Medicinal reference book geotar. Dosage form of Imipenem with cilastatin: powder for the preparation of solution for intramuscular administration Imipenem is destroyed

Imipenem Cilastatin is an antibiotic, according to the instructions it belongs to the group of carbopenems - a subclass of beta-lactams antibacterial agents. It affects many pathogenic microorganisms, disrupting their synthesis cell membranes. The drug has a wide spectrum of action, high bioavailability, and is often included in medical recommendations. Next, we will consider the mechanism of action of imipenem, instructions for its use, indications and side effects.

1. Imipenem cilastatin– powder for injection, whitish or yellow-white in color. Dissolves in dextrose, administered through a dropper. It is produced and sold in boxes of 1-50 pieces in the form of antibiotic vials (transparent bottles with powder).
2. Imipenem-cilastatin Vial– similar to the type of release described above, except for the content of the main active ingredient. Produced in transparent glass bottles, 20 ml each, in cardboard boxes of 1, 10 or 50 bottles.
3. Imipenem and cilastatin Spencer. Available in transparent bottles, it is a powder from which a solution for intravenous drip injection is made.
4. Imipenem-cilastatin Jodas. This form of release is also presented in transparent bottles with antibiotic powder, produced in options of either 1, or 5, or 10 pieces per package.

Within 10 hours, approximately 75% of cilastatin is excreted by the kidneys, and approximately 70% of imipenem. There is no tablet version of the drug. According to the instructions, it is produced and used in medical practice exclusively as powder for injection.

Indications for use

Imipenem is an antibiotic that belongs to the new generation of antimicrobial agents. Based on the official instructions, it affects a wide range of gram-positive (Gr+) and gram-negative (Gr-) dangerous pathogenic strains of bacteria and has a bactericidal effect on them.

β-lactamases are a series of specific enzymes produced by bacteria to combat beta-lactam antibiotics - penicillins, cephalosporins and others. These substances form so-called resistance to them. Imipenem is resistant to microbial β-lactamases and can therefore be prescribed in cases where other β-lactams are not effective. Indications for use in the instructions for imipenem are determined by the spectrum of microorganisms that are sensitive to this antibacterial agent. The sensitivity spectrum for imipenem cilastatin, indicated in the official instructions for the drug:

• Gr+ bacteria of the Staphylococcus family. Under a number of factors - decreased immune reactivity, obesity, underlying diseases - representatives of this family become pathogenic and can cause an inflammatory reaction in almost any tissue and organ of the body system. The most common strains requiring antibacterial treatment — Staphylococcus aureus and Staphylococcus epidermidis (including penicillinase-producing strains).
• Gr+ prokaryotes of the Streptococcus family. Most often, these microorganisms can be cultured from the nasopharynx, oral cavity and intestines. These include Strept. pneumoniae, group B streptococci using the example of Strept. agalactiae, Strept. pyogenes.
• They are aerobic microorganisms, unlike motile streptococci, they do not have the ability to move, they are static. May cause the development of nocardiosis.
• Gr+ representatives of the Listeria family (Listeriaceae).
• Gr+ type Enterococ. faecalis, which is insensitive to many other group of antibacterial agents.
• Prokaryotes of physiological microflora that can acquire pathogenic properties under certain conditions. They are the most common factor in the occurrence of nosocomial complications and diseases due to the reduced growth rate of new blood plexuses and vessels and with infectious lesions of the urinary and reproductive systems.
• Gr-bacillus, including E. coli, are strains that do not form spores.
• Gr-klebsiella – in last years microorganisms of this family are included in the list of the most dangerous types of infectious agents due to their low and poorly controlled sensitivity to antibiotics.
• Pathogenic Gr are representatives of the genus Proteus. They cause the vast majority of diseases of the gastrointestinal tract of an infectious nature.
• Gr- rods from the genus Salmonella (strains that do not form spores), Shigella, Yersinia, family Moraxellaceae.
• Gram-negative Campylobacter bacteria, which cause campylobacteriosis.
• Strict anaerobes of the genus Bacteroidaceae.
• Haemophilus influenzae - can cause infectious conditions in the blood.

Based on the radar and the above spectrum of sensitivity of microorganisms to imipenem, in the instructions it has the following series of indications for use:

• Treatment of infections abdominal cavity
• Infections of the lower respiratory system.
• Infectious processes in the pelvic organs and gynecological problems.
• Sepsis, skin inflammation, life-threatening infections
• Nosocomial infections after operations and other surgical interventions.

Contraindications

Imipenem cilastatin tablets are taken strictly according to the instructions under the supervision of a specialist. There are a number of contraindications for prescribing this drug, namely:

1. Low body weight (weight significantly less than 30 kg)
2. Individual hypersensitivity reactions to penicillins, cross-sensitivity reactions to cephalosporins, beta-lactams, carbapenems or drug components.
3. Age less than 3 months.
4. Severe renal failure in pediatric patients and chronic in adults.
5. Lactation.

According to the instructions, imipenem is prescribed with sufficient caution when taking valproic acid, colitis, diseases and disorders of the central nervous system, moderately low serum creatinine and for elderly patients.

Side effects

Like all drugs, the instructions for imipenem cilastatin contain a list of side effects that can cause taking this medication. The occurrence of side effects is always ordered according to the WHO classification: very often, often, sometimes, isolated cases, rare, purity unknown.

• Psychoneurological disorders: headaches, trembling of extremities (mainly hands), disorders of the functioning of the vestibular region, convulsions.
• Sense organs – taste distortion, hearing loss.
• Digestive system - nausea, vomiting, diarrhea, other disorders, abdominal pain, dyspepsia.
• Heart and vascular system: increase in arterial systolic and diastolic pressure, tachycardia
• Hematopoietic organs and blood parameters: eosinophilia - an increase in the number of eosinophils, leukopenia and neutropenia - a decrease in the number of leukocytes and granulocytes-neutrophils in particular, the number of platelet cells can either increase or decrease. Hematopoietic mechanisms and processes are inhibited.
• Hypersensitivity reactions – erythematous rash, swelling, anaphylaxis, urticaria.
• Genitourinary manifestations: redness of urine, an increase in urine output per day or vice versa, oliguria - slow urine output, renal dysfunction - impaired renal function, which may require discontinuation of the drug.
• Others side effects: fungal infection by representatives of the genus Candida (candidiasis), asthenic syndrome, hyperhidrosis and polyarthralgia.

Instructions for use

The instructions state that imipenem is used for intravenous or drip administration. To prepare the solution, you need 100 ml of solution for injection. It must be administered in an amount of 10-20 ml (depending on the volume of the bottle and required dose) to the powder mass in a bottle of antibiotic. After this, the bottle must be shaken until a suspension of uniform consistency is formed.

It is very important to note that the resulting mixture cannot be used for injection. It must be diluted in the remaining 80-90 ml of injection solution, bringing the total volume to 100 ml. To ensure that fragments of the mixture do not remain in the original vial, the procedure should be repeated again, and then mixed again with general solution. When the solution is properly prepared, with an imipenem content of 0.005 g per ml, it will be colorless or slightly yellowish. Under normal room temperature conditions, the solution is stored for up to four hours. When placing it in the refrigerator – up to a day.

The solution can be made based on the following infusion fluids: saline solution, dextrose solution 5-10%, combination of dextrose solution 5% and 0.45% sodium chloride solution, combination of saline solution and 5% dextrose, 0 .15% KCl solution (potassium chloride) and 5% dextrose solution. Daily dose of the drug imipenem cilastatin (trade name and international generic name(INN) in the instructions are identical): for persons over 12 years old - no more than 4 grams, for children under 12 years old weighing less than 30 kg - no more than 2 grams. In the first case, the daily dosage should not be more than 1 gram per 6 hours. Doctor this instruction can be adjusted - the required dosage is calculated depending on the severity of the infection. Each degree of severity of the infectious process has its own instructions for dosing and administration.

According to the instructions, if the drug is used in patients with renal failure, pathological processes in gastrointestinal tract and the nervous system, an individual choice of dose is required (perhaps it should be proportionally reduced) and duration of treatment. Patients over 65-70 years of age should be carried out with caution and monitoring the state of renal function.

Use during pregnancy

There have been virtually no studies on the effects of imipenem during pregnancy and are not listed in the instructions. It is advisable to use this drug during pregnancy only if the benefit from therapy is higher than the theoretical risk to the fetus. Imipenem cilastatin passes into mother's milk, so it is not prescribed during lactation.

