Imipenem + Cilastatin - instructions for use, dose, side effects, contraindications

Composition:One bottle contains:
Sterile mixture of imipenem, cilastatin and sodium bicarbonate, including: Active substances: imipenem monohydrate (in terms of 100% substance) 530.0 mg, equivalent to 500.0 mg imipenem, cilastatin sodium (in terms of 100% substance) 532.0 mg, equivalent to 500.0 mg cilastatin;
Excipient: sodium hydrogen carbonate 20.0 mg.

Description:Powder from white to light yellow color.

Pharmacotherapeutic group:Antibiotic-carbapenem + dehydropeptidase inhibitor.

ATX: & nbsp

J.01.D.H.51 Imipenem and dehydropeptidase inhibitor

Pharmacodynamics:The drug Iminenum + Cilastatin consists of two components: 1) imipenem, the first representative of a new class of beta-lactam antibiotics - tienamycins; and 2) cilastatin sodium, a specific enzyme inhibitor that inhibits the metabolism of imipenem in the kidneys and significantly increases the concentration of unchanged imipenem in the urinary tract. Imipenem is an inhibitor of bacterial cell wall synthesis and has a bactericidal action against a wide range of pathogenic Gram-positive and Gram-negative microorganisms, both aerobic and anaerobic.
The stability of the drug to cleavage by bacterial beta-lactamases provides its effectiveness against many microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., resistant to the action of most beta-lactam antibiotics.
Cilastatin does not have its own antibacterial activity and does not inhibit beta-lactamase bacteria.
The antibacterial spectrum of the drug covers virtually all clinically relevant pathogens. The spectrum of antimicrobial susceptibility of imipenem in vivo and in vitro:
Aerobic Gram-positive microorganisms:
Enterococcus faecalis (.Entrococcus faecium is not sensitive in vitro), Staphylococcus aureus, including penicillinase-forming strains. Staphylococcus epidermidis, including penicillinase-forming strains (methicillin-resistant staphylococci are insensitive to imipenem), Streptococcus agalactiae (group B Streptococcus), Streptococcus pneumoniae, Streptococcus pyogenes.
Aerobic Gram-negative microorganisms:
Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa (imipenem activity in vitro against Stenotrophomonas [formerly Xanthomonas, formerly Pseudomonas] maltophilia and some strains of Burkholderia cepacia), Serratia spp., including S. marcescens).
Anaerobic Gram-positive microorganisms:
Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.
Anaerobic Gram-negative microorganisms:
Bacteroides spp., Including B. fragilis, Fusobacterium spp.
Sensitive in vitro (clinical efficacy not established):
Aerobic Gram-positive microorganisms:
Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Streptococcus spp. groups C, G and Viridans.
Aerobic Gram-negative microorganisms:
Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducrei, Neisseria gonorrhoeae (including penicillinase-forming strains), Pasteurella spp., Providencia stuartii.
Anaerobic Gram-negative microorganisms:
Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Veillonella spp.
In vitro acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.

Pharmacokinetics:After iv administration of the drug solution Imipenem + Cilastatin time to reach the maximum concentration (TC_max) in the blood plasma is 20 minutes for both components. The maximum concentration (C_max) reaches values of 21 to 58 μg / ml for imipenem and 21 to 55 μg / ml for cilastatin. After the administration of the drug Imipenem + Cilastatin within 4-6 hours C_max Imipenem decreases to a value of 1 μg / ml and lower.
The half-life for each component is 1 hour. Binding to plasma proteins is 20% for imipenem and 40% for cilastatin. Approximately 70% of the IV imipenem administered is excreted by the kidneys within 10 hours. The concentration of imipenem in the urine above 10 μg / ml can persist for 8 hours after intravenous administration. About 70-80% of cilastatin is excreted by the kidneys within 10 hours after intravenous administration of the drug.
With intravenous administration of the drug every 6 hours, patients with normal renal function did not observe imipenem / cilastatin cumulation in plasma or urine.
After intravenous administration of the drug at a dose of 1 g, the following mean values of the concentration of imipenem in tissues and media of the human body were determined:

