Meropenem-Plekhiko - instructions for use, doses, side effects, contraindications

Pharmacodynamics:Antibiotic for parenteral administration of karabapenemov group has a bactericidal action (inhibits bacterial cell wall synthesis), easily penetrates through the cell wall of bacteria resistant to most beta-lactamases, 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-inducing and penicillinase-producing [methicillin-sensitive]); Streptococcus agalactiae, Streptococcus pneumoniae (only penicillin-sensitive); Streptococcus pyogenes, Streptococcus spp. groups viridans.

Gram-negative aerobes:

Escherichia coli, Haemophilus influenzae (penicillinase-inducing 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-inducing and penicillinase-producing [methicillin-sensitive]).

Gram-negative aerobes:

Acinetobacter spp., Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Haemophilus influenzae (ampicillin-resistant, penicillinase-resisting strains), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (penicillinase-inducing and penicillin-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, Eubacterimn lentum, Fusobacterium spp., Prevotella bivia, Prevotella intermedia, Prevotella melaninogenica, Porphyromonas asaccharolytica, Propionibacterium acnes.

Pharmacokinetics:

When intravenous (iv) 250 mg for 30 minutes, the maximum concentration (C max) is about 11 μg / ml, for a dose of 500 mg about 23 μg / ml, 1 g about 49 μg / ml (absolute pharmacokinetic proportional to the administered dose for Cmax and AUC (area under the pharmacokinetic curve "concentration-time") no). When the dose is increased from 250 mg to 2 g, the plasma clearance decreases from 287 to 205 ml / min. When I / in the bolus vvOver 5 minutes, 500 mg Cmah about 52 μg / ml, 1 g about 112 μg / ml. Connection with plasma proteins - 2%.

Well penetrates into most tissues and body fluids, incl. in the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations exceeding those required for the suppression of most bacteria (bactericidal concentrations are created 0.5-1.5 h after the start of infusion).In small amounts penetrates into breast milk.

Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. The half-life period (T1 / 2) is approximately 1 hour, in children under 2 years approximately 1.5-2.3 hours. In the dose range of 10-40 mg / kg in adults and children, a linear dependence of pharmacokinetic parameters is observed. Do not cumulate. 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 the administration of 500 mg. In patients with renal insufficiency, the clearance of corrEluces with creatinine clearance (CC). In elderly patients, a decrease in meropenem clearance correlates with a decrease in QC associated with age. T1 / 2 -1.5 h. It is excreted in hemodialysis.

In patients with liver disease, the pharmacokinetics of meropenem does not change.

Indications:

Infectious-inflammatory diseases (monotherapy or in combination with other antimicrobial drugs), caused by one or more susceptible to meropenem pathogens: infections of the lower respiratory tract (including pneumonia, including hospital); intra-abdominal infections (incl.complicated appendicitis, peritonitis, pelvioperitonitis); infection of the urinary system (including pyelonephritis, pyelitis); infections of the skin and soft tissues (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 drugs) in case of suspected infection in adult patients with febrile episodes with neutropenia.

Contraindications:

Hypersensitivity to meropenem, drug components, other carbapenems; severe hypersensitivity (anaphylactic reactions, severe skin reactions) to other beta-lactam antibiotics (ie to penicillins or cephalosporins), children's age (up to 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:IV bolus (diluted with sterile water 10 ml per 500 mg, 15 ml per 1000 mg), for 5 minutes, or IV infusion, for 15-30 minutes (in dilutions up to 50-200 ml with a compatible infusion fluid ). When diluting, the standard aseptic regimen should be followed. The drug should not be mixed or added to other drugs. Adults with pneumonia, urinary tract infections, pelvic infections, skin and soft tissue infections - IV, 500 mg every 8 hours; with hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, septicemia - in / in, 1 g every 8 hours; with meningitis - 2 g every 8 hours. If the kidney function is altered, the dose is adjusted depending on the creatinine clearance:

Clearance creatinine (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%	After 24 hours

Meropenem is excreted in hemodialysis. To restore the effective plasma concentration after completion of the hemodialysis procedure, it is necessary to administer a single dose of meropenem recommended for the corresponding pathology.

