Cilapenem - instructions for use, dose, side effects, contraindications

active substances: imipenem monohydrate (in terms of imipenem) 0.265 g (0.250 g) or 0.530 g (0.500 g), cilastatin sodium (in terms of cilastatin) 0.266 g (0.250 g) or 0.532 g (0.500 g);

auxiliary substance: sodium bicarbonate - 0.010 g or 0.020 g.

Description:White or white with a yellowish tint powder.

Pharmacotherapeutic group:antibiotic-carbapenem + dehydropeptidase inhibitor

ATX: & nbsp

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

Pharmacodynamics:

Beta-lactam antibiotic of broad spectrum of action. Suppresses the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic. Imipenem - a derivative of tienamycin, belongs to the group of carbapenems. Cilastatin sodium inhibits dehydropeptidase, an enzyme that metabolizes imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastin does not have its own antibacterial activity, does not inhibit beta-lactamase bacteria.

Cilapenem is active against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis. Resistant to degradation by bacterial beta-lactamase, which makes it effective against many microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., which are resistant to most beta-lactam antibiotics. The antibacterial spectrum includes virtually all clinically relevant pathogens.Active in relation to:

- Gram-negative aerobic bacteria: Achromobacter spp., Acinetobacter spp. (before Mima-Herellea), Aeromonas hydrophila, Alcaligenes spp., Bordetella bronchicanis, Bordetella bronchiseptica, Bordetella pertussis, Brucella melitensis, Campylobacter spp., Capnocytophaga spp., Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii), Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including strains forming beta-lactamase), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp (including Klebsiella oxytoca, Klebsiella ozaenae, Klebsiella pneumoniae), Moraxella spp., Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including strains forming penicillinase), Neisseria meningitidis, Yersinia spp. (formerly Pasteurella), incl. Yersinia multocida, Yersinia enterocolitica, Yersinia pseudotuberculosis \ Plesiomonas shigelloides, Proteus spp. (including Proteus mirabilis, Proteus vulgaris), Providenda spp. (including Providenda alcalifaciens, Providenda rettgeri (formerly Proteus rettgeri), Providenda stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, Pseudomonas stutzeri), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens, Serratia proteamaculans), Shigella spp:,

- Gram-positive aerobic bacteria: Bacillus spp., Enterococcus faecalis, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Nocardia spp., Pediococcus spp., Staphylococcus aureus (including strains forming penicillinase), Staphylococcus epidermidis (including strains forming penicillinase), Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus Group C, Streptococcus Group G, greening streptococci including alpha and gamma-hemolytic strains);

- Gram-negative anaerobic bacteria: Bacteroides spp. (incl. Bacteroides distasonis, Bacteroides fragilis, Prevotella melaninogenica (formerly Bacteroides melaninogenicus), Bacteroides ovatus, Bacteroides thetaiotaomicronron, Bacteroides uniformis, Bacteroides vulgatus), Bilophila wadsworthia, Fusobacterium spp in t.ch. (Fusobacterium necrophorum, Fusobacterium nucleatum), Porphyromonas asaccharolytica (formerly Bacteroides asaccharolyticus), Prevotella bivia (formerly Bacteroides bivius), Prevotella disiens (formerly Bacteroides disiens), Prevotella intermedia (formerly Bacteroides intermedius), Veillonella spp.,

- Gram-positive anaerobic bacteria: Actinomyces spp., Bifidobacterium spp., Clostridium spp. (including Clostridium perfringens), Eubacter spp., Lactobacillus spp., Microaerophilic streptococcus, Mobiluncus spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp. (including Propionibacterium acne);

- other microorganisms: Mycobacterium fortuitum, Mycobacterium smegmatis.

Some Staphylococcus spp. (resistant to methicillin), Streptococcus spp. (Group D), Stenotrophomonas maltophilia, Enterococcus faecium and some strains Pseudomonas cepacia insensitive to imipenem. Effective against many infections caused by bacteria, resistant to cephalosporins, aminoglycosides, penicillins.

In vitro acts synergistically with aminoglycosides against certain strains Pseudomonas aeruginosa.

