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

Active substances: imipenem monohydrate 530.0 mg in terms of imipenem anhydrous - 500.0 mg; cilastatin sodium 530.0 mg in terms of cilastatin - 500.0 mg.

Excipient: sodium carbonate anhydrous 20.0 mg

Description:Powder from white to light yellow color.

Pharmacotherapeutic group:antibiotic-carbapenem + dehydropeptidase blocker

ATX: & nbsp

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

Pharmacodynamics:

Aquapenem consists of two components: imipenem, the first representative of a new class of beta-lactam antibiotics, tienamycins, and cilastatin, a specific enzyme inhibitor that inhibits the metabolism of imipenem in the kidneys and significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastatin does not have its own antibacterial activity, it does not inhibit beta-lactamase of bacteria.

Aquapenem suppresses the synthesis of the cell wall of bacteria and has a bactericidal effect against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic.

The drug's resistance to degradation by bacterial beta-lactamase makes it effective against many microorganisms, such as Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, which are resistant to most beta-lactam antibiotics, as well as anaerobes (Bacteroides fragilis).The antibacterial spectrum includes virtually all clinically relevant pathogens.

It is active against the following in vitro of microorganisms, as well as in vivo: Gram-negative aerobes: 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 aerobes: Enterococcus faecalis, Staphylococcus aureus (including strains forming penicillinase), Staphylococcus epidermidis (including strains forming penicillinase), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes;

Gram-negative anaerobes: Bacteroides spp., including Bacteroides fragilis, Fusobacterium spp .;

Gram-positive anaerobes: Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp .; Imipenem has a bactericidal effect in vitro on the following microorganisms: Gram-positive aerobes: Bacillus spp, Listeria monocytogenes, Nocardia spp, Staphylococcus saprophyticus, Streptococcus group C, G and group viridans;.. . Gram-negative aerobes: Aeromonas hydrophila, Alcaligenes spp, Capnocytophaga spp, Haemophilus ducreyi, Neisseria gonorrhoeae, including strains forming penicillinase, Pasteurella spp, Providencia stuartii;..

Gram-negative anaerobes: Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Veillonella spp .;

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

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

Pharmacokinetics:

The maximum concentration (Cmax) of imipenem in intravenous (iv) administration in a dose of 250, 500 or 1000 mg is achieved within 20 minutes - 14-24, 21-58 and 41-83 μg / ml, respectively.Cmax of cilastatin with iv administration at a dose of 250, 500 or 1000 mg is achieved within 20 minutes - 15-25, 31-49 and 56-80 mcg / ml. Connection with plasma proteins of imipenem - 20%, cilastatin - 40%. Quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids and reproductive organs. In low concentrations it is found in the cerebrospinal fluid (CSF). The volume of distribution in adults is 0.23-0.31 l / kg, in children 2-12 years - 0.7 l / kg, in newborns - 0.4-0.5 l / kg.

Blocking tubular secretion of imipenem with cilastatin results in inhibition of its renal metabolism and accumulation in the urine in unchanged form. Cilastatin is metabolized to the N-acetyl compound. With IV introduction, the half-life (T1 / 2) of imipenem and cilastatin in adults is -1 h, in children 2-12 years -1-1.2 h, in infants T1 / 2 imipenem - 1.7-2.4 h, cilastatin - 3.8-8.4 h; if the renal function T1 / 2 imipenem is disrupted - 2.9-4 h, cilastatin -13.3-17.1 h.

It is excreted mainly by the kidneys (70-76% within 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3); 1-2% is excreted by the gastrointestinal tract and 20-25% by the extrarenal route (the mechanism is unknown).Quickly and effectively (73-90%) is removed by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the dose is removed).

