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

Antibiotic for parenteral use from the group of carbapenems, has a bactericidal action (suppresses the synthesis of the bacterial cell wall), easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases, and has a high affinity for proteins that bind penicillin. The minimum bactericidal concentrations (MBCs) are usually the same as the minimum inhibitory concentrations (MICs).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 cell wall enzymes, which in result inIt causes damage and death of bacteria.

The spectrum of antibacterial activity of meropenem includes the majority clinically significant Gram-positive and Gram-negative aerobic and anaerobic strains of bacteria.

Active in vitro and in vivo in a relationship:

Gram-positive aerobes:

Enterococcus faecalis (excluding vancomycin-resistant strains); Staphylococcus aureus (methicillin-sensitive); Streptococcus agalactiae, Streptococcus pneumoniae (only penicillin-sensitive); Streptococcus pyogenes, Group Streptococcus milleri (Streptococcus angiosus, Streptococcus constellatus, Streptococcus intermedius), Staphylococcus epidermidis (methicillin-sensitive).

Gram-negative aerobes:

Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia marcescens.

Anaerobic bacteria:

Clostridium perfringens, Peptoniphilus asaccharolyticus, Peptostreptococcus spp., including Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptococcus magnus, Bacteroides caccae, Bacteroides fragilis, Prevotella bivia, Prevotella disiens.

Microorganisms for which the problem of acquired resistance is relevant:

Gram-positive aerobes: Enterococcus faecium.

Gram-negative aerobes: Acinetobacter spp., Burkholderia cepacia, Pseudomonas aeruginosa.

Microorganisms possessing natural resistance:

Stenotrophomonas maltophilia, Legionella spp., Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetti, Mycoplasma pneumoniae.

Pharmacokinetics:

With a single intravenous injection of 250 mg for 30 minutes, the maximum concentration (C_max) Is about 11 ug / ml for a dose of 500 mg of 23 ug / ml for a dose of 1 g of about 49 ug / ml (the absolute pharmacokinetic proportional to the administered dose for C_max and the area under the pharmacokinetic curve "concentration-time" (AUC) no). When the dose is increased from 250 mg to 2 g, the plasma clearance decreases from 287 to 205 ml / min. With intravenous bolus administration for 5 minutes, 500 mg C_maxabout 52 μg / ml for 1 g about 112 μg / ml. Connection with plasma proteins - 2%.

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

Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. The half-life (T_1/2) is approximately 1 hour, in children under 2 years, approximately 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. 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, clearance of meropenem correlates with creatinine clearance (CC). In elderly patients, a decrease in meropenem clearance correlates with a decrease in QC associated with age. T_1/2 - 1.5 hours. It is excreted during hemodialysis.

In patients with liver disease, the pharmacokinetics of meropenem does not change.

Indications:

Meropenem is indicated for treatment in children older than 3 months and adults of the following infectious-inflammatory diseases (monotherapy or in combination with other antimicrobial drugs) caused by one or more meropenem-sensitive pathogens: infections of the lower respiratory tract (including pneumonia, including hospital); intra-abdominal infections (including complicated appendicite, peritonitis); infection of the urinary system (incl.pyelonephritis, pyelitis); infections of the skin and soft tissues (including erysipelas, impetigo, secondarily infected dermatoses); infections of the pelvic organs (including endometritis); bacterial meningitis; septicemia.

Empirical treatment (alone or in combination with antiviral or antifungal drugs) with suspected infection in adult patients with febrile episodes of neutropenia.

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:

Simultaneous use with nephrotoxic drugs; patients with complaints from the gastrointestinal tract, especially with colitis.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential 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 or infusion.

For intravenous bolus injections, a ready-made solution prepared by diluting the contents of the vial with water for injection (20 ml of water for injection per 1000 mg of meropenem) is used. which is administered for at least 5 minutes.

For intravenous infusion, use a ready-made solution diluted to 50-200 ml with a compatible infusion fluid, which is administered for 15-30 minutes.

Doses and duration of therapy should be determined depending on the type and severity of the infection, and the patient's condition.

Adults with pneumonia, urinary tract infections, pelvic infections, skin and soft tissue infections - intravenously, 500 mg every 8 hours; with hospital pneumonia, peritonitis, septicemia, suspected bacterial infection in patients with neutropenia - intravenously, 1 g every 8 hours; with bacterial meningitis - but 2 g every 8 hours.

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

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

Creatinine clearance (ml / min)	Single vine: the proportion of the recommended single dose corresponding to the pathology (500 mg, or 1000 mg, or 2000 mg)	Periodicity of introduction
26-50	100%	Every 12 hours
10-25	50%	Every 12 hours
<10	50%	Every 24 hours

Meropenem is excreted in hemodialysis. To restore the effective plasma concentration, a single dose of meropenem recommended for the corresponding pathology should be administered after the hemodialysis procedure is completed.

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 normal renal function or creatinine clearance greater than 50 ml / min, dose adjustment is not required.

Children at the age of 3 months to 12 years (with a body weight of less than 50 kg), a single 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: with meningitis 40 mg / kg every 8 hours (maximum single dose of 2 g).

