Meropenem Spencer - instructions for use, dose, side effects, contraindications

Active substance: meropenem trihydrate 570 mg (equivalent to meropeneme anhydrous 500 mg) and meropenem trihydrate 1140 mg (equivalent to meropenem 1000 mg anhydrous);

Excipient: sodium carbonate anhydrous 104.0 mg and 208.0 mg

Description:

From white to white with a yellowish hue of color powder.

Pharmacotherapeutic group:antibiotic - carbapenem

ATX: & nbsp

J.01.D.H.02 Meropenem

J.01.D.H Carbapenems

Pharmacodynamics:

Meropenem is an antibiotic of the carbapenem class, intended for parenteral use, relatively resistant to human dehydropeptidase-1 (DHP-1), does not require additional administration of DHP-1 inhibitor.

Meropenem has a bactericidal effect due to the effect on the synthesis of the bacterial cell wall. High bactericidal activity of meropenem against a wide range of aerobic and anaerobicof bacteria is due to the high capacity of meropenem to penetrate the bacterial cell wall, a high level of stability to most beta-lactamases and a significant affinity for penicillin-binding proteins (BSP). The minimum bactericidal concentrations (MBCs) are usually the same as the minimum inhibitory concentrations (MICs). For 76% of the tested bacterial species, the MBC / MIC ratio was 2 or less.

Tests in vitro show that meropenem acts synergistically with various antibiotics. In the tests in vitro and in vivo shown, that meropenem has a post-antibiotic effect.

The only recommended criteria for sensitivity to meropenem are based on the pharmacokinetics of the drug and on the correlation of clinical and microbiological data - the diameter of the zone and MICs, determined for the respective pathogens.

Category of the pathogen	Diameter of the zone (mm)
Sensitive	≥ 14
Intermediate	from 12 to 13
Resistant	≤11

The following table shows the threshold values of MIC of meropenem in the European Union (EU) for various bacterial pathogens in clinical settings:

Pathogens	Sensitivity (mg / l)	Resistance (mg / l)
Enterobacteriaceae	≤2	>8
Pseudomonas	≤2	>8
Acinetobacter	≤2	>8
Streptococcus groups A, B, C, G	≤2	>2
Streptococcus pneumoniae¹	≤2	>2
Other streptococci	2	2
Enterococcus⁵	-	-
Staphylococcus²	Depends on the availability of sensitivity to methicillin
Haemophilus influenzae¹,	≤2	>2
Moraxella catarrhal is
Neisseria meningitidis2,3	≤0,25	>0,25
Gram-positive anaerobes	≤2	> 8
Gram-negative anaerobes	≤2	> 8
Nonspecific thresholds	≤2	> 8
meanings⁴

¹: Sensitivity threshold for Streptococcus pneumoniae and Haemophilus influenzae when meningitis - 0.25 mg / l.

²: Strains for which MICs are above the sensitivity threshold are rare or not currently detectable. In identifying such strains MIC test is conducted repeatedly, the confirmation result is sent to the reference strain laboratory strain and considered resistant confirmed by obtaining clinical effect relative thereto.

³: Values used only for meningitis.

⁴: For all other pathogens, according to pharmacokinetic and

pharmacodynamic data, without taking into account the specific distribution of MIC specific pathogens.

⁵: The sensitivity test is not recommended, since this agent is not the optimal target for meropenem.

The sensitivity to meropenem should be determined using standard methods. Interpretation of results should be carried out in accordance with local guidelines.

