Medopenem

Medopenem is an antibacterial systemic drug. It belongs to the group of β-lactam antibiotics.

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Indications Medopenema

It is used for the treatment of infections caused by the activity of microbes that are sensitive to drugs:

• pneumonia (this includes its nosocomial form);
• infections affecting the urethra;
• diseases in the intra-abdominal region;
• gynecological lesions (for example, endometritis);
• infections affecting soft tissues and the epidermis;
• septicemia or meningitis;
• empirical form of therapy in situations where bacterial infection is suspected in an adult with neutropenic fever (as monotherapy or in combination with antifungal or antiviral drugs).

Medopenem is used as monotherapy or in combination therapy with other antimicrobial drugs in people with polymicrobial forms of infections (for example, cystic fibrosis or chronic lesions in the lower respiratory tract).

Release form

The drug is produced in the form of a lyophilisate for the production of injection or infusion substances. The bottle has a volume of 500 or 1000 mg. There is 1 such bottle inside the pack.

Pharmacodynamics

Medopenem is a carbapenem antibiotic administered parenterally. It is relatively stable against the human DHP-1 element, so there is no need to add a DHP-1 inhibitor when using it.

The drug has a bactericidal effect, interfering with the process of binding of cell membranes, which is important for the life of microbes. It very easily penetrates into the cell membranes of bacteria, has high stability indices relative to all serine β-lactamases, and also a pronounced affinity with penicillin-synthesizing proteins. This is what ensures the strength of the bactericidal properties of the drug against a wide range of aerobes and anaerobes. Minimum bactericidal indices (MBI) are often similar to minimum inhibition indices (MIS). In 76% of microbes, the MBI/MIS ratio is 2 or lower.

The drug shows stability in sensitivity testing. In vitro studies demonstrate that it has a synergistic interaction with various antibiotics. In vitro and in vivo tests have shown that the drug has a post-antibiotic effect.

The antibacterial range of the drug in vitro includes most of the clinically important gram-negative and -positive microbial strains, as well as anaerobes and aerobes, which are listed below.

Gram-positive aerobes:

• Bacillus subtilis, Corynebacterium diphtheriae, Enterococcus liquifaciens, Enterococcus faecalis and Enterococcus avianus, as well as Nocardia asteroids, Listeria monocytogenes and Lactobacillus spp.;
• Staphylococcus aureus (penicillinase-negative and penicillinase-positive), Staphylococcus cohnii, Staphylococcus epidermidis, S. xylosus, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus simulans, Staphylococcus warneri, Staphylococcus hominis, and also S. sciuri, S. intermedius and Staphylococcus lugdunensis;
• pneumococcus (penicillin-sensitive or penicillin-resistant), Str.equi, pyogenic streptococcus, Str.bovis, Str.mitior, Streptococcus mitis, as well as Str.milleri, Streptococcus agalactiae, Streptococcus morbillorum, Streptococcus viridans, Str.sanguis, salivary streptococcus, R.equi, and streptococci of categories G and F.

Aerobes of the gram-negative type:

• Acinetobacter anitratus, Aeromonas sorbria, Aeromonas hydrophila, Achromobacter xylosoxidans, Acinetobacter baumannii, Acinetobacter lwoffii, hydrophilic aeromonas and faecal alkali former;
• Bordetella bronchiseptica, Brucella maltese, Citrobacter diversus, Campylobacter coli, Campylobacter jeuni, Citrobacter amalonaticus, as well as Citrobacter koseri and Citrobacter freundii;
• Enterobacter aerogenes, Enterobacter cloacae, Enterobacter (Pantoea) aglomeran and Enterobacter sakazakii;
• Escherichia coli, Escherichia hermannii;
• Gardnerella vaginalis, Haemophilus influenzae (this includes strains sensitive to β-lactamases and resistant to ampicillin), Ducray bacillus and Heamophilus parainfluenzae;
• Helicobacter pylori, meningococcus, gonococcus (including strains sensitive to β-lactamases and resistant to spectinomycin) and H.alvei;
• Klebsiella pneumoniae, Klebsiella ozaenae, Klebsiella aerogenes and Klebsiella oxytoca;
• Moraxella catarrhalis and Morgan's bacteria;
• common Proteus, Proteus mirabilis and Proteus penneri;
• Providence Rettger, Providence Stewart, P.alcalifaciens, Pasteurella multocida and Plesiomonas shigelloides;
• Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, B. cepacia, Pseudomonas fluorescens, Pseudomonas stutzeri, Burkholderia mallei, and Pseudomonas acidovorans;
• salmonella, including Salmonella enterica and Salmonella typhi;
• Serratia marcescens, Serratia rubidaea and Serratia liquefaciens;
• Shigella Sonne, Shigella Flexner, Shigella Boyd and the Grigoriev-Shigi bacterium;
• Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus and Yersinia enterocolitica.

