Mepenam

Mepenam is an antimicrobial systemic drug from the carbapenem subgroup.

The drug has bactericidal activity - it slows down the binding of cell membranes of gram-negative and -positive microbes, being synthesized with a protein that is involved in the binding of penicillin (PBP). [1]

Cross-resistance between meropenem, as well as drugs that are included in the subgroups of macrolides, aminoglycosides with tetracyclines and quinolones (taking into account the target bacteria) is not observed. [2]

Indications Mepenam

It is used for the development of the following infections:

• pneumonia , which also includes community-acquired and nosocomial forms;
• damage to the lungs and bronchi in the case of cystic fibrosis;
• proceeding with complications of infection of the urethra or the abdomen;
• lesions that develop during childbirth or after the birth process;
• infections affecting the epidermis and soft tissues (with complications);
• active phase of meningitis of a bacterial nature.

It can also be prescribed in case of neutropenia or a febrile condition, when there is a suspicion of the development of bacterial infection.

Release form

The release of a therapeutic substance is made in the form of an injection lyophilisate - inside bottles with a volume of 500-1000 mg. Inside the package - 1 such bottle.

Pharmacodynamics

As in the case with other β-lactam antibacterial substances, the time values when the level of meropenem was higher than the minimum retarding indicator (T> MIC) demonstrate a markedly pronounced correlation with drug efficacy. There is information that during the preclinical stage, meropenem showed an effect at plasma values that exceeded the MIC level for infecting bacteria by approximately 40% of the dosage interval. This target has not been determined clinically.

Microbial resistance relative to meropenem can develop in such cases:

• strengthening the strength of the outer wall of gram-negative microorganisms (due to a decrease in the production of porins);
• weakening affinity for targeted PBPs;
• an increase in the expression of elements of the efflux pump, as well as the production of β-lactamases capable of hydrolysis of carbapenems.

Pharmacokinetics

The mean plasma half-life in volunteers is approximately 1 hour. Average distribution volumes are approximately 0.25 l / kg (in the range of 11-27 l). The average level of clearance is 287 ml per minute with the introduction of a portion of 0.25 g (if a dosage of 2 g is used, the clearance decreases to 205 ml per minute).

The introduction of portions of 0.5, 1 and 2 g after a 30-minute infusion creates such average Cmax values - about 23, 49 and 115 μg / ml. The AUC level in this case is equal to 39.3, 62.3, as well as 153 μg × h / ml. With the introduction of a 5-minute infusion, the Cmax level is 52 and 112 μg / ml in the case of using dosages of 0.5 and 1 g. The use of several doses of drugs with 8-hour breaks does not lead to the accumulation of meropenem in people with healthy renal activity....

There is information that the use of 1 g of medication at 8-hour intervals after performing an operation associated with lesions of the abdominal region led to the achievement of Cmax values and a half-life term equal to the level recorded in healthy individuals, but at the same time there was a higher distribution rate. Volume (27 l).

Distribution processes.

The average level of protein synthesis of meropenem is about 2% (not tied to the therapeutic concentration of the drug). At a high rate of drug administration (up to 5 minutes), the pharmacokinetic parameters are considered biexponential, but the visibility of this factor is greatly reduced in the case of a half-hour infusion.

The medication easily passes into individual tissues with fluids, including bile with lungs, cerebrospinal fluid, epidermis, bronchial secretions, fascia, tissues of female genitalia, peritoneal exudate and muscles.

Exchange processes.

Mepenam participates in metabolism through hydrolysis of the β-lactam ring, forming a metabolic element that does not have a microbiological effect. In vitro, the drug shows a reduced susceptibility to hydrolysis under the influence of human DHP-I (in comparison with imipenem), therefore, it is not necessary to use additional substances that slow down the activity of DHP-I.

Excretion.

