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

Antibiotic for parenteral applications from the group of carbapenems, relatively resistant to action dehydropeptidase-1 (DHP-1) person, in this connection does not require additional use inhibitor of DHP-1.

Has a bactericidal effect. Meropenem interacts with receptors-specific penicillin-binding proteins (PSD) on the surface cytoplasmic membrane, inhibits synthesis peptidoglycan layer of the bacterial cell wall, which as a result, causes their death.

The mechanism of development of resistance

Resistance of bacteria to Meropenem can develop due to a decrease in permeability outer membrane gram-negative bacteria (in communication with a decrease in the number of porin channels), decrease affinity to target PSB, increase effluiksa and the production of beta-lactamases, capable of hydrolyzing carbapenems.

Cross-resistance between Meropenem and preparations belonging to the class of quinolones, aminoglycosides, macrolides and there are no tetracyclines. Nevertheless, bacteria may have immunity to more than one class of antibacterial drugs, when the mechanism, leading to this resistance, includes a decrease in permeability outer membrane and / or work efflux pumps.

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

Range antibacterial activity of meropenem includes the majority of clinically significant Gram-positive and Gram-negative aerobic and anaerobic strains microorganisms.

Pathogens sensitive to meropenem:

Gram-positive aerobes: Enterococcus faecalis¹ (with the exception of vancomycin-resistant strains), Staphylococcus aureus (methicillin-sensitive)² the genus Staphylococcus (methicillin-sensitive), including Staphylococcus epidermidis, group B Streptococcus agalactiae, 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, clan Peptostreptococcus (including P. micros, P anaerobius, P. magnus)

Gram-negative anaerobes: Bacteroides sassay, Bacteroides fragilis, Prevotella bivia, Prevotella disiens.

Pathogens for which the problem is urgent acquired resistance:

Gram-positive aerobes: Enterococcus faecium¹. Gram-negative aerobes: Genus Acinetobacter, Burkholderia cepacia, Pseudomonas aeruginosa.

Pathogens with natural resistance:

Gram-negative aerobes: Stenotrophomonas maltophilia, clan Legionella.

Other pathogens: Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae.

1 - pathogens with an intermediate sensitivity;

2 - all methicillin-resistant staphylococcus are resistant to meropenem.

Pharmacokinetics:

When intravenously administered (iv) 250 mg of meropenem for 30 minutes, the maximum concentration (C_max) is about 11 μg / ml, for a dose of 500 mg - about 23 μg / ml, for a dose of 1 g - about 49 μg / ml (absolute pharmacokinetic proportional dependence on the administered dose for C_max and AUC (the area under the pharmacokinetic curve "concentration-time") is not). When the dose is increased from 250 mg to 2 g, the plasma clearance decreases from 287 to 205 ml / min. With iv bolus administration for 5 min 500 mg - FROM_max about 52 μg / ml, 1 g - about 112 μg / ml. FROM_max AT blood plasma with iv injection of 1 g of the drug for 2 min, 3 min and 5 min were 110, 91 and 94 μg / ml, respectively. Six hours after IV administration of 500 mg, the level of meropenem in the blood plasma is reduced to 1 μg / ml or less.

With repeated administration of meropenem with an interval of 8 h, patients with normal renal function do not have accumulation of the drug. In healthy patients, the half-life (T_1/2) is 1 hour.

The connection with plasma proteins is independent of the concentration and is approximately 2%.

Meropenem penetrates well into most tissues and body fluids, including lungs, bronchial secretions, bile, cerebrospinal fluid, pelvic organs, skin, fascial, muscle tissue and peritoneal exudate, reaching concentrations higher than those required for the suppression of most bacteria.

Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite.

The half-life (T_1/2) in children under 2 years is approximately 1.5-2.3 hours. In the dose range of 10-40 mg / kg in children, a linear dependence of pharmacokinetic parameters is observed.

