Indications : התוויות

Therapeutic indications                                                                                                                  and the risk of selecting for carbapenem-resistant bacteria.
receiving antibacterial agents. The risk may vary with the underlying infection, age and general status of the patient so that the                                                                                                                 section 4.4), urticaria Mero-Avenir is indicated for treatment in adults and children of the following severe infections caused by single or multiple                                                                                                                                                                contribution of the antibiotic to the increase in INR (international normalised ratio) is difficult to assess. It is recommended that the INR                                                                         Not known                    drug reaction with susceptible bacteria sensitive to meropenem:                                                                                                 Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Resistance should be monitored frequently during and shortly after coadministration of antibiotics with an oral anti-coagulant agent.                                                                                                                         eosinophilia and systemic - Pneumonias and nosocomial pneumonias.                                                                                                      Resistance to Mero-Avenir of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. varies across the European Union.
Prescribers are advised to take into account the local prevalence of resistance in these bacteria to Mero-Avenir.                                                                                                                                                                                                                                                                                  symptoms, acute generalised - Pulmonary infections in patients with cystic fibrosis.                                                                                                                                                                                                                                     Mero-Avenir has been administered concomitantly with many other medications without apparent adverse interaction. However, no                                                                                                                      exanthematous pustulosis - Urinary tract infections.                                                                                                                                                                                                                                                                  specific drug interaction studies other than probenecid were conducted.                                                                                                                                                                            (see section 4.4) - Intra-abdominal infections.                                                                                                                Hypersensitivity reactions - Gynecological infections such as endometritis and pelvic inflammatory disease.                                                             As with all beta-lactam antibiotics, (serious and occasionally fatal) hypersensitivity reactions have been reported (see Section 4.8).
Paediatric population                                                                                                                               Renal and urinary disorders                                       Uncommon                     blood creatinine increased, - Skin and skin structure infections.                                                                                                        Patients who have a history of hypersensitivity to carbapenems, penicillins or other betalactam antibiotics may also be hypersensitive to       Interaction studies have only been performed in adults.                                                                                                                                                                                            blood urea increased - Meningitis.                                                                                                                                Mero-Avenir. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions - Septicemia.                                                                                                                                to beta-lactam antibiotics.                                                                                                                     4.6 Pregnancy and lactation                                                                                                                         General disorders and administration site conditions              Common                       inflammation, pain Mero-Avenir has proved efficacious alone or in combination with other antimicrobial agents in the treatment of polymicrobial                 Mero-Avenir should be used with caution in patients with such a history. If an allergic reaction to meropenem occurs, the drug should be Uncommon                     thrombophlebitis, pain at the infections.                                                                                                                                  discontinued and appropriate measures taken.                                                                                                    Pregnancy injection site
There is no experience in pediatric patients with neutropenia or primary or secondary immunodeficiency.                                      If a severe allergic reaction occurs, the medicinal product should be discontinued and appropriate measures taken. Severe cutaneous The safety of Mero-Avenir in human pregnancy has not been evaluated. Animal studies have not shown any adverse effect on the adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia developing foetus. The only adverse effect observed in animal reproductive studies was an increased incidence of abortions in monkeys           Reporting of suspected adverse reactions 4.2 Posology and method of administration                                                                                                    and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalised exanthematous pustulosis (AGEP) have been at 13 times the expected exposure in man.                                                                                                       Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the reported in patients receiving meropenem (see Section 4.8).
As a precautionary measure, it is preferable to avoid the use of meropenem during pregnancy.                                                    benefit/risk balance of the medicinal product.
