Index of drugs

Treatment of the following infections in adults and children aged 1 year and older: complicated intra-abdominal infections; severe pneumonia, including nosocomial and pneumonia associated with the use of a ventilator; intestinal and postnatal infections; complicated urinary tract infections; complicated skin and soft tissue infections. It can be used to treat patients with neutropenia who have a fever likely caused by a bacterial infection. Treatment of patients with bacteraemia that occurs in connection with the infections mentioned above or is suspected to be associated with these infections. The official guidelines for the correct use of antibacterial drugs should be taken into account.

1 vial contains 500 mg imipenem (as a monohydrate) and 500 mg of cilastatin (as a sodium salt); the drug contains sodium: 37.5 mg in 1 vial.

An antibacterial drug - a combination of a β-lactam antibiotic (imipenem) with cilastatin in a 1: 1 weight ratio. The mechanism of bactericidal action of imipenem is based on inhibition of wall synthesis of Gram-positive and Gram-negative bacteria as a result of binding to penicillin-binding proteins. Imipenem is resistant to hydrolysis by most β-lactamases, including penicillinases and cephalosporinases produced by Gram-positive and Gram-negative bacteria, except for relatively rare carbapenem-β-lactamases that hydrolyse. However, it breaks down the renal dehydropeptidase-I, which is a competitive, reversible and specific inhibitor of cylastatine. The combination of cylastatin and imipenem protects the antibiotic against inactivation. Species usually sensitive to imipenem - Gram-positive aerobic bacteria:Enterococcus faecalis, Staphylococcus aureus (sensitive to methicillin),staphylococcuscoagulase-negative (sensitive to methicillin),Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, groupStreptococcus viridans (green-necked streptococcus); Gram-negative aerobic bacteria:Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Serratia marcescens; Gram-positive anaerobic bacteria:Clostridium perfringens, Peptostreptococcus spp.; Gram-negative anaerobic bacteria: groupBacteroides fragilis, Fusobacterium spp., Porphyromonas asaccharolytica, Prevotella spp., Veillonella spp. Species with acquired resistance:Acinetobacter baumannii, Pseudomonas aeruginosa. Species with congenital resistance:Enterococcus faecium, Burkholderia cepacia (some strains),Legionella spp., Stenotrophomonas maltophilia, Chlamydia spp., Chlamydophila spp., Mycoplasma spp., Ureaplasma urealyticum. All methicillin-resistant staphylococci are resistant to imipenem and cilastatin. Imipenem binds to approximately 20% of plasma proteins. When used alone, it is metabolised in the kidneys with dehydropeptidase-I. Cylastatin is a specific inhibitor of dehydropeptidase-I and effectively inhibits the metabolism of imipenem, therefore the concomitant administration of imipenem and cilastatin allows the therapeutic concentrations of antibiotics to be achieved in both urine and plasma. T_0,5 imipenem in plasma is about 1 hour. Imipenem is excreted in the urine, mainly unchanged; partly in the form of inactive metabolites. Cylastatin binds to plasma proteins in approximately 40%. T_0,5 cilastatin in plasma is about 1 hour. Cylapatin is excreted in the urine, mainly unchanged; partly in the form of an N-acetyl metabolite, the dehydropeptidase activity of which is comparable to the effect of cilastatin. Dehydropeptidase-I activity in kidneys returns to normal shortly after elimination of cilastatin from the bloodstream.

Hypersensitivity to imipenem, other carbapenems, cilastatin or any of the excipients. A history of a severe hypersensitivity reaction to any β-lactam antibiotic (eg penicillin or cephalosporins).