For children

According to the instructions for pediatric patients weighing 40 kg and above, the dose is the same as for adults. With a weight below 40 kg - the maximum dose is 2 grams, divided into 4 doses per day at the rate of 15 mg/kg every 6 hours.

Interaction with other drugs

Today we are considering a combination drug – imipenem with cilastatin. The second component increases the content of the original, unchanged antibiotic imipenem in the urine and urinary tract due to inhibition of its metabolization processes. Drug interactions with the simultaneous use of this antibiotic and other drugs have their own characteristics.

Concomitant use with ganciclovir may cause the development of generalized seizures. These drugs are prescribed together in exceptional cases when the expected effect of therapy is higher than the theoretical risk. The use of probenecid is not advisable because it increases the plasma concentration and half-life of imipenem.

When combined with valproic acid, it is advisable to monitor its plasma concentration, as there is an increased risk of increased seizure activity. To prevent the development of undesirable effects, in patients with epilepsy, antiepileptic drug therapy should be continued throughout the course of antibiotic treatment.

This antibiotic is administered by injection exclusively in mono versions.

Drug price

In Russia, imipenem cilastatin is sold in pharmacies at a price of 460 rubles per bottle. In Ukraine, the price of one bottle reaches 330-370 UAH.

Analogues

There are a number of analogues on the pharmaceutical market with active substance imipenem. These include such combination drugs as: Tienam, Aquapenem, Imipenem and cilastatin Spencer, Imipenem Jodas, Tiepenem, Cilapenem, Grimipenem.

active ingredients:

1 bottle contains imipenem monohydrate 530 mg, which corresponds to 500 mg of imipenem and cilastatin sodium 530 mg, which corresponds to 500 mg of cilastatin;

excipients: sodium bicarbonate.

Dosage form

Powder for the preparation of solution for infusion.

Basic physical and chemical properties: white to almost white or slightly yellowish powder.

Pharmacological group

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

Pharmacological properties

Pharmacological.

Imipenem/Cilastatin-Vista consists of two components: imipenem, the first representative of a new class of b-lactam antibiotics - thienamycin, 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 drug is 1:1.

The class of thienamycin 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. Имипенем / Циластатин-Виста обнаружил свою эффективность при лечении многих инфекций, вызванных аэробными и анаэробными грамположительными и грамотрицательными бактериями, устойчивыми к цефалоспоринам, в том числе и к цефазолина, цефоперазона, цефалотину, цефокситина, цефотаксима, моксалактаму, цефамандола, цефтазидима и цефтриаксона. 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 wide range 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 outstanding feature is the high activity against gram-positive species, previously observed only in 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 group of pathogens that are different in composition and clinically problematic, usually resistant to other antibiotics.

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

The antibacterial spectrum of imipenem/cilastatin is wider than any other already known antibiotic and covers all clinically important pathogenic microorganisms. Microorganisms for which Imipenem/Cilastatin-Vistazavichay is effective in vitro include:

Gram-negative aerobic bacteria

Achromobacter species

Acinetobacter (formerly Mima-Herellea) species

Aeromonas hydrophila

Alcaligenes spp.

Bordetella bronchicanis

Bordetella bronchiseptica

Bordetella pertussis

Brucella melitensis

Burkholderia pseudomallei (formerly Pseudomonas pseudomallei)

Burkholderia stutzeri (formerly Pseudomonas stutzeri)

Campylobacter species

Capnocytophaga spp.

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 b-lactamase producing strains)

Haemophilus parainfluenzae

Klebsiella spp.

Klebsiella oxytoca

Klebsiella ozaenae

Klebsiella pneumoniae

Moraxella spp.

Morganella morganii (formerly Proteus morganii)

Neisseria gonorrhoeae (including penicillinase-producing strains)

Neisseria meningitidis

Pasteurella spp.

Pasteurella multocida

Plesiomonas shigelloides

Proteus spp.

Proteus mirabilis

Proteus vulgaris

Providencia spp.

Providencia alcalifaciens

Providencia rettgeri (formerly Proteus rettgeri)

Providencia stuartii

Pseudomonas species*

Pseudomonas fluorescens

Pseudomonas putida

Pseudomonas aeruginosa

Salmonella spp.

Salmonella typhi

Serratia spp.

Serratia proteamaculans (formerly Serratia liquefaciens)

Serratia marcescens

Shigella spp.

Yersinia (formerly Pasteurella) species

Yersinia enterocolitica

Yersinia pseudotuberculosis

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

Gram-positive aerobic bacteria

Bacillus species

Enterococcus faecalis

Erysipelothrix rhusiopathiae

Listeria monocytogenes

Nocardia spp.

Pediococcus spp.

Staphylococcus aureus (including penicillinase-producing strains)

Staphylococcus epidermidis (including penicillinase-producing strains)

Staphylococcus saprophyticus

Streptococcus agalactiae

Streptococcus group C

Streptococcus group G

Streptococcus pneumoniae

Streptococcus pyogenes

Viridans Streptococci (including α and γ hemolytic strains)

Enterococcus faecium and some methicillin-resistant staphylococci that are not susceptible to Imipenem/Cilastatin-Vista.

Gram-negative anaerobic bacteria

Bacteroides spp.

Bacteroides distasonis

Bacteroides fragilis

Bacteroides ovalus

Bacteroides thelaiotaomicron

Bacteroides uniformis

Bacteroides vulgatus

Bilophila wadsworthia

Fusobacterium species

Fusobacterium necrophorum

Fusobacterium nucleatum

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)

Gram-positive anaerobic bacteria

Actinomyces spp.

Bifidobacterium species

Clostridium spp.

Clostridium perfringens

Eubacterium spp.

Lactoballus spp.

Mobiluncus spp.

Microaerophilic streptococcus

Peptococcus spp.

Peptostreptococcus species

Propionibacterium species (including P. acnes)

Mycobacterium fortuitum

Mycobacterium smegmatis

In vitro tests indicate that imipenem acts synergistically with aminoglycosides against certain isolates of Pseudomonas aeruginosa.

Pharmacokinetics.

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

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

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

The half-life of imipenem from blood plasma was 1:00. Approximately 70% of the applied antibiotic was found intact in urine within 10:00, and no further excretion of the drug in urine was observed. When using the drug Imipenem / Cilastatin-Vista according to the schedule every 6:00, there was no accumulation of imipenem in the blood plasma or urine in patients with normal renal function. Co-administration of Imipenem/Cilastatin-Vistai and probenecid resulted in minimal increases in plasma levels and plasma half-life of imipenem.

Cilastatin. Peak plasma levels of cilastatin after a 20-minute infusion of the drug at a dose of 500 mg ranged from 21 to 55 mcg/ml. The binding of cilastatin to human plasma proteins is approximately 40%. The half-life of cilastatin from blood plasma is approximately 1:00. Approximately 70 - 80% of the dose of cilastatin is excreted unchanged in the urine within 10:00 after administration of the drug. After this, cilastatin was not detected in the urine. Approximately 10% was expressed as the metabolite N-acetyl, which has a dehydropeptidase inhibitory effect comparable to that of the parent drug. Co-administration of the drug and probenecid doubled the plasma levels and half-life of cilastatin, but had no effect on the urinary recovery of cilastatin.

renal failure

Following a single dose of imipenem/cilastatin 250 mg/250 mg, the area under the concentration-time curve (AUC) for imipenem increased 1.1-fold, 1.9-fold, and 2.7-fold, respectively, in patients with low creatinine clearance (CrCL 50 - 80 ml/min/1.73 m2), moderate (CrCL 30-80 ml/min/1.73 m2), and the area under the concentration-time curve (AUC) for cilastatin increased by 1.6, respectively, 2 and 6.2 times in patients with mild, moderate and severe renal failure compared with patients with normal renal function.

After a single 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 greater, respectively, compared with patients with normal kidney function. Urinary excretion, renal clearance and clearance of imipenem and cilastatin decrease along with a decrease in renal function after administration of Imipenem/Cilastatin-Vist. Dose adjustment is necessary for patients with impaired renal function.

liver failure

The pharmacokinetics of imipenem in patients with hepatic impairment have been established. -Due to the limited extent of hepatic metabolism of imipenem, it is not expected that hepatic impairment will affect its pharmacokinetics. Therefore, dose adjustment is not recommended for patients with hepatic impairment.