Adults                                                                                                                                       If signs and symptoms suggestive of these reactions appear, meropenem should be withdrawn immediately and an alternative treatment              Mero-Avenir should not be used in pregnancy unless the potential benefit justifies the potential risk to the foetus. In every case, it should   Any suspected adverse event should be reported to the Ministry of Health according to the National Regulation by using an online form The dosage and duration of therapy shall be established depending on type and severity of infection and the condition of the patient.        should be considered.                                                                                                                           be used under the direct supervision of the physician.                                                                                          https://sideeffects.health.gov.il/ The recommended daily dosage is as follows:
500 mg IV every 8 hours in the treatment of pneumonia, UTI, gynaecological infections such as endometritis, pelvic inflammatory              Antibiotic - associated colitis                                                                                                                 Lactation                                                                                                                                       4.9 Overdose disease, skin and skin structure infections.                                                                                                                                                                                                                                                 Meropenem has been reported to be excreted in small amounts in human milk. Mero-Avenir should not be used in breast-feeding women               Accidental overdosage could occur during therapy, particularly in patients with renal impairment if the dose is not adjusted as described Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all anti-bacterial agents, including unless the potential benefit for the mother justifies the potential risk to the baby.                                                           in section 4.2. Limited post-marketing experience indicates that if adverse events occur following over dosage, they are consistent with 1 g IV every 8 hours in the treatment of nosocomial pneumonias, peritonitis, presumed infections in neutropenic patients, septicaemia.       meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who the adverse event profile described in section 4.8, are generally mild in severity and resolve on withdrawal or dose reduction . Treatment present with diarrhoea during or subsequent to the administration of meropenem (see section 4.8).
In cystic fibrosis, doses up to 2 g every 8 hours have been used; most patients have been treated with 2 g every 8 hours.                                                                                                                                                                    4.7 Effects on ability to drive and use machines                                                                                                of overdosage should be symptomatic. In normal individuals, rapid renal elimination will occur ; in subjects with renal impairment, Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered.                                                                                                                                                          haemodialysis will remove meropenem and its metabolite.
In meningitis the recommended dosage is 2 g every 8 hours.                                                                                   Medicinal products that inhibit peristalsis should not be given.                                                                                No studies on the effect on the ability to drive and use machines have been performed. However when driving or operating machines, it When treating infections known or suspected to be caused by Pseudomonas aeruginosa, a dose of at least 1g every 8 hours in adults                                                                                                                                                            should be taken into account that headache, paraesthesia, and convulsions have been reported for Mero-Avenir.                                   5. PHARMACOLOGICAL PROPERTIES (maximum approved dose is 6g daily given in 3 divided doses) and a dose of at least 20mg/kg every 8 hours in children (maximum               Seizures approved dose is 120mg/kg/ daily given in 3 divided doses) are recommended.                                                                                                                                                                                                                  4.8 Undesirable effects                                                                                                                         5.1 Pharmacodynamic properties Seizures have infrequently been reported during treatment with carbapenems, including meropenem (see section 4.8).
Regular sensitivity testing is recommended when treating Pseudomonas aeruginosa infection.                                                                                                                                                                                                                                                                                                                                                   Pharmacotherapeutic group: antibacterials for systemic use, carbapenems, ATC code: J01DH02 There are limited safety data available to support the administration of a 2g bolus dose in adults as an intravenous bolus injection.                                                                                                                                                        Mero-Avenir is generally well tolerated. Adverse reactions rarely lead to cessation of treatment. Serious adverse reactions are rare.
Hepatic function monitoring
Mechanism of action
Dosage Schedule for Adults with Impaired Renal Function                                                                                      Hepatic function should be closely monitored during treatment with meropenem due to the risk of hepatic toxicity (hepatic dysfunction           Summary of the safety profile in a review of 4,872 patients with 5,026 meropenem treatment exposures, meropenem-related adverse                 Meropenem exerts its bactericidal activity by inhibiting bacterial cell wall synthesis in Gram-positive and Gram-negative bacteria Dosage should be reduced in patients with creatinine clearance less than 51 ml/min, as scheduled below.                                      with cholestasis and cytolysis).                                                                                                                reactions most frequently reported were diarrhoea (2.3%), rash (1.4%), nausea/vomiting (1.4%) and injection site inflammation (1.1%).           through binding to penicillin-binding proteins (PBPs).
Use of Mero-Avenir in patients with hepatic disease should be made with careful monitoring of transaminase and bilirubin levels.