Pharmacokinetics:

Connection with plasma proteins of imipenem - 20%, cilastatin - 40%. Maximum concentration (FROM_mOh) imipenem with intravenous administration at a dose of 250, 500 or 1000 mg for 20 minutes - 14-24, 21-58 and 41-83 μg / ml, respectively; FROM_mOh cilastatin with intravenous administration at a dose of 250, 500 or 1000 mg for 20 minutes - 15-25, 31-49 and 56-80 μg / ml. Quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids and reproductive organs. In low concentrations it is found in the cerebrospinal fluid. The volume of distribution in adults is 0,23-0,31 l / kg, in children 2-12 years - 0,7 l / kg, in newborns - 0,4-0,5 l / kg. Blocking tubular secretion of imipenem with cilastatin results in inhibition of its renal metabolism and accumulation in the urine in unchanged form.Cilastin is metabolized to N-acetyl compound.

With intravenous administration, the half-life of imipenem and cilastatin in adults is 1 hour, in children 2-12 years, 1-1.2 hours, in newborns, T_1/2imipenem - 1,7-2,4 h, cilastatin - 3,8-8,4 h; when renal function is impaired, the half-life of imipenem is 2.9-4 hours, cilastatin is 13.3-17.1 hours. It is mainly excreted by the kidneys (70-76% for 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3); 1-2% is excreted with bile and 20-25% - by the extrarenal route (the mechanism is unknown). Quickly and effectively (73-90%) is excreted by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the dose is removed).

Indications:

Tsilapenem for intravenous administration is used in the treatment of severe infections caused by sensitive microorganisms. And also for the empirical therapy of the infectious process even before the determination of its bacterial pathogens.

- Infections of the lower respiratory tract caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillinase-producing strains), Acinetobacter spp., Enterobacter spp., Escherichia 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., Escherichia coli, Klebsiella spp, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa;

- Intraabdominal infection caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp, Morganella morganii, Proteus spp., Pseudomonas aeruginosa, Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., including B. fragilis, Fusobacterium spp.;

- Gynecological infections caused by Enterococcus faecalis; Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Escherichia coli; Streptococcus agalactiae (Group B Streptococcus), Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Klebsiella spp, Proteus spp, Bifidobacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., Including B. fragilis;

- Bacterial septicemia caused by Streptococcus pneumoniae, Enterococcus faecalis; Staphylococcus aureus (penicillinase-producing strains), Enterobacter spp., Escherichia coli, Klebsiella spp, Serratia spp., Bacteroides spp., Bacteroides fragilis, Pseudomonas aeruginosa;

- Infections of bones and joints caused by Enterococcus faecalis; Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Enterobacter spp., Pseudomonas aeruginosa;

- Infections of the skin and soft tissues caused by Streptococcus pyogenes, Enterococcus faecalis; Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Acinetobacter spp., Citrobacter spp., Enterobacter 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);

- Prevention of postoperative infections in patients at risk with a high probability of postoperative infectious complications, as well as in patients with a high risk of intraoperative infection during surgical intervention.

Contraindications:

Hypersensitivity (including carbapenems and other beta-lactam antibiotics), pregnancy (only for "vital") indications, early childhood (up to 3 months); in children - severe renal failure (serum creatinine concentration more than 2 mg / dl), chronic renal failure (creatinine clearance less than 5 ml / min without hemodialysis).

Carefully:

Pseudomembranous colitis, patients with creatinine clearance less than 70 ml / min / 1.73 m², central nervous system diseases, lactation period, advanced age, history of convulsions, high convulsive readiness, anticonvulsant therapy of valproic acid (decreased effectiveness of therapy), patients with a history of gastrointestinal disease, patients on hemodialysis.

Pregnancy and lactation:

During pregnancy, the drug is used only for "vital" indications, when the expected benefit of the treatment justifies the potential risk to the fetus. Imipenem is found in human breast milk. If the use of Cilapenem is considered necessary, then breastfeeding of the baby should be stopped.