In elderly patients with normal renal function or with QC greater than 50 ml / min, dosage adjustment is not required.

Children aged 3 months. up to 12 years (with body weight less than 50 kg) single dose for IV administration - 10-20 mg / kg every 8 hours, depending on the type and severity of the infection,

sensitivity of the microorganism, the patient's condition; with meningitis 40 mg / kg every 8 hours (maximum single dose of 2 g).

Children with a body weight of more than 50 kg prcall doses for adults. An experience use in children with impairedThere is no kidney function.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, candidiasis of the oral mucosa; pseudomembranous colitis.

From the urinary system: impaired function, kidney (hypercreatininaemia, increased urea concentration in plasma).

Allergic reactions: itching of the skin, skin, rash, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylactic shock.

From the nervous system: headache, paresthesia, convulsions.

Laboratory indicators: thrombocytosis, eosinophilia, thrombocytopenia, leukopenia, neutropenia,agranulocytosis, shortening of partial thromboplastin time; hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (AFP), lactate dehydrogenase (LDH).

Local reactions: inflammation: thrombophlebitis, tenderness at the injection site.

Other: false positive direct or indirect samples of Coombs, hemolytic, anemia, vaginal candidiasis.

The causal relationship with taking meropenem is not established: fainting, hallucinations, depression, anxiety, increased excitability, insomnia; constipation, cholestatic hepatitis, heart failure, cardiac arrest, tachycardia, bradycardia; myocardial infarction, a decrease or increase in blood pressure, pulmonary embolism, dyspnea.

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:

Compatible with the following solutions: 0.9% solution of sodium chloride; 5-10% dextrose solution (glucose); 5% dextrose (glucose) solution with 0.02% sodium bicarbonate solution; 5% dextrose (glucose) solution with 0.225%solution of sodium chloride; 5% dextrose (glucose) solution with 0.15% potassium chloride solution; 2.5 and 10% solution mannitol.

Reduces the plasma concentration of valproic acid, which can lead to a decrease in the anticonvulsant effect.

Drugs that block tubular secretion, slow down excretion and increase the concentration in the plasma.

Special instructions:

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may exhibit hypersensitivity to meropenem.

Treatment of patients with liver disease should be conducted under the control of the activity of "liver" transaminases and bilirubin concentrations.

In the process of treatment, it is possible to develop the resistance of pathogens, and therefore prolonged treatment is carried out under the constant control of the distribution of resistant strains. In persons with diseases of the gastrointestinal tract, especially colitis, it is necessary to take into account the possibility of developing pseudomembranous colitis (toxin produced Clostridium difficile, is one of the main causes of colitis associated with antibiotics), the first symptom of which can be the development of diarrhea on the background of treatment.

When monotherapy of an established or suspected lower respiratory infection of severe course caused by Pseudomonas aeruginosa, It is recommended to regularly determine the sensitivity of the pathogen to meropenem.

Experience with the use of meropenem in children with neutropenia with primary or secondary immunodeficiency is absent.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engage in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Powder for the preparation of a solution for intravenous administration of 500 mg, 1000 mg.

Packaging:For 500 mg or 1000 mg of active substance in bottles of clear glass class III (Hebrew Pharm.), Respectively, 20 ml or 30 ml, sealed with a gray stopper made of butyl rubber with a crimp aluminum ring and plastic lid. Each bottle is placed in a tray of PVC. One pallet with instructions for use in a cardboard box.

Storage conditions:

In dry, 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 the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001202

Date of registration:11.11.2011 / 11.09.2012

Expiration Date:11.11.2016

The owner of the registration certificate:Plethiko Pharmaceuticals Co., Ltd. Plethiko Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

PLETHICO PHARMACEUTICALS, Ltd. India

Representation: & nbspREZLOV ZAO REZLOV ZAO Kazakhstan

Information update date: & nbsp05.09.2016

Illustrated instructions

Instructions

Meropenem-Plekhiko (Meropenem-Plethico)