Primarily unchanged meropenem is excreted via the kidney - approximately 70% (range 50-75%) of a serving over a 12 hour period. In the form of an inactive metabolic component, 28% of drugs are excreted. Only about 2% of the substance is excreted with feces.

The established indicators of intrarenal clearance and activity of probenecid allow us to conclude that meropenem is involved in the processes of tubular secretion, as well as filtration.

Dosing and administration

The following schemes of use and dosage are general, but in general, the selection of the duration of the treatment cycle and the size of the portion is carried out taking into account the severity of the disease, the type of its causative bacterium and the patient's personal sensitivity.

Meropenem, in the case of the introduction of a portion of up to 2 g, 3 times a day (for children weighing over 50 kg and for adults), as well as when using a dosage of up to 40 mg / kg with the same frequency of administration (for children ), is most effective for certain types of infections (among those, hospital lesions associated with the action of acinetobacters or Pseudomonas aeruginosa).

Sizes of 1-time dosage for a child weighing more than 50 kg and an adult, administered at 8-hour intervals:

• pneumonia (this includes its community-acquired and nosocomial forms) - 0.5 or 1 g each;
• infections in the lungs and bronchi, arising against the background of cystic fibrosis - 2000 mg each;
• developing with complications of lesions of the urinary tract, soft tissues with the epidermis or intra-abdominal region - 0.5 or 1 g;
• infections that appear during childbirth or after them - 500 or 1000 mg each;
• having a bacterial nature meningitis in the active phase - 2000 mg each;
• use for neutropenic fever - 1000 mg.

Mepenam is given via an IV infusion, which often lasts 15-30 minutes.

In addition, drug dosages of less than 1000 mg (inclusive) can be used through bolus IV administrations (duration about 5 minutes). There is only limited information regarding the use of bolus IV injections in 2 g portions in adults.

Introduction for renal dysfunctions.

Serving sizes of the medication for an adult and a child weighing over 50 kg, with CC values below 51 ml per minute:

• CC level in the range of 26-50 ml per minute - using a full 1-fold dosage at 12-hour intervals;
• CC value in the range of 10-25 ml per minute - the introduction of half a single serving with 12-hour breaks;
• CC indicator <10 ml per minute - use of half of a 1-fold serving with a 24-hour interval.

The drug can be excreted during hemofiltration and hemodialysis, because of which its dosage should be used only after the end of these processes.

Sizes of 1-fold dosage for a child (from 3 months of age to 11 years of age; weight is less than 50 kg), used with 8-hour breaks:

• nosocomial or community-acquired pneumonia - 10 or 20 mg / kg;
• developing due to cystic fibrosis lesions of the lungs and bronchi - 40 mg / kg;
• complications of infection in the abdomen, urinary tract, soft tissues and epidermis - 10 or 20 mg / kg;
• having an active form of meningitis of bacterial genesis - 40 mg / kg;
• neutropenic fever - 20 mg / kg.

The medication was not used in children with renal dysfunction.

Children are given intravenous infusions that last 15-30 minutes. Also, dosages of the drug less than 20 mg / kg can be used through a bolus intravenous injection, lasting about 5 minutes. There is only limited information regarding the safety of drug use in children in a dose of 40 mg / kg for an intravenous bolus injection.

Before performing an IV bolus injection, it is necessary to prepare a medicinal liquid - dissolve the substance in injection water to obtain a portion of 50 mg / ml (20 ml / g of the drug).

For intravenous infusions, the drug is prepared by diluting Mepenam in 0.9% infusion NaCl or 5% infusion glucose (dextrose). Dissolution is carried out to obtain indicators of 1-20 mg / ml.

• Application for children

The medication is prescribed to persons over 3 months of age.

Use Mepenam during pregnancy

Information regarding the use of meropenem during pregnancy is lacking or limited.

The existing preclinical data show the absence of direct or indirect manifestations of reproductive toxicity. But it is still not recommended to prescribe Mepenam to pregnant women.