Dosing and Administration:

The drug is administered intravenously drip. Medicinal the form for intramuscular injection should not be used for intravenous infusions and vice versa. The recommendations for the dosage of Cilapenem indicate the amount of imipenem to be administered. Calculation of the total daily dose of Cilapenem should be based on the severity of the infection and divided into several doses in equal doses, taking into account the degree of sensitivity of one or more pathogenic microorganisms, kidney function and body weight.

Dosage regimen for adult patients with normal renal function

The dosages of Cilapenem given in Table 1 are calculated for patients with normal renal function (creatinine clearance greater than 70 ml / min / 1.73 m) and body weight> 70 kg. In patients with creatinine clearance <70 ml / min / 1.73 m² (see Table 2) and / or 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 a moderate or severe renal failure.

The average therapeutic daily dose is 1 - 2 g imipenem, divided into 3-4 doses (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 of imipenem per day or 50 mg / kg per day, whichever dose is less.

Each dose of Cilapenem for intravenous infusion, less than or equal to 0.5 g, should administered intravenously for 20-30 minutes. Each dose of more than 0.5 g, should be administered intravenously for 40-60 minutes. Patients who experience nausea during infusions should decrease the rate of administration of the drug.

Table 1. Dosage regimen of Cilapenem for intravenous infusions in adult patients with normal renal function and weighing> 70 kg *

Severity of infection	Dose imipenem	Break between infusions	General information daily dose
Lightweight	0.25 g	6 hours	1.0 g
Average	0.5 g	8 ocloc'k	1.5 g
	1.0 g	12 hours	2.0 g
Severe (sensitive pathogens)	0.5 g	6 hours	2.0 g
Severe and / or life-threatening, caused by less sensitive microorganisms (primarily some strains P.aerusinosa)	1.0 g	8 ocloc'k	3.0 g
	1.0 g	6 hours	4.0 g

* In patients with a body weight of less than 70 kg, a further proportional reduction in the dose to be administered is necessary.

Due to the high antimicrobial activity of Cilapenem, it is recommended that its total daily dose not exceed 50 mg / kg or 4 g (imipenem) / day. However, patients with cystic fibrosis with normal renal function received treatment at a dose of up to 90 mg / kg per day, divided into several doses, with a total dose not exceeding 4 g (imipenem) per day. The drug is used in monotherapy in cancer patients with weakened immunity in the case of confirmed or suspected infections, for example sepsis.

Dosing regimen in adults 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, choose 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. (For calculating the infusion time, see Section "Dosing and Administration: Dosing Scheme for Adult Patients with Normal Kidney Function").

Table 2. Dosing regimen for intravenous infusions in adults with impaired renal function and body weight> 70 kg *

The total daily dose of imipenem in g of Table 1	Creatinine clearance (ml / min / 1.73 m²)
	41-70	21-40	6-20
1.0 g per day	for 0.25 g after 8 hours	0.25 g after 12 hours	0.25 g after 12 hours
1.5 g per day	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours
2.0 g per day	0.5 g after 8 hours	0.25 g after 6 hours	0.25 g after 12 hours
3.0 g per day	0,5 g in 6 hours	0.5 g after 8 hours	0,5 g in 12 hours
4.0 grams per day	at 0.75 g after 8 hours	0,5 g in 6 hours	0,5 g in 12 hours

* Patients with a body weight of less than 70 kg need a further proportional reduction in doses administered.

Table 3. Dosage regimen for intravenous infusions in adults weighing 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	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours	0.25 g after 12 hours
60-69	for 0.25 g after 8 hours	by 0,125 g in 6 hours	0.25 g after 12 hours	for 0.125 g after 12 hours
50-59	by 0,125 g in 6 hours	by 0,125 g in 6 hours	by 0,125 g in 8 hours	for 0.125 g after 12 hours
40-49	by 0,125 g in 6 hours	by 0,125 g in 8 hours	for 0.125 g after 12 hours	for 0.125 g after 12 hours
30-39	by 0,125 g in 8 hours	by 0,125 g in 8 hours	for 0.125 g after 12 hours	for 0.125 g after 12 hours
The maximum daily dose of 1.5 g

