Meropenem powder solution 1g vials, 1pc

Pharmacological action

Pharmacotherapeutic group: Antibiotic, Carbapenem Code ATX: J01DH02 Pharmacological action Antibiotic for parenteral use from the group of carbapenems. It has a bactericidal effect (suppresses the synthesis of the bacterial cell wall), easily penetrates the bacterial cell wall, and is resistant to most beta-lactamases.

Unlike imipenem, it is practically not destroyed in the renal tubules by dehydropeptidase-1 (it does not need to be combined with cilastatin, a specific dehydropeptidase – 1 inhibitor) and, accordingly, nephrotoxic degradation products are not formed, it has a high affinity for penicillin-binding proteins.

Bactericidal and bacteriostatic concentrations practically do not differ.

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, promotes the release of autolytic enzymes of the cell wall, which ultimately causes its damage and bacterial death.

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(penicillinazone-producing and penicillinase-producing [methicillin-sensitive]): Streptococcus agalactiae; Streptococcus pneumoniae (penicillin-sensitive only); Streptococcus pyogenes; Streptococcus spp. viridans groups.

Gram-negative aerobes:  Escherichia coli; Haemophilus influenza (penicillinase-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 in diseases caused by these pathogens has not been proven:

Gram-positive aerobes:  Staphylococcus Epidermidis (penicillinazone-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, penicillinaseproducing ashtami); Hafnia alvei; Klebsiella oxytoca; Moraxella catarrhalis (penicillinaseproducing and penicillinaseproducing); 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 use of 250 mg for 30 minutes with a_{max of} 11 mcg / ml, for a dose of 500 mg-23 mcg/ml,1 g-49 mcg/ml (there is no absolute pharmacokinetic proportional dependence on the administered dose for cmax and AUC). When the dose is increased from 0.25 to 2 g, the clearance decreases from 287 to 205 ml/min. With intravenous bolus use for 5 minutes,500 mg_cmax – 52 mcg / ml,1 g-112 mcg/ml. Binding to plasma proteins is 2%.

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

It underwent minor metabolism in the liver with the formation of a single inactive metabolite. T_1/2-1 h, in children under 2 years of age 1.5-2.3 h. In the dose range of 10-40 mg/kg in adults and children, a linear dependence of pharmacokinetic parameters is observed. It doesn’t accumulate. Excreted by the kidneys-70% unchanged for 12 hours. The concentration of meropenem in the urine, exceeding 10 mcg / ml, is maintained for 5 hours after use of 500 mg. In patients with renal insufficiency, clearance correlates with creatinine clearance (CC). In elderly patients, a decrease in meropenem clearance correlates with a decrease in age-related creatinine clearance. T_1/2-1.5 h. It is excreted during hemodialysis.

Indications

Meropenem is indicated for the treatment of the following infectious and inflammatory diseases caused by one or more meropenem-sensitive pathogens in children (older than 3 months) and adults: – pneumonia, including nosocomial pneumonia; – urinary tract infections; – abdominal infections; – infectious and inflammatory diseases of the pelvic organs, such as endometritis; – infections of the skin and its structures; – meningitis; – septicemia. Empirical treatment of adult patients with suspected infection with symptoms of febrile neutropenia in monotherapy or in combination with antiviral or antifungal drugs. The effectiveness of Meropenem has been proven both in monotherapy and in combination with other antimicrobial agents in the treatment of polymicrobial infections. Intravenous use of meropenem has been shown to be effective in the treatment of cystic fibrosis and chronic lower respiratory tract infections, both as monotherapy and in combination with other antibacterial agents. Microbial eradication has not always been confirmed.

Use during pregnancy and lactation

Pregnancy The safety of using Meropenem in women during pregnancy has not been studied. Animal studies have not shown any adverse effects on the developing fetus. Meropenem should not be used during pregnancy, unless the potential benefit to the mother from its use exceeds the possible risk to the fetus. In each case, the drug should be used under strict medical supervision. Breast-feeding period Data on the excretion of meropenem in breast milk were obtained. Meropenem should not be used during breastfeeding, unless the potential benefit to the mother from using the drug exceeds the possible risk to the child. After evaluating the benefit to the mother, a decision should be made to stop breastfeeding or to discontinue the drug Meropenem.

Contraindications

A history of hypersensitivity to meropenem or other carbapenem drugs.

Severe hypersensitivity (anaphylactic reactions, severe skin reactions) to any antibacterial agent having a beta-lactam structure (i. e., to penicillins or cephalosporins).

Children under 3 months of age.

With caution

Concomitant use with potentially nephrotoxic drugs.

Patients with complaints from the gastrointestinal tract (diarrhea), especially those suffering from colitis.

Side effects

From the digestive system:  epigastric pain, 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 aggravation of heart failure, cardiac arrest, tachy – or bradycardia, decrease or increase in blood pressure, syncope, myocardial infarction, thromboembolism of the branches of the pulmonary artery.

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

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

Nervous system disorders:  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, reduced partial thromboplastin time.

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

Other services:  false positive direct or indirect Coombs test, anemia, hypervolemia, dyspnoea, vaginal candidiasis.