There is no information regarding whether meropenem is excreted in human breast milk. Small indicators of the substance are noted inside breast milk in animals. If a woman needs to use the drug, it is necessary to consider the option of stopping breastfeeding.

Contraindications

It is contraindicated to use in people with severe intolerance to the active element or auxiliary components of drugs, or with hypersensitivity to any antibacterial drugs from the carbapenem subgroup.

It is not prescribed in case of severe hypersensitivity (for example, with anaphylactic symptoms or severe epidermal signs) with respect to any type of β-lactam antibacterial substances (for example, against cephalosporins or penicillins).

Side effects Mepenam

Among the side effects:

• infections that are infectious or invasive in nature: sometimes oral or vaginal candidiasis develops;
• problems with the work of the blood system and lymph: thrombocytopenia often occurs. Leuko- or neutropenia and eosinophilia are sometimes noted. Perhaps the development of a hemolytic type of anemia or agranulocytosis;
• immune lesions: anaphylactic signs or Quincke's edema may appear;
• disturbances in the work of the NA: headaches often develop. Sometimes paresthesias appear. Occasionally there are seizures;
• problems with gastrointestinal function: nausea, diarrhea, abdominal pain and vomiting are often noted. The appearance of colitis associated with the administration of antibiotics is possible;
• disorders of the activity of the liver and gastrointestinal tract: often there is an increase in the blood values of LDH and alkaline phosphatase, as well as transaminases. Sometimes there is an increase in the blood count of bilirubin;
• lesions of the subcutaneous layer and epidermis: often itching or rashes appear. Sometimes hives occur. Development of SJS, erythema or TEN is possible;
• disorders of urinary and renal function: sometimes there is an increase in blood levels of urea or creatinine;
• systemic disorders and lesions in the infusion area: pain and inflammation often appear. Thrombophlebitis sometimes develops.

Overdose

Relative intoxication can develop in persons with renal dysfunction, in situations where drug dosage adjustment has not been performed. In case of an overdose, the development of signs characteristic of side symptoms is usually noted; they are often mild and disappear when the dosage is reduced or the medication is discontinued. In addition, symptomatic actions can be carried out.

In people with healthy kidney function, the drug is rapidly excreted. Meropenem with its metabolic elements can be excreted by hemodialysis.

Interactions with other drugs

Probenecid has a competitive effect relative to meropenem with active secretion of the tubules, which inhibits the renal secretion of the latter. Because of this, the plasma level and the half-life of Mepenam are increased. In this regard, it is necessary to very carefully combine the drug with probenecid.

When administered together with carbapenems, a decrease in blood values of valproic acid was noted - in about 2 days they decreased by 60-100%. Due to the rapid onset of exposure and the high degree of reduction, the use of these drugs in combination is considered unadjustable and should therefore be discarded.

The use of antibiotics together with warfarin enhances its anticoagulant activity. There are many reviews that indicate that when using inside anticoagulants (including warfarin) together with antibacterial drugs, an increase in the anticoagulant effect occurs. The degree of likelihood may fluctuate, taking into account the condition and age of the patient, as well as the underlying infections. Therefore, it is difficult to assess how strongly antibacterial substances are involved in increasing INR values. When using antibiotics together with an oral anticoagulant, you must constantly monitor the INR indicators.

Storage conditions

Mepen should be kept out of the reach of small children. Do not freeze the medication. Temperature - no more than 25 ° С.

Shelf life

Mepenam can be used for 24 months (for 500 mg vials) and 36 months (for 1000 mg vials) terms from the moment the therapeutic substance is sold.

Analogs

The analogs of the medication are the drugs Meromak, Sinerpen, Demopenem with Meromek, Merospin and Europen, and in addition Meronem, Lastin and Inwanz. Also on the list are Romenem, Inemplus, Meropenem with Mesonex, Tienam and Merobocid, and besides that, Prepenem, Merotsef and Ronem.