Composition, form of production and packaging
Powder for solution preparation for intravenous administration 1 fl.
meropenem (in the form of trihydrate) 1 g
1 g - bottles (1) - packs of cardboard.
1 g - bottles (10) - packs of cardboard.
1 g - bottles (100) - cardboard boxes.
1 g - bottles (200) - cardboard boxes.
Powder for solution preparation for intravenous administration 1 fl.
meropenem (in the form of trihydrate) 500 mg
500 mg - bottles (1) - packs of cardboard.
500 mg - bottles (10) - packs of cardboard.
500 mg - bottles (200) - cardboard boxes.
500 mg - bottles (400) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Meropenem is an antibiotic for parenteral use from the group of carbapenems, it has a bactericidal action (inhibits the synthesis of the cell wall of bacteria), easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases.
Unlike imipenem, meropenem practically does not break down in the renal tubules, dehydropeptidase-1 (does not need to be combined with cilastatin-specific inhibitor of dehydropeptidase-1) and, accordingly, nephrotoxic degradation products do not form, has high affinity for proteins that bind penicillin.
Bactericidal and bacteriostatic concentrations practically do not differ.
It interacts with receptors-specific penicillin-binding proteins on the surface of the cytoplasmic membrane, inhibits the synthesis of the peptidoglycan layer of the cell wall, suppresses transpeptidase, promotes the release of autolytic enzymes of the cell wall, which eventually causes its damage and death of bacteria.
The spectrum of antibacterial activity of meropenem includes the majority of clinically significant Gram-positive and Gram-negative aerobic and anaerobic strains of bacteria:
Gram-positive aerobes:
Enterococcus faecalis (including vancomycin-resistant strains), Staphylococcus aureus (penicillinase-sparing and penicillin-producing (methicillin-sensitive));Streptococcus agalactiae, Streptococcus pneumoniae (only penicillin-sensitive); Streptococcus pyogenes, Viridans group streptococci.
Gram-negative aerobes:
Escherichia coli, Haemophilusi nfluenzae (penicillinase-inducing and penicillinase-producing), Klebsiella pneumoniae, Neisseria meningitides, Pseudomonas aeruginosa, Proteus mirabilis .
Anaerobic bacteria:
Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus spp.
Meropenem is effective in vitro in the control of the following microorganisms, but clinically its effectiveness in diseases caused by these pathogens is not proved:
Gram-positive aerobes:
Staphylococcus epidermidis (penicillinase-inducing and penicillinase-producing (methicillin-sensitive)).
Gram-negative aerobes:
Acinetobacter spp., Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Haemophilus influenzae, Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis, Morganella morganii, Pasteurella multocida, Proteus vulgaris, Salmonella spp., Serratia marcescens, Shigella spp., Yersinia enterocolitica.
Anaerobic bacteria:
Bacteroides distasonis, Bacteroides ovatus, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus, Clostridium difficile, Clostridium perfringens, Eubacterium lentum, Fusobacterium spp., Prevotella bivia, Prevotella intermedia, Prevotella melaninogenica, Porphyromonas asaccharolytic, Propionibacterium acnes.
PHARMACOKINETICS
Intravenous administration of 250 mg meropenem for healthy volunteers during 30 minutes creates C max equal to about 11 Ојg / ml, 500 mg to 23 Ојg / ml and 1000 mg to 49 Ојg / ml (C max and area under the concentration-time curve AUC) from the amount of the administered dose was not observed).
With an increase in the dose of meropenem from 250 to 2000 mg, the clearance decreases from 287 to 205 ml / min. When intravenously sprayed for 5 minutes, 500 mg C max is 52 Ојg / ml, 1000 mg - 112 Ојg / ml.
With max in the plasma, after intravenous administration of 1000 mg of the drug for 2 min, 3 min, and 5 min, respectively, 110, 91 and 94 Ојg / ml.
After 6 hours after intravenous administration of 500 mg, the concentration of meropenem in the blood plasma is reduced to 1 Ојg / ml and below.
With repeated administration of meropenem with an 8-hour interval, patients with normal renal function do not observe cumulation of the drug. Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. In patients with normal renal function, T 1/2 is approximately 1 hour.
The connection with plasma proteins is approximately 2%.
About 70% of the intravenous dose of meropenem is excreted by the kidneys unchanged for 12 hours. The concentrations of meropenem in the urine, exceeding 10 Ојg / ml, are maintained for 5 hours after the administration of a dose of 500 mg.
Meropenem penetrates well into most tissues and biological fluids of the body, incl. in cerebrospinal fluid in patients with bacterial meningitis, reaching concentrations exceeding those required for the destruction of most bacteria.
Peculiarities of pharmacokinetics in different age groups
The pharmacokinetics of meropenem in children is the same as in adults. T 1/2 meropenem in children under 2 years is approximately 1.5-2.3 hours, a linear dependence of the pharmacokinetic parameters of meropenem is observed in the dose range of 10-40 mg / kg.