The mean clearance and volume of distribution for imipenem were approximately 45% higher in children (aged 3 months to 14 years) compared with adults. Area under the concentration-time curve (AUC) for imipenem after dosing of imipenem/ cilastatin 15/15 mg/kg body weight in children was approximately 30% higher than exposure in adults receiving the 500 mg/500 mg dose. At the higher dose, exposure after imipenem/cilastatin 25/25 mg/kg in children was 9% higher compared to exposure in adults receiving the 1000 mg/1000 mg dose.

Elderly patients

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

Indications

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

• intra-abdominal infections;
• infections of the lower respiratory tract(severe pneumonia, including hospital and ventilator-associated pneumonia)
• Intrapartum and postpartum infections;
• complicated infections genitourinary system;
• complicated infections of the skin and soft tissues;
• bone and joint infections;
• septicemia,
• endocarditis.

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

Treatment of patients with bacteremia that is associated or likely to be associated with any of the above infections.

Contraindications

Increased sensitivity to the components of the drug, other carbapenem drugs, acute manifestations hypersensitivity (eg anaphylactic reactions, severe skin reactions) to other ß-lactam antibiotics (eg penicillin or cephalosporins).

Interaction with other drugs and other types of interactions

In patients receiving ganciclovir with imipenem/cilastatin for intravenous use, generalized convulsions were noted.

These drugs can be used together only when the expected benefit outweighs the possible risk.

Decreased plasma levels of valproic acid have been reported when used concomitantly with carbapenems, and in some cases sudden seizures have been reported. Therefore, concomitant use of imipenem and valproic acid/sodium valproate is not recommended.

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 taking antibiotics concomitantly. The risk may vary depending on the type of infection, age and general status patient. 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 (unabsorbed) imipenem was reduced to approximately 60% of the dose when the drug was administered with probenecid. Concomitant use of the drug and probenecid doubled the plasma levels of cilastatin and the half-life of cilastatin, but had no effect on the urinary excretion of cilastatin.

Features of application

When choosing imipenem/cilastatin as a drug for treatment in each specific case, the appropriateness of using carbapenems should be taken into account, taking into account the severity of the infection, the prevalence of resistance to other acceptable antibacterial agents and taking into account the possibility of the presence of carbapenem-resistant bacteria.

Hypersensitivity.

Some clinical and laboratory data are known that indicate partial cross-allergenicity of the drug Imipenem / Cilastatin-Vista and other b-lactam antibiotics, penicillins and cephalosporins. Severe reactions (including anaphylaxis) occur with most b-lactam antibiotics. Before starting drug therapy, the patient's medical history should be carefully examined for the presence of hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other b-lactam antibiotics and other allergens (see Section "Contraindications").

If an allergic reaction develops while using the drug, the drug should be discontinued and appropriate measures taken. Serious anaphylactic reactions require emergency treatment.

Liver functions.

During treatment with imipenem/cilastatin, liver function should be carefully monitored due to the risk of liver toxicity (increased transaminases, liver failure and fulminant hepatitis).

Patients with pre-existing liver disease should monitor liver function during treatment with imipenem/cilastatin. There is no need for dose adjustment.

Hematology.

During treatment with imipenem/cilastatin, positive direct or indirect sample Coombs.

Antibacterial spectrum.

Before any empirical treatment, the antibacterial spectrum of imipenem/cilastatin should be considered, especially for conditions that pose a threat to the patient's life. In addition, caution should be exercised due to the limited susceptibility of certain pathogens (associated, for example, 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 particular pathogen has already been documented and is known to be susceptible or when there is very good reason to believe that the most likely pathogen(s) 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 aminoglycosides may be indicated when Pseudomonas aeruginosa infections are suspected or proven to be involved in approved indications.

Clostridium difficile

The development of pseudomembranous colitis has been reported as a complication with the use of almost all antibiotics; its forms can range from mild to those that threaten the patient’s life. Therefore, antibiotics should be prescribed with caution to patients with a history of gastrointestinal diseases, especially colitis. It is important to remember the possibility of developing pseudomembranous colitis, when a patient develops diarrhea during treatment or after stopping treatment with antibiotics. Discontinuation of imipenem/cilastatin therapy and use of Clostridium difficile-specific treatment should be considered. Medicines that inhibit peristalsis should not be prescribed.

Kidney failure.

In patients with impaired renal function, imipenem/cilastatin accumulates. If the dose of the drug is not reduced due to the state of renal function, adverse reactions from the central nervous system may develop (see “Dosage and Administration” and below).

Central nervous system (CNS).

As with β-lactam antibiotic therapy, CNS side effects such as myoclonus, confusion or convulsions have been described with the use of Imipenem / Cilastatin-Vista, especially if recommended doses are exceeded, which were determined depending on renal function and body weight . Typically, such disorders have been observed in patients with central nervous system damage (brain injuries or a history of seizures) and/or in patients with impaired renal function, in which accumulation of the drug in the body is possible. In this regard, especially for such patients, it is extremely necessary 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 receiving concomitant treatment medications to reduce the intensity of the trial.

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

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

Excipients.

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

Use during pregnancy or breastfeeding.

Pregnancy.

The use of the drug for the treatment of pregnant women has not been properly studied, therefore it can be prescribed during pregnancy only if the expected benefit to the pregnant woman outweighs the potential risk to the fetus.

Breastfeeding period.

Imipenem and cilastatin are excreted in small amounts in breast milk. If it is necessary to use the drug, breastfeeding should be discontinued.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

Considering the risk of side effects such as hallucinations, drowsiness, dizziness, you should avoid driving vehicles and operating machinery when using the drug.

Directions for use and doses

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

Adult patients with normal renal function

Doses for patients with normal renal function (creatinine clearance > 70 ml/min/1.73 m2) and body weight of at least 70 kg:

• 500 mg/500 mg every 6:00 or
• 1000 mg / 1000 mg every 8:00 or every 6:00.

For the treatment of infections known or probable to be caused by less susceptible bacterial species (eg, Pseudomonas aeruginosa), and severe infections (eg, neutropenic patients with fever), a dose of 1000 mg/1000 mg every 6:00 is recommended.

The dose should be reduced for patients with:

• CC ≤ 70 ml / min / 1.73 m 2 and / or
• with body weight less than 70 kg. Dose reduction based on body weight is especially important for patients with body weight significantly less than 70 kg and/or moderate/severe renal impairment.

The dose for patients weighing less than 70 kg is determined using the formula:

actual body weight (kg) * standard dose

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

Adult patients with impaired renal function

To determine a reduced dose for adult patients with impaired renal function:

1. Determine the total daily dose (i.e., 2000/2000, 3000/3000, or 4000/4000 mg) typically administered to patients with normal renal function.
2. Select the required mode of administration of a reduced dose (see Table 1) according to the patient’s creatinine clearance and the duration of the infusion (see “Method of administration”).

Table 1

Doses of imipenem/cilastatin for adults with impaired renal function and weight ≥ 70 kg *

* For patients weighing less than 70 kg, the dose should be proportionally reduced. Proportional dose for patients with body weight

** When using a dose of 500 mg / 500 mg in patients with a creatinine clearance of 6-20 ml / min / 1.73 m 2, the risk of seizures increases significantly.

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

Imipenem/Cilastatin-Vista for intravenous administration should not be prescribed unless they are undergoing hemodialysis within the next 48 hours.

hemodialysis

When treating patients with creatinine clearance ≤ 5 ml/min/1.73 m2 and undergoing hemodialysis, doses recommended for patients with creatinine clearance 6-20 ml/min/1.73 m2 are used (see Table 1 ).

Both imipenem and cilastatin are eliminated during hemodialysis. The patient must be administered imipenem/cilastatin immediately after the hemodialysis session and subsequently administered every 12:00 after its completion. Hemodialysis patients, especially those whose underlying disease is central nervous system disease, require close monitoring; It is recommended to prescribe imipenem/cilastatin to such patients only if the expected effect outweighs the possible risk of seizures (see “Peculiarities of use”).

To date, there is insufficient data regarding the use of the drug in patients on peritoneal dialysis, so it is not recommended to use it to treat this category of patients.

liver failure

No dose adjustment is required for patients with impaired liver function.

Elderly patients

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

Children aged 1 year and older.