The effectiveness of the drug against the pathogens listed below is confirmed by clinical experience and guidelines for antibiotic therapy:

Pathogens sensitive to meropenem:

Gram-positive aerobes:

Enterococcus faecalis¹,

Staphylococcus aureus (methicillin-sensitive)²

Genus Staphylococcus (methicillin-sensitive), including Staphylococcus epidermidis

Group B Streptococcus agalactiae

Group Streptococcus milleri (S. angiosus, S. constellatus, and S. intermedius)

Streptococcus pneumoniae

Streptococcus pyogenes group A

Gram-negative aerobes:

Citrobacter freudii

Citrobacter koseri

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Morganella morganii

Neisseria meningitidis

Proteus mirabilis

Proteus vulgaris

Serratia marcescens

Gram-positive anaerobes:

Clostridium perfringens

Peptoniphilus asaccharolyticus

Genus Peptostreptococcus (including P. micros, P anaerobius, P. magnus)

Gram-negative anaerobes:

Bacteroides caccae

Bacteroides fragilis

Prevotella bivia

Prevotella disiens

Pathogens for which the problem of acquired resistance is relevant:

Gram-positive aerobes:

Enterococcus faecium^1,3

Gram-negative aerobes:

Genus Acinetobacter

Burkholderia cepacia

Pseudomonas aeruginosa

Pathogens with natural resistance:

Gram-negative aerobes:

Stenotrophomonas maltophilia

Legionella spp.

Other pathogens:

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetii

Mycoplasma pneumoniae

¹:pathogens with intermediate sensitivity;

²: all methicillin-resistant staphylococci are resistant to meropenem;

³: the resistance level is> 50% in one or more EU countries.

Pharmacokinetics:With a single intravenous (IV) administration within 30 minutes, the maximum concentration (Cma) of meropenem in plasma is 23 μg / ml for a dose of 500 mg and 49 μg / ml for a dose of 1 g. Cmax in plasma after 5 min of bolus injection is 52 μg / ml for a dose of 500 mg and 112 μg / ml for a dose of 1 g .

Extended (up to 3 hours) infusion of carbapenems can lead to optimization of their pharmacokinetic and pharmacodynamic parameters. With a standard 30-minute infusion in healthy volunteers, two doses of 500 mg and 2000 mg every 8 hours, the value of% T> MIC (the ratio between the period of time when the concentration of the drug exceeds MIC and the dosing interval, MIC = 4 μg / ml) was 30 % and 58%. When volunteers were given the same doses by a 3-hour infusion every 8 hours, the% T> MIC index increased to 43 and 73%, respectively, for 500 mg and 2000 mg. The mean plasma concentration in healthy volunteers after intravenous bolus administration for 1000 min exceeded the MIC of 4 μg / ml for 42% of the dosing interval, compared to 59% for a 3-hour infusion of 1000 mg.

Well penetrates into most tissues and body fluids, incl. in the cerebrospinal fluid (CSF) of patients with bacterial meningitis, reaching concentrations,exceeding the required for suppression of the majority of bacteria (bactericidal concentrations are created 0.5-1.5 h after the start of infusion). In small amounts penetrates into breast milk.

Binding to plasma proteins is approximately 2%. Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. Half-life (T1 / 2) - 1 hour, in children under 2 years - 1.5-2.3 hours. In the dose range of 10-40 mg / kg in children, a linear dependence of pharmacokinetic parameters is observed. Do not cumulate.

It is excreted by the kidneys - 70% unchanged for 12 hours. The concentration of meropenem in the urine, exceeding 10 μg / ml, is maintained for 5 hours after the administration of 500 mg. In patients with renal insufficiency, the clearance of meropenem correlates with creatinine clearance. It is in hemodialysis. In elderly patients, a decrease in meropenem clearance correlates with a decrease in QC associated with age. T1 / 2 -1.5 hours. In patients with liver disease, the pharmacokinetics of meropenem does not change.

Indications:Infectious-inflammatory diseases caused by one or several microorganisms that are sensitive to meropenem: lower respiratory tract infections (pneumonia, including hospital pneumonia); Intra-abdominal infections (complicated appendicitis,peritonitis); urinary tract infection (pyelonephritis, pyelitis); infections of the skin and soft tissues (including erysipelas, impetigo, secondarily infected dermatoses); bacterial meningitis; septicemia; infectious inflammatory diseases of the pelvic organs (such as endometritis).

