Meropenabol^® (Powder) Instructions for Use

Marketing Authorization Holder

PFC Prebend, LLC (Russia)

ATC Code

J01DH02 (Meropenem)

Active Substance

Meropenem (Rec.INN registered by WHO)

Dosage Forms

	Meropenabol®	Powder for preparation of solution for intravenous administration 1 g: vial 1 pc.
		Powder for preparation of solution for intravenous administration 500 mg: vial 1 pc.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous administration white or white with a yellowish tint.

Excipients: sodium carbonate.

Glass vials (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the carbapenem group

Pharmacotherapeutic Group

Antibiotic-carbapenem

Pharmacological Action

An antibiotic of the carbapenem group for parenteral use. It interacts with receptors – specific penicillin-binding proteins on the surface of the cytoplasmic membrane, inhibits transpeptidase, and inhibits the synthesis of peptidoglycans of the cell wall (due to structural similarity), which ultimately causes its damage and death of bacteria.

It is resistant to renal dehydropeptidase-1, acts bactericidally, easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases, and has a high affinity for penicillin-binding proteins.

Among known beta-lactam antibiotics, it has the highest activity against most aerobic and anaerobic gram-positive and gram-negative microorganisms.

Active against gram-positive aerobes Bacillus spp., Corynebacterium diphtheriae, Enterococcus liquefaciens, Enterococcus avium, Enterococcus faecalis, Listeria monocytogenes, Lactobacillus spp., Nocardia asteroides, Staphylococcus aureus (including strains producing penicillinase), Staphylococcus spp. (coagulase-negative strains), including Staphylococcus saprophyticus, Staphylococcus capitis, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus mitis, Streptococcus viridans, Streptococcus salivarius, Streptococcus morbillorum, Streptococcus spp. (groups G and F), Rhodococcus equi; gram-negative aerobes Achromobacter xylosoxidans, Acinetobacter anitratus, Acinetobacter lwoffii, Acinetobacter baumannii, Aeromonas hydrophila, Aeromonas sorbria, Aeromonas caviae, Alcaligenes faecalis, Bordetella bronchiseptica, Brucella melitensis, Campylobacter coli, Campylobacter jejuni, Citrobacter freundii, Citrobacter diversus, Citrobacter amalonaticus, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae (including strains producing beta-lactamases, and ampicillin-resistant strains), Haemophilus parainfluenzae, Haemophilus ducreyi, Helicobacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae (including strains producing beta-lactamases, resistant to penicillins and spectinomycin), Hafnia alvei, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia alcalifaciens, Pasteurella multocida, Pseudomonas shigelloides, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, Burkholderia cepacia, Pseudomonas fluorescens, Pseudomonas stutzeri, Stenotrophomonas spp., Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia marcescens, Serratia liquefaciens), Shigella sonnei, Shigella flexneri, Shigella dysenteriae, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Yersinia enterocolitica; anaerobic bacteria Actinomyces israelii, Bacteroides spp. (including Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variabilis, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniformis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron), Prevotella spp. (including Prevotella melaninogenica, Prevotella buccae, Prevotella denticola, Prevotella levii), Porphyromonas spp. (including Porphyromonas asaccharolyticus), Bifidobacterium spp., Clostridium perfringens, Clostridium difficile, Clostridium sporogenes, Clostridium cadaveris, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Clostridium tetani, Eubacter lentum, Eubacter aerofaciens, Fusobacterium mortiferum, Fusobacterium necrophorum, Mobiluncus curtisii, Mobiluncus mulieris, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus saccharolyticus, Peptococcus magnus, Peptococcus prevotii, Propionibacterium acne, Propionibacterium avidium, Propionibacterium granulosum.

Pharmacokinetics

Distribution

When administered intravenously at a dose of 250 mg, C_max is reached within 30 minutes and is 11 mcg/ml, at a dose of 500 mg C_max is 23 mcg/ml, at a dose of 1 g – 49 mcg/ml (there is no absolute pharmacokinetic proportional dependence on the administered dose for C_max and AUC). When the dose is increased from 250 mg to 2 g, clearance decreases from 287 to 205 ml/min.

When administered as an intravenous bolus at a dose of 500 mg, C_max is reached within 5 minutes and is 52 mcg/ml, at a dose of 1 g – 112 mcg/ml.

Plasma protein binding – 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 0.5-1.5 hours after the start of infusion). It penetrates into breast milk in small amounts. Does not accumulate.

Metabolism

It undergoes minor metabolism in the liver to form a single inactive metabolite.

Excretion

T_1/2 – 1 hour, in children under 2 years – 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. It is excreted by the kidneys – 70% unchanged within 12 hours. The concentration of meropenem in urine, exceeding 10 mcg/ml, is maintained for 5 hours after administration of the drug at a dose of 500 mg. It is excreted during hemodialysis.

Pharmacokinetics in special clinical cases

In patients with renal failure, the clearance of meropenem correlates with creatinine clearance.

In elderly patients, the decrease in meropenem clearance correlates with the age-related decrease in creatinine clearance. T_1/2 – 1.5 hours.

Indications

Infectious and inflammatory diseases caused by susceptible pathogens:

• Bacterial meningitis;
• Infections of the lower respiratory tract (including pneumonia, including hospital-acquired), infections caused by Pseudomonas aeruginosa (especially in patients with cystic fibrosis);
• Abdominal infections (peritonitis, pelvic peritonitis, complicated appendicitis);
• Pyelonephritis, pyelitis;
• Infections of the skin and soft tissues (including erysipelas, impetigo, secondarily infected dermatoses);
• Dysentery;
• Sepsis;
• Bacterial endocarditis;
• Infectious and inflammatory diseases of the pelvic organs (including endometritis);
• Suspected bacterial infection in adults with febrile episodes against the background of neutropenia (empirical treatment).