Body weight, (kg)	Creatinine clearance (ml / min / 1.73 m²)
Body weight, (kg)	>71	41-70	21-40	6-20
>70	0.5 g after 8 hours	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours
60-69	0.25 g after 6 hours	for 0.25 g after 8 hours	for 0.25 g after 8 hours	0.25 g after 12 hours
50-59	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours	0.25 g after 12 hours
40-49	for 0.25 g after 8 hours	by 0,125 g in 6 hours	by 0,125 g in 8 hours	for 0.125 g after 12 hours
30-39	by 0,125 g in 6 hours	by 0,125 g in 8 hours	by 0,125 g in 8 hours	for 0.125 g after 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	0,5 g in 6 hours	0.5 g after 8 hours	0.25 g after 6 hours	0.25 g after 12 hours
60-69	0.5 g after 8 hours	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours
50-59	0.25 g after 6 hours	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours
40-49	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours	0.25 g after 12 hours
30-39	for 0.25 g after 8 hours	by 0,125 g in 6 hours	by 0,125 g in 8 hours	for 0.125 g after 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	for 1.0 g after 8 hours	0,5 g in 6 hours	0.5 g after 8 hours	0,5 g in 12 hours
60-69	at 0.75 g after 8 hours	0.5 g after 8 hours	0.5 g after 8 hours	0,5 g in 12 hours
50-59	0,5 g in 6 hours	0.5 g after 8 hours	0.25 g after 6 hours	0.25 g after 12 hours
40-49	0.5 g after 8 hours	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours
30-39	0.25 g after 6 hours	for 0.25 g after 8 hours	for 0.25 g after 8 hours	0.25 g after 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	for 1.0 g after 6 hours	at 0.75 g after 8 hours	0,5 g in 6 hours	0,5 g in 12 hours
60-69	for 1.0 g after 8 hours	at 0.75 g after 8 hours	0.5 g after 8 hours	0,5 g in 12 hours
50-59	at 0.75 g after 8 hours	0,5 g in 6 hours	0.5 g after 8 hours	0,5 g in 12 hours
40-49	0,5 g in 6 hours	0.5 g after 8 hours	0.25 g after 6 hours	0.25 g after 12 hours
30-39	0.5 g after 8 hours	0.25 g after 6 hours	for 0.25 g after 8 hours	0.25 g after 12 hours

When administering a dose of Cilapenem in 0.5 g to patients with a creatinine clearance of 6-20 ml / min / 1.73 m² may increase the risk of seizures. Cilapenem 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 carried out no later than 48 hours after the infusion of Cilapenem.

Hemodialysis

When treating patients with creatinine clearance less than 5 ml / min / 1.73 m², who are on hemodialysis, should be guided by recommendations on the dosage regimen of Cilapenem for patients with creatinine clearance of 6-20 ml / min / 1.73 m² (see Section "Dosage and administration: Dosing regimen for adult patients with impaired renal function ").

Both imipenem and cilastatin are excreted during hemodialysis from the circulatory system. In this regard, cilapenem for intravenous infusion should be administered to patients after hemodialysis and then at 12-hour intervals from the completion of the procedure. Patients on hemodialysis, especially if they have central nervous system diseases, should be carefully monitored; the appointment of Cilapenem to patients undergoing hemodialysis is recommended only in cases where the benefit of treatment exceeds the potential risk of seizures (see Section "Carefully").

At present, there is insufficient data to recommend a drug for intravenous administration 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.

Prevention: dosing regimen for adult patients

For the prevention of postoperative infections in adults Tsilapenem for intravenous infusions should be administered at a dose of 1 g with anesthesia and then 1 g in three 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 0.5 g should be administered at 8 and 16 hours after the initial anesthesia.

Dosage regimen for children from 3 months of age:

- Children older than 3 months with a body weight of less than 40 kg are administered at a dose of 15 mg / kg every 6 hours;

- Children with a body weight of more than 40 kg should receive the same dose as adult patients.

The total daily dose should not exceed 2 g. Enter by intravenous infusion.

Preparation of a solution for intravenous infusion

Add 100 ml of solvent to the powder bottle. As the solvent can be used: isotonic sodium chloride solution; 5% aqueous solution of dextrose; 10% aqueous solution of dextrose; a solution of 5% dextrose and 0.9% sodium chloride; a solution of 5% dextrose and 0.45% sodium chloride; solution 5% dextrose and 0.225% sodium chloride; a solution of 5% dextrose and 0.15% potassium chloride; mannitol 5% and 10%. The resulting solution (imipenem concentration 2.5 or 5 mg / ml) should be shaken until a clear liquid forms.Differences in the color of the solution from yellow to colorless are allowed.

Table 4 provides data on the timing of the use of the Cilapenem solution for intravenous infusions, prepared on the basis of a number of infusion solutions and stored at room temperature or in a refrigerator.

Table 4. The shelf life of the prepared solution at room temperature or in the refrigerator.

Solvent	Stability time
Solvent	Room temperature (25 ° C)	Cooling (4 ° C)
Isotonic sodium chloride solution	4 hours	24 hours
5% aqueous dextrose solution	4 hours	24 hours
10% aqueous solution of dextrose	4 hours	24 hours
5% dextrose and 0.9% sodium chloride	4 hours	24 hours
5% dextrose and 0.45% sodium chloride	4 hours	24 hours
5% dextrose and 0.225% sodium chloride	4 hours	24 hours
5% dextrose and 0.15% potassium chloride	4 hours	24 hours
Mannitol 5% and 10%	4 hours	24 hours

Side effects:

The incidence of side effects is given in the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), including individual messages.

From the nervous system: infrequently: drowsiness, myoclonia, mental disorders, hallucinations, confusion,epileptic seizures; rarely: hearing loss; very rarely: headache, encephalopathy, paresthesia, asthenia, vertigo, tremor.

From the sense organs: rarely: hearing loss, ringing in the ears, perversion of taste.

From the urinary system: rarely: oliguria, anuria, polyuria, proteinuria, acute erythrocyte, leukocyte and cylindruria, increased bilirubin concentration and a change in urine color (safe and should not be mistaken for hematuria), renal insufficiency. The effect of the drug in changes in renal function is difficult to assess, since there are usually other factors predisposing to prerenal azotemia or impaired renal function.

From the gastrointestinal tract: often: nausea, vomiting, diarrhea; rarely: heartburn, hypertrophy of the papillae of the tongue, pain in the throat, abdominal pain, glossitis, hypersalivation, pigmentation of the teeth and / or tongue, pseudomembranous colitis (clinically significant, as in the case of other broad-spectrum antibacterials) (see section "Carefully"), both during and after treatment, hepatitis; very rarely: gastroenteritis, fulminant hepatitis, hepatic insufficiency, jaundice.

From the respiratory system: very rarely: a feeling of discomfort in the chest, shortness of breath, hyperventilation, pain in the thoracic spine.

From the cardiovascular system: infrequently: lowering blood pressure; rarely: palpitation, tachycardia.

Laboratory indicators:

- biochemical: often: increased activity of "liver" transaminases and alkaline phosphatase; Hyperbilirubinemia, hypercreatininaemia, increased urea nitrogen concentration; an increase in the concentration of low-density lipoproteins, a false positive Coombs direct test.

- hematologic: infrequently: pancytopenia, thrombocytopenia, thrombocytosis, leukopenia, neutropenia, leukocytosis, monocytosis, lymphocytosis, an increase in the number of basophils, a decrease in hemoglobin and hematocrit, an increase in prothrombin time; often: eosinophilia, rarely: agranulocytosis; very rarely: oppression of red bone marrow function, hemolytic anemia.

Against the background of granulocytopenia, more frequent episodes of nausea and vomiting are noted.

Electrolyte balance: infrequently: a decrease in serum sodium and chlorine concentrations, an increase in potassium concentration.

Allergic reactions: often: skin rash, itching; infrequently: urticaria; rarely: multiform exudative erythema (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis, exfoliative dermatitis, fever; very rarely: anaphylactic reactions, cyanosis, hyperhidrosis.