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to imipenem:

- Lower respiratory tract infections caused by Streptococcus pneumoniae, Staphylococcus aureus (strains forming penicillinase), Acinetobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Serratia marcescens;

- urinary tract infections (complicated and uncomplicated) caused by Enterococcus faecalis, Staphylococcus aureus (strains forming penicillinase), Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa;

- intra-abdominal infections caused by Enterococcus faecalis, Staphylococcus aureus (strains forming penicillinase), Staphylococcus epidermidis, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp., Pseudomonas aeruginosa, Bifidobacterium spp., Clostridium spp ., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., Including Bacteroides fragilis, Fusobacterium spp .;

- skin and soft tissue infections caused by Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus (strains forming penicillinase), Staphylococcus epidermidis, Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp.,

Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp., Peptococcus spp., Peptostreptococcus spp., Bacteroides spp., Including Bacteroides fragilis, Fusobacterium spp .;

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

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

- endocarditis caused by Staphylococcus aureus (strains forming penicillinase);

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

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

Contraindications:Hypersensitivity to imipenem and / or cilastatin, other carbapenems and beta-lactam antibiotics and other components of the drug, chronic renal failure (creatinine clearance less than 5 ml / min without hemodialysis), early childhood (up to 3 months); in children - severe renal failure (serum creatinine concentration more than 2 mg / dL).

Carefully:Central nervous system diseases, history of seizures, high convulsive readiness, anticonvulsant therapy with valproic acid (decreased effectiveness of therapy), chronic renal failure (CC less than 70 ml / min), patients on hemodialysis, elderly, patients with gastrointestinal diseases a path in the anamnesis (including pseudomembranous colitis).

Pregnancy and lactation:

The use of the drug during pregnancy is permissible only if the possible benefit of treatment for the mother exceeds the potential risk to the fetus. Both imipenem and cilastatin penetrate small amounts in breast milk, therefore, the issue of stopping breastfeeding during treatment with the drug should be resolved.

Dosing and Administration:

Intravenously infuzionalno.

The following doses are calculated for adult patients with a body weight of 70 kg and more and CC 70 ml / min / 1.73 m2 and more. For patients with SC less than 70 ml / min / 1.73 m2 and / or less body weight, the dose should be proportionally reduced. The recommendations for dosing the drug indicate the amount of imipenem to be administered. The introduction is divided into several methods.

The average therapeutic dose for adults (calculation for imipenem) is 1-2 g / day, divided into 3-4 injections; the maximum daily dose is 4 g or 50 mg / kg, depending on which dose is lower. Patients over 12 years with cystic fibrosis were prescribed up to 90 mg / kg / day, but not more than 4 g / day.

Adult patients with mild infection severity - 250 mg 4 times a day (total daily dose of 1 g),average severity - 500 mg 3 times a day or 1 g 2 times a day (total daily dose of 1.5-2 g), severe severity (high-sensitivity strains) - 500 mg 4 times a day (total daily dose of 2 g), with Severe severity (less sensitive strains, primarily Pseudomonas aeruginosa), with an infection that threatens the patient's life, -1 g 3-4 times a day (total daily dose 3-4 g). Every 250-500 mg is administered intravenously for 20-30 minutes, and every 750-1000 mg for 40-60 minutes. If there is nausea during administration, the rate of administration of the drug is reduced.

For the prevention of postoperative infections in adult patients - 1 g during the introductory anesthesia and 1 g - after 3 hours. In the case of surgical intervention with a high risk of infection (operation on the colon and rectum), additionally 500 mg at 8 and 16 h after initial anesthesia.

Adult patients with renal dysfunction (CC less than 70 ml / min / 1.73 sq.m.) or / and body weight less than 70 kg first need to determine the total daily dose, depending on the severity of infection, appropriate for adult patients with a body weight> 70 kg and in the absence of chronic renal failure. Then select the appropriate reduced dose, based on the daily dose, QC and body weight of the patient.