Fabric or medium	The concentration of imipenem is μg / ml or μg / g	Time of change (h)
Vitreous body of the eyeball	3,4	3,5
Intraocular fluid	2,99	2,0
Lung tissue	5,6	1,0
Sputum	2,1	1,0
Pleural fluid	22,0	1,0

Peritoneal fluid	23,9	2,0
Bile	5,3	2,25
Liquor (without inflammation)	1,0	4,0
Liqvor (with inflammation)	2,6	2,0
The secret of the prostate	0,2	1,0-1,5
Prostate tissue	5,3	1,0-2,75
Fallopian tubes	13,6	1,0
Endometrium	11,1	1,0
Myometrium	5,0	1,0
Bone	2,6	1,0
Interstitial fluid	16,4	1,0
Leather	4,4	1,0
Connective tissue	4,4	1,0

Indications:A drug Imipenem + Cilastatin is used in the treatment of severe infections caused by sensitive microorganisms, as well as for empirical therapy of the infectious process even before the determination of its bacterial pathogens. A drug Imipenem + Cilastatin is indicated for treatment:
- Lower respiratory infections caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillinase-producing strains), Acinetohacter spp, Enterobacter spp, Esherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp, Serratia marcescens;...
- Urinary tract infections (complicated and uncomplicated) caused by Enterococcus faecalis, Staphylococcus aureus (Penicillinase producing strains), Enterobacter spp., Esherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa;
- Intra-abdominal infections caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Citrobacter spp., Enterobacter spp., Esherichia coli, Klebsiella spp., Morganella morganii, Proteus spp., Pseudomonas aeruginosa, Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., including Bacteroides fragilis, Fusobacterium spp .;
- Gynecological infections caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase producing strains), Staphylococcus epidermidis, Streptococcus agalactiae (Group B streptococci), Enterohacter spp., Escherichia coli, Gardnerella vaginalis, Klebsiella spp., Proteus spp., Bifidobacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., Including Bacteroides fragilis;
- Bacterial septicemia caused by Streptococcus pneumonia, Enterococcus faecalis, Staphylococcus aureus (Penicillinase-producing strains), Enterohacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia spp., Bacteroides spp., Including Bacteroides fragilis;
- Infections of bones and joints caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Enterohacter spp., Pseudomonas aeruginosa;
- Skin and soft tissue infections caused by Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Acinetobacter spp., Citrobacter spp., Enterohacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris , Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp., Peptococcus spp., Peptostreptococcus spp., Bacteroides spp., Including B. fragilis, Fusobacterium spp .;
- Infective endocarditis caused by Staphylococcus aureus (penicillinase-producing strains);
- To prevent postoperative infections in patients at risk with a high probability of developing a postoperative infectious complication, as well as in patients with a high risk of intraoperative infection during surgical intervention.

Contraindications:Hypersensitivity to any of the components of the drug, beta-lactam antibiotics, penicillins, cephalosporins; children up to 3 months; chronic renal failure (creatinine clearance less than 5 ml / min / 1.73 m²); in children - severe renal failure (serum creatinine concentration> 2 mg / dL).

Carefully:Pseudomembranous colitis; patients with a history of gastrointestinal disease; patients with SC less than 70 ml / min / 1.73 m²; patients on hemodialysis; diseases of the central nervous system.

Pregnancy and lactation:Studies in pregnant women have not been conducted. A drug Imipenem + Cilastatin should be used during pregnancy only if the benefit of treatment for the mother justifies the potential risk to the fetus.
Both imipenem and cilastatin penetrate in small amounts into breast milk, so the question of stopping breastfeeding during treatment with the drug should be resolved.

