Meropenem (Powder) Instructions for Use

ATC Code

J01DH02 (Meropenem)

Active Substance

Meropenem (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibiotic of the carbapenem group

Pharmacotherapeutic Group

Antibiotic, carbapenem

Pharmacological Action

An antibiotic for parenteral use from the carbapenem group. It exerts 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 degraded in the renal tubules by dehydropeptidase-1 (does not require combination with cilastatin, a specific inhibitor of dehydropeptidase-1) and, accordingly, no nephrotoxic degradation products are formed; it has a high affinity for penicillin-binding proteins.

Bactericidal and bacteriostatic concentrations are practically the same.

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, and 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 most clinically significant gram-positive and gram-negative aerobic and anaerobic bacterial strains.

Gram-positive aerobes: Enterococcus faecalis (including vancomycin-resistant strains); Staphylococcus aureus (penicillinase-non-producing and penicillinase-producing [methicillin-sensitive]): Streptococcus agalactiae; Streptococcus pneumoniae (only penicillin-sensitive); Streptococcus pyogenes; Streptococcus spp. of the viridans group.

Gram-negative aerobes: Escherichia coli; Haemophilus influenzae (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 microorganisms listed below; however, its clinical efficacy in 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, penicillinase-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 urealyticus; Bacteroides vulgatus; Clostridium difficile; Clostridium perfringens; Eubacterium lentum; Fusobacterium spp.; Prevotella bivia; Prevotella intermedia; Prevotella melaninogenica; Porphyromonas asaccharolytica; Propionibacterium acnes.

Pharmacokinetics

After intravenous administration of 250 mg over 30 minutes, C_max is 11 µg/ml; for a dose of 500 mg – 23 µg/ml; 1 g – 49 µg/ml (there is no absolute pharmacokinetic proportional dependence of C_max and AUC on the administered dose). When the dose is increased from 0.25 to 2 g, clearance decreases from 287 to 205 ml/min. After intravenous bolus administration over 5 minutes of 500 mg, C_max is 52 µg/ml; 1 g – 112 µg/ml. Plasma protein binding is 2%.

It penetrates well into most tissues and body fluids, including the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations exceeding those required to suppress most bacteria (bactericidal concentrations are achieved within 0.5-1.5 hours after the start of the infusion). It penetrates into breast milk in insignificant amounts.

It undergoes insignificant metabolism in the liver to form a single inactive metabolite. T_1/2 is 1 hour; in children under 2 years, 1.5-2.3 hours. A linear dependence of pharmacokinetic parameters is observed in the dose range of 10-40 mg/kg in adults and children. It does not accumulate. It is excreted by the kidneys – 70% unchanged within 12 hours. The concentration of meropenem in urine exceeding 10 µg/ml is maintained for 5 hours after administration of 500 mg. In patients with renal insufficiency, clearance correlates with creatinine clearance (CrCl). In elderly patients, the decrease in meropenem clearance correlates with the age-related decrease in CrCl. T_1/2 is 1.5 hours. It is removed by hemodialysis.

Indications

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

• Lower respiratory tract infections (including pneumonia, including hospital-acquired);
• Intra-abdominal infections (including complicated appendicitis, peritonitis, pelvic peritonitis);
• Urinary system infections (including pyelonephritis, pyelitis);
• Skin and soft tissue infections (including erysipelas, impetigo, secondarily infected dermatoses);
• Pelvic organ infections (including endometritis);
• Bacterial meningitis;
• Septicemia.

Empirical treatment (as monotherapy or in combination with antiviral or antifungal drugs) for suspected infection in adult patients with febrile episodes with neutropenia.

ICD codes

Dosage Regimen

Powder

Intravenously as a bolus over at least 5 minutes, or as an intravenous infusion over 15-30 minutes.

Doses and duration of therapy should be established depending on the type and severity of the infection and the patient’s condition. The following daily doses are recommended:

Adults and children over 12 years and weighing more than 50 kg

500 mg intravenously every 8 hours for pneumonia, urinary tract infections, gynecological infections and pelvic inflammatory diseases, skin and soft tissue infections.

1 g intravenously every 8 hours for hospital-acquired pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, and septicemia. For meningitis, the recommended dose is 2 g every 8 hours.

In chronic renal failure, the dose is adjusted depending on CrCl: with CrCl 26-50 ml/min – 0.5-1 g twice daily, 10-25 ml/min – 250-500 mg twice daily, less than 10 ml/min – 500 mg once daily.

Meropenem is removed by hemodialysis. If prolonged treatment is required, it is recommended that a unit dose (determined depending on the type and severity of the infection) be administered after the hemodialysis procedure to restore effective plasma concentration.

Children

For children aged 3 months to 12 years, or weighing less than 50 kg, 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.

For meningitis, the recommended dose is 40 mg/kg every 8 hours.

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

Preparation of solutions

For intravenous bolus injections, the drug is dissolved in sterile water for injections (10 ml per 500 mg of meropenem). This provides a solution concentration of 50 mg/ml.

For intravenous infusions, the drug is dissolved in sterile water for injections or in a compatible infusion fluid (from 50 to 200 ml). Meropenem is compatible with the following infusion fluids:

• Sodium chloride 0.9% solution;
• Dextrose 5% or 10% solution;
• 5% dextrose solution with 0.02% sodium bicarbonate;
• 0.9% sodium chloride solution 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% mannitol solution.

Meropenem must not be mixed with solutions containing other drugs.

Adverse Reactions

From the digestive system: pain in the epigastric region, nausea, vomiting, diarrhea, constipation, anorexia. Jaundice, cholestatic hepatitis, hyperbilirubinemia, increased activity of hepatic 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, pulmonary artery thromboembolism.

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

Allergic reactions: skin itching, skin rash, urticaria, multiform exudative erythema, malignant exudative erythema (Stevens-Johnson syndrome), angioneurotic edema, anaphylactic shock.

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

Laboratory parameters: 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.

Contraindications

• Hypersensitivity to any of the components of the drug;
• Children under 3 months of age (no data on efficacy and tolerability).

Use in Pregnancy and Lactation

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

Use in Hepatic Impairment

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

Use in Renal Impairment

In impaired renal function, the dose is adjusted depending on creatinine clearance.

Pediatric Use

Contraindicated in children under 3 months of age (no data on efficacy and tolerability).

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

There is no experience with the use of the drug in children with neutropenia, with primary or secondary immunodeficiency.

Special Precautions

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 “hepatic” transaminases and bilirubin concentration.

During treatment, the development of pathogen resistance is possible, therefore, long-term treatment is carried out under constant monitoring of the spread of resistant strains. In persons with complaints from the gastrointestinal tract, especially with colitis, it is necessary to consider the possibility of developing pseudomembranous colitis (the 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.

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

There is no experience with the use of the drug in children with neutropenia, with primary or secondary immunodeficiency.

Overdose

In case of overdose, possible mainly when treating patients with impaired renal function, symptomatic treatment is carried out. Hemodialysis may be performed.

Drug Interactions

Compatible with the following solutions:

• 0.9% sodium chloride solution;
• 5-10% dextrose (glucose) solution;
• 5% dextrose (glucose) solution with 0.02% sodium bicarbonate 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 drugs.

It reduces the plasma concentration of valproic acid, which may lead to a decrease in the anticonvulsant effect.

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

Storage Conditions

List B.

The drug should be stored in a dry, light-protected place, at a temperature not exceeding 30°C (86°F), in places inaccessible to children.

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.