MEROPENEM

The tables below provide general recommendations for dosing. The dose of meropenem administered and the duration of treatment should take into account the type of infection to be treated, including its severity, and the clinical response.

g. ), or very severe infections. Additional considerations for dosing are needed when treating patients with renal insufficiency (see further below). Adults and adolescents Infections Dose to be administered every 8 hours Severe pneumonia including hospital and ventilator- associated pneumonia.

6) Alternatively, doses up to 1 g can be given as an intravenous bolus injection over approximately 5 minutes. There are limited safety data available to support the administration of a 2 g dose in adults as an intravenous bolus injection.

Renal Impairment The dose for adults and adolescents should be adjusted when creatinine clearance is less than 51 ml/min, as shown below. There are limited data to support the application of these dose adjustments for a unit dose of 2 g.

Creatinine clearance (ml/min) Dose (based on “unit” dose range of 500 mg or 1 g or 2 g, see table above Frequency 26-50 10-25 <10 one unit dose half of one unit dose half of one unit dose every 12 hours every 12 hours every 24 hours Meropenem is cleared by haemodialysis and haemofiltration.

The required dose should be administered after completion of the haemodialysis cycle. There are no established dose recommendations for patients receiving peritoneal dialysis. 4). Dose in elderly patients No dose adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 ml/min.

Paediatric population Children under 3 months of age The safety and efficacy of meropenem in children under 3 months of age have not been established and the optimal dose regimen has not been identified. 2) Children from 3 months to 11 years of age and up to 50 kg body weight The recommended dose regimens are shown in the table below: Infection Dose to be administered every 8 hours Severe pneumonia including hospital and ventilator- associated pneumonia.

10 or 20 mg/kg Broncho-pulmonary infections in cystic fibrosis 40 mg/kg Complicated urinary tract infections 10 or 20 mg/kg Complicated intra-abdominal infections 10 or 20 mg/kg Complicated skin and soft tissue infections 10 or 20 mg/kg Acute bacterial meningitis 40 mg/kg Management of febrile neutropenic patients 20 mg/kg Children over 50 kg body weight The adult dose should be administered There is no experience in children with renal impairment.

1 %). 3 %). Tabulated risk of adverse reactions In the table below all adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1,000 to <1/100); rare (≥ 1/10,000 to <1/1,000); very rare (< 1/10,000) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class Frequency Event Infections and infestations Uncommon oral and vaginal candidiasis Common thrombocythaemiaBlood and lymphatic system disorders Uncommon eosinophilia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis, haemolytic anaemia.

4) Common transaminases increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased. Hepato-biliary disorders Uncommon blood bilirubin increased, Drug-induced liver injury* Skin and subcutaneous tissue Common rash, pruritis Uncommon urticaria toxic epidermal necrolysis, Stevens Johnson syndrome, erythema, multiforme disorders Unknown Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome) Renal and urinary disorders Uncommon blood creatinine increased, blood urea increased Common inflammation, painGeneral disorders and administration site conditions Uncommon thrombophlebitis pain at the injection site Metabolism and nutrition disorders Uncommon Hypokalaemia *DILI includes hepatitis and liver failure.

Paediatric population Meropenem is licensed for children over 3 months of age. There is no evidence of an increased risk of any adverse drug reaction in children based on the limited available data. All reports received were consistent with events observed in the adult population.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the National reporting system listed below.

The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.

Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. resistance Resistance to penems of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp. varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in these bacteria to penems.

8). Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta- lactam antibiotics may also be hypersensitive to meropenem. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.

If a severe allergic reaction occurs, the medicinal product should be discontinued and appropriate measures taken. Antibiotic-associated colitis Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all anti-bacterial agents, including meropenem, and may range in severity from mild to life threatening.

8). Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given. 8). 8). If severe DILI occurs, treatment discontinuation should be considered as clinically appropriate.

Meropenem should be reintroduced only if assessed as essential for treatment. Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem. 2). Direct antiglobulin test (Coombs test) seroconversion A positive direct or indirect Coombs test may develop during treatment with meropenem.

1. Hypersensitivity to any other carbapenem antibacterial agent. g. penicillins or cephalosporins).