Specified microorganisms that cause e.g.bacterial skin and soft tissue infections have limited sensitivity to imipenem with cilastatin. The use of imipenem with cilastatin is not suitable for the treatment of these infections, unless a type of pathogenic microorganism has already been documented and known to be susceptible to these antibiotics or it is very likely that the micro-organisms that cause the infection will be sensitive to this therapy. If it is suspected or found that the infection has caused a methicillin-resistant strainStaphylococcus aureus (MRSA), the approved indications may be appropriate for the concomitant use of an appropriate anti-MRSA drug. If you suspect or find an infectionPseudomonas aeruginosain the approved indications, it may be appropriate to use the aminoglycoside antibiotic together. The drug is not recommended for the treatment of meningitis. In any patient who has experienced diarrhea due to the use of an antibiotic, the possibility of pseudomembranous colitis should be considered; if this disease is diagnosed, discontinuation of the preparation and treatment of infections should be consideredClostridium difficile. Before administering the drug, make sure that the patient is not allergic to β-lactam antibiotics or other allergens, due to the possibility of anaphylactic reactions. In the event of a severe hypersensitivity reaction, the antibiotic should be discontinued, adrenaline or other rescue procedures may be required. Hepatic function should be closely monitored during treatment due to the risk of hepatotoxicity, particularly in patients with liver disease. Due to the risk of side effects regarding o.u.n. (myoclonus, convulsions, confusion), cautiously used in patients with o.u.n. (eg, changes in the brain or seizures) and / or impaired renal function - it is advisable to strictly follow the recommended dosing regimen in order to prevent the accumulation of given doses, especially in these groups of patients. In patients with convulsive disorders, anticonvulsant therapy should be continued. Special attention should be paid to neurological symptoms or convulsions in children who have risk factors for seizures or who are taking concomitant medications that lower the seizure threshold. If focal tremors, myoclonus or convulsions occur, a neurological examination should be performed and anticonvulsant treatment should be instituted if it has not been previously used. If symptoms from o.u.n. persist, reduce the dose of antibiotic or stop using it. Do not use the preparation in patients with a creatinine clearance of ≤5 ml / min / 1.73 m²if they are not subjected to hemodialysis within the Next 48 hours. In hemodialysis patients, the drug is only recommended if the benefits of the medicine outweigh the risk of seizures. The preparation is not recommended for use in children up to 1 year of age or in children with impaired renal function (serum creatinine ≥ 2 mg / dl). Sodium content: 37.5 mg (1.6 mEq) sodium per 1 vial should be taken into account in patients who are controlling the sodium content of the diet.

During pregnancy, use only if the potential benefits outweigh the risk to the fetus. Imipenem and cilastatin are penetrated in a small amount to human breast milk. After oral administration, each component of the drug is absorbed to a small extent. Therefore, it is unlikely that a breast-fed child will be exposed to the drug to a significant extent. If the use of the drug is considered necessary, the benefit of breastfeeding should be weighed against the risk to the child.

Common: eosinophilia, thrombophlebitis, diarrhea, vomiting, nausea, rash (eg, sputum), increase in transaminases, alkaline phosphatase. Uncommon: pancytopenia, neutropenia, leukopenia, thrombocytopenia, thrombocytosis, psychiatric disorders (including hallucinations and confusion), convulsions, myoclonus, dizziness, drowsiness, hypotension, urticaria, pruritus, fever, pain and induration at the injection site, erythema at the injection site, positive Coombs test, prolonged prothrombin time, decreased hemoglobin, increased bilirubin in the blood, increased blood creatinine, increased blood urea nitrogen.Rare: pseudomembranous colitis, candidiasis, agranulocytosis, anaphylactic reactions, encephalopathy, paresthesia, focal throats, change of taste, hearing loss, tooth discoloration and / or tongue, liver failure, hepatitis, toxic epidermal necrolysis, angioneurotic edema, syndrome Stevens-Johnson, erythema multiforme, exfoliative dermatitis, acute renal failure, oliguria or anuria, polyuria, change in urine (harmless). Very rare: gastroenteritis, haemolytic anemia, bone marrow suppression, worsening of myasthenia gravis, headache, labyrinthine dizziness, tinnitus, cyanosis, tachycardia, palpitations, hot flushes, shortness of breath, hyperventilation, sore throat, hemorrhagic fever colon, abdominal pain, heartburn, tongue inflammation, hypertrophy of the tongue warts, increased salivation, fulminant hepatitis, excessive sweating, changes in skin structure, polyarticular pain, thoracic spine pain, vulvar itching, chest discomfort, weakness.

