MERIGO [Meropenem] 1 g Powder for solution for intravenous administration

instructions for the medical use of the medicinal product

MERIGO

Tradename:

Merigo, Мериго

International non-proprietary name or generic name:

Meropenem, Меропенем

Dosage form: powder for solution for I/V. injection.

Composition

Each bottle contains:

active substance: meropenem 1 g;

excipients: sodium carbonate anhydrous.

Pharmacotherapeutic group: Antibiotic carbapenem.

ATX code: J01DH02

Pharmacological properties

Pharmacodynamics

Antibiotic for parenteral use from the carbapenem group. It has a bactericidal effect (inhibits the synthesis of the bacterial cell wall), easily penetrates the bacterial cell wall, and is resistant to the action of most beta-lactamases. Unlike imipenem, it is practically not destroyed in the renal tubules by dehydropeptidase-1 (does not need to be combined with cilastatin, a specific inhibitor of dehydropeptidase-1) and, accordingly, no nephrotoxic breakdown products are formed, and has a high affinity for penicillin-binding proteins. Bactericidal and bacteriostatic concentrations are practically the same. 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, inhibits transpeptidase, promotes the release of autolytic enzymes of the cell wall, which ultimately 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 (non-penicillinase-producing and penicillinase-producing [methicillin-sensitive]): Streptococcus agalactiae; Streptococcus pneumoniae (penicillin-sensitive only); Streptococcus pyogenes; Streptococcus spp. viridans group.

Gram-negative aerobes: Escherichia coli; Haemophilus influenza (penicillinase-non-producing and penicillinase-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, however, its clinical effectiveness against diseases caused by these pathogens has not been proven:

Gram-positive aerobes: Staphylococcus epidermidis (penicillinase-non-producing and penicillinase-producing [methicillin-sensitive]).

Gram-negative aerobes: Acinetobacter spp.; Aeromonas hydrophila; Campylobacter jejuni; Citrobacter diversus; Citrobacter freundii; Enterobacter cloacae; Haemophilus influenzae (ampicillin-resistant, penicillinzone-non-producing strains); Hafnia alvei; Klebsiella oxytoca; Moraxella catarrhalis (penicillinase-non-producing 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 melaninogenica; Porphyromonas asaccharolytica; Propionibacterium acnes.

Pharmacokinetics

With intravenous administration of 1 g over 30 minutes, Cmax is 49 mcg/ml. When the dose is increased to 2 g, clearance decreases to 205 ml/min. With intravenous bolus administration of 500 mg Cmax - 52 mcg/ml, 1 g - 112 mcg/ml. Communication with plasma proteins - 2%. Penetrates well into most tissues and body fluids, incl. into the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations exceeding those required to suppress most bacteria (bactericidal concentrations are created 0.5-1.5 hours after the start of the infusion). Passes into breast milk in small quantities. Subjects to minor metabolism in the liver with the formation of a single inactive metabolite. T1/2 - 1 hour, in children under 2 years of age 1.5-2.3 hours. In the dose range of 10-40 mg/kg in adults and children, a linear dependence of the pharmacokinetic parameters is observed. Does not accumulate. Excreted by the kidneys - 70% unchanged within 12 hours. The concentration of meropenem in the urine exceeding 10 mcg/ml is maintained for 5 hours after administration of 500 mg. In patients with renal failure, clearance correlates with creatinine clearance (CC). In elderly patients, decreased clearance of meropenem correlates with age-related decreases in creatinine clearance. T1/2 – 1.5 hours. Excreted during hemodialysis.

Indications for use

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

• lower respiratory tract infections (including pneumonia, including hospital-acquired);

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

• infections of the urinary system (including pyelonephritis, pyelitis);

• infections of the skin and soft tissues (including erysipelas, impetigo, secondary infected dermatoses);

• infections of the pelvic organs (including endometritis);

• bacterial meningitis;

• septicemia.

Empirical treatment of adult patients with suspected infection and symptoms of febrile neutropenia, either alone or in combination with antiviral or antimicrobial agents.

The effectiveness of the drug has been proven both in monotherapy and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications

• hypersensitivity to any of the components of the drug;

• children's age up to 3 months.

Method of administration and dosage

IV bolus diluted in sterile water for injection over at least 5 minutes.

IV infusion diluted in 0.9% sodium chloride solution for infusion or 5% dextrose (glucose) solution for infusion for 30 minutes.

It is recommended to administer the prepared solution immediately after preparation.

The dose of the drug and duration of therapy are determined depending on the severity of the infection and the patient’s condition.

