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

1 bottle contains:
Active substances:
Imipenema monohydrate (in terms of imipenem)	500 mg
Cilastatin sodium (in terms of cilastatin)	500 mg
Excipient:
sodium hydrogen carbonate	20 mg

Description:

White or white with a yellowish tint powder.

Pharmacotherapeutic group:Antibiotic-carbapenem + dehydropeptidase inhibitor

ATX: & nbsp

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

Pharmacodynamics:

Imipenem is a broad-spectrum beta-lactam antibiotic, is a derivative of tienamycin and belongs to the carbapenem group. Suppresses the synthesis of the bacterial cell wall and has a bactericidal action against a wide range of gram-positive and gram-negative 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, it does not inhibit beta-lactamase bacteria.

Grimipenem^® is resistant to degradation by bacterial beta-lactamases, which makes it effective against most beta-lactamase microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., resistant to penicillins and cephalosporins.

Grimipenem^® is active against:

- Gram-negative aerobic bacteria: Achromobacter spp., Acinetobacter spp., Aeromonas hydrophila, Alcaligenes spp., Bordetella bronchicanis, B. bronchiseptica, B. pertussis, Brucella melitensis, Campylobacter spp., Capnocytophaga spp., Citrobacter spp., C. diversus, C. freundii, Eikenella corrodens, Enterobacter spp., E. aerogenes, E. agglomerans, E. cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, H. influenzae(including strains producing beta-lactamases), H. parainfluenzae, Hafnia alvei, Klebsiella spp. (K. oxytoca, K. ozaenae, K. pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae (including strains producing beta-lactamases), N. meningitidis, Pasteurella spp., Pasteurella multocida, Plesiomonas shigelloides, Proteus spp., P. mirabilis, P. vulgaris, Providencia spp., P. alcalifaciens, P. rettgeri, P. stuartii, Pseudomonas aeruginosa, P. fluorescens, P . pseudomallei, P. putida, P. stutzeri, Salmonella spp., in t.ch. S. typhi, Serratia spp. (S. proteamaculans, S. marcescens), Shigella spp., Yersinia spp., Y.enterocolitica, Y. pseudotuberculosis;

- Gram-positive aerobic bacteria: Bacillus spp., Enterococcus faecalis, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Nocardia spp., Pediococcus spp., Staphylococcus aureus (including strains producing penicillinases), S. epidermidis (including strains producing penicillinases), S. saprophyticus, Streptococcus agalactiae, S. pneumoniae, S. pyogenes, green streptococci, including alpha and gamma-hemolytic strains, streptococcus groups C and G;

- Gram-negative anaerobic bacteria: Bacteroides fragilis, Bacteroides spp. (including B. distasonis, B. ovatus, B. thetaiotaomicronron, B. uniformis, B. vulgatus), Bilophila wadsworthia, Fusobacterium spp. (incl. F. necrophorum, F. nucleatum), Porphyromonas asaccharolytica, Prevotella bivia, P. disiens, P. intermedia, P. melaninogenica, Veillonella spp.;

- Gram-positive anaerobic bacteria: Actinomyces spp., Bifidobacterium spp., Clostridium spp. (including C. perfringens), Eubacterium spp., Lactobacillus spp., Mobiluncus spp., microaerophilic streptococci, Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp. (includingP. acnes);

- other microorganisms: Mycobacterium fortuitum, Mycobacterium smegmatis.

In vitro acts synergistically with aminoglycosides against certain strains Pseudomonas aeruginosa.

Insensitive to grimipenem^®: strains Staphylococcus spp., resistant to methicillin, Stenotrophomonas maltophilia, Enterococcus faecium and some strains Burkholderia cepacia.

Pharmacokinetics:

At the end of a 20-minute infusion of 500 + 500 mg of imipenem / cilastatin, the maximum concentration (C_mOh) of imipenem in serum is 21-58 μg / ml; FROM_mOh cilastatin 31-49 μg / ml, respectively. 20% of the administered dose of imipenem and 40% of cilastatin reversibly bind to blood plasma proteins. Imipenem is quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids, reproductive organs. In low concentrations it is found in the cerebrospinal fluid. 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.

Both components of the drug are excreted mainly by the kidneys (70-76% within 10 h) by glomerular filtration (2/3) and active tubular secretion (1/3); 1-2% is excreted through the intestine and 20-25% - non-adrenal (the mechanism is unknown). Blocking tubular secretion of imipenem with cilastatin results in inhibition of its renal metabolism and accumulation in the urine in unchanged form. With IV introduction, the elimination half-life (T_1/2) imipenem and cilastatin in adults - about 1 hour, in newborns - 4.0-8.5 h, in the elderly - 1.5 h.