70% of the drug is excreted by the kidneys unchanged for 12 hours, another 28% as an inactive metabolite, 2% is excreted by the intestine. The concentration of meropenem in the urine, exceeding 10 μg / ml, is maintained for 5 hours after administration of 500 mg.

With regimens of 500 mg every 8 hours or 1 g every 6 hours, there was no cumulation of meropenem in blood plasma and urine in volunteers with normal liver function.

Meropenem is excreted from the body by hemodialysis and hemofiltration.

Have patients with renal insufficiency the clearance of meropenem correlates with the clearance of creatinine (CC), therefore dose adjustment is necessary.

Have elderly patients the decrease in the clearance of meropenem correlates with the decrease in QC associated with age.There is no need for dose adjustment in elderly patients, except for cases of moderate and severe renal failure.

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

Indications:Meropenem is indicated for treatment with the following infectious-inflammatory diseases caused by one or more meropenem-sensitive pathogens:

- infections lower respiratory tract (including pneumonia, including nosocomial);

- intra-abdominal infection (including complicated appendicitis, peritonitis);

- urinary tract infection (including pyelonephritis, pyelitis);

- infections of the pelvic organs, such as endometritis and inflammatory diseases of the pelvic organs, as well as pelvioperitonitis;

- infections of the skin and soft tissues;

- bacterial meningitis;

- septicemia;

- empirical treatment (in the form of monotherapy or in combination with antiviral or antifungal drugs) in case of suspected infection in adult patients with febrile neutropenia.

The effectiveness of the drug has been proven both in monotherapy and in combination from other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications:

- hypersensitivity to meropenem or any of the components of the drug;

- hypersensitivity to other drugs of the carbapenem group;

- severe hypersensitivity (anaphylactic reactions, severe skin reactions) to other beta-lactam antibiotics (for example, to penicillins or cephalosporins);

- pregnancy;

- the period of breastfeeding;

- Children's age up to 3 months.

Carefully:

- with simultaneous use with nephrotoxic drugs;

- patients with gastrointestinal complaints (diarrhea), especially those suffering from colitis.

Pregnancy and lactation:

The safety of the use of meropenem in women during pregnancy has not been studied. Studies in animals have not shown any adverse effects on fetal development.

The use of meropenem during pregnancy is contraindicated. Meropenem is determined in the breast milk of animals in very low concentrations. Meropenem should not be used during breastfeeding. If it is necessary to use meropenem during lactation, the question of stopping breastfeeding should be resolved.

Dosing and Administration:Intravenous bolus or infusion.

Dose and duration of therapy are established depending on the type and severity of the infection, as well as on the patient's condition.

Recommended daily doses:

Adults and children over 12 years of age:

- for pneumonia, infections urinary tract paths, Infectious-inflammatory diseases of the pelvic organs, infections of the skin and soft tissues - 500 mg every 8 hours;

- with hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, septicemia - 1000 mg every 8 hours;

- with meningitis - 2000 mg every 8 hours.

In patients with creatinine clearance less than 51 ml / min, the dose should be adjusted as follows way:

Clearance creatinine (ml / min)	Single dose: the proportion of the recommended single dose (500 mg, or 1000 mg, or 2000 mg)	Frequency of administration
26-50	100% single dose	Every 12 hours
10-25	50% of a single dose	Every 12 hours
<10	50% of a single dose	Every 24 hours

Meropenem is excreted in hemodialysis and hemofiltration. The dose of the drug should be administered after the end of the hemodialysis session.

Daily doses for patients undergoing peritoneal hemodialysis have not been established.

Children aged 3 months to 12 years:

- single dose for intravenous administration: 10-20 mg / kg every 8 hours, depending on the severity of the infection, the sensitivity of the pathogen and the patient's condition;

- with bacterial meningitis, the recommended dose is 40 mg / kg every 8 hours (maximum single dose of 2 g).

Children with a body weight of more than 50 kg use doses for adults and adolescents.

Experience of application in children with impaired renal and hepatic function absent.

Method of administration

Meropenem for of internal use should be administered as an intravenous bolus injection for at least 5 minutes, or as an intravenous infusion for 15-30 minutes, using appropriate infusion liquid.

Methods for preparing solutions for intravenous bolus or infusion administration

Possibility of application Meropenem in the regime of prolonged infusion (up to 3 h) is based on pharmacokinetic and pharmacodynamic parameters. At present time clinical Data confirming this regime are limited.

If a decision is made about patient therapy method extended infusion, then you should pay attention to the data on the stability of compatible infusion liquids (see table below).The drug Penemera® for application in the form intravenous bolus injection should be planted with sterile water for injection (5 ml on 250 mg of meropenem), while the concentration of the solution is 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.

Meropenem compatible with the following infusion liquids:

- sterile water for injections;

- 0.9% solution of sodium chloride;

- 5% dextrose solution.

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) if sterile water for injections.

The resulting solution remains stable for 3 hours at a temperature of up to 25 ° C and for 24 hours when stored in a refrigerator (2-8 ° C) if 0.9% chloride solution was used for its preparation sodium. A solution prepared using 5% solution dextrose, should be used immediately.

When diluting meropenem, standard aseptic rules should be applied.

Penemer® Do not mix with solutions, containOther drugs.

Before use, the diluted solution should be shaken.

All vials are for single use only.

For intravenous injections and infusions, a freshly prepared solution is recommended.

Patients with impaired hepatic function: correction of the dose is not required.

Elderly patients: with normal kidney function and creatinine clearance (CK) of more than 50 ml / min, dose adjustment is not required.

Side effects:According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Disorders from organs hematopoiesis*

often: thrombocytosis;

infrequently: eosinophilia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia.

Violations from the nervous system:

often: headache;

infrequently: paresthesia, syncope **, hallucinations **, depression **, anxiety **, increased excitability **, insomnia **;

rarely: convulsions.

Disorders from the gastro-intestinal tract:

often: nausea, vomiting, diarrhea, pain in the abdomen, increase activity "hepatic" transaminase, alkaline phosphatase, lactate dehydrogenase and concentration bilirubin in blood serum;

infrequently: constipation **, cholestatic hepatitis *, pseudomembranous colitis.

Disturbances from skin integument:

often: rash, itching;

infrequently: urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Immune system disorders:

infrequently: angioedema, manifestations of anaphylaxis.

Disorders from the cardiovascular system:

infrequently: cardiac failure**, stop heart **, tachycardia**, bradycardia **, myocardial infarction **, decrease or rise arterial pressure (BP) **, thromboembolism of the branches of the pulmonary artery **.

Disorders from the kidneys and urinary tract:

infrequently: an increase in the concentration of creatinine and urea in the blood plasma.

Disturbances from the respiratory system:

infrequently: dyspnea **.

Other:

often: local reactions - inflammation, pain;

infrequently: thrombophlebitis, pain at the injection site, vaginal candidiasis and candidiasis of the oral mucosa.

* There were reported cases of positive direct or indirect Coombs test, as well as cases of partial thromboplastin time reduction.

** Causal relationship with taking meropenem ns is established. However, these side effects were identified in clinical trials using meropenem. Against a background of a serious condition of patients, numerous diseases and multiple concomitant therapy with other medications, it was not possible to conclude that the side effect was related to meropenem therapy.

Overdose:

There is a chance of an overdose, particularly in patients with impaired renal function, if the dose has not been adjusted.

In case of an overdose, treatment is symptomatic.

In patients with normal renal function, the drug is rapidly excreted through the kidneys. Meropenem and its metabolite are excreted from the body by hemodialysis.

Interaction:

Probenecid competitively inhibits renal excretion of meropenem and thus increases the half-life and plasma concentration of meropenem. In this regard, the joint application of Probenecid and meropenem is not recommended.