Interaction

Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and plasma concentration of meropenem. Since the efficacy and duration of action of Meropenem administered without probenecid are adequate, co-use of probenecid with Meropenem is not recommended. The possible effect of Meropenem on the degree of binding of other drugs to plasma proteins or metabolism has not been studied. The association of Meropenem with plasma proteins is low (about 2%), so interaction with other drugs based on the mechanism of displacement from the connection with plasma proteins is not expected. Concomitant use of carbapenems and valproic acid preparations resulted in a decrease in the concentration of valproic acid in blood plasma by 60-100% after 2 days of therapy. Due to the rapid and significant decrease in the concentration of valproic acid, the combined use of Meropenem and valproic acid preparations is not recommended.The use of Meropenem while taking other medications was not accompanied by the development of adverse pharmacological interactions. Studies on the interaction of meropenem with other drugs (with the exception of probenecid) have not been conducted. Cases of increased anticoagulant effect have been repeatedly reported with the combined use of indirect anticoagulants (for example, warfarin) and antibacterial drugs. The risk of increasing the 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 an increase in the international normalized ratio (INR). Frequent monitoring of INR is recommended during co-use of an antibacterial drug and an indirect anticoagulant and for some time after its discontinuation.

How to take, course of use and dosage

of IV.

Intravenous bolus diluted with sterile water for injection 10 ml per 500 mg,15 mg per 1000 mg for at least 5 minutes.

Intravenous infusion for 15-30 minutes in a dilution of up to 50-200 ml of a compatible infusion fluid.

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

For adults:

• in pneumonia, infections of the urinary tract, infectious-inflammatory diseases of the pelvic organs, infections of skin and soft tissue/V. 500 mg every 8 h;
• in-hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, septicemia – I/1 g 3 times/day;
• in meningitis 2 g every 8 h

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

Meropenem is eliminated by hemodialysis. To restore the effective plasma concentration at the end of the hemodialysis procedure, a single dose of meropenem recommended for the relevant pathology should be administered.

For children:

• at the age of 3 months to 12 years, a single dose for intravenous use is 10-20 mg / kg 3 times / day;
• for children with a body weight of more than 50 kg, adult doses are used;
• for meningitis, IV 40 mg/kg every 8 hours.

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

Overdose

Accidental overdose may occur during treatment, especially in patients with impaired renal function. Treatment in case of overdose should be symptomatic. Normally, rapid elimination of the drug through the kidneys occurs. In patients with impaired renal function, hemodialysis effectively removes meropenem and its metabolite.

Special instructions

There is no experience of using the drug in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency.

As with other antibiotics, when meropenem is used as monotherapy in critically ill patients with a suspected lower respiratory tract infection caused by Pseudomonas aeruginosa, regular sensitivity testing is recommended.

Severe skin adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic syndromes (DRESS-syndrome), erythema multiforme, acute generalized exanthematous pustulosis, have been observed in patients receiving Meropenem therapy (see section “Side effects”). In case of signs and symptoms that indicate the development of these reactions, meropenem therapy should be discontinued immediately and alternative treatment should be considered.

In rare cases, when using Meropenem, as with almost all antibiotics, pseudomembranous colitis develops, which can vary in severity from mild to life-threatening forms. It is important to keep in mind the possibility of developing pseudomembranous colitis if diarrhea occurs during the use of Meropenem. If pseudomembranous colitis develops, Meropenem should be discontinued. The use of drugs that inhibit intestinal motility is contraindicated.

Seizures have been reported infrequently with carbapenems, including meropenem. Caution should be exercised when using the drug

Meropenem in patients with a reduced threshold of convulsive readiness.

There are clinical and laboratory signs of cross-allergic reactions between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. There are rare reports of hypersensitivity reactions (including fatal ones) when using Meropenem, as well as other beta-lactam antibiotics (see the section “Side effects”). Before starting meropenem therapy, the patient should be thoroughly interviewed, paying special attention to the history of hypersensitivity reactions to beta-lactam antibiotics. Meropenem should be used with caution in patients with a history of hypersensitivity reactions to beta-lactam antibiotics (i. e. penicillins and cephalosporins). If there is an allergic reaction to meropenem, then it is necessary to stop the drug use and take appropriate measures.

The use of Meropenem in patients with liver diseases should be carried out under careful monitoring of transaminase activity and bilirubin concentration.

As with the use of other antibiotics, excessive growth of insensitive microorganisms is possible, and therefore constant monitoring of the patient is necessary.

The prevalence of acquired antibiotic resistance of various pathogens may vary depending on the region and over time, and it is desirable to have up-to-date information on the resistance of common pathogens in a particular region, especially in the treatment of severe infections. If the resistance is such that the effectiveness of the drug against at least some infections becomes questionable, you should consult an expert.

Co-use of Meropenem and valproic acid preparations is not recommended due to a possible decrease in the concentration of valproic acid in the blood serum.

In some patients, the concentration may be lower than the therapeutic one (see the section “Interaction with other drugs”). The use of the drug for infections caused by methicillin-resistant staphylococcus is not recommended.

Influence on the ability to drive vehicles and mechanisms

No studies have been conducted on the effect of Meropenem on the ability to drive a car or other equipment. However, it should be taken into account that when taking Meropenem, headache, paresthesia and convulsions may occur.

Storage conditions

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Meropenem

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection