Meropenem-Vial - instructions for use, dose, side effects, contraindications

Antibiotic class of carbapenems for parenteral use. Resistant to dehydropeptidase-1 (DHP-1), does not require additional administration of DHP-1 inhibitor. It acts bactericidal (inhibits the synthesis of the bacterial cell wall), easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases, and has a high affinity for proteins that bind penicillin. The minimum bactericidal concentration (MBC) and the minimum inhibitory concentration (MIC) are virtually indistinguishable.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 (due to structural similarity), suppresses transpeptidase, promotes the release of autolytic enzymes of the cell wall, which eventually causes damage and death of bacteria. Tests in vitro show the synergistic effect of meropenem with various antibiotics. Tests in vitro and in vivo show the post-antibiotic effect of meropenem.

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 (lenicillin-nitrogen-producing and penicillin-producing [methicillin-sensitive]); Streptococcus agalactiae, Streptococcus pneumoniae (only penicillin-sensitive); Streptococcus pyogenes, Streptococcus groups viridans.

Gram-negative aerobes: Escherichia coli, Haemophilus influenzae (penicillin-producing and penicillin-producing), Klebsiella pneumoniae, Neisseria meningitidis, Pseudomonas aeruginosa, Proteus mirabilis.

Anaerobic bacteria: Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus spp.

Meropenem is effective in vitro for the following microorganisms: Gram-positive aerobes: Staphylococcus epidermidis (penicillinase-inducedand penicillinase-producing [methicillin-sensitive]).

Gram-negative aerobes: Acinetobacter spp ,, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter feundii, Enterobacter cloacae, Haemophilus influenzae (ampicillin-resistant, penicillinase-sparing strains), Hafiiia alvei, Klebsiella oxytoca, Moraxella catarrhalis (peninillinazoeducing and penicillinase-producing), 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 melanino-genica, Porphyromonas asaccharolytica, Propionibacterium acnes.

Pharmacokinetics:

When intravenously administered 250 mg for 30 minutes, the maximum concentration (C_max) is 11 μg / ml, for a dose of 500 mg - 23 μg / ml, for a dose of 1000 mg - 49 μg / ml. Absolute pharmacokinetic proportionality to the administered dose for C_max and AUC (area under the pharmacokinetic curve "concentration-time"). With an increase in the dose from 250 mg to 2000 mg, the plasma clearance decreases from 287 to 205 ml / min. With intravenous bolus administration for 5 min 500 mg C_mOh - 52 mcg / ml, 1000 mg - 112 mcg / ml. Connection with plasma proteins - 2%.

After 6 hours after intravenous administration of 500 mg, the concentration of meropenem in the blood plasma is reduced to 1 μg / ml or less.

With the administration of 500 mg every 8 hours and 1000 mg every 6 hours, patients with normal renal function of cumulation of meropenem in urine and blood plasma are not observed.

In patients with normal renal function, the half-life (T1 / 2) is approximately 1 hour.

Meropenem penetrates well into most tissues and body fluids, including cerebrospinal fluid in patients with bacterial meningitis, reaching concentrations sufficient to ensure bactericidal action against most bacteria. In small amounts penetrates into breast milk.

Meropenem undergoes a slight metabolism in the liver with the formation of a single inactive metabolite.

It is excreted by the kidneys - 70% unchanged for 12 hours. The concentration of meropenem in the urine, exceeding 10 μg / ml, is maintained for 5 hours after administration of 500 mg.

In patients with renal insufficiency, the clearance of meropenem correlates with creatinine clearance (CC). Such patients require dose adjustment. In elderly patients, a decrease in meropenem clearance correlates with a decrease in QC associated with age. T1 / 2 - 1.5 hours. It is excreted during hemodialysis.In patients with liver disease, the pharmacokinetics of meropenem does not change.

Studies in children have shown that the pharmacokinetics of meropenem in children and adults are similar. T1 / 2 meropenem in children under 2 years is approximately 1.5-2.3 hours, a linear dependence of pharmacokinetic parameters is observed in the dose range of 10-40 mg / kg.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation, including in case of polymicrobial infections (as monotherapy or combination with other antibacterial, antiviral and antifungal drugs):

- Lower respiratory tract infections (including pneumonia, including hospital pneumonia, infections caused by Pseudomonas aeruginosa);

- urinary tract infections (including pyelonephritis, pyelitis);

- skin and soft tissue infections (including erysipelas, impetigo, secondarily infected dermatoses);

- intra-abdominal infections (complicated appendicitis, peritonitis, pelvioperitonitis);

- septicemia;

- infections of the pelvic organs (including endometritis);

- bacterial meningitis;

- suspected bacterial infection in adults with febrile neutropenia (empirical treatment in the form of monotherapy or in combination with antiviral or antifungal agents).

