Meropidel - instructions for use, doses, side effects, contraindications

Name of components	Amount, mg
	500 mg	1000 mg
Active substance
Meropenem trihydrate (in terms of	570,0	1140,0
meropenem)	(500,0)	(1000.0)
Excipient
Sodium carbonate	104,0	208,0
(in terms of sodium)¹	(45,1)	(90,2)
Total weight of the contents of the bottle	674,0	1348,0

1 - a mixture of meropenem trihydrate and sodium carbonate is used as the active substance. The content of sodium carbonate in the mixture is 15.4%;

Description:White or white with a yellowish tint powder.

Pharmacotherapeutic group:Antibiotic carbapenem

ATX: & nbsp

J.01.D.H.02 Meropenem

J.01.D.H Carbapenems

Pharmacodynamics:

Mechanism of action

Meropenem has bactericidal activity, inhibiting the synthesis of the cell wall of Gram-positive and Gram-negative bacteria by binding to penicillin-binding proteins (PSB).

The mechanism of development of resistance

The resistance of bacteria to meropenem can develop due to: a decrease in the permeability of the outer membrane of Gram-negative bacteria (due to a reduction in the number of porin channels), a decrease in affinity to the target PSB, an increase in efflux and the production of beta-lactamases capable of hydrolyzing carbapenems. Cross-resistance between meropenem and drugs belonging to the classes of quinolones, aminoglycosides, macrolides and tetracyclines, due to their mechanism of action, is absent. However, if the resistance mechanism is caused by a violation of the permeability of the cell wall and / or efflux, bacteria can develop resistance to drugs belonging to different classes.

The antibacterial spectrum of meropenem, determined experimentally on models in vitro, includes the majority of gram-positive and gram-negative, aerobic and anaerobic strains of bacteria of clinical significance.

Gram-positive aerobes

Enterococcus faecalis

Staphylococcus aureus (methicillin-sensitive)

Staphylococcus spp. (methicillin-sensitive), including Staphylococcus epidermidis Streptococcus agalactiae (group B)

Group Streptococcus milleri (S. anginosus, 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

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

Gram-negative anaerobes

Bacteroides caccae

Group Bacteroides fragilis

Prevotella bivia

Prevotella disiens

Types for which the acquired resistance is possible

Gram-positive aerobes

Enterococcus faecium

Gram-negative aerobes

Acinetobacter spp.

Burkholderia cepacia

Pseudomonas aeruginosa

Species with natural resistance

Gram-negative aerobes

Stenotrophomonas maltophilia

Legionella spp.

Other microorganisms

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetii

Mycoplasma pneumoniae

Pharmacokinetics:

Suction

In healthy volunteers, after a thirty-minute intravenous infusion of a single dose of meropenem, its maximum plasma concentration is 11 μg / ml when a dose of 250 mg, 23 μg / ml is given with a dose of 500 mg and 49 μg / ml when a dose is given , equal to 1 g.

However, in this case, there is no absolute pharmacokinetic relationship between the maximum concentration and the administered dose, which is confirmed byCmah (the maximum concentration in the blood plasma) and AUC (area under the concentration-time curve).Moreover, when a dose of the drug was administered in the range from 250 mg to 2 g, a decrease in plasma clearance from 287 ml / min to 205 ml / min was observed.

In healthy volunteers, after a five-minute intravenous bolus administration of meropenem, its peak plasma concentration is 52 μg / ml with a dose of 500 mg and 112 μg / ml when a dose of 1 g is administered.

With repeated administration of meropenem, patients with normal renal function with an interval of 8 h accumulate the drug in the body does not occur.

With normal renal function, the half-life of meropenem is approximately 1 hour.

Distribution

The binding of meropenem to plasma proteins is about 2% and does not depend on the concentration of the drug. After rapid administration (no more than 5 minutes) of meropenem, its pharmacokinetics corresponds to bi-exponential. After the infusion introduction for 30 minutes, this correspondence becomes less obvious. It was shown that meropenem penetrates into some tissues and fluids of the human body: lung tissue, the secret of bronchi, bile, cerebrospinal fluid, female genital tissue, skin, fascia, muscle tissue and peritoneal exudate.

Metabolism

Metabolism of meropenem occurs by hydrolysis of the beta-lactam ring with the formation of a microbiologically inactive metabolite. In the models in vitro Meropenem, unlike imipenem, demonstrates a low susceptibility to hydrolysis by dehydropeptidase-I (DHP-I) rights. For this reason, there is no need for simultaneous application of an inhibitor DHP-I.