For the treatment of infections known or likely to be caused by less susceptible bacterial species (eg, Pseudomonas aeruginosa), and severe infections (eg, neutropenic patients with fever), a dose of 25/25 mg/kg every 6 hours is recommended.

Children under 1 year of age and/or with impaired renal function.

Mode of application.

Each bottle is for single use only.

Before use, the contents of the bottle (powder) must be dissolved and diluted appropriately (see.

Recommendations below). Each dose not exceeding 500 mg / 500 mg 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, it is necessary to reduce the rate of drug administration.

Preparation of solution for intravenous administration.

Imipenem/Cilastatin-Vista for infusion is available as a sterile powder in vials containing 500 mg imipenem equivalent and 500 mg cilastatin equivalent.

The composition of the drug Imipenem / Cilastatin-Vista includes sodium bicarbonate as a buffer, which provides a solution with a pH from 6.5 to 8.5. These pH changes are not significant if the solution is prepared and stored according to the directions given. Imipenem/Cilastatin-Vista for intravenous use contains 37.5 mg sodium (1.6 mEq).

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

Table 2.

Preparation of Imipenem / Cilastatin-Vista solution for intravenous administration

The contents of the vial must be suspended and diluted to 100 ml with an appropriate solution for injection.

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

Shake well and transfer the suspension formed into the container with the injection solution.

Warning: The suspension is not a ready-made solution for injection.

Repeat the procedure, adding again 10 ml of solution for infusion so that the entire contents of the bottle are transferred to the solution for infusion. The resulting mixture must be shaken until it becomes transparent.

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

pharmachologic effect

Broad-spectrum carbapenem antibiotic. It has a bactericidal effect due to inhibition of the bacterial cell wall.

Active against aerobic gram-positive bacteria: Staphylococcus spp. (including strains producing penicillinase), Streptococcus spp., Enterococcus faecalis, Nocardia spp., Listeria spp.; aerobic gram-negative bacteria: Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus spp., Providencia spp., Salmonella spp., Serratia spp., Shigella spp., Yersinia spp., Pseudomonas aeruginosa, Acinetobacter spp., Campylobacter spp., Haemophilus influenzae, Neisseria spp.; anaerobic bacteria: Bacteroides spp.

Imipenem is not active against Chlamydia trachomatis, Mycoplasma spp., fungi and viruses.

Resistant to β-lactamases.

Pharmacokinetics

After intramuscular administration, bioavailability is 95%. Quickly and widely distributed in most tissues and body fluids. Plasma protein binding - 20%. Metabolized in the kidneys by hydrolysis of the beta-lactam ring under the action of renal dehydropeptidase.

Dosage

IV for adults and children over 12 years old - 0.25-1 g every 6 hours. Children over 3 months and weighing less than 40 kg - 15 mg/kg body weight every 6 hours.

IM for adults and children over 12 years old - 500-750 mg every 12 hours.

Maximum doses: the maximum daily dose for adults with intravenous administration is 4 g, with intramuscular administration - 1.5 g, for children weighing less than 40 kg with intravenous administration - 2 g.

Drug interactions

With the simultaneous use of a combination of imipinem with cilastatin and ganciclovir, the development of seizures is possible.

Pregnancy and lactation

Use during pregnancy is possible only when the expected benefit to the mother outweighs the potential risk to the fetus.

It is not known whether imipenem is excreted in breast milk, therefore, if use during lactation is necessary, the issue of stopping breastfeeding should be considered.

Side effects

Allergic reactions: skin rash, fever, urticaria, eosinophilia, anaphylactic shock.

From the side digestive system: nausea, vomiting, diarrhea, change in taste, pseudomembranous colitis, increased activity of liver transaminases.

From the side of the central nervous system: convulsions, epileptic seizures.

Reactions associated with chemotherapeutic effects: candidiasis.

Local reactions: pain, thrombophlebitis (with intravenous administration).

Indications

Infections of the abdominal organs, lower respiratory tract, genitourinary system, gynecological infections, septicemia, infective endocarditis, infections of bones and joints, skin and soft tissues. Prevention of postoperative infections.

Contraindications

Hypersensitivity to imipenem.

special instructions

Use with caution in patients with diseases of the central nervous system and impaired renal function. Dose adjustment is indicated for this category of patients.

It should be taken into account that imipenem is used in combination with cilastatin, which is an inhibitor of renal dehydropeptidase and, by blocking the renal metabolism of imipenem, promotes its accumulation in the urine unchanged. Cilastatin does not have antibacterial activity and does not affect beta-lactamases, nor does it alter the effects of imipenem.

Patients who have allergic reactions to other beta-lactam antibiotics may develop an allergy to imipenem.

It should be taken into account that when using imipenem, the development of a false-positive Coombs reaction is possible.

Preparations containing IMIPENEM

IMIPENEM & CILASTATIN JODAS powder for preparation. solution for intravenous administration 500 mg+500 mg: vial. 1, 5 or 10 pcs.
. TIENAM ® (TIENAM) powder for preparation. r-ra d/inf. 500 mg+500 mg: vial. 10 pcs., set (bottle 10 pcs. and connecting tubes 5 pcs.) 1 pc.
. GRIMIPENEM ® powder for preparation. r-ra d/inf. 500 mg+500 mg: vial. 1 PC.
. IMIPENEM AND CILASTATIN SPENSER powder for preparation. solution for intravenous administration 500 mg+500 mg: vial. 1 PC.
. CILASPEN powder for preparation. r-ra d/inf. 500 mg+500 mg: vial. 1 PC.
. TIENAM ® (TIENAM) powder for preparation. d/v/m solution introduced. 500 mg+500 mg: vial. 1 PC.

IMIPENEM - description and instructions provided by the reference book medicines Vidal.

Antibiotic of the carbapenem group

Active ingredients

Cilastatin
- imipenem (monohydrate form) (imipenem)

Release form, composition and packaging

Powder for solution for infusion white or white with a yellowish tint.

bottles (1) - cardboard packs.
bottles (10) - cardboard boxes.
bottles (50) - cardboard boxes (for hospitals).
bottles (1-50) - cardboard boxes (for hospitals).

pharmachologic effect

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

Imipenem + cilastatin is resistant to destruction by bacterial beta-lactamases, which makes it effective against most beta-lactamase-producing microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacler spp., resistant to penicillins and cephalosporins.

Imipenem + cilastatin has a bactericidal effect in vivo on the following microorganisms:

Enterococcus faecalis, Staphylococcus aureus (including penicillinase-producing strains), Slaphylococcus epidermidis (including penicillinase-producing strains). Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes;

Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp., including Serratia marcescens;

gram-positive anaerobic bacteria: Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.

gram-negative anaerobic bacteria: Bacleroides spp., including Bacteroides fragilis, Fusobacterium spp.

Imipenem has a bactericidal effect in vitro against the following microorganisms:

gram-positive aerobic bacteria: Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Streptococcus groups C, G and viridans group;

gram-negative aerobic bacteria: Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including penicillinase-producing strains, Pasteurella spp., Providencia stuartii; gram-negative anaerobic bacteria: Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Veillonella spp.

Insensitive: Enterococcus faecium, methicillin-resistant Staphylococcus spp., Xanthomonas maltophilia, Pseudomonas cepacia.

In vitro, it acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.

Pharmacokinetics

The maximum concentration (Cmax) of imipenem when administered intravenously at a dose of 250 mg, 500 mg, 1000 mg for 20 minutes - 14-24 μg/ml, 21-58 μg/ml, 41-83 μg/ml respectively. C max of cilastatin when administered intravenously at a dose of 250 mg, 500 mg, 1000 mg for 20 minutes - 15-25 μg/ml, 31-49 μg/ml, 56-80 μg/ml, respectively. 20% of the administered dose of imipenem and 40% of cilastatin are reversibly bound to blood proteins.

Imipenem is well and quickly distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids, reproductive organs. Found in low concentrations in cerebrospinal fluid (CSF). The volume of distribution in adults is 0.23-0.31 l/kg, in children 2-12 years old - 0.7 l/kg, in newborns -0.4-0.5 l/kg. Both components of the drug are excreted primarily by the kidneys (70-76% within 10 hours) through glomerular filtration (2/3) and active tubular secretion (1/3): 1-2% is excreted through the intestines and 20-25% through the extrarenal route ( mechanism unknown).

