Mepenam

Mepenam is a systemic antimicrobial drug from the carbapenem subgroup.

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

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

Indications Mepenam

It is used in the development of the following infections:

• pneumonia, including also community-acquired and nosocomial forms;
• damage to the lungs and bronchi in the case of cystic fibrosis;
• complicated by infections of the urethra or abdominal area;
• lesions that develop during childbirth or after the birth process;
• infections affecting the epidermis and soft tissues (with complications);
• active phase of bacterial meningitis.

It may also be prescribed in case of neutropenia or fever when there is a suspicion of the development of a bacterial infection.

Release form

The therapeutic substance is released in the form of an injection lyophilisate - inside vials of 500-1000 mg. Inside the package - 1 such vial.

Pharmacodynamics

As with other β-lactam antibacterials, the times at which meropenem levels are above the minimum inhibitory value (T>MIC) show a marked correlation with efficacy. During preclinical studies, meropenem was reported to be effective at plasma levels that were approximately 40% of the dosing interval above the MIC of the infecting bacteria. This target has not been defined clinically.

Microbial resistance to meropenem may develop in the following cases:

• increasing the strength of the outer wall of gram-negative microorganisms (due to a decrease in the production of porins);
• decreased affinity for target PBPs;
• increased expression of efflux pump elements, as well as the production of β-lactamases capable of hydrolyzing carbapenems.

Pharmacokinetics

The mean plasma half-life in volunteers is approximately 1 hour. The mean distribution volume is approximately 0.25 L/kg (range 11–27 L). The mean clearance is 287 mL/min when a 0.25 g dose is administered (if a 2 g dose is used, the clearance decreases to 205 mL/min).

Administration of 0.5, 1 and 2 g doses via 30-minute infusion creates the following average Cmax values: about 23, 49 and 115 mcg/ml. The AUC level is 39.3, 62.3 and 153 mcg×hour/ml. When administered via 5-minute infusion, the Cmax level is 52 and 112 mcg/ml for doses of 0.5 and 1 g. Administration of several doses of the drug with 8-hour intervals does not result in meropenem accumulation in people with healthy renal function.

There is information that the use of 1 g of the drug at 8-hour intervals after surgery involving the abdominal area resulted in Cmax and half-life values equal to those recorded in healthy individuals, but a higher distribution volume (27 l) was observed.

Distribution processes.

The average level of protein synthesis of meropenem is about 2% (not related 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 noticeability of this factor is greatly reduced in the case of a half-hour infusion.

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

Exchange processes.

Mepenam is involved in metabolism via hydrolysis of the β-lactam ring, forming a metabolic unit that has no microbiological effect. In vitro, the drug shows reduced susceptibility to hydrolysis by human DHP-I (compared to imipenem), so there is no need to use additional substances that inhibit the activity of DHP-I.

Excretion.

Primarily unchanged meropenem is excreted via the kidneys - approximately 70% (in the range of 50-75%) of the dose, over a period of 12 hours. 28% of the drug is excreted in the form of an inactive metabolic component. Only about 2% of the substance is excreted with feces.

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

Dosing and administration

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

Meropenem, in the case of administration of a dose of up to 2 g, 3 times a day (for children weighing over 50 kg and 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 (including hospital infections associated with the action of acinetobacter or pseudomonas aeruginosa).

Sizes of single doses 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;
• infections in the lungs and bronchi that occur against the background of cystic fibrosis - 2000 mg;
• developing 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 or after childbirth - 500 or 1000 mg;
• meningitis of bacterial origin in the active phase - 2000 mg;
• use in neutropenic fever - 1000 mg.

Mepenam is administered via intravenous infusion, which often lasts between 15 and 30 minutes.

In addition, doses of the drug less than 1000 mg (inclusive) may be administered via bolus intravenous injections (duration approximately 5 minutes). There is limited information regarding the use of bolus intravenous injections in adult doses of 2 g.

Introduction in renal dysfunction.

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

• CC level in the range of 26-50 ml per minute – use of a full 1-time dose at 12-hour intervals;
• the CC value is within 10-25 ml per minute – administration of half of a single portion with 12-hour breaks;
• CC rate <10 ml per minute – use of half of a single dose at 24-hour intervals.