The following doses are recommended:

For adults:

• for pneumonia, urinary tract infections, infectious and inflammatory diseases of the pelvic organs, infections of the skin and soft tissues - i.v. 500 mg every 8 hours;

• for hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, septicemia - 1 g iv 3 times a day;

• for meningitis - 2 g every 8 hours.

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

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

For children:

• at the age of 3 months to 12 years, a single dose for intravenous administration is 10-20 mg/kg 3 times a day;

• children weighing more than 50 kg are given adult doses;

• for meningitis - IV 40 mg/kg every 8 hours.

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

Side effect

From the digestive system: pain in the epigastric region, nausea, vomiting, diarrhea, constipation, anorexia. jaundice, cholestatic hepatitis, hyperbilirubinemia, increased activity of liver transaminases, alkaline phosphatase, LDH; rarely - oral candidiasis, pseudomembranous colitis.

From the cardiovascular system: development or worsening of heart failure, cardiac arrest, tachy- or bradycardia, decrease or increase in blood pressure, fainting, myocardial infarction, thromboembolism of the branches of the pulmonary artery.

From the urinary system: dysuria, edema, impaired renal function (hypercreatininemia, increased concentration of urea in plasma), hematuria.

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

From the nervous system: headache, dizziness, paresthesia, insomnia, drowsiness, increased excitability, agitation, anxiety, depression, impaired consciousness, hallucinations, epileptiform seizures, convulsions.

Laboratory indicators: eosinophilia, neutropenia, leukopenia; rarely - agranulocytosis, hypokalemia, leukocytosis, reversible thrombocytopenia, decreased partial thromboplastin time.

Local reactions: inflammation, phlebitis, thrombophlebitis, pain at the injection site.

Other: false-positive direct or indirect Coombs test, anemia, hypervolemia, dyspnea, vaginal candidiasis.

If any of the side effects indicated in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Special instructions and precautions

Before using the drug, consult your doctor.

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

Treatment of patients with liver diseases should be carried out under careful monitoring of the activity of liver transaminases and bilirubin concentration.

During treatment, the development of resistance of pathogens is possible, and therefore, long-term treatment is carried out under constant monitoring of the spread of resistant strains. In persons with gastrointestinal complaints, especially colitis, it is necessary to consider the possibility of developing pseudomembranous colitis (a toxin produced by Clostridium difficile is one of the main causes of antibiotic-associated colitis), the first symptom of which may be the development of diarrhea during treatment.

When monotherapy of known or suspected severe lower respiratory tract infection caused by Pseudomonas aeruginosa, regular testing of the sensitivity of the pathogen is recommended.

Use during pregnancy and breastfeeding

The use of the drug during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Interaction with other medicinal products

Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and plasma concentration of meropenem. Because the efficacy and duration of action of meropenem administered without probenecid are adequate, coadministration of probenecid with meropenem is not recommended. The possible effect of meropenem on the plasma protein binding or metabolism of other drugs has not been studied. The binding of meropenem to plasma proteins is low (about 2%), therefore, interactions with other drugs based on the mechanism of displacement from plasma proteins are not expected. Co-administration of carbapenems and valproic acid preparations led to a decrease in the concentration of valproic acid in the blood plasma by 60-100% after 2 days of therapy.

Due to the rapid and significant decrease in the concentration of valproic acid, co-administration of meropenem and valproic acid preparations is not recommended. The use of meropenem while taking other drugs was not accompanied by the development of adverse pharmacological interactions. Studies examining the interaction of meropenem with other drugs (except probenecid) have not been conducted. Cases of increased anticoagulant effect have been repeatedly reported when indirect anticoagulants (for example, warfarin) and antibacterial drugs are taken together. The risk of increased anticoagulant effect may depend on the nature of the infection, age and general condition of the patient, so it is difficult to assess the effect of an antibacterial drug on increasing the international normalized ratio (INR). Frequent INR monitoring is recommended during co-administration of an antibacterial drug and an indirect anticoagulant and for some time after its cessation.

Overdose

Symptoms: overdose is possible mainly when treating patients with impaired renal function. There are no specific symptoms.

Treatment: carry out symptomatic therapy. Normally, the drug is rapidly eliminated through the kidneys. In patients with renal impairment, hemodialysis is effective in removing meropenem and its metabolite.

Release form

1 vial of powder along with instructions for use in a cardboard box.

Storage conditions

Store in a dry place, at a temperature not exceeding 30°C.

Keep out of the reach of children!

Shelf life

3 years. Do not use after the expiration date stated on the packaging.

Vacation conditions

By prescription.