Excretion

The excretion of meropenem is carried out mainly by the kidneys; about 70% (from 50% to 75%) of the dose of the drug is excreted unchanged for 12 hours. 28% of the dose is excreted as a microbiologically inactive metabolite. 2 % The dose of the drug is excreted through the gastrointestinal tract. The magnitude of renal clearance and the effect of probenecid show that meropenem is subjected to both filtration and tubular secretion.

Pharmacokinetics in children

Studies involving children have shown that in children the pharmacokinetic parameters of meropenem are similar to those of adults. Have of children less than two years, the half-life of meropenem ranged from 1.5 hours to 2.3 hours, and when administered in a dose range of 10 mg / kg to 40 mg / kg, the pharmacokinetics corresponded to the linear model.

Pharmacokinetics in elderly patients

Results of pharmacokinetic studies involving healthy elderly volunteers (from 65 years to 80 years) demonstrated a decrease in plasma clearance, associated with an age-related decrease in creatinine clearance and a slight decrease in the extrarenal clearance. Elderly patients do not need a dose adjustment, except for moderate or severe renal failure.

Pharmacokinetics in patients with renal insufficiency

Results of pharmacokinetic studies with participation of patients, suffering renal insufficiency, showed the relationship between plasma clearance of meropenem and creatinine clearance. Patients with renal insufficiency require a dose adjustment.

Pharmacokinetics in patients with impaired hepatic function

Results of pharmacokinetic research from participation of patients, suffering liver disease, showed no influence of diseases liver on pharmacokinetics of meropenem.

Indications:

Treatment of infectious and inflammatory diseases caused by microorganisms that are sensitive to meropenem, in adults and children older than 3 months:

- pneumonia, including nosocomial pneumonia;

- urinary tract infection;

- infection of the abdominal cavity;

- Infectious-inflammatory diseases of the pelvic organs, such as endometritis;

- infection of the skin and its structures;

- meningitis;

- septicemia.

Empirical therapy of adult patients with a presumed infection with symptoms of febrile neutropenia in monotherapy or in combination with antiviral and antifungal agents.

The effectiveness of the drug Meropidel is proven both in monotherapy mode and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications:

- Hypersensitivity to the active substance or any auxiliary substance of the drug;

- hypersensitivity to any other antibacterial agent of the carbapenem group;

- high-sensitivity (for example, anaphylactic reactions, severe skin reactions) to any other beta-lactam antibacterial drug (for example, to penicillins or cephalosporins) (see "Special instructions", "Side effects");

- children under 3 months.

Carefully:

In patients with concomitant impairment of liver function.

Simultaneous use with potentially nephrotoxic drugs.

Patients with complaints from the gastrointestinal tract (especially with colitis).

Pregnancy and lactation:

Pregnancy

During pregnancy meropenem should not be used, except when the expected benefit of therapy for the mother exceeds the possible risk to the fetus. The safety of the use of meropenem during pregnancy in women has not been studied. In preclinical studies, there was no adverse effect on fetal development.

Breastfeeding period

Do not use meropenem in nursing mothers, unless the expected benefit of therapy for the mother exceeds the possible risk to the child. It should be decided whether to stop breastfeeding or stop using meropenem, taking into account the benefits of treatment for a woman.

Meropenem is determined in the milk of animals in very low concentrations. The isolation of meropenem in breast milk in women has not been studied.

Dosing and Administration:

For intravenous administration.

To determine the dose of Msrnspsma and The duration of treatment is take into account the type of infection, severity and clinical situation.

Adults and children over 12 years of age

The following daily doses are recommended:

500 mg intravenously every 8 hours for treatment of pneumonia. infections urinary tract, gynecological infections such as endometritis, infections skin and skin structures;

1 g intravenously every 8 hours for treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with symptoms neutropenip, and also septicemia.

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

Safety of taking a dose of 2 g in the form bolus injection is not well understood.

Special patient groups

Children

Children aged from 3 months to 12 years with body weight up to 50 kg

Recommended dose for intravenous administration is 10-20 mg / kg every 8 hours depending on type and severity infection, the sensitivity of the pathogenic microorganism and the patient's condition.

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

The safety of taking a dose of 40 mg / kg in the form of bolus injection is not well understood.