With intravenous administration, the half-life (T 1/2) of imipenem and cilastatin in adults is 1 hour, in children 2-12 years old - 1-1.2 hours, in newborns T 1/2 of imipenem - 1.7-2.4 hours , cilastatin -3.8-8.4 hours; in case of impaired renal function T1/2 of imipenem - 2.9-4 hours. Cilastatin - 13.3-17.1 hours.

Imipenem and cilastatin are rapidly and effectively (73-90%) eliminated by hemodialysis (a 3-hour session of intermittent hemofiltration removes 75% of the administered dose).

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

• lower respiratory tract infections;
• infections urinary tract;
• intra-abdominal infections;
• gynecological infections;
• bacterial septicemia;
• bone and joint infections;
• skin and soft tissue infections;
• bacterial endocarditis.

Prevention of postoperative infectious complications.

Contraindications

• hypersensitivity to one of the components of the drug, as well as to other carbapenems, beta-lactam antibiotics, penicillins and cephalosporins;
• chronic renal failure with CC less than 5 ml/min/1.73 m2 without hemodialysis;
• early childhood (up to 3 months);
• in children - severe renal failure (serum creatinine concentration more than 2 mg/dl).

Carefully

Diseases of the central nervous system (CNS), pseudomembranous colitis, patients with a history of gastrointestinal diseases, with creatinine clearance less than 70 ml/min/1.73 m2, patients on hemodialysis, anticonvulsant therapy (reduced effectiveness of therapy), elderly age.

Dosage

Intravenous drip.

The dosage form for intravenous administration should not be administered intramuscularly.

Average therapeutic dose for adults with a body weight greater than or equal to 70 kg and normal renal function (creatinine clearance 70 ml/min/1.73 m2 or more) - 1-2 g/day (based on imipenem), divided into 3-4 administrations.

The maximum daily dose is 4 g or 50 mg/kg, whichever is lower.

• at mild infections and uncomplicated urinary tract infections- 250 mg 4 times a day (total daily dose 1 g);
• at moderate course- 500 mg 3 times a day or 1000 mg 2 times a day (total daily dose 1.5-2 g);
• at severe and complicated urinary tract infections- 500 mg 4 times a day (total daily dose 2 g);
• at infection that threatens the patient's life- 1000 mg 3-4 times a day (total daily dose 3-4 g).

For prevention of postoperative infections- 1000 mg during induction of anesthesia and 1000 mg after 3 hours. In case of surgical intervention with a high risk of developing infection (surgery on the colon and rectum), an additional dose of 500 mg is administered 8 hours and 16 hours after general anesthesia.

For patients with CC less than 70 ml/min/1.73 m2 and/or body weight less than 70 kg the dose should be proportionally reduced (dose calculation based on imipenem):

Maximum daily dose 1.0 g

Body weight, kg
	≥71	41-70	21-40	6-20
≥70	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
60-69	250 mg every 8 hours	125 mg every 6 hours	250 mg every 12 hours	125 mg every 12 hours
50-59	125 mg every 6 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
40-49	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours
30-39	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours

Maximum daily dose 1.5 g

Body weight kg	Creatinine clearance, ml/min/1.73 m2
	≥71	41-70	21-40	6-20
≥70	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
60-69	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours
50-59	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
40-49	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
30-39	125 mg every 6 hours	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours

Maximum daily dose 2.0 g

Body weight, kg	Creatinine clearance, ml/min/1.73 m2
	≥71	41-70	21-40	6-20
≥70	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
60-69	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
50-59	250 mg every 6 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
40-49	250 mg every 6 hours	250 mg every X hour	250 mg every 12 hours	250 mg every 12 hours
30-39	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours

Maximum daily dose 3.0 g

Body weight, kg	Creatinine clearance. ml/min/1.73 m2
	≥71	41-70	21-40	6-20
≥70	1000 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
60-69	750 mg every 8 hours	500 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
50-59	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
40-49	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
30-39	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours

Maximum daily dose 4.0 g

Body weight, kg	Creatinine clearance, ml/min/1.73 m2
	≥71	41-70	21-40	6-20
≥70	1000 mg every 6 hours	750 mg every 8 hours	500 mg every 6 hours	500 mg every 12 hours
60-69	1000 mg every 8 hours	750 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
50-59	750 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
40-49	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
30-39	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours

In patients with CC less than 5 ml/min/1.73 m2 the drug is administered only if hemodialysis will be carried out no later than 48 hours later.

In patients with CC less than 5 ml/min/1.73 m2 patients undergoing hemodialysis, the drug should be administered in doses recommended for patients with CC 6-20 ml/min/1.73 m2, immediately after the hemodialysis session and at 12-hour intervals from the completion of the procedure. Patients undergoing hemodialysis, especially those with central nervous system disease, should be closely monitored. The use of the drug in patients on hemodialysis is recommended only in cases where the benefit of treatment outweighs the potential risk of developing seizures. Currently, there is insufficient data to recommend the use of the drug in patients undergoing peritoneal dialysis.

U children starting from 3 months of age, weighing up to 40 kg, single dose is 15 mg/kg, which is administered every 6 hours. The maximum daily dose is 2 g.

Children weighing 40 kg or more the same doses are prescribed as for adults (see tables).

Preparation of solution for infusion and administration

Add 10 ml or 20 ml of a suitable solvent to the bottle with the drug. Shake the bottle well to obtain a homogeneous suspension.

The resulting suspension cannot be used for administration!

The resulting suspension is transferred to a bottle with the rest of the solvent (80-90 ml). The total volume of the solution is 100 ml. To completely transfer the drug (residues of the drug on the walls of the bottle), add 20 ml of the previously obtained solution to the bottle, shake well, then combine both solutions. Stir the resulting solution thoroughly until it becomes clear. Only after this the solution is ready for use. The total volume of solution is 100 ml. Differences in the color of the solution from colorless to yellow do not affect the activity of the drug.

Administered intravenously.

The duration of the infusion depends on the chosen dose: 250-500 mg is administered over 20-30 minutes; over 500 mg - within 40-60 minutes. Patients who experience nausea during infusion should reduce the rate of drug administration.

Prepared solutions for infusion (imipenem concentration 5 mg/ml) can be stored for 4 hours at room temperature or for 24 hours in the refrigerator.

The table presents data on the stability periods of drug solutions prepared on the basis of a number of infusion solutions.

Side effects

From the central nervous system: dizziness, drowsiness, myoclonus, mental disorders, hallucinations, confusion, convulsions, paresthesia, encephalopathy, tremor, headache, vertigo.

From the senses: hearing loss, ringing in the ears, taste disturbance.

From the urinary system: oliguria, anuria, polyuria, acute renal failure, changes in urine color.

From the digestive system: nausea, vomiting, diarrhea, pseudomembranous colitis, hemorrhagic colitis, hepatitis (including fulminant), liver failure, jaundice, gastroenteritis, abdominal pain, glossitis, hypertrophy of the tongue papillae, staining of the teeth or tongue, pain in the throat, hypersalivation, heartburn.

From the respiratory system: feeling of discomfort in the chest, shortness of breath, hyperventilation.

From the hematopoietic organs: eosinophilia. leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, leukocytosis, basophilia, pancytopenia, inhibition of bone marrow hematopoiesis, hemolytic anemia.

Laboratory indicators: increased activity of “liver” transaminases and alkaline phosphatase, lactate dehydrogenase, hypercreatininemia, hyperbilirubinemia, increased concentration of urea nitrogen; false-positive direct Coombs test; decrease in hemoglobin and hematocrit, prolongation of prothrombin time; increased concentration of low-density lipoproteins; hyponatremia, hyperkalemia, hypochloremia; the appearance of protein, red blood cells, leukocytes, casts, increased concentration of bilirubin in the urine.

Allergic reactions: skin rash, itching, urticaria, erythema multiforme, Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis, exfoliative dermatitis, fever, anaphylactic reactions.

From the outside of cardio-vascular system: decreased blood pressure, palpitations, tachycardia.

Local reactions: skin hyperemia, painful infiltrate at the injection site, phlebitis/thrombophlebitis.

Others: candidiasis, vaginal itching, cyanosis, hyperhidrosis, polyarthralgia, asthenia, burning sensation behind the sternum, pain in thoracic region spine.

Overdose

Drug interactions

Pharmaceutically incompatible with lactic acid salts and solutions of other antibiotics.

When used simultaneously with penicillins and cephalosporins, cross-allergy is possible; exhibits antagonism to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

When used simultaneously, the risk of developing generalized seizures increases. These drugs should not be used together unless the potential benefits outweigh the potential risks.