The drug can be excreted during hemofiltration and hemodialysis, which is why its dosages should be used only after these processes have been completed.

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

• nosocomial or community-acquired pneumonia – 10 or 20 mg/kg;
• lesions of the lungs and bronchi developing due to cystic fibrosis - 40 mg/kg;
• complicated infections in the abdominal area, 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 drug was not used in children with renal dysfunction.

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

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

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

• Application for children

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

Use Mepenam during pregnancy

There is limited or no information regarding the use of meropenem during pregnancy.

Existing preclinical data show no direct or indirect manifestations of reproductive toxicity. However, Mepenam is not recommended for use in pregnant women.

There is no information on whether meropenem is excreted in human breast milk. Small amounts of the substance are found in animal breast milk. If a woman needs to use the drug, she should consider discontinuing breastfeeding.

Contraindications

Contraindicated for use in people with severe intolerance to the active ingredient or auxiliary components of the drug, or hypersensitivity to any antibacterial drug from the carbapenem subgroup.

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

Side effects Mepenam

Side effects include:

• infections of an infectious or invasive nature: sometimes oral or vaginal candidiasis develops;
• problems with the blood system and lymph: thrombocytopenia often occurs. Sometimes leuko- or neutropenia and eosinophilia are observed. The development of a hemolytic type of anemia or agranulocytosis is possible;
• immune damage: anaphylactic symptoms or Quincke's edema may occur;
• disorders in the functioning of the nervous system: headaches often develop. Sometimes paresthesia appears. Convulsions occur occasionally;
• problems with the gastrointestinal tract: nausea, diarrhea, abdominal pain and vomiting are often observed. Colitis associated with the administration of antibiotics may occur;
• liver and biliary tract disorders: there is often an increase in blood levels of LDH and ALP, as well as transaminases. Sometimes there is an increase in blood bilirubin;
• subcutaneous and epidermal lesions: itching or rashes often occur. Urticaria sometimes occurs. Development of SJS, erythema or TEN is possible;
• urinary and renal dysfunction: sometimes there is an increase in blood urea or creatinine levels;
• systemic disorders and lesions in the area of infusion: pain and inflammation often occur. Sometimes thrombophlebitis develops.

Overdose

Relative intoxication may develop in individuals with renal dysfunction, in situations where the dosage of the drug has not been adjusted. Overdose usually involves the development of signs characteristic of side effects; they are often mild and disappear after the dosage is reduced or the drug is discontinued. In addition, symptomatic actions may be taken.

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

Interactions with other drugs

Probenecid has a competitive effect relative to meropenem in active tubular secretion, thereby inhibiting the renal excretion of the latter. Because of this, the plasma level and half-life of Mepenam increase. In this regard, it is necessary to combine the drug with probenecid very carefully.

When administered together with carbapenems, a decrease in blood levels of valproic acid was observed - in approximately 2 days they decreased by 60-100%. Due to the rapid onset of action and the high degree of reduction, the use of these drugs in combination is considered unmanageable, which is why it should be abandoned.

The use of antibiotics together with warfarin enhances its anticoagulant activity. There are many reviews indicating that when using oral anticoagulants (including warfarin) together with antibacterial drugs, the anticoagulant effect increases. The degree of probability may vary depending on the patient's condition and age, as well as the underlying infections. Therefore, it is difficult to estimate how much antibacterial substances contribute to increasing INR values. When using antibiotics together with an oral anticoagulant, INR values should be constantly monitored.

Storage conditions

Mepenam should be stored in a place inaccessible to small children. Do not freeze the medicine. Temperature – no more than 25°C.

Shelf life

Mepenam can be used for a period of 24 months (for 500 mg vials) and 36 months (for 1000 mg vials) from the date of sale of the therapeutic substance.

Analogues

The analogs of the drug are the drugs Meromak, Sinerpen, Demopenem with Meromek, Merospen and Evropenem, as well as Meronem, Lastinem and Invanz. Also on the list are Romenem, Inemplus, Meropenem with Mesonex, Tienam and Merobocid, as well as Prepenem, Merocef and Ronem.