Dosing and Administration:Intravenously (intravenously) is drip.
The dosage form for intravenous use should not be given intramuscularly.
In the recommendations for dosing the drug Imipenem + Cilastatin the amount of imipenem to be administered is indicated. The calculation of the total daily dose should be based on the severity of the infection and be divided into several applications in equal doses, taking into account the degree of sensitivity of one or more pathogenic microorganisms, kidney function and body weight of the patient.
Dosing regimen for adult patients with normal renal function:
The dosages given in Table 1 are calculated for patients with normal renal function (CC greater than 70 ml / min / 1.73 m²) and body weight ≥ 70 kg. In patients with CC ≤ 70 mL / min / 1.73 m² (see Table 2) and / or with a body weight of less than 70 kg (see Table 3), a reduction in the dose of the drug is necessary.
It is especially important to reduce the dose depending on body weight in those patients whose weight is well below 70 kg and / or there is moderate or severe renal failure.
The average therapeutic daily dose is 1-2 g imipenem, divided into 3-4 applications (see Table 1). For treatment of moderate infections, the drug can also be applied at a dose of 1 g twice daily.
In the case of infections caused by less sensitive microorganisms, the daily dose of the drug for intravenous infusions can be increased to a maximum of 4 g(imipenem) per day or 50 mg / kg per day, depending on which dose is less.
Each dose of the drug Imipenem + Cilastatin A dose of less than or equal to 500 mg should be administered intravenously for 20-30 minutes. Each dose of more than 500 mg, should be administered intravenously for 40-60 minutes. Patients who experience nausea during infusion should slow the rate of injection.
Table 1. Dosage regimen of the drug Imipenem + Cilastatin adult patients with normal renal function and body weight ≥70 kg *

Severity of infection	Dose imipenem, mg	Break between infusions	General information daily dose
Lightweight	250 mg	6 hours	1.0 g
Average	500 mg	8 ocloc'k	1.5 g
	1000 mg	12 hours	2.0 g
Severe (sensitive pathogens)	500 mg	6 hours	2.0 g
Severe and / or life-threatening, caused by less	1000 mg	8 ocloc'k	3.0 g
sensitive microorganisms (primarily some strains R. aeruginosa)	1000 mg	6 hours	4.0 g

* - in patients with a body weight of less than 70 kg, a further proportional reduction of the administered doses is necessary.
Due to the high antimicrobial activity of the drug Imipenem + Cilastatin it is recommended that its total daily dose not exceed 50 mg / kg or 4 g (imipenem) / day, whichever dose is lower.Although patients with cystic fibrosis with normal renal function were treated with the drug Imipenem + Cilastatin in a dose up to 90 mg / kg per day, divided into several applications, the total dose did not exceed 4 g (imipenem) per day.
A drug Imipenem + Cilastatin successfully used in monotherapy in cancer patients with weakened immunity in the case of confirmed or suspected infections, for example, sepsis.
Dosage regimen for adult patients with impaired renal function:
To correct the dose of the drug in the treatment of adult patients with impaired renal function, it is necessary:
- Based on the characteristics of the infection, select from Table 1 the total daily dose of the drug.
- From Table 2, select the appropriate reduced dose of the drug, based on the daily dose (Table 1) and the creatinine clearance of this patient. (To calculate the infusion time, see the "Dosing Scheme for Adult Patients with Normal Kidney Function" section).
- From Table 3, choose in the left column the body weight nearest to the body weight of the patient (kg).
Table 2. Dosage regimen of the drug Imipenem + Cilastatin adult patients with impaired renal function and body weight ≥70 kg *

The usual daily dose of imipenem, from Table 1	Creatinine clearance (ml / min / 1.73 m²)
The usual daily dose of imipenem, from Table 1	41-70	21-40	6-20
1.0 g per day	250 mg every 8 hours	250 mg in 12 hours	250 mg in 12 hours
1.5 g per day	250 mg in 6 hours	250 mg every 8 hours	250 mg in 12 hours
2.0 g per day	500 mg in 8 hours	250 mg in 6 hours	250 mg in 12 hours
3.0 g per day	500 mg in 6 hours	500 mg in 8 hours	500 mg in 12 hours
4.0 grams per day	750 mg in 8 hours	500 mg in 6 hours	500 mg in 12 hours

* - in patients with a body weight of less than 70 kg, a further proportional reduction of the administered doses is necessary.
Table 3. Dosage regimen of the drug Imipenem + Cilastatin adult patients with impaired renal function and / or body weight less than 70 kg.
The maximum daily dose of 1.0 g