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

When using the drug, the serum concentration of valproic acid decreases, which leads to a decrease in the effectiveness of anticonvulsant therapy, therefore, during the treatment period it is recommended to monitor the serum concentration of valproic acid.

special instructions

Strict adherence to the recommended dosage and dosage regimen is strictly required, especially in patients predisposed to seizure activity. Therapy with anticonvulsants in patients with a history of epilepsy should continue throughout the period of treatment with the drug. If local tremor, myoclonus, or seizures are observed, patients should undergo a neurological examination and be prescribed anticonvulsant therapy. The dosage of the drug in this case should be reviewed to determine whether it should be reduced or the drug should be discontinued.

The dosage form contains 37.56 mg (1.63 mEq) sodium.

Before initiating therapy, a thorough medical history should be obtained regarding previous allergic reactions to beta-lactam antibiotics. During development allergic reaction the drug should be discontinued immediately.

Individuals with a history of gastrointestinal diseases (especially colitis) have an increased risk of developing pseudomembranous colitis.

When using the drug, both during administration and after 2-3 weeks. after stopping treatment, diarrhea caused by Clostridium difficile (pseudomembranous colitis) may develop. In mild cases, it is sufficient to discontinue treatment and use ion exchange resins (colestyramine, colestipol); in severe cases, replacement of loss of fluid, electrolytes and protein, and the appointment of vancomycin and metronidazole are indicated. Do not use medications that inhibit intestinal motility.

As with other beta-lactam antibiotics, Pseudomonas aeruginosa can quickly develop resistance to the drug during treatment. Therefore, during the treatment of infections caused by Pseudomonas aeruginosa, it is recommended to conduct periodic antibiotic sensitivity tests according to the clinical situation.

Elderly patients are likely to have age-related disorders renal function, which may require dose reduction.

Colors urine reddish.

Impact on the ability to drive vehicles and operate machinery

Caution should be exercised when driving and engaging in other potentially dangerous activities. dangerous species activities requiring increased attention and speed of psychomotor reactions.

Pregnancy and lactation

Use during pregnancy is only permissible if possible benefit from treatment for the mother exceeds the potential risk to the fetus.

Imipenem and cilastatin pass into breast milk in small quantities, so the issue of stopping breastfeeding during treatment with the drug should be considered.

Available according to prescription.

Storage conditions and periods

In a place protected from light at a temperature not exceeding 25°C. Keep out of the reach of children. Best before date. 2 years.

INN: Imipenem, Cilastatin

Manufacturer: Khimpharm JSC

Anatomical-therapeutic-chemical classification: Imipenem in combination with beta-lactamase inhibitors

Registration number in the Republic of Kazakhstan: No. RK-LS-5No. 010367

Registration period: 03.08.2015 - 03.08.2020

KNF (medicine included in the Kazakhstan National Formulary of Medicines)

ED (Included in the List of drugs within the framework of the guaranteed volume of free medical care, subject to purchase from the Single Distributor)

Limit purchase price in the Republic of Kazakhstan: 6 479.51 KZT

Instructions

Tradename

Let's prepenem ®

International nonproprietary name

Dosage form

Powder, for the preparation of solution for intravenous administration

Compound

One bottle contains

a sterile mixture of imipenem, cilastatin and sodium bicarbonate, including:

active substances: imipenem

(in terms of anhydrous imipenem) 500.0 mg

cilastatin sodium

(in terms of cilastatin) 500.0 mg,

excipient: sodium bicarbonate.

Description

The powder is white to slightly yellowish in color.

Pharmacotherapeutic group

Antibacterial drugs for systemic use. Beta-lactam antibacterial drugs others. Carbapenems. Imipenem and dehydropeptidase inhibitor.

ATX code J01DH51

Pharmacological properties

Pharmacokinetics

After intravenous (IV) administration, the bioavailability of imipenem is 98%. Quickly and widely distributed in most tissues and body fluids. Binding to blood plasma proteins - 20%. The half-life is 1 hour. Metabolized in the kidneys by hydrolysis of the beta-lactam ring under the action of renal dehydropeptidase.

After intravenous administration of imipenem/cilastatin solution, the time to reach maximum concentration (TCmax) in plasma is 20 minutes for both components. In this case, the maximum concentration (Cmax) for imipenem/cilastatin reaches values ​​from 21 to 58 μg/ml for imipenem and from 31 to 49 μg/ml for cilastatin. After administration of imipenem/cilastatin, Cmax decreases to 1 mcg/ml or lower within 4-6 hours.

The half-life for each component is 1 hour. Plasma protein binding is 20% for imipenem and 40% for cilastatin. Approximately 70% of imipenem/cilastatin administered intravenously is excreted by the kidneys within 10 hours. Concentrations of the antibiotic in urine above 10 mcg/ml may persist for 8 hours after intravenous administration of imipenem/cilastatin. About 70% of cilastatin is excreted by the kidneys within 10 hours after intravenous administration of the drug.

After intravenous administration, imipenem/cilastatin is determined in the following tissues and environments of the human body: in the vitreous body of the eyeball, intraocular fluid, lung tissue, pleural fluid, peritoneal fluid, bile, cerebrospinal fluid, connective, bone tissue.

Pharmacodynamics

Let's prepenem ® is a broad-spectrum antibiotic consisting of two components: imipenem and cilastatin.

Imipenem inhibits bacterial cell wall synthesis and has a bactericidal effect against a wide range of gram-positive and gram-negative pathogenic microorganisms. Imipenem is active against those gram-positive species for which only narrow-spectrum beta-lactam antibiotics were previously active.

Cilastatin sodium, a competitive, reversible and specific inhibitor of dihydropeptidase-I, is a renal enzyme that is metabolized and inactivated by imipenem, thereby depriving it of its own antibacterial activity, but does not affect the antibacterial activity of imipenem.

Spectrum of action imipenem/cilastatin includes Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis and Bacteroides fragilis, a diverse group of problematic pathogens that are usually resistant to other antibiotics.

Imipenem is resistant to destruction 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.

Antimicrobial spectrum imipenem/cilastatin includes virtually all clinically significant pathogenic microorganisms.

Imipenem/cilastatin is active in vitro against aerobic gram-negative bacteria: Achromobacter spp., Acinetobacter spp. (formerly 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 influenzae, Haemophilus ducreyi (including beta-lactamase producing strains), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella ozaenae), Legionella spp., Moraxella spp., Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Pasteurella multocida, Proteus spp . (including Proteus mirabilis, Proteus vulgaris) Plesiomonas shigelloides, Providencia spp. (including Providencia rettgeri (formerly Proteus rettgeri), Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, P. stutzeri), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia liquefaciens, Serratia marcescens), Shigella spp., Yersinia spp. (including Yersinia enterocolitica, Yersinia pseudotuberculosis);

Aerobic gram-positive bacteria: Bacillus spp., Enterococcus faecalis, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Staphylococcus epidermidis (including penicillinase-producing strains), Staphylococcus saprophyticus, Streptococcus spp. group B (including Streptococcus agalactiae), Streptococcus spp. groups C, G, Streptococcus pneumoniae, Streptococcus viridans (including hemolytic strains alpha and gamma);

Anaerobic gram-negative bacteria: Porph romonas asaccharolytica (formerly Bacteroides asaccharolytica), Prevotella bivia (formerly Bacteroides bivius), Prevotella disiens (formerly Bacteroides disiens), Prevotella intermedia (formerly Bacteroides intermedius), Bacteroides melaninogenicus, Bacteroides uniformis, Bilophila wadswerthia, Fusobacterium spp. (including Fusobacterium necrophorum, Fusobacterium nucleatum), Veillonella spp.;

Anaerobic gram-positive bacteria: Actinomyces spp., Clostridium spp. (including Clostridium perfringens), Eubacterium spp., microaerophilic streptococcus, Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp. (including Propionibacterium acnes), Bifidobacterium spp., Lactobacillus spp., Mobiluncus spp., Mycobacterium fortuitum, Mycobacterium smegmatis.

Xanthomonas maltophilia (formerly Pseudomonas maltophilia) and some strains of Pseudomonas cepacia are resistant to imipenem/cilastatin.

In vitro tests show that imipenem/cilastatin acts synergistically with aminoglycoside antibiotics against certain isolates of Pseudomonas aeruginosa.

