Meropenem-LEXVM, 1 g

Meropenem-LEXVM is an antibiotic for parenteral use from the group of carabapenems, it has a bactericidal effect (inhibits the synthesis of the bacterial cell wall), easily penetrates through the cell wall of bacteria, resistant to the action of most beta-lactamases.

In contrast to imipenem it is practically not degraded in renal tubules by dehydropeptidase-1 (it does not need to be combined with cilastatin – specific inhibitor of dehydropeptidase-1) and, correspondingly, nephrotoxic degradation products are not formed, it has high affinity to proteins binding penicillin. Bactericidal and bacteriostatic concentrations practically do not differ.

It interacts with receptors – specific penicillin-binding proteins on the surface of cytoplasmic membrane, inhibits synthesis of pentidoglycan layer of cell wall, inhibits transpeptidase, promotes release of autolytic enzymes of cell wall which eventually causes its damage and death of bacteria.

The spectrum of antibacterial activity of meropenem includes most clinically relevant Gram-positive and Gram-negative aerobic and anaerobic bacterial strains:

• Gram-positive aerobes: Enterococcus faecalis (including vancomycin-resistant strains), Staphylococcus aureus(penicillin-unproducing and penicillin-producing [methylline-sensitive]); Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive only); Streptococcus pyogenes, Streptococcus spp. groups viridans.
• Generative 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 against the following microorganisms, but clinically its effectiveness against diseases caused by these pathogens has not been proven:

• Gram-positive aerobes: Staphylococcus epidermidis (penicillinase-producing and penicillinase-producing [methylline-sensitive]).
• Gram-positive aerobes: Acinetobacter spp, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Haemophilus influenzae (ampicillin-resistant, penicillin-zoon-producing strains), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (penicillinase-producing and penicillinase-producing strains), Morganella morganii, Pasteurella multocida, Proteus vulgaris, Salmonella spp., Serratia marcesccns, Shigella spp, Yersinia enterocolitica.
• Anaerobic bacteria: Bacteroides distasonis, Bacteroides ovatus, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus, Clostridium difficile, Clostridium peifringens, Eubacterium lentum, Fusobacterium spp, Prevotella bivia, Prevotella intermedia, Prevotella melaninogenica, Porpliyroiiionas asaccharolylica, Propionibacterium acnes.

Pharmacokinetics:

At an intravenous injection of 250 mg within 30 minutes, the Cmax of the active substance in plasma reaches 11 µg/mL, for a dose of 500 mg, 23 µg/mL, and 1 g, 49 µg/mL (absolute pharmacokinnetic proportional relationship to the dose administered for Cmax and AUC. When the dose is increased from 0.25 to 2 g, clearance decreases from 287 to 205 mL/min. When administered by IV bolus for 5 min, 500 mg Cmax is 52 mcg/ml, 1 g is 112 mcg/ml. The binding to plasma proteins is 2%.

It penetrates well into most tissues and body fluids, including cerebrospinal fluid (CSF) of patients with bacterial meningitis, reaching concentrations higher than required for suppression of most bacteria (bactericidal concentrations are formed 0.5-1.5 hours after the beginning of infusion). It penetrates into breast milk in insignificant amounts.
It is subject to minor metabolism in the liver with the formation of a single inactive metabolite. T1/2 – 1 hour, in children under 2 years old – 1.5-2.3 hours. There is a linear dependence of pharmacokinetic parameters in the dose range of 10-40 mg/kg in adults and children. It does not cumulate.

It is excreted by the kidneys – 70% unchanged within 12 hours. Urinary concentration of meropenem exceeding 10 µg/ml is maintained for 5 h after administration of 500 mg. In patients with renal insufficiency, clearance correlates with creatinine clearance. In elderly patients, decreased clearance of meropenem correlates with decreased creatinine clearance associated with age. T1/2 is 1.5 h. It is excreted by hemodialysis.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to meropenem, including polymicrobial infections (as monotherapy or in combination with other antibacterial, antiviral and antifungal medicines):

– lower respiratory tract infections (including pneumonia, including hospital pneumonia);

– urinary tract infections (including pyelonephritis, pyelitis);

– skin and soft tissue infections (including

– intra-abdominal infections (appendicitis complicated, peritonitis, pelvio-peritonitis);

– septicemia;

– infections of the pelvic organs (including endometritis).

– bacterial meningitis;

– suspected bacterial infection in adults with febrile neutropenia (empirical treatment as monotherapy or in combination with antiviral or antifungal agents).

Active ingredient

Composition

Powder Meropenem-LEXVM for preparation of a solution for I/V injection
1 fl:

How to take, the dosage

IV.

In/v bolus: diluted with sterile water for injection 15 ml per 1000 mg for at least 5 min.

In/v infusion: for 15-30 min, diluted to 50-200 ml with compatible infusion fluid.