In elderly patients, the clearance of meropenem decreases, correlating with a decrease in creatinine clearance.
Renal insufficiency
The clearance of meropenem in patients with renal insufficiency correlates with creatinine clearance. Such patients need a dose adjustment. It is in hemodialysis.
Liver failure
Studies of pharmacokinetics in patients with liver disease have shown that these pathological changes do not affect the pharmacokinetics of meropenem.
INDICATIONS
Cyroneme for intravenous administration is indicated for the treatment of infectious inflammatory diseases in children and adults (monotherapy or in combination with other antimicrobial agents) caused by one or more meropenem-sensitive pathogens:
- Lower respiratory tract infections (including pneumonia, including hospital ones);
- intra-abdominal infections (including complicated appendicitis, peritonitis, pelvioperitonitis);
- urinary tract infection (including pyelonephritis, pyelitis);
- skin and soft tissue infections (including erysipelas, impetigo, secondarily infected dermatoses);
- infections of the pelvic organs (including endometritis);
- bacterial meningitis;
- empirical treatment (in the form of monotherapy or in combination with antiviral or antifungal agents) with suspected infection in adult patients with febrile episodes with neutropenia.
Experience in the use of the drug in children with neutropenia, with primary or secondary immunodeficiency is not.
DOSING MODE
Cyroneme is injected intravenously for 5 minutes (diluted with sterile water for injection at a rate of 1 ml per 50 mg, or drip for 15-30 minutes (diluted with 50-200 ml of compatible infusion fluid).
The cyanone can be dissolved in the following solutions:
- 0.9% solution of sodium chloride;
- 5% and 10% dextrose solution;
- 5% dextrose solution with 0.02% sodium bicarbonate solution;
- 0.9% solution of sodium chloride with 5% dextrose solution;
- 5% dextrose solution with 0.225% sodium chloride solution;
- 5% dextrose solution with 0.15% potassium chloride solution;
- 2.5% or 10% solution of mannitol.
The resulting solution is a clear, colorless or pale yellow liquid. Saeronem should not be confused with other drugs.
When diluting the saironem should follow the standard mode of asepsis and antiseptics. The diluted solution must be shaken before use. All vials are for single use only.
Adults
Doses and duration of therapy are determined depending on the type and severity of the infection and the patient's condition.
The following daily doses are recommended:
- 500 mg intravenously every 8 hours with pneumonia, urinary tract infections, infectious and inflammatory diseases of the pelvic organs, infections of the skin and soft tissues;
- 1 g intravenously every 8 hours with hospital pneumonia, peritonitis, with suspected bacterial infection in patients with neutropenia, and septicemia.
In the treatment of meningitis, the recommended dose is 2 g every 8 hours.
Dosing regimen in adult patients with impaired renal function
In patients with creatinine clearance less than 51 mL / min, doses should be reduced as follows:
Creatinine clearance Dose (based on the recommended single dose 0.5, 1 or 2 g) Chaetov introduction
26-50 ml / min single dose every 12 h
10-25 ml / min 1/2 dose every 12 hours
<10 ml / min 1/2 dose every 24 hours
Meropenem is excreted in hemodialysis. If long-term treatment with Cyroneme is required, it is recommended that a single dose (based on the type and severity of the infection) be administered at the end of the hemodialysis procedure in order to restore the effective concentration of the drug in the blood plasma.
There is no experience of using Syronem in patients on peritoneal dialysis.
Dosing regimen in adult patients with impaired hepatic function
In patients with hepatic insufficiency, there is no need for dose adjustment (see section "Special instructions").
Dosage regimen in elderly patients
In elderly patients with normal renal function or a decrease in creatinine clearance of at least 50 ml / min, dose adjustment is not required.
Dosage regimen in children
For children aged 3 months to 12 years, the recommended dose for intravenous administration is 10-20 mg / kg every 8 hours, depending on the type and severity of the infection, the sensitivity of the pathogen and the patient's condition. In children with a body weight of more than 50 kg, the drug should be used in a dose similar to that used in adults.
With meningitis, the recommended dose is 40 mg / kg every 8 hours.
Efficacy and tolerability of the drug in children under 3 months of age is not established, and therefore the appointment of Sironone to children of this age group is not recommended.
There is no experience of using the drug in children with impaired liver and kidney function.
SIDE EFFECT
Local reactions: inflammation, thrombophlebitis, tenderness at the injection site; necrosis of tissues with concomitant elevation of creatine phosphokinase (with intramuscular injection).
Systemic reactions
Allergic reactions: in rare cases, there may be systemic allergic reactions (hypersensitivity). These reactions can manifest as angioedema and anaphylactic shock, as well as skin rash, itching, urticaria. In rare cases, serious skin reactions can occur, such as erythema multiforme (exudative), Stevens-Johnson syndrome and toxic epidermal necrolysis.
Digestive system: pain in the epigastric region, nausea, vomiting, diarrhea, cholestatic hepatitis, hyperbilirubinemia, increased activity of "liver" transaminases and alkaline phosphatase, lactate dehydrogenase, rarely candidiasis of the oral mucosa, pseudomembranous enterocolitis.