Body weight, kg		Creatinine clearance (ml / min / 1.73 m²)
Body weight, kg		≥71		41-70	21-40	6-20
≥70	250 mg in 6 hours		250 mg every 8 hours	250 mg in 12 hours	250 mg in 12 hours
60	250 mg every 8 hours		125 mg in 6 hours	250 mg in 12 hours	125 mg in 12 hours
50	125 mg in 6 hours		125 mg in 6 hours	125 mg every 8 hours	125 mg in 12 hours
40	125 mg in 6 hours		125 mg every 8 hours	125 mg in 12 hours	125 mg in 12 hours
30	125 mg every 8 hours		125 mg every 8 hours	125 mg in 12 hours	125 mg in 12 hours

≥70	500 mg in 8 hours	250 mg in 6 hours	250 mg every 8 hours	250 mg in 12 hours
60	250 mg in 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg in 12 hours
50	250 mg in 6 hours	250 mg every 8 hours	250 mg in 12 hours	250 mg in 12 hours
40	250 mg every 8 hours	125 mg in 6 hours	125 mg every 8 hours	125 mg in 12 hours
30	125 mg in 6 hours	125 mg every 8 hours	125 mg every 8 hours	125 mg in 12 hours

The maximum daily dose of 2.0 g

Body weight, kg	Creatinine clearance (ml / min / 1.73 m²)
Body weight, kg	≥71	41-70	21-40	6-20
≥70	500 mg in 6 hours	500 mg in 8 hours	250 mg in 6 hours	250 mg in 12 hours
60	500 mg in 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
50	250 mg in 6 hours	250 mg in 6 hours	250 mg every 8 hours	250 mg in 12 hours
40	250 mg in 6 hours	250 mg every 8 hours	250 mg in 12 hours	250 mg in 12 hours
30	250 mg every 8 hours	125 mg in 6 hours	125 mg every 8 hours	125 mg in 12 hours

The maximum daily dose of 3.0 g

Body weight, kg	Creatinine clearance (ml / min / 1.73 m²)
Body weight, kg	≥71	41-70	21-40	6-20
≥70	1000 mg after 8 hours	500 mg in 6 hours	500 mg in 8 hours	500 mg in 12 hours
60	750 mg in 8 hours	500 mg in 8 hours	500 mg in 8 hours	500 mg in 12 hours
50	500 mg in 6 hours	500 mg in 8 hours	250 mg in 6 hours	250 mg in 12 hours
40	500 mg in 8 hours	250 mg in 6 hours	250 mg every 8 hours	250 mg in 12 hours
30	250 mg in 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg in 12 hours

The maximum daily dose of 4.0 g

Body weight, kg	Creatinine clearance (ml / min / 1.73 m²)
Body weight, kg	≥71	41-70	21-40	6-20
≥70	1000 mg after 6 hours	750 mg in 8 hours	500 mg in 6 hours	500 mg in 12 hours
60	1000 mg after 8 hours	750 mg in 8 hours	500 mg in 8 hours	500 mg in 12 hours
50	750 mg in 8 hours	500 mg in 6 hours	500 mg in 8 hours	500 mg in 12 hours
40	500 mg in 6 hours	500 mg in 8 hours	250 mg in 6 hours	250 mg in 12 hours
30	500 mg in 8 hours	250 mg in 6 hours	250 mg every 8 hours	125 mg in 12 hours