ICD codes

Dosage Regimen

Meropenabol^® is administered as an intravenous bolus injection over at least 5 minutes, or as an intravenous infusion over 15-30 minutes.

The dosage and duration of therapy should be established depending on the type, severity of the infection and the patient’s condition.

The following daily doses are recommended.

Adults

For treatment of pneumonia, urinary tract infections, gynecological infections (endometritis and inflammatory diseases of the pelvic organs), skin and soft tissue infections, 500 mg is administered intravenously every 8 hours.

For treatment of hospital-acquired pneumonia, peritonitis, bacterial infection in patients with neutropenia (febrile neutropenia), and sepsis – 1 g intravenously every 8 hours.

For treatment of meningitis, the recommended dose is 2 g every 8 hours.

In chronic renal failure, the dose is adjusted depending on CC: for CC 26-50 ml/min, 0.5-1 g is prescribed 2 times/day; for CC 10-25 ml/min – 250-500 mg 2 times/day; for CC less than 10 ml/min – 500 mg once a day.

Meropenem is excreted during 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 upon completion of the hemodialysis procedure to restore the effective plasma concentration of the antibiotic.

Children

For children aged 3 months to 12 years, 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 children weighing more than 50 kg, adult dosages should be used.

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

The maximum dose should not exceed 2 g every 8 hours.

Meropenabol^® is not recommended for use in children under 3 months.

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

Rules for preparation of solutions

For intravenous bolus injections, Meropenabol^® should be diluted with sterile water for injections (10 ml per 500 mg of meropenem). This provides a solution concentration of 50 mg/ml.

For intravenous infusions, Meropenabol^® should be diluted with sterile water for injections or a compatible infusion fluid and then diluted also with a compatible infusion fluid (50-200 ml).

Meropenabol^® is compatible with the following infusion fluids

• 0.9% sodium chloride solution for intravenous infusion;
• 5% or 10% dextrose (glucose) solution for intravenous infusion;
• 5% dextrose (glucose) solution for intravenous infusion with 0.02% sodium bicarbonate solution;
• 0.9% sodium chloride and 5% dextrose (glucose) solution for intravenous infusion;
• 5% dextrose (glucose) solution with 0.225% sodium chloride solution for intravenous infusion;
• 5% dextrose (glucose) solution with 0.15% potassium chloride solution for intravenous infusion;
• 2.5% and 10% mannitol solution for intravenous infusion.

Meropenabol^® should not be mixed with solutions containing other drugs.

Adverse Reactions

From the digestive system epigastric pain, nausea, vomiting, diarrhea, cholestatic hepatitis, hyperbilirubinemia, increased activity of hepatic transaminases and ALP, LDH; rarely – oral candidiasis, pseudomembranous enterocolitis.

From the cardiovascular system tachy- or bradycardia, decrease or increase in blood pressure, fainting.

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

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

From laboratory parameters eosinophilia, neutropenia, leukopenia, anemia; rarely – agranulocytosis, reversible thrombocytopenia, decreased partial thromboplastin time.

Allergic reactions skin itching, skin rash, urticaria, multiform exudative erythema, angioedema, anaphylactic shock.

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

Other positive direct or indirect Coombs test, dyspnea, vaginal candidiasis.

Contraindications

• Children under 3 months of age;
• Hypersensitivity to the drug.

With caution, the drug should be prescribed to patients with a history of allergic reactions to penicillins and cephalosporins; with a history of colon diseases, including ulcerative colitis; patients with renal and hepatic insufficiency.

Use in Pregnancy and Lactation

The safety of the drug during pregnancy has not been established.

Breastfeeding should be discontinued during treatment.

Use in Renal Impairment

In chronic renal failure, the dose is adjusted depending on CC: for CC 26-50 ml/min, 0.5-1 g is prescribed 2 times/day, for CC 10-25 ml/min – 250-500 mg 2 times/day, for CC less than 10 ml/min – 500 mg once a day.

Pediatric Use

Contraindicated in patients under 3 months of age.

For children aged 3 months to 12 years, 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 children weighing more than 50 kg, adult dosages should be used.

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

The maximum dose should not exceed 2 g every 8 hours.

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

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 resistance of pathogens is possible, therefore long-term treatment is carried out under constant monitoring of the spread of resistant strains.

In persons with gastrointestinal diseases, especially colitis, it is necessary to take into account the possibility of developing antibiotic-associated diarrhea and 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 the pathogen’s sensitivity is recommended.

Overdose

Accidental overdose is possible during treatment, especially in patients with impaired renal function. Treatment in case of overdose should be symptomatic. Rapid elimination of the drug is achieved with hemodialysis.

Drug Interactions

Ganciclovir increases the risk of developing generalized seizures.

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

Not compatible with heparin.

Storage Conditions

List B. The drug should be stored in a dry place, protected from light and out of reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

For intravenous injections and intravenous infusions, it is recommended to use a freshly prepared solution of Meropenabol^®a, however, diluted Meropenem can retain its activity for 6 hours when storing the solution at a temperature not exceeding 25°C (77°F) and 36 hours when storing the solution at a temperature not exceeding 5°C (41°F). Do not freeze the solution!

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.