Cardiovascular system: development or aggravation of heart failure, cardiac arrest, tachycardia or bradycardia, a decrease or increase in blood pressure, fainting, myocardial infarction, thromboembolism of the branches of the pulmonary artery.
The hemopoietic system: anemia, thrombocytosis, eosinophilia, thrombocytopenia, leukopenia and neutropenia (including isolated cases of agranulocytosis). Some patients may have a positive direct or indirect Coombs test, a decrease in partial thromboplastin time.
Urinary system: dysuria, edema, renal dysfunction (hypercreatininaemia, increased urea concentration in plasma), hematuria.
Nervous system: headache, paresthesia, insomnia, increased excitability, anxiety, depression, impaired consciousness, hallucinations. There have been reports of seizures, although their cause-and-effect relationship with the use of meropenem has not been proven.
Other: vaginal candidiasis.
CONTRAINDICATIONS
- hypersensitivity to meropenem;
- Children under 3 months.
Carefully:
- with concomitant administration with nephrotoxic drugs;
- Persons with gastrointestinal diseases (especially those suffering from chronic colitis), as well as with severe renal failure;
- Persons who had a history of allergic reactions to other beta-lactam antibiotics.
PREGNANCY AND LACTATION
Pregnancy
The safety of the use of meropenem in women during pregnancy has not been studied. Studies in animals have not shown any adverse effects on the developing fetus.
A saironem should not be used during pregnancy, except when the potential benefit of using it for the mother exceeds the possible risk to the fetus.
Lactation
Meropenem is determined in the breast milk of animals in very low concentrations. Cyronemia should not be used in breastfeeding women, except when the potential benefit from its use for the mother exceeds the possible risk to the child. When using the drug during lactation, consideration should be given to stopping breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with creatinine clearance less than 51 ml / min, doses should be adjusted according to the "Dosage regimen" section.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with hepatic insufficiency, there is no need for dose adjustment (see section "Special instructions").
APPLICATION FOR CHILDREN
The drug is contraindicated in children under 3 months.
SPECIAL INSTRUCTIONS
Before the appointment of meropenem, it is necessary to carefully collect the patient's allergic anamnesis, paying special attention to the tolerability of other beta-lactam antibiotics (caution is required when it is prescribed to patients with hypersensitivity reactions to them in the anamnesis). With the development of allergic reactions on Sieron it is necessary to abolish it and take appropriate measures.
The use of saironem in patients with liver disease should be controlled by the activity of serum transaminases and the level of bilirubin in the blood.
In the process of treatment, the development of resistance of pathogens is possible, in connection with this, long-term treatment is carried out under the constant control of the distribution of resistant strains.
When unmotivated diarrhea appears against the background of taking meropenem, the possibility of developing pseudomembranous colitis should be taken into account (the toxin produced by Clostridium difficile is one of the main causes of colitis associated with antibiotics), the first symptom of which can be the development of diarrhea against the background of treatment.
When Syronome monotherapy with severe infections of the respiratory tract caused by Pseudomona saeruginosa is recommended, a regular determination of the sensitivity of the pathogen is recommended.
As in the case of the use of other antibiotics, the growth of insensitive microorganisms is possible against the background of Cyronem.
Pediatric Use
The effectiveness and safety of the use of Sironen in children under the age of 3 months is not established. There is no data on the use of the drug in children with impaired liver function and / or kidney function. There is no experience with the use of meropenem in children with neutropenia or with primary / secondary immunodeficiency.
Influence on the ability to drive and work with machinery
Special studies on the impact of Cyroneme on the rate of psychomotor reactions have not been carried out, however, given the spectrum of its pharmacological activity, one should not expect a significant impact on the ability to drive a car and other equipment.
OVERDOSE
Due to the rapid excretion of the drug by the kidneys, an overdose is unlikely, but it can occur during the treatment of patients with impaired renal function. Treatment of an overdose is symptomatic. In patients with renal insufficiency, hemodialysis effectively removes meropenem and its metabolites.
DRUG INTERACTION
Meropenem is pharmaceutically incompatible with heparin.
Ganciclovir increases the risk of developing generalized seizures.
Meropenem shows antagonism when interacting with beta-lactam antibiotics.
Drugs that block tubular secretion, slow down excretion and increase the concentration of meropenem in the plasma.
The joint administration of meropenem with potentially nephrotoxic drugs increases the risk of developing nephrotoxic reactions.
The possible effect of meropenem on the association with plasma proteins of other drugs has not been studied, but given its weak affinity (see kinetics) for blood plasma proteins, interaction with other drugs at this level is unlikely.
Meropenem can reduce the concentration of valproic acid in the serum until subtherapeutic, which may require correction of its dose.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. In a dry, the dark place at a temperature of no higher than 30 В° C. Keep out of the reach of children. Shelf life - 2 years.
