AQUAPENEM (AQUAPENEM) 
Universal reference book for medicines
Product name: AQUAPENEM (AQUAPENEM)

Active substance: cilastatin, imipenem

Type: Carbapenem Group Antibiotic

Manufacturer: РђР РЎ (Russia) produced by AQUARIUS ENTERPRISES (India)
Composition, form of production and packaging
Powder for solution for infusions
from white to light yellow color.

1 f.

imipenem monohydrate 530 mg,

which corresponds to the content of imipenem 500 mg

cilastatin sodium 530 mg,

which corresponds to the content of cilastatin 500 mg

Excipients: sodium carbonate anhydrous - 20 mg.

bottles (1) - packs of cardboard.

bottles (5) - cardboard boxes (for hospitals).

bottles (10) - cardboard boxes (for hospitals).

bottles (50) - cardboard boxes (for hospitals).

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

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, does not inhibit? -lactamase 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 ОІ-lactamase makes it effective against many microorganisms such as Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Serratia spp., Enterobacter spp., 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 microorganisms in vitro, as well as in vivo: Gram-negative aerobes (Acinetobacler 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 groups C, G and viridans group);
Gram-negative aerobes (Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including strains forming penicillinase, Pasteurella spp., Providencia sluartii); 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

Suction and distribution

The maximum concentration (C max ) 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 Ојg / ml, respectively.
With max cystastatin 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. Binding to plasma proteins 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). V d in adults - 0.23-0.31 l / kg.
Metabolism and excretion

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 (T 1/2 ) of imipenem and cilastatin in adults is 1 hour.
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 through the gastrointestinal tract and 20-25% by the extrarenal route (the mechanism is unknown).
Quickly and effectively (73-90%) is excreted by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the dose is removed).

Pharmacokinetics in specific patient groups

V d in children aged 2-12 years - 0.7 l / kg, in newborns -0.4-0.5 l / kg.

With IV introduction, the half-life (T 1/2 ) of imipenem and cilastatin in children aged 2-12 years is 1-1.2 hours, in newborns T 1/2 imipenem is 1.7-2.4 hours, cilastatin is 3.8-8.4 hours.

If the renal function T 1/2 imipenem is broken - 2.9-4 h, cilastatin - 13.3-17.1 h.

INDICATIONS

Infectious-inflammatory diseases caused by microorganisms sensitive to imipenem:

- Lower respiratory tract infections caused by Streptococcus pneumoniae, Staphylococcus aureus (strains forming penicillinase), Acinetobacler 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 rettgei, Pseudomonas aeruginosa, Serratia spp., Peptococcus spp., Peptostreptococcus spp., Bacteroides spp., Including Bacteroides fragilis, Fusobacterium spp .;

- Bone and joint infections 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.

DOSING MODE

Intravenously infuzionalno.

The following doses are calculated for adult patients with a body weight of 70 kg and more and a CC of 70 ml / min / 1.73 m 2 or more.
For patients with SC less than 70 ml / min / 1.73 m 2 and / or less body weight, 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 / day (total daily dose of 1 g), moderate severity - 500 mg 3 times / day or 1 g 2 times / day (total daily dose of 1.5-2 g), (high sensitive strains) - 500 mg 4 times / day (total daily dose of 2 g), with severe severity (less sensitive strains, especially Pseudomonas aeruginosa), in case of an infection endangering the patient's life - 1 g of 3- 4 times / day (total daily dose of 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), 500 mg after 8 and 16 hours after initial anesthesia.

Adult patients with renal dysfunction (KC less than 70 ml / min / 1.73 m 2 ) 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 h;

- 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 h;

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

- 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 h;

- 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 h.

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

a) The maximum daily dose of 1 g

Body weight (kg) KK (ml / min / 1.73 m 2 )

> 71 41-70 21-40 6-20

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

b) The maximum daily dose of 1.5 g

Body weight (kg) KK (ml / min / 1.73 m 2 )

> 71 41-70 21-40 6-20

60-69 250 mg every 6 hours 250 mg every 8 hours 250 mg every 8 hours 250 mg every 12 hours

50-59 By 250 mg every 6 hours By 250 mg every 8 hours By 250 mg every 12 hours By 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

c) The maximum daily dose of 2 g

Body weight (kg) KK (ml / min / 1.73 m 2 )

> 71 41-70 21-40 6-20

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 8 hours 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

d) The maximum daily dose of 3 g

Body weight (kg) KK (ml / min / 1.73 m 2 )

> 71 41-70 21-40 6-20

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

e) The maximum daily dose of 4 g

Body weight (kg) KK (ml / min / 1.73 m 2 )

> 71 41-70 21-40 6-20

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 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 CNS 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 m 2 .

Taking into account the reduced functions of the cardiovascular system, liver, kidneys, as well as the presence of concomitant diseases and concomitant drug therapy, it is necessary to adhere to the lower limits of recommended doses in the choice of dose.
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 doses to such patients, the definition of QA is recommended.
Children with a body weight of 40 kg or more are prescribed the same doses as adults.
Children older than 3 months and with a body weight of less than 40 kg- 15 mg / kg 4 times / day; the maximum daily dose is 2 g.
Rules for the preparation of solution

The following solvents are used to prepare the infusion solution: 0.9% sodium chloride solution, 5% dextrose solution, 10% dextrose solution, 5% dextrose solution and 0.9% sodium chloride solution, 5% dextrose solution 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 EFFECT

From the side of 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 urinary bilirubin concentration and urine color change, increased plasma concentration of urea nitrogen and creatinine, acute renal failure.