No experience of using the drug in children with a violation of the liver and kidneys.

Children with a body weight of more than 50 kg

The drug should be used in a dose, used in adults.

Elderly patients

In elderly patients with normal kidney function or creatinine clearance more than 50 ml / min dose adjustment not required.

Adults and children older than 12 years with impaired renal function

Correction of the dose of the drug is required if the creatinine clearance is less than 51 ml / min, as shown below.

Creatinine clearance (ml / min)	The dose (calculated on the basis of standard doses equal to 500 mg, 1 g, 2 g)	Frequency of administration
26-50	one standard dose	every 12 hours
10-25	half the standard dose	every 12 hours
<10	half the standard dose	every 24 hours

Meropenem is excreted from the body during hemodialysis and hemofiltration. If long-term treatment with Meronidel® is required, it is recommended that the drug (depending on the type and severity of the infection) be administered at the end of the hemodialysis procedure in order to restore an effective concentration in the blood plasma.

Currently, there is no data on the experience of using the drug Meropidel® for administration to patients on peritoneal dialysis.

Adults and children older than 12 years with impaired liver function

In patients with hepatic insufficiency, dose adjustment is not required (see section "Special instructions").

Cooking method

Solution of the drug Meropidel® introduce by intravenous bolus injection in for 5 minutes or by intravenous infusion lasting from 15 minutes up to 30 minutes.

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. To prepare a solution for intravenous infusion, 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.

During the preparation of the reconstituted solution should be used standard methods of asepsis. Before using a reconstituted solution should be shaken.

For intravenous injections and infusions it is recommended to apply freshlyprepared drug solution Meropidel®.

Side effects:

The adverse events presented below are listed in accordance with the damage to organs and organ systems and according to the frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥ 1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1000 and <1/100), rarely (≥ 1/10 000 and <1/1000), rarely (<1/10 000, including individual cases) and unknown (can not be estimated based on available data). Frequency categories were formed on the basis of post-registration observation.

Frequency of occurrence of undesirable phenomena

Infections and parasitic diseases

Infrequently: candidiasis of the oral cavity, vaginal candidiasis.

Violations of the blood and lymphatic system

Often: thrombocythemia.

Infrequently: eosinophilia, thrombocytopenia. leukopenia, neutropenia.

Unknown: agranulocytosis, hemolytic anemia.

Immune system disorders

Unknown: angioedema, anaphylactic reaction (cm. "Disturbances from the skin and subcutaneous tissue").

Disturbances from the nervous system

Often: headache.

Infrequently: paresthesia, fainting¹, hallucinations¹, depression¹, anxiety¹, increased excitability¹, insomnia¹.

Rarely: convulsions (see "Special instructions").

Disorders from the digestive system

Often: nausea, vomiting, diarrhea, abdominal pain.

Infrequently: constipation¹, cholestatic hepatitis¹.

Unknown: antibiotic-associated colitis."Special instructions").

Disturbances from the liver and bile ducts

Often: increased activity of "liver" transaminases, alkaline phosphatase and lactate dehydrogenase in the blood.

Infrequently: increase in the level of bilirubin in the blood.

Disturbances from the skin and subcutaneous tissue

Often: rash, itching.

Infrequently: hives.

Unknown: multiform erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis. "Impaired immune system").

Disorders from the kidneys and urinary tract

Infrequently: increasing the concentration of creatinine and urea in the blood.

Heart Disease

Infrequently: heart failure, stop hearts¹, tachycardia¹, bradycardia¹, myocardial infarction¹.

Vascular disorders

Infrequently: thromboembolism branches pulmonary arteries¹, decline or increase in blood pressure¹.

Disturbances from the respiratory system, organs of the chest and mediastinum

Infrequently: dyspnoea¹.

General disorders and reactions at the site of administration

Often: inflammation, pain.

Infrequently: thrombophlebitis.

Unknown: pain in the injection site.

¹ - a causal relationship with the use of the drug is not established.

Overdose:

In patients with renal insufficiency, a relative overdose is possible if dose adjustment has not been performed (see the section "Dosing and Administration").

Symptoms

Increased dose-dependent side effects.

Treatment

Treatment of an overdose should be symptomatic. With normal kidney function, the drug is rapidly excreted by the kidneys; with renal insufficiency meropenem and its metabolite are excreted from the body by hemodialysis.

Interaction:

Special Interaction Studies This drug with other drugs, except probenecid, not conducted.