The maximum daily doses for IV administration in adult patients (body weight> 70 kg) with renal insufficiency, depending on the severity of infection and CC values (ml / min / 1.73 m 2):

- The maximum daily dose of 1 g: KK 41-70 ml / min - 250 mg after 8 hours, KK 21-40 ml / min - 250 mg after 12 hours, KK 6-20 ml / min - 250 mg after 12 hours ;

- The maximum daily dose of 1.5 g: KK 41-70 ml / min - 250 mg after 6 hours, KK 21- 40 ml / min - 250 mg after 8 hours, KK 6-20 ml / min - 250 mg after 12 hours ;

- The maximum daily dose of 2 g: KK 41-70 ml / min - 500 mg every 8 hours, KK 21-40 ml / min - 250 mg after 6 hours, KK 6-20 ml / min - 250 mg after 12 hours ;

- The maximum daily dose of 3 g: KK 41-70 ml / min - 500 mg after 6 hours, KK 21-40 ml / min - 500 mg after 8 hours, KK 6-20 ml / min - 500 mg after 12 hours ;

- The maximum daily dose of 4 g: KK 41-70 ml / min - 750 mg after 8 hours, KK 21-40 ml / min - 500 mg after 6 hours, KK 6-20 ml / min - 500 mg after 12 hours .

Below is the dosing regimen for adult patients with renal dysfunction and / or body weight less than 70 kg.

The maximum daily dose of 1.0 g

Body weight, kg

Creatinine clearance, ml / min / 1.73 m²

>71

41-70

21-40

6-20

60-69

250 mg every

8 h

125 mg every

6 hours

250 mg every

12 h

125 mg every

12 h

50-59

125 mg every

6 hours

125 mg every

6 hours

125 mg every

8 h

125 mg every

12 h

40-49

125 mg every

6 hours

125 mg every

8 h

125 mg every

12 h

125 mg every

12 h

30-39

125 mg every

8 h

125 mg every

8 h

125 mg every

12 h

125 mg every

12 h

The maximum daily dose of 1.5 g

Body weight, kg

Creatinine clearance, ml / min / 1.73 m²

>71

41-70

21-40

6-20

60-69

250 mg every

6 hours

250 mg every

8 h

250 mg every

8 h

250 mg every

12 h

50-59

250 mg every

6 hours

250 mg every

8 h

250 mg every

12 h

250 mg every

12 h

40-49

250 mg every

8 h

125 mg every

6 hours

125 mg every

8 h

125 mg every

12 h

30-39

125 mg every

6 hours

125 mg every

8 h

125 mg every

8 h

125 mg every

12 h

The maximum daily dose of 2.0 g

Body weight, kg

Creatinine clearance, ml / min / 1.73 m²

>71

41-70

21-40

6-20

60-69

500 mg every

8 h

250 mg every

6 hours

250 mg every

8 h

250 mg every

12 h

50-59

250 mg every

6 hours

250 mg every

6 hours

250 mg every

8 h

250 mg every

12 h

40-49

250 mg every

6 hours

250 mg every

8 h

250 mg every

12 h

250 mg every

12 h

30-39

250 mg every

8 h

125 mg every

6 hours

125 mg every

8 h

125 mg every

12 h

The maximum daily dose of 3.0 g

Body weight, kg

Creatinine clearance, ml / min / 1.73 m²

>71

41-70

21-40

6-20

60-69

750 mg every

8 h

250 mg every

6 hours

500 mg every

8 h

500 mg every

12 h

50-59

500 mg every

6 hours

250 mg every

6 hours

500 mg every

6 hours

250 mg every

12 h

40-49

500 mg every

8 h

250 mg every

8 h

250 mg every

8 h

250 mg every

12 h

30-39

250 mg every

6 hours

125 mg every

6 hours

250 mg every

8 h

250 mg every

12 h

The maximum daily dose of 4.0 g

Body weight, kg

Creatinine clearance, ml / min / 1.73 m²

>71

41-70

21-40

6-20

60-69

1000 mg every

8 h

750 mg every

8 h

500 mg every

8 h

500 mg every

12 h

50-59

750 mg every

8 h

500 mg every

6 hours

500 mg every

8 h

500 mg every

12 h

40-49

500 mg every

6 hours

500 mg every

8 h

250 mg every

6 hours

250 mg every

12 h

30-39

500 mg every

8 h

250 mg every

6 hours

250 mg every

8 h

250 mg every

12 h

In adults with SC less than 5 ml / min, the drug is used only if at least 48 hours after the infusion of the drug, hemodialysis is performed. The introduction of the drug to such patients is recommended only in cases when the benefit from its use exceeds the potential risk of seizures. In the treatment of adult patients with SC less than 5 ml / min on hemodialysis, doses should be used for adult patients with a CC of 6-20 ml / min and / or a body weight of less than 70 kg. The drug is administered after a hemodialysis session and then at 12-hour intervals from the end of the procedure, with careful monitoring of adult patients (especially if they have central nervous system diseases).