Anaerobes:

• Actinomyces meyeri and Actinomyces odontolyticus;
• Bacteroides-Prevotella-Porphynomonas spp., Bacteroides fragilis, B. distasonis, Bacteroides vulgatus, B.pneumosintes, B.gracilis, as well as B.coagulans, B.variabilis, and B.levii. Also on the list are B.capsillosis, B.ovatus, thetayotaomicron, Bacteroides eggerthii, as well as B.uniformis, and Bacteroides ureolyticus;
• P.bivia, P.buccalis, P.melaninogenica, Prevotella splanchnicus, P.disiens, P.intermedia, P.oris, Prevotella oralis, P.buccae, P.rumenicola, Prevotella denticola, P.corporis;
• Porphyromonas gingivalis, bifidobacteria and Bilophila wadsworthia;
• Clostridium perfringens, Clostridium sordellii, C.bifermentalis, Clostridium sporogenes, C.cadaveris, C.clostridiiformis, C.subterminale, Clostridium ramosum, C.butyricum, Clostridium innocuum and C.tertium;
• Eubacterium aerofaciens and E.lentum;
• F.mortiferum, Schmorl's bacillus, Plaut's bacillus and Fusobacterium varium;
• M. mulieris, as well as Mobiluncus curtisii;
• Peptostreptococcus anaerobius, Peptostreptococcus saccharolyticus, P.magnus, Peptostreptococcus micros, as well as Peptostreptococcus asaccharolyticus and P.prevotii;
• Propionibacterium acnes, Propionibacterium granulosum, and Propionibacterium avidum.

Stenotrophomonas maltophilia, Enterococcus faecium and methicillin-resistant staphylococci were found to be resistant to Medopenem.

Pharmacokinetics

With intravenous injections, taking into account the portion size (500 or 1000 mg), as well as the method of administration (bolus or via IV), the Cmax values in the blood serum are equal to 23, 45, 49 and 112 mcg/ml, respectively.

Protein synthesis occurring within the plasma is 2%. The drug easily penetrates into various fluids (for example, cerebrospinal fluid) and tissues; bactericidal values are noted after 30-90 minutes after injection.

Weak biotransformation processes occur inside the liver, during which a single metabolic product (without medicinal activity) is formed. The half-life is 60 minutes.

Most of the substance is excreted through the kidneys (more than 70% in an unchanged state).

In individuals with renal insufficiency, drug clearance is in direct proportion to the decrease in CC.

The pharmacokinetic characteristics of the drug in children are similar to those in adults. The half-life in children under 2 years of age is about 1.5-2.3 hours; there is also a linear dependence of the drug values on the dosage size within portions of 10-40 mg/kg.

In elderly subjects, the clearance rate of Medopenem is reduced, correlating with the age-related decrease in creatinine clearance values.

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Dosing and administration

Scheme for an adult.

The dose size and duration of treatment are selected taking into account the patient’s condition, as well as the intensity and type of infection.

It is recommended to take the medicine in the following dosages per day:

• for infections in the urinary tract, pneumonia, and also for infections of a gynecological nature (for example, endometritis) and lesions affecting the subcutaneous layer and epidermis - 0.5 g of the drug at intervals of 8 hours;
• in case of peritonitis or nosocomial pneumonia, or if there is a suspicion of infection developing in people with septicemia or neutropenia - 1 g of the drug at 8-hour intervals;
• for cystic fibrosis, 2000 mg of the drug is used at 8-hour intervals;
• For meningitis, 2000 mg of the drug should be administered with 8-hour intervals.

As with other antibiotics, meropenem should be used with extreme caution as monotherapy in people with severe disease and diagnosed or suspected Pseudomonas aeruginosa in the lower respiratory tract.

During treatment of a patient infected with Pseudomonas aeruginosa, it is necessary to constantly test for susceptibility.

Dosage regimen for adults with renal insufficiency.

For individuals with CC values less than 51 ml/minute, the dosage should be reduced according to the scheme described below:

• CC values within the range of 26-50 ml/minute – 1 dosage unit*, applied at intervals equal to 12 hours;
• QC indicators within 10-25 ml/minute – 0.5 dosage units, applied at intervals of 12 hours;
• CC level <10 ml/minute – 0.5 dosage unit used at 24-hour intervals.

*compiled on the basis of dosage units equal to 0.5, 1 and 2 g.

Medopenem can be excreted by hemodialysis. If prolonged use of the drug is required, 1 dosage unit (depending on the severity and type of damage) should be administered at the end of the hemodialysis session. This is required to restore the drug's effective plasma values.

The drug was not used in people undergoing peritoneal dialysis.