When a dose of 500 mg is administered to patients with a creatinine clearance of 6-20 ml / min / 1.73 m² may increase the risk of seizures.
The preparation Imipenem + Cilastatin should not be administered intravenously to patients with a creatinine clearance less than 5 ml / min / 1.73 m² with the exception of cases when hemodialysis will be performed no later than 48 hours after the infusion of the drug.
Hemodialysis
When treating patients with SC less than 5 ml / min / 1.73 m², who are on hemodialysis, recommendations should be applied to the dosing regimen for patients with CK of 6-20 ml / min / 1.73 m² (see section "Dosing Scheme for Adult Patients with Impaired Renal Function").
Both imipenem and cilastatin are excreted during hemodialysis from the circulatory system. In this regard, the preparation Imipenem + Cilastatin should be administered to patients after hemodialysis and then at 12-hour intervals from the end of the procedure. Patients on hemodialysis, especially if they have central nervous system diseases, should be carefully monitored; administration of the preparation Imipenem + Cilastatin to patients undergoing hemodialysis is recommended only in cases when the benefit of treatment exceeds the potential risk of seizures (see the section "With caution").
At present, there is insufficient data to recommend the preparation Imipenem + Cilastatin to patients on peritoneal dialysis. The state of the kidney in elderly patients can not be fully determined only on the basis of measuring the level of residual blood nitrogen or creatinine. To determine the dosage of such patients, it is recommended to determine the clearance of creatinine.
Elderly patients
For elderly patients with normal renal function, dose adjustment is not required.
Impaired liver function
For patients with impaired liver function, dose adjustment is not required.
Prevention: dosing regimen for adult patients
For the prevention of postoperative infections in adults, the preparation Imipenem + Cilastatin should be administered at a dose of 1 g with anesthesia and then 1 g in 3 hours. In the case of surgical intervention with a high degree of risk (for example, in operations on the thick and rectum), two additional doses of 500 mg should be administered at 8 and 16 hours after the initial anesthesia.
Dosage regimen in children from 3 months of age
The following dosing regimen is recommended for children:
- Children with a body weight> 40 kg should receive the same doses as adult patients.
- Children older than 3 months with a body weight of less than 40 kg should receive the drug at a dose of 15 mg / kg with 6-hour intervals. The maximum daily dose should not exceed 2 g.
The drug Imipenem + Cilastatin is not recommended for the treatment of meningitis. If suspected of having meningitis, appropriate antibiotics should be prescribed.
Rules for the preparation of solution
The drug should not be mixed or added to other antibiotics.
The drug is pharmaceutically incompatible with lactic acid (lactate) and should not be prepared on the basis of solvents containing it.However, intravenously, the drug can be administered via the same infusion system as the lactate-containing solution. The following solvents are used to prepare the infusion solution: 5% dextrose solution, 10% dextrose solution, 5% dextrose solution and 0.9% sodium chloride solution, 5% dextrose solution and 0.45% sodium chloride solution, 5% dextrose solution and 0.225 % solution of sodium chloride, 5% dextrose solution and 0.15% potassium chloride solution, mannitol 5% and 10%, in a ratio of 500 mg imipenem to 100 ml of the solvent. The contents of the vial must be previously dissolved. To do this, 10 ml of a suitable solvent should be transferred with a syringe into the vial with the drug. The resulting solution can not be used for administration!
After dilution, the vial is shaken well, and then the contents are transferred to a vial or container with the rest of the solvent (90 ml). Total volume of solvent
is 100 ml. For the complete transfer of the drug (drug residues on the walls of the vial) 10 ml of the previously obtained solution are added to the same vial, shaken well and transferred back to the vial or container with the solution already obtained. Only after this, the solution is ready for use.
The concentration of imipenem in the resulting solution is 5 mg / ml.