Imipenem and cilastatin are rapidly and effectively (73-90%) excreted by hemodialysis (within a 3-hour session of intermittent haemofiltration, 75% of the dose is removed).

Indications:

Infections of the lower respiratory tract caused by Staphylococcus aureus (penicillinase-producing strains), Acinetobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Serratia marcescens.

Urinary tract infections caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa.

Intraabdominal infections caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), 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 B. fragilis, Fusobacterium spp.

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

Bacterial septicemia caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Enterobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia spp., Bacteroides spp., including B. fragilis.

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

Infections of the skin and soft tissues caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), 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 B. fragilis, Fusobacterium spp.

Bacterial endocarditis caused by Staphylococcus aureus (penicillinase-producing strains).

Prevention of postoperative infectious complications.

Contraindications:

Hypersensitivity to one of the components of the drug, as well as other carbapenems, beta-lactam antibiotics, penicillins and cephalosporins; pregnancy (only for "vital" indications), 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, lactation period, elderly age.

Dosing and Administration:

Introduced in / in the drip. The dosage form for intravenous administration should not be given intramuscularly.

The average therapeutic dose for adults with a body weight greater than or equal to 70 kg and normal kidney function (creatinine clearance (CC) 70 ml / min / 1.73 m² and more) - 1-2 g / day (in terms of imipenem), divided into 3-4 injections; the maximum daily dose is 4 g or 50 mg / kg, depending on which dose is lower.

Depending on the severity of the infection, the following doses of Grimipenema® are recommended: for a mild infection and uncomplicated urinary tract infections, 250 mg (hereinafter referred to as imipenem) 4 times a day; medium-heavy current - 500 mg 3 times a day or 1 g 2 times a day; severe current - 500 mg 4 times a day; with an infection that threatens the patient's life, - 1 g 3-4 times a day.

For the prevention of postoperative infections - 1 g of Grimipenema ® during the initial anesthesia. In the case of surgical intervention with a high risk of infection (operation on the colon and rectum), 500 mg are additionally administered at 8 and 16 hours after the end of the operation.

For patients with SC less than 70 ml / min / 1.73 m² and / or body weight less than 70 kg should be proportionately reduced dose (see table below).

Table. 1. Dosage of grimipenem ® in patients with a body weight of less than 70 kg and / or impaired renal function (calculation of doses by imipenem).

An easy course of infection (250 mg every 6 hours)
Weight bodies	Creatinine clearance, ml / min / 1.73 m²
Weight bodies	≥71	41-70	21-40	6-20
≥71	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
60	250 mg every 8 hours	125 mg every 6 hours	250 mg every 12 hours	125 mg every 12 hours
50	125 mg every 6 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
40	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours
30	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours

Moderately severe infection (500 mg every 8 hours)
Weight bodies	Creatinine clearance, ml / min / 1.73 m²
Weight bodies	≥71	41-70	21-40	6-20
≥71	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
60	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours
50	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
40	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
30	125 mg every 6 hours	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours

Severe course of infection (500 mg every 6 hours)
Weight bodies	Creatinine clearance, ml / min / 1.73 m²
Weight bodies	≥71	41-70	21-40	6-20
≥71	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
60	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
50	250 mg every 6 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
40	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
30	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours

severe infection (1000 mg every 8 hours)
weight bodies	Creatinine clearance, ml / min / 1.73 m2
weight bodies	≥71	41-70	21-40	6-20
≥71	1000 every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
60	750 mg every 8 hours	500 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
50	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
40	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
30	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours

Life-threatening infections (1000 mg every 6 hours)
weight bodies	Creatinine clearance, ml / min / 1.73 m²
weight bodies	≥71	41-70	21-40	6-20
≥71	1000 mg every 6 hours	750 mg every 8 hours	500 mg every 6 hours	500 mg every 12 hours
60	1000 mg every 8 hours	750 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
50	750 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
40	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
30	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours

patients with kc less than 5 ml / min / 1.73 m² appoint only if every 48 hours, hemodialysis is carried out. in patients on hemodialysis, grimipenem® should be administered at the doses recommended for patients with creatinine clearance of 6-20 ml / min / 1.73 m², immediately after the hemodialysis session and at 12-hour intervals from the end of the procedure.