Portions for a child.

Children aged 3 months to 12 years should be administered 10-20 mg/kg of the substance at 8-hour intervals, taking into account the type and degree of intensity of the lesion, the patient's condition and the sensitivity of the pathogenic microbe. Children weighing more than 50 kg should be prescribed adult dosages.

For children aged 4-18 years with cystic fibrosis, as well as in cases of exacerbation of chronic lesions in the lower respiratory tract, doses of 25-40 mg/kg are prescribed at 8-hour intervals. For the treatment of meningitis, 40 mg/kg should be used at 8-hour intervals.

Methods of using drugs.

The prepared liquid must be shaken before administration.

Bolus administration is carried out over 5 minutes, and infusion over approximately 15-30 minutes.

For a bolus injection, the substance is diluted using sterile injection water (5 ml per 0.25 g of the drug), obtaining a concentration equal to 50 mg/ml. The finished liquid becomes colorless (or has a pale yellow tint) and transparent.

For infusions, the medication is prepared using compatible infusion fluids (required volume 50-200 ml). Compatible medicinal substances include:

• 0.9% NaCl solution;
• 5% or 10% glucose solution;
• 5% glucose solution supplemented with 0.02% sodium bicarbonate;
• 5% glucose solution with 0.9% NaCl;
• 5% glucose solution with 0.225% NaCl;
• 5% glucose solution with 0.15% potassium chloride;
• 2.5% or 10% mannitol solution.

Use Medopenema during pregnancy

The drug is prohibited to use during pregnancy or lactation, except in situations where there is a possibility that the benefit to the woman is more expected than the development of severe consequences in the fetus or child. The drug should be used only under the supervision of the attending physician.

During therapy, breastfeeding must be discontinued.

Contraindications

Contraindicated for use in people with hypersensitivity to the medication.

Side effects Medopenema

The use of the medication may provoke the occurrence of various side effects:

• lesions in the lymphatic and circulatory system: thrombocytopenia often appears. Occasionally, eosinophilia occurs. Neutro- or leukopenia, hemolytic anemia or agranulocytosis may develop;
• disorders affecting the functioning of the nervous system: headaches often develop. Seizures appear sporadically. Paresthesia may develop;
• problems with digestive function: vomiting, abdominal pain, diarrhea or nausea often occur, and in addition, there is an increase in the values of alkaline phosphatase or transaminases, as well as LDH in the serum. Pseudomembranous colitis may occur;
• subcutaneous and epidermal lesions: itching or rashes often occur. Erythema multiforme, urticaria, TEN, and Stevens-Johnson syndrome may occur;
• systemic disorders and signs at the injection site: pain or inflammation often develops. Candidiasis (vaginal or oral form) or thrombophlebitis may occur;
• dysfunction of the hepatobiliary system: occasionally, an increase in bilirubin levels is observed;
• immune damage: signs of anaphylaxis or Quincke's edema may occur.

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Overdose

In case of intoxication, symptoms develop that are described as side effects.

Symptomatic measures and hemodialysis sessions are used to eliminate the disorders.

Interactions with other drugs

The drug should be used with great caution in combination with drugs that are potentially toxic to the kidneys.

Probenecid is a competitor of meropenem regarding tubular excretion, therefore it inhibits secretion through the kidneys, which results in an extension of the half-life and an increase in plasma values of the drug. Since the duration and severity of the effect of the drug used without probenecid is identical, it is prohibited to use them in combination.

Medopenem can reduce serum valproic acid levels, which in some individuals can reach subtherapeutic levels.

The drug is used together with other medications without any negative therapeutic interactions (except for the above-mentioned probenecid).

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Storage conditions

Medopenem should be kept in a place closed to children. Temperature values are maximum 25°C.

The liquid ready for intravenous administration should be used immediately, although the stability of such solutions is maintained for some time at temperatures of 2-8°C and up to 25°C.

It is prohibited to freeze the ready injection liquid. Vials can be used only once.

When preparing medicinal products and administering injections, it is necessary to follow the standards of existing aseptic conditions.

Shelf life

Medopenem can be used within 24 months from the date of manufacture of the drug.

Application for children

Medopenem is not used in infants under 3 months of age, nor in children with kidney or liver problems.

There is no experience of administration to children with immunodeficiency, either primary or secondary stage, or with neutropenia.

Analogues

The analogs of the drug are the drugs Merospen, Aris, Mepenem with Europenem, Meronem with Exipenem, as well as Merobocide, Alvopenem, Romenem and Merogram.

Reviews

Medopenem receives good reviews from people who have used it. The drug demonstrates high efficiency even in severe forms of diseases. With such a high-quality therapeutic effect, even the high cost of the drug is not considered its disadvantage.