Vaborem

1). 1). 2). Renal impairment Table 2 shows the recommended dose adjustments for patients with a CrCl ≤39 ml/min. 2). Doses adjusted for renal impairment should be administered after a dialysis session. 2). Paediatric population The safety and efficacy of meropenem/vaborbactam in children and adolescents younger than 18 years of age have not yet been established.

No data are available. Method of administration Intravenous use. Vaborem is administered by intravenous infusion over 3 hours. 6.

2%). 6 %), one infusion related reaction and one blood alkaline phosphatase increased respectively. 3%). Tabulated list of adverse reactions The following adverse reactions have been reported with meropenem alone and/or identified during the Phase 3 studies with Vaborem.

Adverse reactions are classified according to frequency and System Organ Class. Adverse reactions listed in the table with a frequency of “unknown” were not observed in patients participating in studies with Vaborem or meropenem but have been reported in the post-marketing setting for meropenem alone.

Frequencies are defined as: 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); unknown (cannot be estimated from the available data). Within each System Organ Class, undesirable effects are presented in order of decreasing seriousness.

4) Musculoskeletal and connective tissue disorders Rhabdomyolysis2 Renal and urinary disorders Renal impairment Incontinence Blood creatinine increased Blood urea increased General disorders and administration site conditions Infusion site phlebitis Pyrexia Chest discomfort Infusion site reaction Infusion site erythema Injection site phlebitis Infusion site thrombosis Pain Investigations Blood creatine phosphokinase increased Direct and indirect Coombs test positive Injury, poisoning and procedural complications Infusion related reaction 1 DILI includes hepatitis and liver failure 2 Observed post-marketing with meropenem, a component of Vaborem 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 in Appendix V.

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

If a severe allergic reaction occurs, treatment with Vaborem must be discontinued immediately and adequate emergency measures must be initiated. 8). If signs and symptoms suggestive of these reactions appear, meropenem should be withdrawn immediately and an alternative treatment should be considered.

5 Rhabdomyolysis Rhabdomyolysis has been reported with the use of meropenem, a component of meropenem/vaborbactam. If signs or symptoms of rhabdomyolysis are observed, meropenem/vaborbactam should be discontinued and appropriate therapy initiated.

8). Patients with known seizure disorders should continue anticonvulsant therapy. Patients who develop focal tremors, myoclonus, or seizures should be evaluated neurologically and placed on anticonvulsant therapy if not already instituted.

2). 5). 8). If severe DILI occurs, treatment discontinuation should be considered as clinically appropriate. Meropenem/vaborbactam should be reintroduced only if assessed as essential for treatment. Patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem/vaborbactam.

2). 8). Clostridioides difficile-associated diarrhoea Clostridioides difficile-associated diarrhoea has been reported with meropenem/vaborbactam. 8). Discontinuation of therapy with Vaborem and the administration of specific treatment for Clostridioides difficile should be considered.

Medicinal products that inhibit peristalsis should not be given. Concomitant use with valproic acid/sodium valproate/valpromide Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium may reduce plasma levels of valproic acid to concentrations below the therapeutic range as a result of this interaction, thus increasing the risk of breakthrough seizures.

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