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

Children with a body weight of 40 kg or more are given the same doses as adults (Table 1.)

rules for solution preparation and administration

grimipenem® (imipenem 500 mg and cilastatin 500 mg), 125 ml glass bottles.

To prepare the infusion solution in a vial containing 0.5 g of imipenem, 100 ml of solvent are added.the following infusion media should be used as a solvent: 0.9% sodium chloride solution, 5% dextrose solution, an aqueous solution containing 5% dextrose and 0.9% sodium chloride. The resulting solution (concentration of imipenem 5 mg / ml) should 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.

grimipenem® (imipenem 500 mg and cilastatin 500 mg), bottles of glass 30 ml.

preparation of the infusion solution is carried out in two stages:

1) 10 ml of one of the following solvents: 0.9% solution of sodium chloride, 5% dextrose solution, an aqueous solution containing 5% dextrose and 0.9% sodium chloride are added to the vial with powdered antibiotic for initial dissolution. then the vial is shaken to obtain a uniform suspension;

2) the resulting suspension with a sterile syringe is transferred to a vial containing 100 ml of a compatible infusion medium used for the initial dissolution.

in order to completely transfer the contents of the vial with the antibiotic into the infusion solution, the steps described above are repeated once more.

injected intravenously drip.

the duration of the infusion depends on the chosen dose: 250-500 mg administered for 20-30 minutes; 750-1000 mg - for 40-60 minutes.

the ready-made infusion solution (imipenem concentration 5 mg / ml or less) can be stored at room temperature for 4 hours or for 24 hours in a refrigerator at a temperature of 4 from.

Side effects:

Imipenem / cilastatin therapy is usually well tolerated; adverse reactions with observance of the indicated dosages and regimens of administration develop rarely and in most cases are stopped on their own.

From the nervous system: myoclonia, mental disorders, hallucinations, confusion, epileptic seizures, paresthesia.

From the urinary system: oliguria, anuria, polyuria, acute renal failure (rarely).

From the digestive system: nausea, vomiting, diarrhea, pseudomembranous colitis, hepatitis (rarely).

On the part of the organs of hematopoiesis and the system of hemostasis: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, decreased hemoglobin, prolonged prothrombin time; false positive test of Coombs.

Changes in laboratory indicators: an increase in the activity of "hepatic" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininaemia, an increase in the concentration of urea nitrogen.

Allergic reactions: skin rash, itching, urticaria, multiforme erythema (including Stevens-Johnson syndrome), angioneurotic edema, toxic epidermal necrolysis (rare), exfoliative dermatitis (rarely), fever, anaphylactic reaction.

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

Other: candidiasis, a taste disorder.

Interaction:

Pharmaceutically incompatible with salts of lactic acid (lactate), solutions of other antibiotics.

With simultaneous application with penicillins and cephalosporins, a cross-allergy is possible; with other beta-lactam antibiotics (penicillins, cephalosporins and monobactams) antagonism of action is observed.

With simultaneous use with ganciclovir, the risk of developing generalized seizures increases.

Drugs that block tubular secretion, slightly increase the concentration in the plasma and T_1/2imipenem (if high concentrations of imipenem are required, it is not recommended to use these medicines at the same time).

Special instructions:

Not recommended for the treatment of meningitis. Patients with indications of central nervous system diseases should be used with caution and follow the recommended dosages, avoiding exceeding this dose.

Stains urine in a reddish color.

People with a history of gastrointestinal disease, especially the colon, have an increased risk of developing pseudomembranous colitis.

Therapy with antiepileptic drugs in patients with brain injuries or epileptic seizures in the history should continue throughout the entire period of treatment with Grimipenem ® to avoid side effects from the central nervous system.

In elderly patients, the presence of age-related renal dysfunction is likely, which may require a dose reduction.

Form release / dosage:

Powder for solution for infusion, 500 mg + 500 mg.

Packaging:

(500 mg + 500 mg) of the drug into glass bottles with a capacity of 30 ml.

(500 mg + 500 mg) of the drug in bottles or glass bottles with a capacity of 125 ml.

1 a 30 ml bottle with instruction for use or 1 bottle (125 ml bottle) with or without a connecting tube and the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008834/08

Date of registration:06.11.2008 / 22.09.2014

Expiration Date:Unlimited

The owner of the registration certificate:PREBAND PFC, LLCPREBAND PFC, LLC Russia

Manufacturer: & nbsp

PREBAND PFC LLC Russia

Information update date: & nbsp10.05.2017

Illustrated instructions

Instructions

Grimipenem® (GRIMIPENEM®)