Intravenously.Adults and adolescents: (500 mg + 500 mg) every 6 h or (1000 mg + 1000 mg) every 8 h or every 6 h. If it is suspected or found that the infection is caused by less sensitive species of bacteria (e.g.Pseudomonas aeruginosa) or the infection is very severe (eg in patients with febrile neutropenia), it is recommended to administer the dose (1000 mg + 1000 mg) every 6 hours. In patients with a <70 kg should be reduced by the formula - (actual body x standard dose): 70 kg. Do not exceed the maximum total dose (4000 mg + 4000 mg) / day.Children aged ≥ 1 year: (15 mg + 15 mg) or (25 mg + 25 mg) / kg every 6 h. If it is suspected or confirmed that the infection is caused by less sensitive species of bacteria (e.g.Pseudomonas aeruginosa) or the infection is very severe (eg in children with febrile neutropenia), the dose (25 mg + 25 mg) / kg should be administered. every 6 hours.Special groups of patients. In patients with bw ≥70 kg (adults and adolescents) with renal impairment (creatinine clearance ≤70 ml / min / 1.73 m²) recommended daily doses resulting from the severity of infection should be adjusted for creatinine clearance (CCr). For a total daily dose in patients with normal renal function of 2000 + 2000, the following dosage should be used: CCr 41-70 ml / min / 1.73 m²500 + 500 every 8 hours; CCr 21-40 ml / min / 1.73 m²250 + 250 every 6 h; CCr 6-20 ml / min / 1.73 m²250 + 250 every 12 h. For the total daily dose in patients with normal kidney function of 3000 + 3000, the following dosage should be used: CCr 41-70 ml / min / 1.73 m²500 + 500 every 6 hours; CCr 21-40 ml / min / 1.73 m²500 + 500 every 8 hours; CCr 6-20 ml / min / 1.73 m²: 500 + 500 every 12 h. For the total daily dose in patients with normal renal function of 4000 + 4000, the following dosage should be used: CCr 41-70 ml / min / 1.73 m²: 750 + 750 every 8 hours; CCr 21-40 ml / min / 1.73 m²500 + 500 every 6 hours; CCr 6-20 ml / min / 1.73 m²: 500 + 500 every 12 h. In patients with b. <70 kg should be reduced dose proportionally. A dose proportional to patients with bw. <70 kg can be calculated by dividing the real month. patient (in kg) for 70 kg and multiplying the result by the appropriate dose in accordance with the indications given above. Patients with CCr ≤5 ml / min / 1.73 m² you can only give your medicine if you are going hemodialysis within the next 48 hours. Patients undergoing dialysis, with CCr ≤5 ml / min / 1.73 m² it is recommended to administer such doses of the drug as to patients with CCr 6-20 ml / min / 1.73 m². Since both imipenem and cilastatin are removed from the bloodstream during hemodialysis, patients should be given hemodialysis and then every 12 hours after the hemodialysis session. Currently available clinical data are insufficient to recommend the use of the drug to patients undergoing peritoneal dialysis. Clinical data are inadequate for a dose recommendation in children with impaired renal function (serum creatinine ≥2 mg / dl). In patients with hepatic and elderly dysfunction, no dosage adjustment is necessary.
Before administration, the drug should be dissolved and then diluted. Each dose ≤ (500 mg + 500 mg) should be given as an intravenous infusion over 20-30 min; each dose> (500 mg + 500 mg) should be given as an infusion lasting 40-60 min.If you get sick during the infusion, you can reduce the infusion rate.