Meropenem is compatible with the following fluids:

– 0.9% sodium chloride solution; 5-10% dextrose (glucose) solution;

– 5% dextrose (glucose) solution with 0.02% sodium hydrogen carbonate solution;

– 5% dextrose (glucose) solution with 0.225% sodium chloride solution;

– 5% dextrose (glucose) solution with 0.15% potassium chloride solution;

– 2.5 and 10% mannitol solution.

Meropenem should not be mixed or added to other medications.

The dose and duration of therapy are determined according to the severity of the infection and the patient’s condition. The following doses are recommended:

Adults:

For pneumonia, urinary tract infections, pelvic organ infections, skin and soft tissue infections, v/v, 500 mg every 8 h;

In hospital pneumonia, peritonitis, septicemia, suspected bacterial infection in patients with neutropenia – intravenously, 1000 mg 3 times a day;

In case of meningitis – 2000 mg every 8 hours.

In case of impaired renal function, the dose is adjusted depending on creatinine clearance:

Meropenem is excreted by hemodialysis. A single dose of meropenem recommended for the relevant pathology should be administered to restore effective plasma concentration upon completion of the hemodialysis procedure.

Children:

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

– children with a body weight greater than 50 kg use adult doses;

– for meningitis 40 mg/kg every 8 hours.

There is no experience of use in children with impaired renal function.

Interaction

Compatible with 0.9% sodium chloride solution, 5-10% dextrose solution, 0.02% sodium androcarbonate solution, 5% dextrose solution with 0.225% sodium chloride solution, 5% dextrose solution with 0.15% potassium chloride solution, 2.5% and 10% mannitol solution.

Decreases plasma concentration of valproic acid, which may lead to decreased anticonvulsant effect. Drugs that block tubular secretion retard excretion and increase plasma concentrations.

Special Instructions

Patients with a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may be hypersensitive to meropenem.

The treatment of patients with liver disease should be carried out under control of the activity of “hepatic” transaminases and bilirubin concentrations.

In the course of treatment development of resistance of pathogens is possible, therefore long-term treatment is carried out under constant control of the spread of resistant strains. In patients with diseases of the gastrointestinal tract (GIT), especially colitis, it is necessary to consider the possibility of development of pseudomembranous colitis (toxin produced by Clostridium difficile is one of the main causes of colitis associated with antibiotics), the first symptom of which can be development of diarrhea during treatment.

In monotherapy of established or suspected severe lower respiratory tract infection caused by Pseudomonas aeruginosa, regular determination of pathogen sensitivity is recommended. There is no experience with meropenem in children with neutropenia or primary or secondary immunodeficiency.

During treatment, caution should be exercised when driving motor vehicles and engaging in potentially hazardous activities that require increased concentration and quick psychomotor reactions.

Contraindications

High sensitivity to any of the ingredients of the drug. Children under 3 months of age (no data on efficacy and tolerability).

With caution. Concomitant administration with nephrotoxic drugs; patients with colitis.

The use in liver disorders

The treatment of patients with liver disease should be carried out under control of the activity of “hepatic” transaminases and bilirubin concentration.

Periodic use in renal impairment

The dose is adjusted according to creatinine clearance if renal function is impaired.

Performance in children

It is contraindicated in children under 3 months of age (no data on efficacy and tolerability are available). No experience of use in children with impaired renal function.

Side effects

Digestive system disorders: epigastric pain, nausea, vomiting, diarrhea, constipation, anorexia, jaundice; oral candidiasis; pseudomembranous colitis.

Urinary system disorders: dysuria, edema, renal dysfunction (hypercreatininemia, increased concentration of urea in plasma), hematuria.

Allergic reactions: skin itching, skin rash, urticaria, erythema multiforme; malignant erythema exudative (Stevens-Johnson syndrome), angioedema, anaphylactic shock.

Nervous system disorders: headache, dizziness, paresthesia; very rarely – agitation, disturbance of consciousness, epileptiform seizures, convulsions.

Laboratory findings: Thrombocytosis, eosinophilia, thrombocytopenia, decreased hemoglobin (Hb), hematocrit, leukopenia, shortened prothrombin and partial thromboplastin time, leukocytosis, hypokalemia; gtrbilrubinemia, increased alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activity.

Local reactions: inflammation, phlebitis, thrombophlebitis, pain, swelling at the injection site; tissue damage with a concomitant rise in creatine phosphokinase (CPK) – when administered in /m.

Others: positive direct or indirect Coombs test, anemia, hypervolemia, vaginal candidiasis.

The causal relationship to meropenem administration has not been established: Syncope, hallucinations, depression, anxiety, hyperexcitability, insomnia, cholestatic hepatitis, heart failure (CHF), dyspnea, tachycardia, bradycardia, decreased or increased blood pressure (BP); cardiac arrest, myocardial infarction, pulmonary embolism (TELA).

Overdose

Accidental overdose is possible during treatment, especially in patients with impaired renal function.

Treatment: symptomatic. In patients with impaired renal function meropenem and its metabolites are eliminated by hemodialysis.

Similarities