The efficacy of meropenem has been demonstrated both in monotherapy mode and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications:Hypersensitivity to meropenem or other drugs of the carbapenem group in the anamnesis. Severe hypersensitivity (anaphylactic reactions, severe skin reactions) to any antibacterial agent having a beta-lactam structure (ie to penicillins or cephalosporins). Children under 3 months.

Carefully:

- simultaneous administration with nephrotoxic drugs;

- patients with colitis.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:Intravenously.

Intravenous bolus: the drug should be dissolved with sterile water for injection (5 ml per 250 mg), with a solution concentration of 50 mg / ml, injected for at least 5 minutes.

The safety of taking a 2 g dose as a bolus injection has not been adequately studied.

Intravenous infusion: a drug should be dissolved 0.9% solution sodium chloride or 5% solution dextrose, with the concentration solution should be from 1 to 20 mg / ml, administered over a 15-30 min.

Meropenem is compatible with following liquids:

- 0.9% solution of sodium chloride;

- 5% dextrose solution;

- water for injections.

Meropenem should not be mixed or added to others medicinal products. The dose and duration of therapy are set depending on type, severity of infection and condition patient.

Recommended the following doses:

Adults:

- With pneumonia, infections urinary tract, infections of small pelvis, infections of the skin and soft tissues - intravenously, by 500 mg every 8 hours;

- With hospital pneumonia, peritonitis, septicemia, suspicion of a bacterial infection in patients with neutropenia - intravenously, 1000 mg 3 times a day;

- When meningitis - 2000 mg every 8 hours.

If the renal function is impaired, the dose is adjusted depending on the creatinine clearance:

Creatinine clearance (ml / min)	Single dose: the proportion of the recommended single dose, corresponding pathology (500 mg, or 1000 mg, or 2000 mg)	Periodicity of introduction
26-50	100%	In 12 hours
10-25	50%	In 12 hours
<10	50%	In 24 hours

Meropenem is excreted in hemodialysis and hemofiltration. If continuation of treatment is required, it is recommended that the drug depending on the type and severity of the infection) was administered at the end of the hemodialysis procedure to restore effective concentration in the blood plasma. AT There is currently no evidence of experience with the use of meropenem in patients on peritoneal dialysis. Patients with hepatic insufficiency no the need for dose adjustment (see section "Special instructions"). In elderly patients with normal renal function or with creatinine clearance greater than 50 ml / min, dose adjustment is not required.

Children:

- at the age of 3 months to 12 years (or with a body weight of less than 50 kg), a single dose for intravenous administration is 10-20 mg / kg every 8 hours;

- Children weighing more than 50 kg are given doses for adults;

- with meningitis 40 mg / kg every 8 hours.

The safety of taking a dose of 40 mg / kg as a bolus injection has not been adequately studied.

There is no experience of using the drug in children with impaired liver and kidney function.

Side effects:

Allergic reactions: skin rash (including erythematous eruptions), skin itching, multi-form exudative erythema (including Stevens-Johnson syndrome), urticaria, angioedema, anaphylactic shock.

From the nervous system: headache, dizziness, insomnia, drowsiness, paresthesia, increased excitability, agitation, anxiety, depression, impaired consciousness, hallucinations, epileptiform seizures, convulsions (causal connection with the use of meropenem is not established).

From the urinary system: dysuria, edema, renal dysfunction (hypercreatininaemia, increased urea concentration in plasma), hematuria.

From the digestive system: pain in the epigastric region, nausea, vomiting, diarrhea, constipation, anorexia, jaundice, cholestatic hepatitis; rarely - candidiasis of the oral mucosa, pseudomembranous colitis.

From the cardiovascular system: development or exacerbation of heart failure, cardiac arrest, tachy- or bradycardia, a decrease or increase in blood pressure (BP), syncope, myocardial infarction, thromboembolism of the branches of the pulmonary artery.

Laboratory indicators: eosinophilia, yeethropenia, leukopenia, rarely - agranulocytosis, hypokalemia, leukocytosis, reversible thrombocytopenia, reduced activated partial thromboplastin time.

Local reactions: inflammation, phlebitis, thrombophlebitis, tenderness at the injection site. Other: positive direct or indirect samples of Coombs, anemia, hypervolemia, dyspnea, vaginal candidiasis.

Overdose:

In case of an overdose, which is possible mainly in the treatment of patients with impaired renal function, symptomatic treatment is performed. Hemodialysis is possible.

Interaction:Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and concentration of meropenem in plasma. Since the efficacy and duration of action of meropenem administered without probenecid is adequate, joint administration of probenecid with meropenem is not recommended. The possible effect of meropenem on the degree of association of other drugs with plasma proteins or metabolism has not been studied. The connection of meropenem with plasma proteins low (about 2%), therefore, interaction with other drugs, based on the mechanism of displacement from the connection with plasma proteins, is not expected. The simultaneous administration of carbapenems and valproic acid preparations led to a decrease in the concentration of valproic acid inblood plasma at 60-100% after 2 days of therapy. Due to the rapid and significant decrease in concentration valproic acids not It is recommended that joint use of meropenem and valproic acid preparations is recommended. The use of meropenem during the intake of other drugs was not accompanied by development unfavorable pharmacological interactions. Studies on the interaction of meropenem with other drugs (for exclusion of probenecid) was not carried out. Repeatedly reported cases of increased anticoagulant effect in joint admission of indirect anticoagulants (eg, warfarin) and antibacterial drugs. The risk of enhancing the anticoagulant effect may depend on the nature of the infection, the age and general condition of the patient, so it is difficult to assess the effect of the antibacterial drug on increasing the international normalized ratio (INR).

During joint administration of an antibacterial drug and an indirect anticoagulant, and for some time after its termination, frequent monitoring of INR is recommended.

Special instructions:

Experience in the use of the drug in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency is not present.

As with the use of other antibiotics, when using meropenem in the monotherapy regimen, npatients, of the at critical condition from infection of the lower respiratory tract caused by Pseudomonas aeruginosa, or if it is suspected, regular testing of sensitivity is recommended. In rare cases, with the use of meropenem, as with almost all antibiotics, pseudomembranous colitis develops, which can vary in severity from mild to life-threatening forms. It is important to remember the possibility development of pseudomembranous colitis in the occurrence of diarrhea on the background of the use of meropenem. With the development of pseudomembranous colitis should be canceled meropenem. Contraindicated application of drugs, inhibitory peristalsis of the intestine.

Against the background of the use of carbapenems, including meropenem, infrequently reported the occurrence seizures. Should follow caution when application of Meropenem in patients with a reduced threshold of convulsive readiness.

There are clinical and laboratory symptoms cross-cutting allergic reactions between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. There are rare reports of cases of hypersensitivity reactions (including fatal outcome) when using meropenem, as well as others beta-lactam antibiotics (see section "Side effect"). Before the start of therapy with meropenem, the patient should be carefully examined, paying special attention to on reactions hypersensitivity to beta-lactam antibiotics in the anamnesis. Meropenem should be used with caution in patients with a history of hypersensitivity reactions to beta-lactam antibiotics (ie to penicillins and cephalosporins). If there was a allergic reaction to meropenem, it is necessary to stop the drug and to accept appropriate measures.

The use of meropenem in patients with liver disease should be conducted under careful monitoring of transaminase activity and concentrations bilirubin.

As with other antibiotics, available excess growth of insensitive microorganisms, and therefore constant monitoring of the patient is necessary.

The prevalence of acquired antibiotic resistance of various pathogens may vary depending on the region and over time, it is desirable to have up-to-date information on the resistance of common pathogens in a particular region, especially when treating severe infections. In cases where the resistance is such that the effectiveness of the drug against at least some infections becomes questionable, an expert should be consulted. The combined use of meropenem and valproic acid preparations is not recommended because of a possible reduction in the concentration of valproic acid in the serum. In some patients, a concentration below the therapeutic level can be achieved (see "Interaction with other drugs").

The use of the drug for infections caused by methicillin-resistant staphylococcus is not recommended.

Effect on the ability to drive transp. cf. and fur:There have been no studies of the effect of meropenem on the ability to drive a car and other equipment. Nevertheless, it should be taken into account that when taking Meropenem-Vial, headache, paresthesia and convulsions can be observed.

Form release / dosage:

Powder for the preparation of a solution for intravenous administration of 0.5 g and 1 g.

Packaging:

0.5 g or 1 g in terms of meropenem anhydrous is placed in a bottle of colorless clear glass with a capacity of 10 ml (0.5 g) and 20 ml (1 g), sealed with a rubber stopper, crimped with an aluminum cap with a plastic protective cover.

One bottle together with the instruction for use is placed in a cardboard pack.

Storage conditions:

List B. Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001145/10

Date of registration:18.02.2010 / 23.04.2010

Expiration Date:Unlimited

The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia

Representation: & nbspVIAL, LLCVIAL, LLC

Information update date: & nbsp11.12.2016

Illustrated instructions

Instructions

Meropenem Vial (Meropenem-Vial)