Empirical treatment (in the form of monotherapy or combination with antiviral or antifungal agents) with suspected bacterial infection in adult patients with febrile episodes against neutropenia. The effectiveness of the drug has been proven both in monotherapy mode and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications:

Hypersensitivity to meropenem, other components of the drug and other carbapenems, severe hypersensitivity (anaphylactic reactions, severe skin reactions) to other beta-lactam antibiotics (ie to penicillins or cephalosporins); children's age (up to 3 months).

Carefully:

When used simultaneously with nephrotoxic drugs, patients with complaints from the gastrointestinal tract, especially with colitis.

Pregnancy and lactation:

The safety of the use of meropenem in women during pregnancy has not been studied. The drug should not be used during pregnancy, except when the potential benefit of its use for the mother exceeds the possible risk to the fetus. In each case, the drug should be administered under strict medical supervision. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:Intravenous bolus for at least 5 minutes, or as an intravenous infusion during 15-30 minutes.

The possibility of using meropenem in the regime of prolonged infusion (up to 3 hours) is based on pharmacokinetic and pharmacodynamic parameters (see the section "Pharmacokinetics"). To date, clinical data and safety data that support this regimen are limited.

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

Adults

0.5 g intravenously every 8 hours for pneumonia, infections of the urinary system, infectious and inflammatory diseases of the pelvic organs, infections of the skin and soft tissues.

1 g intravenously every 8 hours with hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, and septicemia.

With bacterial meningitis, the recommended dose is 2 g every 8 hours.

The safety of administering a dose of 2 g as a bolus injection has not been sufficiently studied.

In chronic renal insufficiency, the dose is adjusted depending on the creatinine clearance (CC): for KK 26-50 ml / min - 0.5-1-2 g 2 times a day, 10-25 ml / min - 250-500-1000 mg 2 times a day, less than 10 ml / min - but 250-500-1000 mg once a day.

Meropenem is excreted in hemodialysis and hemofiltration. If long-term treatment is required, it is recommended that the dose unit (determined depending on the type and severity of the infection) be administered at the end of the hemodialysis procedure to restore the effective concentration in the blood plasma. Currently, there is no evidence of experience with the use of meropenem in patients on peritoneal dialysis.

In patients with hepatic insufficiency, dose adjustment is not required.

In elderly patients with QC more than 50 ml / min dose adjustment is not required.

Children

For children aged 3 months to 12 yearsthe recommended dose for intravenous administration is 10-20 mg / kg body weight every 8 hours, depending on the type and severity of the infection, the sensitivity of the pathogen and the patient's condition. Children with a body weight of more than 50 kg should use doses for adults.

With meningitis, the recommended dose is 40 mg / kg every 8 hours. The safety of administering a dose of 40 mg / kg as a bolus injection has not been sufficiently studied. There is no experience of using the drug in children with impaired liver and kidney function.

Preparation of solutions To prepare a solution for intravenous bolus injections, the drug should be dissolved with sterile water for injection (5 ml per 250 mg), with a solution concentration of 50 mg / ml. The resulting solution remains stable for 3 hours at a temperature of up to 25 ° C and for 16 hours when stored in a refrigerator (2-8 ° C).

For solution preparation

For intravenous infusions, the drug should be dissolved with 0.9% sodium chloride solution or 5% dextrose solution, with the concentration of the solution should be from 1 to 20 mg / ml. The resulting solution remains stable for 3 hours at a temperature of up to 25 ° C and for 24 hours when it is frozen in the refrigerator (2-8 ° C), if 0.9% sodium chloride solution was used for its preparation.A solution prepared using a 5% dextrose solution should be used immediately.

Meropenem should not be mixed with solutions containing other drugs. The drug solution should not be frozen. The prepared solution is recommended to be administered immediately after preparation (from the microbiological point of view), if the conditions for the preparation of the solution do not exclude the possibility of microbiological contamination.

Side effects:

Generally, meropenem is characterized by good tolerability. In rare cases side effects led to the abolition of therapy.

Serious adverse reactions are rare.

From the digestive system: nausea, vomiting, diarrhea, increased activity of "liver" transaminases, alkaline phosphatase, lactate dehydrogenase, hyperbilirubinemia, pseudomembranous colitis.