Dose (based on “unit” doses of                                                                                                                                                                                                           The most commonly reported meropenem-related laboratory adverse events were thrombocytosis (1.6%) and increased hepatic enzymes                 Pharmacokinetic/Pharmacodynamic (PK/PD) relationship Creatinine clearance (ml/min)                                                                         Frequency                           Patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem. There is no dose 500 mg, 1 g, 2 g)                                                                                                                                                                                                                        (1.5-4.3%). Tabulated risk of adverse reactions in the table below all adverse reactions are listed by system organ class and frequency.        Similar to other beta-lactam antibacterial agents, the time that meropenem concentrations exceed the MIC (T>MIC) has been shown to adjustment necessary (see section 4.2).
best correlate with efficacy. In preclinical models meropenem demonstrated activity when plasma concentrations exceeded the MIC of    26-50                                            one unit dose                                        every 12 hours                                                                                                                                                                      The following adverse reactions have been identified following clinical studies with Mero-Avenir. Their frequency is presented in Table         the infecting organisms for approximately 40% of the dosing interval. This target has not been established clinically.
Direct antiglobulin test (Coombs test) seroconversion
10-25                                            one-half unit dose                                   every 12 hours                                                                                                                                                                      1 Frequency of Adverse Reactions (data derived from clinical trial data sources) using CIOMS III frequency classification and then A positive direct or indirect Coombs test may develop during treatment with meropenem.
listed by MedDRA SOC and at the preferred level. Frequencies of occurrence of undesirable effects are defined as: very common                   Mechanism of resistance <10                                              one-half unit dose                                   every 24 hours                                                                                                                                                                      (≥1/10; ≥10%); common (≥1/100 to <1/10; ≥1% to <10%); uncommon (≥1/1,000 to <1/100; ≥0.1% to <1%); rare (≥1/10,000 to                           Bacterial resistance to meropenem may result from: (1) decreased permeability of the outer membrane of Gram-negative bacteria (due to Concomitant use with valproic acid/sodium valproate/valpromide Meropenem is cleared by haemodialysis and hemofiltration; if continued treatment with Mero-Avenir is necessary, it is recommended                                                                                                                                                            <1/1,000; ≥0.01% to <0.1%); very rare (<1/10,000; <0.01%) ; not known (cannot be estimated from the available data).                            diminished production of porins) (2) reduced affinity of the target PBPs (3) increased expression of efflux pump components, and (4) The concomitant use of meropenem and valproic acid/sodium valproate/valpromide is not recommended (see section Interactions with that the unit dose (based on the type and severity of infection) is administered at the completion of the haemodialysis procedure to         other medicinal products and other forms of interaction ).                                                                                                                                                                                                                                      production of beta-lactamases that can hydrolyse carbapenems.
Table 1: Frequency of Adverse Reactions (data derived from clinical trial data sources)                                                         Localised clusters of infections due to carbapenem-resistant bacteria have been reported in the European Union.
restore therapeutically effective plasma concentrations.                                                                                     Mero-Avenir may reduce serum valproic acid levels. Sub-therapeutic levels may be reached in some patients.
There is no target-based cross-resistance between meropenem and agents of the quinolone, aminoglycoside, macrolide and tetracycline As with other antibiotics, overgrowth of non-susceptible organisms may occur and, therefore, continuous monitoring of each patient is                System Organ Class                                                   Frequency                Reaction                                     classes. However, bacteria may exhibit resistance to more than one class of antibacterial agents when the mechanism involved include There is no experience with the use of Mero-Avenir in patients under peritoneal dialysis.
necessary.                                                                                                                                                                                                            Uncommon                    oral and vaginal candidiasis                  impermeability and/or an efflux pump(s).
Infections and infestations
Dosage in Adults with Hepatic Insufficiency                                                                                                  Use in infections caused by methicillin resistant staphylococci is not recommended.
Blood and lymphatic system disorders                             Common                      thrombocythaemia                              Breakpoints No dosage adjustment is necessary in patients with hepatic insufficiency (see Section 4.4).
The co-administration of Mero-Avenir with potentially nephrotoxic drugs should be considered with caution. For dosage see Section                                                                                                                                                               European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints for MIC testing are presented below.