Probenecid

Probenecid competes with meropenem for active tubular secretion, such way, inhibits excretion meropenema by the kidneys, causing an increase its half-life and concentration in the blood plasma. Joint introduction Probenecid and meropenem are not recommended.

Linking others medicinal preparations with proteins

Potential influence of meropenem on binding of other medicinal products preparations with proteins or their metabolism not studied. However, its binding to proteins is so insignificant that interaction with other substances this mechanism is unlikely.

Valproic acid

With simultaneous application valproic acid and carbapenems decreased its concentration in blood from 60% to 100% after 2 days therapy. Due to the rapid and significant decrease in concentration valproic acid should be avoided simultaneous use of valproic acid and drug Meropidel®.

Indirect anticoagulants

With the simultaneous use of antibiotics and warfarin, the anticoagulant effect of the latter may worsen. Patients receiving antibacterial drugs often noted an increase in the anticoagulant effect of concomitantly receiving indirect anticoagulants. including warfarin. The risk of developing this effect varies depending on the type of infection, age and general condition of the patient, so the impact of antibiotics on increasing the international standardized ratio (INR) is difficult to assess. With the simultaneous use of antibiotics of non-direct anticoagulants, careful and frequent monitoring of INR during and some time after the application of these drugs.

Pharmaceutical compatibility

The drug Meropidel® can not be confused or add to other medicinal drugs.

Meropenem is compatible with the following infusion solutions:

- 0.9% solution of sodium chloride;

- 5% solution of dextrose.

Special instructions:

When choosing meropenem for treatment patient needs determine the feasibility of antibiotic group of carbapenems, based on from the severity of the infectious diseases, prevalence of cases resistance to others antibacterial agents. suitable for the treatment of this infection and the risk of bacterial resistance to carbapenems.

Against the background of the use of carbapenems, including meropenem, infrequent reports of seizures occurred, caution should be exercised when using the drug in patients with a reduced threshold of convulsive readiness.

As with the use of other beta-lactam antibiotics, severe hypersensitivity reactions have been described, sometimes with a fatal outcome.

If a severe allergic reaction develops, discontinue the administration of this medication and take the necessary measures.

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may exhibit hypersensitivity to meropenem. Before the beginning of treatment meropenem it is necessary to familiarize in detail with hypersensitivity reactions to the beta-lactam antibiotics, available in the anamnesis.

With almost all antibacterial agents, including meropenem, cases of development of antibiotic-associated and pseudomembranous colitis, the severity of which varied from mild to life-threatening. Therefore, it is important to consider this diagnosis if the patient has diarrhea during or after the application of meropenem (see section "Side effects"). In this case consideration should be given to discontinuing therapy with meropenem and specific treatment Clostridium difficile. Do not use drugs that suppress the intestinal peristalsis. With the development of pseudomembranous colitis should cancel the drug. Contraindicated use of drugs that inhibit intestinal peristalsis.

In rare cases, with carbapenem therapy, including meropenem, cases of epileptic seizures have been described (see section "Side effects").

In the treatment of patients with renal insufficiency, a dose reduction of the drug is required (see section "Dosing method").

When treating meropenem, you need to carefully monitor the function of the liver due to the risk of hepatotoxicity of this drug (a violation of liver function with cholestasis and cytolysis) (see section "Side effects"). Patients with liver disease should carefully to control its function when using the drug. At the same time, dose adjustment is not required (see section "Method of administration and dose").

During treatment meropenem can be observed positive straight line or indirect reaction Coombs.

Meropenem contains sodium, which should be taken into account in the treatment patients, (500 mg of meropema contains approximately 2.0 mEq of sodium, 1 g - 4 mEq).

Effect on the ability to drive transp. cf. and fur:

Given the likelihood of side effects from the central nervous system, care should be taken when driving vehicles and working with mechanisms.

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

Packaging:

For 500 mg or 1000 mg of meropenem in a clear glass vial (type 1) sealed with a cork made of bromobutyl rubber and coated with an aluminum cap with a snap-fit lid type "Flip-off".

One bottle with instructions for use is placed in a cardboard box.

Storage conditions:

Store in a dark place at a temperature of no higher than 30 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002459

Date of registration:12.05.2014

Expiration Date:12.05.2019

Date of cancellation:2017-07-06

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp01.05.2018

Illustrated instructions

Instructions

Meropidel® (Meropidel®)