Local reactions: often: thrombophlebitis; infrequent: skin hyperemia, painful infiltration at the injection site.

Other: rarely: itching of the vagina, candidiasis, taste disorder, polyarthralgia, vein compression, phlebitis at the site of administration.

Overdose:

Symptoms: specific symptoms are absent. When an overdose of the drug may increase dose-dependent side effects.

Treatment: There is no specific information on the treatment of an overdose of Cilapenem. Cilapenem undergoes hemodialysis. However, the effectiveness of this procedure with an overdose is unknown.

Interaction:

Pharmaceutically incompatible with lactic acid salt, other antibacterial drugs. With simultaneous application with penicillins and cephalosporins, a cross-allergy is possible; shows antagonism towards other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

Ganciclovir increases the risk of developing generalized seizures. It is not recommended simultaneous administration of drugs, except in cases where the potential benefits exceed the possible risk.

Administration of cilapenem is associated with a decrease in serum valproic acid concentration with an associated risk of increased seizure activity (cases reported in clinical practice), therefore it is recommended to monitor the serum concentration of valproic acid during the treatment period.

Drugs that block tubular secretion, slightly increase the concentration in the plasma and the half-life of imipenem (if high concentrations of imipenem are required, it is not recommended to use these medicines at the same time).

Special instructions:

Application in pediatric practice: in children older than 3 months, the drug is used for the same indications as in adult patients. Data on the effectiveness and safety of the drug for intravenous administration in children up to 3 months and with impaired renal function (serum creatinine more than 2 mg / dl) is not enough.

Application in elderly patients: efficiency and safety imipenem / cilastatin with intravenous administration in elderly persons over the age of 65 does not differ from those in younger patients. However, taking into account the reduced functions of the cardiovascular system, liver, kidneys, as well as the presence of concomitant diseases and concomitant medication, characteristic for this age group, care should be taken in choosing the dose, adhering to the lower limits of the recommended doses. It is advisable to monitor the excretory function of the kidneys. Do not mix in one syringe with other antibiotics, while simultaneous - isolated administration with other antibiotics (aminoglycosides) is allowed.

When using the drug, both on the background of taking and 2-3 weeks after discontinuation of treatment, it is possible to develop diarrhea caused by Clostridium difficile (pseudomembranous colitis). In mild cases, it is sufficient to discontinue treatment and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, administration of vancmycin, bacitracin or metronidazole is indicated. Do not use drugs that inhibit the intestinal motility.

Not recommended for the treatment of meningitis.

Stains urine in a reddish color.

Before the start of therapy, a thorough anamnesis should be made about the previous allergic reactions to beta-lactam antibiotics. People with a history of gastrointestinal disease (especially colitis) have an increased risk of developing pseudomembranous colitis. Therapy with antiepileptic drugs in patients with brain injuries or fits in the anamnesis should continue throughout the treatment period with the drug (to avoid side effects from the central nervous system).

Effect on the ability to drive transp. cf. and fur:

Given the potential for side effects on the background of treatment with the drug Tsilapenem, you need to take extra care when driving and working with mechanisms.

Form release / dosage:

Powder for solution for infusion, 0.25 g + 0.25 g and 0.5 g + 0.5 g.

Packaging:

For 0.25 g imipenem + 0.25 g cilastatin or 0.5 g imipenem + 0.5 g cilastatin powder in glass bottles with a capacity of 100 ml. Each bottle, together with instructions for use, is placed in a pack of cardboard.

Packing for hospitals: 12 bottles together with the corresponding number of instructions for use in the group boxes.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001141

Date of registration:09.11.2011

Date of cancellation:2016-11-09

The owner of the registration certificate:BELMEDPREPARATY, RUP BELMEDPREPARATY, RUP Republic of Belarus

Manufacturer: & nbsp

BELMEDPREPARATY, RUP Republic of Belarus

Information update date: & nbsp11.10.2015

Illustrated instructions

Instructions

Cilapenem (Cilapenem)