At present, there is insufficient data to recommend the use of the drug to adult patients on peritoneal dialysis.

At present, there is insufficient data on the dosing regimen for preoperative prophylaxis of adult patients with SC less than 70 ml / min / 1.73 sq.m.

Considering the characteristic of older patients reduced function of the cardiovascular system, liver, kidney, and the presence of concomitant illnesses and concomitant drug therapy, should be in dose selection adhere lower boundaries of the recommended doses. The state of the kidneys in elderly patients can not be fully determined only on the basis of measuring the level of residual blood nitrogen or creatinine. To determine the dosage of such patients, it is recommended to determine the clearance of creatinine.

Children with a body weight of 40 kg and more - the same dose as an adult.

Children older than 3 months and with a body weight of less than 40 kg - 15 mg / kg 4 times a day; the maximum daily dose is 2 g.

Rules for the preparation of solution

To prepare the infusion solution, the following solvents: 0.9% sodium chloride solution, 5% dextrose solution, 10% dextrose, 5% dextrose and 0.9% sodium chloride solution, 5% dextrose and 0.45% sodium chloride solution, 5% dextrose solution and 0.225% sodium chloride solution, 5% dextrose solution and 0.15% potassium chloride solution, 5% and 10% mannitol solution in a ratio of 500 mg imipenem to 100 ml solvent.The concentration of imipenem in the resulting solution is 5 mg / ml.

Vials with a capacity of 20 ml

When using the drug in vials of 20 ml capacity, the contents of the vial are previously dissolved in 10 ml of a suitable solvent. The resulting solution can not be used for administration!

After dilution, the solution is shaken well, after which it is transferred to a vial or container with the rest of the solvent (90 ml). The total volume of the solvent is 100 ml. For the complete transfer of the drug (remnants of the drug on the walls of the vial with a capacity of 20 ml), add 20 ml of the previously obtained solution to the vial, shake well and re-transfer to a vial or container with the solution already obtained. Only after this, the solution is ready for use. The concentration of imipenem in the resulting solution is 5 mg / ml.

Vials with a capacity of 100 ml

When using the drug in vials of 100 ml capacity, the contents of the vial are dissolved in 100 ml of a suitable solvent. The concentration of imipenem in the resulting solution is 5 mg / ml.

Side effects:

From the central nervous system: encephalopathy, tremor, confusion, myoclonia, paresthesia, vertigo, headache, mental disorders, including hallucinations, convulsions.

From the urinary system: oliguria, anuria, polyuria, proteinuria, erythrocyturia, leukocyturia, cylindruria, increased bilirubin concentration in urine and a change in urine color, increased plasma concentrations of urea nitrogen and creatinine, acute renal failure.

From the gastrointestinal tract: nausea, vomiting, diarrhea, pseudomembranous colitis, hemorrhagic colitis, hepatitis (including fulminant), hepatic insufficiency, jaundice, gastroenteritis, abdominal pain, glossitis, tongue hypertrophy, dental or language staining, sore throat, hypersalivation, heartburn.

On the part of the organs of hematopoiesis and the system of hemostasis: pancytopenia, oppression of bone marrow hematopoiesis, hemolytic anemia, eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, leukocytosis, basophilia, hemoglobin and hematocrit decrease, prothrombin time lengthening.

Laboratory indicators: increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, increased concentration of low-density lipoproteins, false positive Coombs direct test, hyponatremia, hyperkalemia, hypochloraemia.

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

From the sense organs: hearing loss, ringing in the ears, a violation of taste.

On the part of the respiratory system: a feeling of discomfort in the chest, shortness of breath, hyperventilation.

From the cardiovascular system: palpitation, tachycardia.