The safety of administering a dose of 40 mg / kg as a bolus injection has not been sufficiently studied.

Children with a body weight of more than 50 kg are given doses for adults.

Experience with children with impaired renal and hepatic function is absent.

The diluted solution should be used immediately after preparation.

Do not freeze the prepared mortar.

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.

The frequency of adverse reactions is presented in the form of the following gradation: very often ( ≥1 / 10); chahundred (≥1/100, <1/10); infrequently (≥1/1000, <1/100); rarely (≥ 1/10000, <1/1000); very rarely 1/10000), of the frequency, unspecified.

From the digestive system:

Hasto: nausea, vomiting, diarrhea;

Infrequent: constipation *, cholestatic hepatitis *;

Rarely: Candidiasis of the oral mucosa;

Very rarely: pseudomembranous colitis.

Co side of the urinary system:

Often: renal dysfunction (gyercercreatinemia, increased urea concentration in plasma).

Allergic reactions:

Infrequent: skin itching, skin rash, hives;

Very rarely: multiforme exudative erythema, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, angyneurotic edema, anaphylactic shock.

From the nervous system:

Infrequently: head pain, paresthesia, fainting*, hallucinations *, depression*, anxiety *, increased excitability *, insomnia *;

Rarely: convulsions.

Laboratory indicators:

Often: thrombocytosis, hyperbilirubinemia, increased activity alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (APF), lactate dehydrogenase (LD);

Infrequently: eosinophilia, thrombocytopenia;

Rarely: leukopenia, neutropenia, agranulocytosis;

Very rarely: hemolytic anemia;

Unspecified frequency: false positive or indirect Coombs test, shortening of partial thromboplastin time.

The cardiovascular system:

Infrequent: heart failure *, cardiac arrest *, tachycardia *, bradycardia *, myocardial infarction *, decreased or increased blood pressure *, thromboembolism of the pulmonary artery *.

Respiratory tract:

Infrequently: shortness of breath.

Local reactions:

Often: inflammation, phlebitis, thrombophlebitis, tenderness, edema at the site of administration.

Other:

Rarely: vaginal candidiasis.

*Cause-and-effect relationship with taking meropenem is not established.

Overdose:

In case of an overdose, which is possible mainly in the treatment of patients with impaired renal function, symptomatic treatment is performed. It is possible hemodialysis.

Interaction:

Compatible with the following solutions: 0.9% solution of sodium chloride; 5 or 10% solution of dextrose; 5% dextrose solution with 0.02% sodium bicarbonate solution; 5% dextrose solution with 0.225% sodium chloride solution; 5% dextrose solution with 0.15% potassium chloride solution; 2.5 and 10% mannitol solution; 0.9% solution of sodium chloride and 5% solution of dextrose.

Meropenem should not be mixed with solutions containing other drugs. 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 clowering the concentration of valproic acid in blood plasma by 60-100% after 2 days therapy. Due to the rapid and significant decrease in concentration waltzThe use of meropenem and the preparations of valproic acid.

Drugs that block tubular secretion, slow down excretion and increase the concentration in the plasma.

Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in T1/2 and the concentration of meropenem in plasma. So as the effectiveness and duration of action of meropenem administered without probenecid are 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.

With the simultaneous use of antibiotics and indirect anticoagulants, including warfarin, anticoagulant effects may be intensified. 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 simultaneous use of antibiotics and indirect anticoagulants, frequent monitoring of INRs is recommended during and some time after discontinuation of treatmentwith these drugs. There are no specific data on possible drug interactions (with the exception of probenecid).

Special instructions:

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.

When monotherapy of a known or suspected lower respiratory tract infection of severe course caused by Pseudomonas aeruginosa, a regular determination of the sensitivity of the pathogen is recommended.

When using meropenem, there may be a development of pseudomembranous colitis (toxin produced Clostridium difficile, is one of the main reasons 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.With the development of pseudomembranous colitis should cancel the drug. Patients with developed pseudomembranous colitis are contraindicated in the use of drugs that inhibit intestinal peristalsis.

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 adjusted with the constant control of the distribution of resistant strains, the use of meropenem in infections caused by methicillin-resistant strains Staphylococcus spp.

Against the background of the use of carbapenems, including meropenem, there were reports of seizures. Care should be taken when using the drug in patients with a reduced threshold of convulsive readiness.

The prevalence of acquired antibiotic resistance of various pathogens may vary depending on the region and over time, it is desirable to have up-to-date information on the resistance of common pathogens in a particular region, especially when treating severe infections.In case the resistance is such that the efficacy of the drug against at least some infections becomes questionable, an expert should be consulted.

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

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 1000 mg.

Packaging:

The amount of active substance equivalent to 1000 mg of meropenem in a 40 ml glass of colorless glass, sealed with a rubber stopper, crimped with an aluminum cap with a tear ring and a closed removable polypropylene disc of red color with an engraved inscription "FLIP OFF ".

1 bottle with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Do not freeze the prepared mortar.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003133

Date of registration:10.08.2015 / 26.04.2016

Expiration Date:10.08.2020

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp31.08.2016

Illustrated instructions

Instructions

Nerinam (Nerinam)