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

On the part of the hematopoiesis and hemostasis system: 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 hepatic 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, multi-form exudative erythema (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis, exfoliative dermatitis, fever, anaphylactic reactions.

From the senses: a decrease in hearing, 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: a feeling of 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.

CONTRAINDICATIONS

- chronic renal failure (CC 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);

- hypersensitivity to imipenem and / or cilastatin, other carbapenems and beta-lactam antibiotics and other components of the drug.

Precautions: CNS disease, a history of seizures, convulsive high availability, anticonvulsant therapy with valproic acid (reducing the effectiveness of therapy);chronic renal failure (creatinine clearance less than 70 mL / min), patients on hemodialysis; elderly age; patients with a history of gastrointestinal disease (including pseudomembranous colitis).
PREGNANCY AND LACTATION

Use of the drug during pregnancy is permissible only if the potential benefit of treatment to the mother outweighs the potential risk to the fetus.
Imipenem and cilastatin are allocated in small amounts in breast milk, therefore it is necessary to resolve the issue of termination of breastfeeding at the time of treatment with the drug.
APPLICATION FOR FUNCTIONS OF THE LIVER

Contraindicated for use in patients with chronic renal failure (creatinine clearance less than 5 ml / min, without dialysis).
In the treatment of adult patients with CC less than 5 ml / min, hemodialysis , use dosages for adult patients with CC 6-20 ml / min and / or weighing less than 70 kg. The drug is administered after the dialysis session and then at 12-hour intervals from the time the procedure is complete, thus for older patients should be carefully monitored (especially if they have CNS diseases).
Adult patients with impaired renal function (creatinine clearance less than 70 mL / min / 1.73 m 2 )and / or weighing less than 70 kg must first determine the total daily dose depending on the severity of infection, the appropriate adult patients weighing> 70 kg and in the absence of chronic renal failure. Then pick up the corresponding reduced dosage, based on a daily dose, QC and weight of the patient.
APPLICATION FOR CHILDREN

Use of the drug is contraindicated in infancy (up to 3 months), and patients with severe renal failure children (serum creatinine concentration of greater than 2 mg / dl).
APPLICATION IN ELDERLY PATIENTS

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. Kidney condition in the elderly can not be fully determined only by measuring the blood level of residual nitrogen or creatinine. For the selection of such patients doses recommended QC determination.
SPECIAL INSTRUCTIONS

B / in the preferred route of administration used in the initial stages of treatment of bacterial septicemia, endocarditis, serious and life-threatening infections, including lower respiratory tract infections caused by Pseudomonas aeruginosa, and in the case of severe complications.
It is not recommended for treatment of meningitis.
Urine stains in a reddish color (safe and money had to be mistaken for hematuria).
Before starting therapy should be collected a thorough medical history on the subject of previous allergic reactions to beta-lactam antibiotics. With the development of allergic reactions should be discontinued immediately medication.
In patients with a history of gastrointestinal indications of disease (especially colitis), there is an increased risk of pseudomembranous colitis.
Therapy antiepileptic drugs in patients with brain injuries or a history of seizures must continue throughout the period of drug treatment (to avoid side effects from the CNS).
It should be borne in mind that in elderly patients likely to have age-related renal dysfunction, which may require dose reduction. It is advisable to monitor renal excretory function.
In applying the drug, both in patients receiving and 2-3 weeks after cessation of treatment may develop diarrhea caused by Clostridium difficile (pseudomembranous colitis).
In mild cases, it is sufficient to cancel treatment and use ion-exchange resins (colestyramine, 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, in the course of treatment is necessary to periodically determine the sensitivity of Pseudomonas aeruginosa antibiotic according to the clinical situation.
With caused proved (or positive) sensitive to imipenem microorganisms order to prevent the development of resistance and maintaining imipenem efficacy in clinical practice, the drug should be used to treat infections.
Impact on the ability to drive vehicles and manage mechanisms

Given the likelihood of side effects from the central nervous system, caution should be exercised when driving and busy with other potentially hazardous activities that require high concentration and psychomotor speed reactions. When the side effects of the central nervous system should refrain from carrying out these activities.
OVERDOSE

Symptoms intensified dose-related side effects.
Treatment: In case of overdose it is recommended removal of the drug, the appointment of symptomatic and supportive therapy. Imipenem and cilastatin output by hemodialysis. However, the effectiveness of this procedure with an overdose of the drug is unknown.
DRUG INTERACTION

Preparation pharmaceutically incompatible with lactic acid (lactate), and should not get ready solvent-based, containing it. However / in a preparation can be administered through the same infusion system, and the solution containing lactate.
While the use of penicillins and cephalosporins can be cross-allergy; antagonises in relation to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).
In an application with ganciclovir increases the risk of generalized seizures. These drugs should not be used at the same time, except when the potential benefits outweigh the possible risk.
Drugs that block tubular secretion, and slightly increase the concentration in plasma and T 1/2imipenem (if required high concentration of imipenem, to use these drugs at the same time is not recommended).
In applying the drug decreases serum concentrations of valproic acid, which reduces the efficacy of the anticonvulsant therapy, so the period of treatment is recommended to monitor the plasma concentrations of valproic acid.
The drug should not be mixed in the same syringe with other antibiotics, and the allowed simultaneous (isolated) administration with other antibiotics (aminoglycosides).
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C.
Shelf life - 3 years.

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