On the part of the hematopoiesis system: thrombocytosis, eosinophilia, thrombocytopaia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia.

From the nervous system: headache, paresthesia, convulsions.

Allergic reactions: itching of the skin, skin rash, urticaria, multiforme exudative erythema, Stevens-Johnson syndrome,toxic epidermal necrolysis, angioedema, anaphylactic shock.

From the urinary system:hyperkreatininemia, increased urea concentration in plasma.

Local reactions: inflammation, thrombophlebitis, tenderness at the injection site.

Other: positive direct or indirect samples of Coombs, reduction of partial thromboplastin time, vaginal candidiasis, candidiasis of the oral mucosa.

The cause-and-effect relationship with the use of meropenem is not established: fainting, hallucinations, depression, anxiety, increased excitability, insomnia, constipation, cholestatic hepatitis, heart failure, cardiac arrest, tachycardia, bradycardia, myocardial infarction, decrease or increase of arterial pressure, pulmonary thromboembolism , dyspnea.

Overdose:Accidental overdose is possible during treatment, especially in patients with impaired renal function.

Treatment in case of an overdose should be symptomatic. When hemodialysis occurs, rapid elimination of the drug.

Interaction:

Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and concentration of meropenem in plasma.Since the efficacy and duration of action of meropenem administered without probenecid is adequate, joint administration of probenecid with meropenem is not recommended.

The possible effect of meropenem on the degree of association of other drugs with 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 plasma protein binding is not expected.

Meropenem can reduce the concentration of valproic acid in the blood serum. In some patients, concentrations below therapeutic may be achieved. The combined use of carbapenems and valproic acid preparations led to 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.

There are no specific data on possible drug interactions (with the exception of probenecid).

The use of meropenem during the administration of other drugs was not accompanied by the development of unfavorable pharmacological interactions.

Special instructions:

Experience with the use of meropenem in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency is not present.

When monotherapy of a known or suspected lower respiratory tract infection of severe course caused by Pseudomonas aeruginosa, It is recommended to regularly determine the sensitivity of the pathogen

When using meropenem, the development of pseudomembranous colitis (toxin produced Clostridium difficile, is one of the main causes of colitis associated with antibiotics), which can vary in severity from mild to life-threatening forms. It is important to remember the possibility of developing pseudomembranous colitis when diarrhea occurs on the background of treatment.

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may exhibit hypersensitivity to meropenem. Before starting treatment, you should carefully question the patient for any history of allergic reactions. If there is an allergic reaction to meropenem, it is necessary to stop the introduction of the drug and take appropriate measures.

Treatment of patients with liver disease should be conducted under careful monitoring of the activity of "liver" transaminases and bilirubin concentrations.

In the process of treatment, the development of resistance of pathogens is possible, in connection with which the treatment is carried out with a constant control of the distribution of resistant strains.

The use of meropenem in infections caused by methicillin-resistant strains is not recommended Staphylococcus spp.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Powder for the preparation of a solution for intravenous administration of 500 mg and 1000 mg.

Packaging:For 500 mg of active substance in glass bottles with a capacity of 20 ml and 1000 mg of active substance in glass bottles with a capacity of 30 ml, closed with a rubber stopper, crimped with an aluminum ring and plastic lid.

For 1 or 10 vials with the drug, along with instructions for use in a cardboard pack with the control of the first opening.

Storage conditions:Keep in dry the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

4 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001342/07

Date of registration:29.06.2007 / 07.05.2015

Expiration Date:Unlimited

The owner of the registration certificate:Spencer Pharma UK LimitedSpencer Pharma UK Limited United Kingdom

Manufacturer: & nbsp

COOPER PHARMA India

Acorn India Pvt. Ltd. India

Representation: & nbspSharan Pharma, LLCSharan Pharma, LLC

Information update date: & nbsp27.11.2016

Illustrated instructions

Instructions

Meropenem Spencer (Meropenem Spencer)