Indications for use

Adults and children over 1 year of age for the treatment of the following infections:

Complicated intra-abdominal infections

Severe pneumonia, including nosocomial pneumonia and pneumonia associated artificial ventilation lungs

Birth and postpartum infections

Complicated urinary tract infections

Complicated skin and soft tissue infections

Let's prepenem ® can be used in the treatment of febrile patients with neutropenia when a bacterial infection is suspected, in the treatment of patients with bacteremia occurring in combination with or when the presence of any of the above infections is suspected.

Official guidelines for the proper use of antibacterial agents should be consulted.

Directions for use and doses

The daily dose depends on the type and severity of the infection, the pathogen(s) isolated, renal function, and the patient's body weight.

Adults and teenagers

For patients with normal renal function (creatinine clearance > 70 ml/min/1.73 m2), the following doses are recommended:

500 mg/500 mg every 6 hours OR

1000 mg/1000 mg every 8 hours OR every 6 hours.

It is recommended to prescribe 1000 mg/1000 mg every 6 hours for suspected or proven infection associated with a less susceptible species of bacteria (for example, Pseudomonas aeruginosa) and for very severe infections (in febrile patients with neutropenia).

Dose reduction is necessary when:

Creatinine clearance ≤70 ml/min/1.73m2 (see Table 1) or

Body weight<70 кг.

Dose for patients<70 кг будет рассчитываться по следующей формуле:

Patient body weight (kg) * standard dose of the drug

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

Kidney failure

Dose determination for adult patients with impaired renal function:

1. The daily dose (i.e. 2000/2000, 3000/3000 or 4000/4000 mg) can generally be used in the treatment of patients with normal renal function.

2. According to Table 1, it is advisable to reduce the dose of the drug in accordance with the patient’s creatinine clearance. Duration of infusions - see subsection “Method of administration”.

Table 1: Dose reduction in adult patients with renal impairment and body weight >70 kg*

*For patients with weight<70 кг следует рассчитать дальнейшее пропорциональное снижение дозы путем деления массы тела больного (в кг) на 70 кг и умножения на соответствующую рекомендуемую дозу согласно табл.1.

** When using doses of 500 mg/500 mg in patients with creatinine clearance from 6 to 20 ml/min/1.73 m2, there is a risk of developing seizures.

Patients with creatinine clearance<5мл/мин/1.73м2

Let's prepenem ® should not be prescribed to such patients, unless they have received hemodialysis within 48 hours.

Patients on hemodialysis

When treating patients with creatinine clearance ≤5 ml/min/1.73 m2 on hemodialysis, it is recommended to use the doses indicated in Table 1 for patients with creatinine clearance from 6 to 20 ml/min/1.73 m2 (see Table 1).

Imipenem and cilastatin are eliminated from the circulation during hemodialysis. The patient must receive Prepenem ® at intervals of 12 hours after the end of the hemodialysis session. Patients receiving hemodialysis, especially those with underlying central nervous system diseases, should be closely monitored. For patients on hemodialysis, Prepenem ® recommended only if the benefit outweighs the potential risk of seizures (see section "Special Instructions").

There is currently no reliable data to recommend the use of Prepenem ® patients on peritoneal dialysis.

Liver failure

For patients with impaired liver function, no dose adjustment is required (see section “Pharmacodynamics/pharmacokinetics”).

Application in geriatrics

For elderly patients without renal pathology, no dose changes are required (see section “Pharmacodynamics/pharmacokinetics”).

Use in pediatrics

It is recommended that if infection is suspected or non-susceptible bacterial species are detected (for example: Pseudomonas aeruginosa) and for very severe infections (for example: in febrile patients with neutropenia), doses of 25/25 mg/kg are prescribed every 6 hours.

For children<1 года

Pediatric population with renal failure

Mode of application

Preparation of solution for intravenous infusion

Add 100 ml of solvent to the bottle with the powder. The following solvents can be used: isotonic sodium chloride solution; 5% aqueous dextrose solution; 10% aqueous dextrose solution; solution of 5% dextrose and 0.9% sodium chloride; a solution of 5% dextrose and 0.45% sodium chloride; a solution of 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 5 mg/ml) must be shaken until a clear liquid forms. Differences in the color of the solution from yellow to colorless do not affect the activity of the drug.

To prepare Prepenem solution ® Do not use solvents containing lactic acid salt (lactate).

Each dose ≤500 mg/500 mg should be administered intravenously over 20 to 30 minutes. Each dose >500 mg/500 mg should be administered over 40 to 60 minutes. If the patient experiences nausea during the infusion, the infusion rate may be reduced.

Side effects

In clinical studies (1723 patients received imipenem/

cilastatin intravenously) the most frequently reported systemic adverse reactions associated with this therapy were: nausea (2.0%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5%), arterial hypotension (0.4%), convulsions (0.4%), dizziness (0.3%), itching (0.3%), urticaria (0.2%), drowsiness ( 0.2%). Of the local adverse reactions, the most frequently identified were: phlebitis/thrombophlebitis (3.1%), pain at the injection site (0.7%), erythema at the injection site (0.4%) and venous thickening (0.2%). Also recorded were: increased serum transaminases and alkaline phosphatase.

The following adverse reactions have been reported in clinical and post-marketing studies:

All adverse reactions are listed according to organ classification and frequency: very often (≥1/10), often (≥1/100 to<1/10), нечасто (≥1/1000 до <1/100), редко (≥ 1/10000 до <1/1000), очень редко (<1/10000) и неизвестная частота (может не быть оценена по имеющимся данным).

Within each frequency group, adverse effects are presented in descending order of severity of adverse events.

System	Frequency	Side effects
Infections and manifestations		pseudomembranous colitis, candidiasis
	very rarely	gastroenteritis
Diseases of the blood and lymphatic system		eosinophilia
		pancytopenia, neutropenia, leukopenia, thrombocytopenia, thrombocytosis
		agranulocytosis
	very rarely	hemolytic anemia, bone marrow suppression
Immune system diseases		anaphylactic reactions
Mental illness		mental disorders, including hallucinations and disorientation
Nervous system disorders		convulsions, myoclonic activity, dizziness, drowsiness
		encephalopathy, paresthesia, focal tremor, taste perversion
	very rarely	exacerbation of myasthenia gravis, headache
ENT disorders		hearing loss
	very rarely	tinnitus, dizziness
Heart diseases	very rarely	cyanosis, tachycardia, palpitations
Vascular diseases		thrombophlebitis
		hypotension
	very rarely
Respiratory system disorders	very rarely	shortness of breath, hyperventilation, sore throat
Gastrointestinal disorders		diarrhea, nausea, vomiting. Drug-induced nausea and vomiting is more common in patients with granulocytopenia than in patients without it during treatment with imipenem/cilastatin
		staining of the tongue and/or teeth
	very rarely	hemorrhagic colitis, abdominal pain, heartburn, glossitis, hypertrophy of the tongue papillae, hypersalivation
Liver diseases		liver failure, hepatitis
	very rarely	fulminant hepatitis
Diseases of the skin and subcutaneous tissue		rash, including exanthematous)
		hives, itching
		toxic epidermal necrolysis, angioedema, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis
	very rarely	hyperhidriosis, skin changes
Diseases of the musculoskeletal system	very rarely	polyarthralgia, pain in the thoracic spine
Diseases of the urinary system		acute renal failure, oliguria/anuria, polyuria, discoloration of urine (harmless, not to be confused with hematuria). It is difficult to assess the role of imipenem/cilastatin in changes in renal function if there are no predisposing factors such as prerenal azotemia and renal failure
Diseases of the mammary glands and reproductive system	very rarely	itching of the vulva
Common diseases and side effects in the area of ​​drug administration		fever, local pain and induration, erythema at the injection site
	very rarely	chest discomfort, asthenia/weakness
Research		increased transaminases and alkaline phosphatase in the blood serum
		positive direct Coombs reaction, prolongation of prothrombin time, decrease in hemoglobin, increase in bilirubin, increase in serum creatinine and urea

In pediatric practice

Children (≥3 months)

In a study of 178 sick children ≥3 months of age, adverse reactions were consistent with data among adult patients.

