or 4000/4000 mg) that is usually used in patients with normal renal function. Select the appropriate reduced dose regimen (see Table 1) according to the patient's creatinine clearance and the duration of infusion (see "Method of administration").

Table 1

Patients with creatinine clearance <15 mL/min

Imipenem/Cilastatin-Vista for intravenous administration should not be administered unless hemodialysis is to be performed within the next 48 hours.

Hemodialysis

When treating patients with creatinine clearance <15 ml/min and who are on hemodialysis, the doses recommended for patients with creatinine clearance
15–29 ml/min (see Table 1).

Both imipenem and cilastatin are removed by haemodialysis. Imipenem/cilastatin should be administered to the patient immediately after haemodialysis and every 12 hours thereafter. Patients undergoing haemodialysis, particularly those with underlying central nervous system disease, require close monitoring; imipenem/cilastatin should only be administered to such patients if the expected benefit outweighs the potential risk of convulsions (see section 4.4).

Currently, there is insufficient data on the use of the drug in patients undergoing peritoneal dialysis, therefore its use is not recommended for the treatment of this category of patients.

Liver failure

No dose adjustment is required for patients with hepatic impairment.

Elderly patients

No dose adjustment is necessary for elderly patients with normal renal function.

Children from 1 year of age.

For children > 1 year of age, the recommended dose is 15/15 or 25/25 mg/kg/dose every 6 hours.

For the treatment of infections known or suspected to be caused by less susceptible species of bacteria (such as Pseudomonas aeruginosa) and severe infections (e.g. in neutropenic patients with fever), a dose of 25/25 mg/kg every 6 hours is recommended.

Children under 1 year of age and children with impaired renal function

The drug is not recommended for use in children under 1 year of age and in children with impaired renal function (serum creatinine > 2 mg/dl) due to insufficient clinical data.

Method of application.

Each vial is intended for single use only.

The contents of the vial (powder) must be reconstituted and diluted appropriately before use (see recommendations below). Each dose not exceeding 500 mg/500 mg of Imipenem/Cilastatin-Vista for intravenous use should be administered over 20–30 minutes. Each dose exceeding 500 mg/500 mg should be administered over 40–60 minutes. If the patient experiences nausea during the infusion, the rate of administration should be reduced.

Preparation of solution for intravenous administration.

Imipenem/Cilastatin-Vista contains sodium bicarbonate as a buffer to provide a solution with a pH of 6.5 to 8.5. These pH changes are not significant if the solution is prepared and stored as directed. Imipenem/Cilastatin-Vista for intravenous use contains 37.5 mg sodium (1.6 mEq).

Imipenem/Cilastatin-Vista sterile powder should be diluted as indicated in Table 2. The resulting solution should be shaken until a clear liquid is formed. The color of the solution varies from colorless to yellow and does not affect the activity of the drug.

Table 2

Preparation of Imipenem/Cilastatin-Vista solution for intravenous administration

The contents of the vial should be suspended and made up to 100 ml with a suitable infusion solution.

In the first step, it is recommended to add approximately 10 ml of 0.9% sodium chloride solution to the vial. In exceptional circumstances, when 0.9% sodium chloride solution cannot be used for clinical reasons, 5% glucose can be used as a diluent.

Shake well and transfer the resulting suspension to the container with the infusion solution.

Warning: The suspension is not a ready-to-use solution for infusion.

Repeat the procedure by adding another 10 ml of infusion solution to ensure that the entire contents of the vial are transferred to the infusion solution. The resulting mixture should be shaken until it becomes clear.

The concentration of the reconstituted solution after the above procedure is approximately 5 mg/mL of imipenem and cilastatin.

Diluted solutions should be used immediately. The time interval between the start of dilution and the end of intravenous infusion should not exceed 2 hours.

Do not freeze the reconstituted solution.

Unused materials and product residues must be disposed of in accordance with applicable requirements.

Children

Due to insufficient clinical data, the use of Imipenem/Cilastatin-Vista in children under 1 year of age and in children with impaired renal function (serum creatinine > 2 mg/dl) is not recommended (see “Method of administration and dosage”).

Overdose

Symptoms of overdose that may occur are consistent with the adverse reaction profile; they may include convulsions, confusion, tremor, nausea, vomiting, hypotension, bradycardia.

There is no specific information on the treatment of overdose with the drug. The drug is removed by hemodialysis. However, the effectiveness of this procedure in overdose has not been established. Treatment is symptomatic.

Adverse reactions

The most common systemic adverse reactions possibly related to imipenem/cilastatin treatment were nausea (2%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5%), hypotension (0.4%), convulsions (0.4%), dizziness (0.3%), pruritus (0.3%), urticaria (0.2%), and somnolence (0.2%).

The most common local adverse reactions were: phlebitis/thrombophlebitis (3.1%), injection site pain (0.7%), injection site erythema (0.4%), and vein induration (0.2%).

Increased serum transaminase and alkaline phosphatase levels were also noted.

Adverse reactions are listed in Table 3 by system organ class and frequency: very common
(> 1/10), common (> 1/100 to <1/10), uncommon (> 1/1000 to <1/100), rare (> 1/10000 to <1/1000), very rare (<1/10000) and not known (cannot be estimated from the available data).

Table 3

When imipenem/cilastatin was used in children > 3 months of age, adverse reactions were reported that were quite similar to those observed in adult patients.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after a medicinal product has been authorised. This allows for continued monitoring of the benefit/risk balance of the medicinal product. Qualified healthcare professionals are asked to report all suspected adverse reactions.

Expiration date

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25°C. Keep out of the reach of children.

Packaging

1 g of powder in colorless glass vials. 10 vials in a cardboard box.

Vacation category

According to the recipe.

Producer

ACS DOBFAR SPA/ACS DOBFAR SPA

Location of the manufacturer and its business address

Nucleo Industriale S. Atto (loc. S. Nicolo' A Tordino), 64100, Teramo (TE), Italy/Nucleo Industriale S.Atto (loc. S. Nicolo' A Tordino), 64100 Teramo (TE), Italy.