Imipenem and Cilastatin, 500 mg+500 mg 20 ml 10 pcs.

A broad spectrum beta-lactam antibiotic. Inhibits synthesis of the bacterial cell wall and has bactericidal effect against a wide range of Gram-positive and Gram-negative microorganisms, aerobic and anaerobic.

Imipenem is a derivative of thienamycin and belongs to the group of carbapenems.

Cilastatin sodium inhibits dehydropeptidase, the enzyme that metabolizes imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastatin has no intrinsic antibacterial activity and does not inhibit β-lactamase of bacteria.

The drug is active against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis. It is resistant to degradation by bacterial β-lactamase, which makes it effective against many microorganisms such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp. that are resistant to most beta-lactam antibiotics. The antibacterial spectrum includes almost all clinically relevant pathogens.

Active against Gram-negative aerobic 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. Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp.Klebsiella oxytoca, Klebsiella ozaenae, Klebsiella pneumoniae), Moraxella spp, Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Yersinia spp.Yersinia multocida, Yersinia enterocolitica, Yersinia pseudotuberculosis; Plesiomonas shigelloides, Proteus spp. (including Proteus mirabilis, Proteus vulgaris), Providencia spp. Providencia alcalifaciens, Providencia rettgeri (formerly Proteus rettgeri), Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, Pseudomonas stutzeri), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens, Serratia proteamaculans), Shigella spp; positive aerobic bacteria: Bacillus spp, Enterococcus faecalis, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Nocardia spp, Pediococcus spp, Staphylococcus aureus (including penicillinase strains), Staphylococcus epidermidis (including penicillinase strains), Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus group C, Streptococcus group G, green streptococci including alpha- and gamma-hemolytic strains); Gram-negative anaerobic bacteria: Bacteroides spp. (including. Bacteroides distasonis, Bacteroides fragilis, Prevotella melaninogenica (formerly Bacteroides melaninogenicus), Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus), Bilophila wadsworthia, Fusobacterium spp. (Fusobacterium necrophorum, Fusobacterium nucleatum), Porphyromonas asaccharolytica (previously Bacteroides asaccharolyticus), Prevotella bivia (previously Bacteroides bivius), Prevotella disiens (previously Bacteroides disiens), Prevotella intermedia (previously Bacteroides intermedius), Veillonella spp; Gram-positive anaerobic bacteria: Actinomyces spp, Bifidobacterium spp., Clostridium spp. (including Clostridium perfringens), Eubacter spp., Lactobacillus spp., Microaerophilic streptococcus, Mobiluncus spp, Peptostreptococcus spp., Propionibacterium spp. (including Propionibacterium acne); other microorganisms: Mycobacterium fortuitum, Mycobacterium smegmatis.

Some Staphylococcus spp. (resistant to methicillin), Streptococcus spp. (group D), Stenotrophomonas maltophilia, Enterococcus faecium and some strains of Pseudomonas cepacia are insensitive to imipenem. Effective against many infections caused by bacteria resistant to cephalosporins, aminoglycosides, penicillins. In vitro it acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.

Indications

How to take, the dosage

Intravenous drip. The doses given below are for a body weight of 70 kg or more and a CK of 70 ml/min/1.73 sq.m or more. For patients with a CKR less than 70 ml/min/1.73 sq.m. and/or lower body weight, the dose should be proportionally reduced.

The average therapeutic dose for adults (imipenem calculation) when administered by IV is 1-2 g/day divided into 3-4 injections; the maximum daily dose is 4 g or 50 mg/kg, whichever is lower.

For patients with mild infection, 250 mg 4 times/day; for moderate infection, 500 mg 3 times/day or 1 g 2 times/day; for severe infection, 500 mg 4 times/day; for life-threatening infection, 1 g 3-4 times/day.

The dose of imipenem less than or equal to 500 mg should be administered by IV within 20-30 minutes. Doses over 500 mg should be administered by IV for 40-60 minutes. Patients who experience nausea during infusion should slow down the rate of infusion.

For prophylaxis of postoperative infections it is 1 g during the introduction anesthesia and 1 g after 3 hours. In case of surgical interventions with high risk of infection development (colorectal surgery) 500 mg is administered additionally in 8 and 16 hours after general anesthesia.