Local reactions: skin hyperemia, painful infiltration at the injection site, phlebitis / thrombophlebitis, infection at the injection site, vein tightening.

Other: Candidiasis, cyanosis, hyperhidrosis, pain in the thoracic spine.

Overdose:Symptoms: increased dose-related side effects. In case of an overdose, it is recommended to cancel the drug, the appointment of symptomatic and maintenance therapy. Imipenem and cilastatin are excreted by hemodialysis. However, the effectiveness of this procedure with an overdose of the drug is unknown.

Interaction:

The drug is pharmaceutically incompatible with lactic acid (lactate) and should not be prepared on the basis of solvents containing it.However, intravenously, the drug can be administered via the same infusion system as the lactate-containing solution. With simultaneous application with penicillins and cephalosporins, a cross-allergy is possible; shows antagonism in relation to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

With simultaneous use with ganciclovir, the risk of developing generalized seizures increases. These drugs can not be used at the same time, except when the potential benefits exceed the possible risk.

Drugs that block tubular secretion, slightly increase the concentration in the plasma and T1 / 2 imipenem (if high concentrations of imipenem are required, it is not recommended to use these medicines at the same time).

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

The drug should not be mixed in one syringe with other antibiotics,while simultaneous - isolated - administration with other antibiotics (aminoglycosides) is allowed.

Special instructions:

Intravenous route of administration is preferable to use in the initial stages of therapy of bacterial septicemia, endocarditis, severe and life-threatening infections, including lower respiratory tract infections caused by Pseudomonas aeruginosa, and in case of severe complications. Not recommended for the treatment of meningitis.

Stains urine in a reddish color (it is safe and should not be mistaken for hematuria).

Before the start of therapy, a thorough anamnesis should be made about the previous allergic reactions to beta-lactam antibiotics. When developing an allergic reaction, the drug should be immediately discontinued.

People with a history of gastrointestinal disease (especially colitis) have an increased risk of developing pseudomembranous colitis. Therapy with antiepileptic drugs in patients with brain injuries or seizures in history should continue throughout the treatment period with the drug (to avoid side effects from the central nervous system).

It should be borne in mind that elderly patients are likely to have age-related renal dysfunction, which may require a dose reduction. It is advisable to monitor the excretory function of the kidneys.

With the use of the drug, both on the background of taking and 2-3 weeks after the treatment is stopped, the development of diarrhea caused by Clostridium difficile (pseudomembranous colitis) is possible. In mild cases, it is sufficient to discontinue treatment and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole. Do not use drugs that inhibit the intestinal motility. The preparation contains 37.5 mg of sodium (1.6 mEq) per 1 vial.

As with other beta-lactam antibiotics, Pseudomonas aeruginosa can quickly acquire resistance to imipenem. Therefore, during the treatment it is necessary to periodically determine the sensitivity of Pseudomonas aeruginosa to the antibiotic according to the clinical situation.

In order to prevent the development of resistance and maintain the effectiveness of imipenem in clinical practice, the drug should be used only for the treatment of infections caused by proven (or suspected) susceptible to imipenem microorganisms.

Effect on the ability to drive transp. cf. and fur:Given the likelihood of side effects from the central nervous system, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions. When there are side effects from the central nervous system should refrain from performing these activities.

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

Packaging:

The amount of the drug, corresponding to 500 mg of imipenem and 500 mg of cilastatin, in a vial of clear glass with a capacity of 20 ml or 100 ml, sealed with a stopper of chlorobutyl rubber, crimped with an aluminum ring.

1 bottle with instructions for use in a pack of cardboard.

By 5, 10 or 50 bottles with an equal number of instructions for use in a cardboard box (for hospitals).

Storage conditions:

Keep in dry the dark place at a temperature of no higher than 25 0 C. Keep out of reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002698

Date of registration:07.11.2014

The owner of the registration certificate:Aquarium EnterpriseAquarium Enterprise India

Manufacturer: & nbsp

Representation: & nbspARS, LLCARS, LLC

Information update date: & nbsp30.06.2015

Illustrated instructions

Instructions

Aquapenem (Aquapenem)