Side effects:The most frequent systemic side effects probably associated with the use of the drug were nausea (2.0%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5 %), lowering blood pressure (0.4%), convulsions (0.4%) (see "Special instructions"), dizziness (0.3%), pruritus (0.3%), urticaria (0, 2%), drowsiness (0.2%). The most frequent local side effects were phlebitis / thrombophlebitis (3.1%), pain at the injection site (0.7%), erythema at the site of injection (0.4%) and vein scarring (0.2%). It has also often been reported that the activity of serum transaminases and alkaline phosphatase increases.
The side effects listed in clinical trials and post-registration experience are listed below.
Registered side effects are classified by frequency: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥ 1/10 000, <1/1000), very rarely (<1/10 000) and the frequency is unknown (can not be estimated from available data).
Infectious and parasitic diseases: rarely - pseudomembranous colitis, candidiasis; very rarely - gastroenteritis.
Violations from the blood and lymphatic system: often - eosinophilia; infrequently - pancytopenia, neutropenia, leukopenia, thrombocytopenia,thrombocytosis; rarely agranulocytosis; very rarely - hemolytic anemia, suppression of bone marrow function.
Immune system disorders: rarely anaphylactic reactions.
Disorders from the psyche: infrequently - mental disorders, including hallucinations and confusions.
Impaired nervous system: infrequently - convulsions, myoclonia, dizziness, drowsiness; rarely - encephalopathy, paresthesia, tremor, perversion of taste; very rarely - exacerbation of myasthenia gravis, headache; frequency is unknown. -Digestion, dyskinesia.
Hearing disorders and labyrinthine disturbances: rarely - hearing loss, very rarely - vertigo, ringing in the ears.
Heart Disease: very rarely - cyanosis, tachycardia, palpitation.
Vascular disorders: often - thrombophlebitis; infrequently - lowering blood pressure; very rarely - "hot flashes".
Disturbances from the respiratory system, chest and mediastinal organs: very rarely - shortness of breath, hyperventilation, sore throat.
Disorders from the gastrointestinal tract: often diarrhea, nausea, vomiting (nausea and / or vomiting,associated with taking the drug, are observed more often in patients with granulocytopenia); rarely staining the teeth and / or tongue; very rarely hemorrhagic colitis, abdominal pain, heartburn, glossitis, hypertrophy of the papillae of the tongue, hypersalivation.
Disorders from the liver and bile ducts: rarely - hepatic insufficiency, hepatitis; very rarely - fulminant hepatitis.
Disturbances from the skin and subcutaneous tissues: often - a rash (including, exanthematous), infrequently - hives, itching; rarely - toxic epidermal necrolysis, angioedema, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis; very rarely - a hyperhidrosis, a change in the structure of the skin.
Disturbances from the musculoskeletal and connective tissue: very rarely - polyartralgia, pain in the thoracic spine.
Disorders from the kidneys and urinary tract: rarely - acute renal failure, oliguria / anuria, polyuria, change in color of urine (it is safe and should not be mistaken for hematuria). The role of the drug in changes in renal function is difficult to assess, since there are other factors predisposing to prerenal azotemia and impaired renal function.
Violations of the genitals and breast: very rarely - genital itching.
General disorders and disorders at the site of administration: infrequently - fever, pain and denseness at the site of administration of the drug, erythema at the injection site; very rarely - a feeling of discomfort in the chest, asthenia / weakness.
Laboratory indicators: often - increased activity of serum transaminases, increased activity of alkaline phosphatase; infrequent positive Coombs direct test, increased prothrombin time, decreased hemoglobin, increased serum bilirubin concentration, increased serum creatinine concentration, increased urea nitrogen concentration in the blood.
Children (over 3 months)
Side effects in children older than 3 months were comparable with the side effects recorded in adult patients.

Overdose:Symptoms of overdose correspond to the profile of adverse reactions and can include convulsions, confusion, tremor, nausea, vomiting, lowering blood pressure, bradycardia.
Special information on the treatment of drug overdose Imipenem + Cilastatin no. Imipenem-cilastatin sodium is excreted during hemodialysis, however,the effectiveness of this procedure in case of an overdose of the drug is unknown.

Interaction:In patients taking both ganciclovir and drug Imipenem + Cilastatin, generalized convulsions were observed. These drugs can not be administered concomitantly, except when the potential benefits exceed the possible risk.
Simultaneous application with probenecid is accompanied by a minimal increase in plasma concentration and a half-life of imipenem, so that the simultaneous use of probenecid and the drug Imipenem + Cilastatin Not recommended.
Clinical cases described in the literature show that the simultaneous use of carbapenems, including iminen, with valproic acid or sodium divalproate, leads to a decrease in the concentration of valproic acid. As a result of this interaction, the concentration of valproic acid may fall below the therapeutic level, which increases the risk of developing seizures. Although the interaction mechanism is unknown, in vitro data and animal studies suggest that carbapenems may inhibit hydrolysis,as a result of which the glucuronide metabolite of valproic acid (VPA-g) is converted back to valproic acid, which leads to a decrease in the concentration of valproic acid in the blood plasma (see section "Special instructions").
Oral anticoagulants
The simultaneous use of antibiotics with warfarin can enhance its anticoagulant effect. There are numerous reports of increased anticoagulant effect of orally administered anticoagulants, including warfarin, in patients who simultaneously take antibacterial drugs. The risk may vary depending on the infectious agent, the age and general condition of the patient, so it is difficult to assess the effect of antibiotics on the increase in INR (the international normalized ratio). It is recommended to periodically monitor the value of INR during and immediately after the simultaneous use of antibiotics with oral anticoagulants.
A drug Imipenem + Cilastatin should not be confused with other antibiotics, while simultaneous - isolated - with other antibiotics (eg, aminoglycosides) is allowed.