The maximum daily doses for IV administration in patients with renal insufficiency depending on the severity of infection and CK values (ml/min/1.73 sq.m) and body weight ≥70 kg:

b) Maximum daily dose 1.5 g

c) Maximum daily dose 2 g

d) Maximum daily dose 3 d

Body weight (kg) Creatinine clearance (ml/min/173 sq.m) ≥71 41-70 21-40 6-20 By 250 mg every 6 h By 250 mg every 12 h 40-49 By 500 mg every 8 h By 250 mg every 6 h By 250 mg every 8 h By 250 mg every 12 h 30-39 By 250 mg every 6 h By 250 mg every 8 h 250 every 8 hours 250 every 12 hours

e) Maximum daily dose 4 g

Body weight (kg) Creatinine clearance (ml/min/173 sq.m) ≥71 41-70 21-40 6-20 By 500 mg every 8 h By 250 mg every 6 h By 250 mg every 12 h 30-39 By 500 mg every 8 h By 250 mg every 6 h By 250 every 8 h By 250 every 12 h

There is currently insufficient data to recommend use of the drug in patients on peritoneal dialysis.

Children weighing 40 kg or more are prescribed the same doses as adults. For children older than 3 months and with a body weight less than 40 kg – 15 mg/kg 4 times/day; the maximum daily dose is 2 g.

Preparation of solution for intravenous infusion

Imipenem+cilastatin for intravenous infusion must not be mixed or added to other antibiotics.

The following solvents are used for preparation of the infusion solution: 0.9% sodium chloride solution, 5% aqueous dextrose solution, 10% aqueous dextrose solution, 5% dextrose solution and 0.9% sodium chloride solution. In the ratio of 100 ml of solvent and 500 mg of imipenem. The concentration of imipenem in the resulting solution is 5 mg/ml.

Vials with a capacity of 20 ml and 30 ml

When using the drug in vials with a capacity of 20 ml or 30 ml, the contents of the vial should be dissolved in 10 ml of a suitable solvent.

The resulting solution must not be used for injection!

The solution is shaken well and then transferred to a vial or container with the remaining part of the solvent (90 ml). The total volume of the solvent is 100 ml. For complete transfer of the drug: 20 ml of the previously obtained solution is added to the vial, shaken well and transferred back to the vial or container with the already obtained solution. Only then is the solution ready for use.

Interaction

Pharmaceutically incompatible with lactic acid salt, other antibacterial drugs.

In concomitant use with penicillins and cephalosporins cross-allergy is possible; shows antagonism to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

Hanciclovir increases the risk of generalized seizures.

Drugs that block tubular secretion slightly increase plasma and T1/2 concentrations of imipenem (if high concentrations of imipenem are required, concomitant use of these drugs is not recommended).

Contraindications

For suspension in case of intravenous injection prepared with lidocaine hydrochloride as a solvent:

With caution: CNS diseases, lactation, advanced age.

Side effects

CNS and peripheral nervous system disorders: myoclonia, psychiatric disorders, hallucinations, confusion, epileptic seizures, paresthesias.

Urinary system disorders: oliguria, anuria, polyuria, acute renal failure (rare).

In the digestive system: nausea, vomiting, diarrhea, pseudomembranous enterocolitis, hepatitis (rare).

Hematopoietic and hemostatic system disorders: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, decrease of hemoglobin, prolongation of prothrombin time, positive Coombs reaction.

Laboratory tests: increase of liver transaminases and alkaline phosphatase activity, hyperbilirubinemia, hypercreatininemia, increased concentration of urea nitrogen; direct positive Coombs test.

Allergic reactions: skin rash, pruritus, urticaria, erythema multiforme (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis (rare), exfoliative dermatitis (rare), fever, anaphylactic reactions.

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

Others: candidiasis, taste disorders.

Overdose

Symptoms: there may be increased side effects.

The treatment is symptomatic. Imipenem and cilastatin are subjected to hemodialysis. However, the effectiveness of this procedure in case of drug overdose is unknown.