Possible effects of meropenem the degree of association of other drugs with plasma proteins or metabolism has not been studied. However, given the low association of meropenem with plasma proteins (about 2%), what interaction with other drugs should not be.

The combined administration 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.

In connection with the rapid and significant decrease concentrations valproic acids not it is recommended to take a joint drug Penemera® and preparations of valproic acid.

In connection with the possible intensification of the effect oral anticoagulants (eg, warfarin) during simultaneous use with antibiotics and for some time after its termination it is recommended to control the indicators as often as possible of international normalized relations (INR).

There are no specific data on possible drug interactions (with the exception of probenecid). The use of meropenem during the intake of other drugs was not accompanied development of adverse pharmacological interactions.

Special instructions:

As with the use of other antibiotics, when using meropenem in monotherapy in patients who are in critical condition with an identified lower respiratory tract infection caused by Pseudomonas aeruginosa or if it is suspected, it is recommended that the sensitivity test be performed on a regular basis.

In rare cases, with the use of meropenem, as with almost all antibiotics, pseudomembranous colitis develops, which can vary in severity from lungs to life-threatening forms. It is important to remember the possibility of developing pseudomembranous colitis in the event of diarrhea on the background of the use of Penemer ®. With the development of pseudomembranous colitis should cancel the drug. Contraindicated use drugs, inhibiting peristalsis of the intestine.

There are clinical and laboratory symptoms cross-allergic reactions between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. There are rare reports of cases reactions hypersensitivity (including, with a lethal outcome) with the use of Penemer ®,as well as other beta-lactam antibiotics. Before the therapy with meropenem is necessary carefully to question patient, paying special attention to hypersensitivity reactions to beta-lactam antibiotics in the anamnesis. A drug Penemura® must be used with caution in patients with a history of such events. If there was an allergic reaction to meropenem, it is necessary to stop the drug and to accept appropriate measures.

As with other antibiotics, excessive growth is possible insensitive microorganisms, which requires continuous monitoring for the patient.

Treatment of patients with liver disease should be conducted under careful monitoring of the activity of "hepatic" transaminase and concentration of bilirubin. The prevalence of acquired antibiotic resistance of various pathogens can vary in dependencies from region and 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 This is, what efficiency preparation at at least some infections become questionable, you should consult a specialist.

Application preparation at infections caused by methicillin-resistant staphylococcus are not recommended.

When using carbapenems, including meropenem, infrequently reported the emergence seizures. It should be observed caution when using the drug in patients with a reduced threshold of convulsive readiness.

During the treatment with meropenem, you can get direct or indirect positive results from the Coombs test.

Patients who adhere to a diet with controlled sodium content should be informed that 500 mg of Penemer's preparation® contains about 2.0 mEq of sodium, and 1.0 g of the drug - about 4.0 mEq of sodium.

Experience in the use of the drug 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 period of Penemer ® treatment caution should be exercised when driving vehicles and engaging in other activities that require an increased concentration of attention and speed of psychomotor reactions.When there are such undesirable phenomena as headache, paresthesia and convulsions, one should refrain from controlling vehicles, mechanisms.

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

Packaging:

For 500 mg of meropenem in transparent glass bottles with a capacity of 20 ml, sealed with rubber bromobutyl plugs, crimped aluminum caps with a protective plastic cover in blue.

By 1000 mg of meropenem in bottles of clear glass with a capacity of 30 ml, sealed with rubber bromobutyl plugs, crimped aluminum caps with a protective plastic cover in red.

10 bottles are placed in a pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children!

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused Penemer's preparation®.

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package!

Terms of leave from pharmacies:On prescription

Registration number:LP-002730

Date of registration:27.11.2014

Expiration Date:27.11.2019

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SANDOZ PRIVATE, Limited India

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp31.08.2016

Illustrated instructions

Instructions

Penemura® (Penemera®)