Special instructions:The dosage form for intravenous administration should not be used for intramuscular administration.
A drug Imipenem + Cilastatin is not recommended for the treatment of meningitis.
Stains urine in a reddish color (it is safe and should not be mistaken for hematuria).
Drug therapy Imipenem + Cilastatin should be started only after assessing the advisability of using carbapenems, taking into account factors such as the severity of the infection, resistance to other antibiotics and the risk of carbapenem-resistant microorganisms.
Before the beginning of therapy, a thorough allergological anamnesis should be collected for previous allergic reactions to beta-lactam antibiotics. It should immediately stop therapy if an allergic reaction to the drug has appeared. Serious anaphylactic reactions require urgent emergency care.
Care should be taken to monitor liver function during drug treatment Imipenem + Cilastatin because of the risk of developing hepatotoxicity reactions (for example, an increase in the level of transaminases, liver failure, fulminant hepatitis).Patients with impaired liver function require careful monitoring of liver function during drug therapy Imipenem + Cilastatin.
There have been reports of the development of antibiotic-associated colitis and pseudomembranous colitis from mild to life-threatening severity, which developed both with drug treatment Imipenem + Cilastatin, and other antibiotics. In patients with diarrhea that occurred during or after therapy with the drug Imipenem + Cilastatin it is necessary to differentiate this diagnosis. In this case, consideration should be given to abolishing the drug and prescribing appropriate therapy for Clostridium difficile. Do not use drugs that inhibit peristalsis.
A drug Imipenem + Cilastatin cumulated in patients with reduced renal function, so in such patients (in case of improper dose selection), the development of adverse reactions from the side of the central nervous system is possible.
Therapy with antiepileptic drugs in patients with brain injuries or seizures in the history should continue the entire period of treatment with the drug (to avoid side effects from the CNS).
Particular care should be taken in children with neurological symptoms and convulsions in the history, especially if there are known risk factors for seizures or with concomitant medications that reduce the convulsive threshold of sensitivity.
In the event of a small tremor, clonic convulsions or seizures, a consultation of a neurologist is needed to prescribe anticonvulsant therapy. If symptoms from the central nervous system continue, the dose of the drug Imipenem + Cilastatin should be reduced or completely stopped taking the drug.
Patients with creatinine clearance from ≤ 5 ml / min / 1.73 m², should not receive the drug Imipenem + Cilastatin, except for cases where hemodialysis was performed within 48 hours. For patients on hemodialysis, the drug is recommended only if the benefit exceeds the potential risk of seizures.

Effect on the ability to drive transp. cf. and fur:Some of the undesirable reactions observed with the use of the drug may affect the ability to drive vehicles and work with mechanisms (see section "Side effect").

Form release / dosage:Powder for solution for infusion, 500 mg + 500 mg.

Packaging:The amount of the drug, corresponding to 500 mg of imipenem and 500 mg of cilastatin, in glass bottles, hermetically sealed with rubber stoppers, crimped with aluminum or combined "FLIPP OFF" caps.
Each label is labeled.
Each bottle, together with the instructions for use, is placed in a pack of cardboard.
For 100 bottles, together with an equal number of instructions for use, put in a pallet of cardboard, pasted with a shrink film (for hospital).

Storage conditions:At a temperature of no higher than 25 ° C.
Keep out of the reach of children!

Shelf life:2 years.
Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003845

Date of registration:20.09.2016

Expiration Date:20.09.2021

The owner of the registration certificate:HIMFARM, JSC HIMFARM, JSC Kazakhstan

Manufacturer: & nbsp

HIMFARM, JSC Kazakhstan

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp2016-10-11

Illustrated instructions

Instructions

Imipenem + Cilastatin (Imipenem + Cilastatin)