Contraindications

Hypersensitivity to the active substances or to any of the excipients

Hypersensitivity to any other carbapenem antibacterial drug

Severe hypersensitivity (eg, anaphylactic reaction, severe skin reactions) to any other type of beta-lactam antibacterial agent (eg, penicillins or cephalosporins)

Children's age up to 1 year

Children with impaired renal function (serum creatinine >2 mg/l)

Adult patients with creatinine clearance less than 5 ml/min

Drug interactions

Generalized seizures have been reported in patients receiving ganciclovir and imipenem/cilastatin. These drugs should not be coadministered unless the potential benefit outweighs the risk of complications.

The administration of imipenem/cilastatin is accompanied by a decrease in the serum concentration of valproic acid with an associated risk of increased seizure activity (cases reported in clinical practice), therefore, during treatment with Prepenem ® Monitoring serum concentrations of valproic acid is recommended.

Let's prepenem ® should not be mixed in the same syringe with other antibiotics, while simultaneous but isolated administration with other antibiotics (aminoglycosides) is allowed.

Concomitant administration of antibiotics with warfarin may increase the anticoagulant effect of the latter. There are numerous reports of an increase in the anticoagulant effect of oral anticoagulants, including warfarin, in patients receiving antibiotics at the same time. Risks may vary depending on the type of infection, age and general condition of the patient, so the contribution of the antibiotic to the increase in INR (international normalized ratio) is difficult to assess. It is recommended to monitor the INR, especially frequently during and immediately after co-administration of antibiotics with oral anticoagulants.

Co-administration of imipenem/cilastatin and probenecid results in a minimal increase in imipenem plasma levels and an increase in its plasma half-life. Urinary recovery of active (unmetabolized) imipenem is reduced by approximately 60% when imipenem/cilastatin is administered with probenecid. Concomitant use of imipenem/cilastatin and probenecid doubles the plasma level of cilastatin and its half-life, but has no effect on its recovery in urine.

special instructions

When selecting imipenem/cilastatin for the treatment of a particular patient, the appropriateness of prescribing a carbapenem must be calculated based on factors such as the severity of the infection, resistance to other antibiotics, and the risk of selecting carbapenem-resistant bacteria.

Increased sensitivity

Serious and sometimes fatal cases of hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam therapy. These reactions are more likely in people with a history of sensitivity to multiple allergens. Before starting treatment with Prepenem ® it is necessary to carefully question the patient regarding previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins and other beta-lactams and allergens (see section “Contraindications”).

Treatment should be discontinued immediately if an allergic reaction to Prepenem occurs. ® . Serious anaphylactic reactions require immediate emergency treatment.

From the liver

Liver function should be carefully monitored during treatment with Prepenem. ® due to the risk of developing liver toxicity (for example, increased transaminases, development of liver failure and fulminant hepatitis).

When prescribing Prepenem ® in patients with liver disease, it is necessary to monitor liver function during treatment. Adjust Prepenem dosage ® optional (see section “Method of application”).

Hematology

During treatment with Prepenem ® a positive Coombs test (direct or indirect) may develop.

Antibacterial spectrum

Before starting empirical treatment, it is necessary to take into account the antibacterial spectrum of Prepenem ® , especially in conditions that threaten the patient’s life. In addition, caution should be exercised when prescribing Prepenem ® due to the limited susceptibility of specific pathogens causing, for example, bacterial infections of the skin and soft tissues. Let's prepenem ® should not be prescribed for the treatment of such infections until the pathogen has been identified, positive sensitivity to it has been determined, and there is a high probability that the pathogen will respond to treatment. Concomitant administration of an appropriate anti-MRSA agent may be necessary if MRSA infection is suspected or there is evidence indicated in the indications for use. Concomitant use of Prepenem ® and aminoglycoside may be indicated if an infection caused by Pseudomonas aeruginosa is suspected or there is evidence of the presence of the indications approved in this instruction (see section “Indications for use”).

Interaction with valproic acid

Concomitant use of Prepenem ® and valproic acid/sodium valproate is not recommended (see section “Drug Interactions”).

Clostridium difficile

When prescribing Prepenem ® As with almost all antibiotics, antibiotic-associated and pseudomembranous colitis have been reported, the severity of which varies from mild to life-threatening. It is important to keep this diagnosis in mind in patients who develop diarrhea during or after use of Prepenem ® (see section "Side effects"). For this category of patients, it is necessary to consider the possibility of discontinuing Prepenem therapy. ® and prescribing specific treatment for Clostridium difficile. It is not recommended to prescribe medications that inhibit intestinal motility.

Kidney failure

Let's prepenem ® may accumulate in patients with reduced renal function and cause adverse reactions from the central nervous system if the dose of the antibiotic is inadequate (see section “Method of Administration”)

central nervous system

Adverse reactions from the central nervous system such as myoclonic activity, convulsions, disorientation, confusion, which occurred when the recommended doses were exceeded, calculated on the basis of creatinine clearance and the patient’s body weight, were identified. These adverse reactions have been reported more frequently in patients with central nervous system disorders (eg, brain damage or a history of seizures) and/or renal impairment, in whom accumulation of administered doses may occur. In this regard, it is recommended to strictly adhere to the calculations of dosages of drug administration in these categories of patients (see section “Method of administration and doses”). It is necessary to continue anticonvulsant therapy in patients who have already had a seizure disorder.

Particular caution should be exercised in children with neurological symptoms and a history of seizures, especially those with known risk factors for seizures or concomitant treatment with drugs that lower the seizure threshold.

If minor tremor, clonic convulsions or seizures occur, an urgent consultation with a neurologist is necessary to prescribe anticonvulsant therapy. If CNS symptoms continue, the dose of Prepenem ® the drug should be reduced or completely stopped.

Patients with creatinine clearance ≤5 ml/min/1.73 m2 should not receive Prepenem ® , unless hemodialysis was performed within 48 hours. For patients on hemodialysis, imipenem/cilastatin is recommended only if the benefit outweighs the potential risk of seizures (see Dosage and Administration).

Pediatric population

Let's prepenem ® 500 mg/500 mg contains 37.5 mg sodium (1.6 mmol), which should be taken into account when calculating sodium content when choosing a diet.

Pregnancy and lactation

Pregnancy

There are no reliable controlled studies on the use of imipenem/cilastatin in pregnant women.

Studies in pregnant monkeys have shown the presence of reproductive toxicity. The potential risk to humans is unknown.

Let's prepenem ® should be used during pregnancy only if the benefit to the mother justifies the potential risk to the fetus.

Breast-feeding

Imipenem/cilastatin is found in human breast milk in small quantities. If the use of Prepenem ® is considered necessary, it is necessary to compare the balance between the benefits of feeding and the possible risk for the child

Fertility

There are no data regarding the potential effects of imipenem/

cilastatinan affects the fertility of men or women.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Clinical studies have not been conducted to study the effect of the drug on the ability to drive vehicles. However, given the possibility of side effects (development of hallucinations and drowsiness) during treatment with Prepenem ® , you need to take special care when driving a car and working with potentially dangerous mechanisms.

Overdose

Symptoms: increased side effects of the drug, which may include: convulsions, confusion, tremor, nausea, vomiting, hypotension, bradycardia.

Treatment: There is no specific information on the treatment of overdose with imipenem/cilastitin. The drug is eliminated during hemodialysis, but the effectiveness of this procedure in case of drug overdose is unknown.

Release form and packaging

500 mg of active substances are placed in vials hermetically sealed with rubber stoppers, crimped with aluminum caps or combined “FLIPP OFF” caps.

A label made of label or writing paper, or an imported self-adhesive label is affixed to each bottle. Each bottle, together with approved instructions for medical use in the state and Russian languages, is placed in a cardboard pack.

It is allowed to place the text from the approved instructions for medical use in the state and Russian languages ​​on the pack.

Storage conditions

Store in dry place, protected from light, at a temperature not

above 25 °C.

Keep out of the reach of children!

Shelf life

Do not use after expiration date.

Conditions for dispensing from pharmacies

On prescription

Manufacturer

Registration Certificate Holder

JSC "Khimpharm", Republic of Kazakhstan

Address of the organization that accepts claims from consumers regarding the quality of products (products) on the territory of the Republic of Kazakhstan

JSC "Khimpharm", Shymkent, Republic of Kazakhstan,

st. Rashidova, 81, t/f: 560882

Phone number 7252 (561342)

Fax number 7252 (561342)

E-mail address [email protected]

Attached files

060667411477976385_ru.doc	159.5 kb
588601521477977580_kz.doc	197.5 kb