Exblifep

5 g cefepime/enmetazobactam every 8 hours administered as an intravenous infusion over 2 hours. 2). 5 g cefepime/enmetazobactam every 8 hours administered as an intravenous infusion over 4 hours. 3 The usual duration of treatment is 7 to 10 days.

In general, administration should not be less than 7 days and not longer than 14 days. In patients with bacteraemia treatment up to 14 days may be required. 2). 2). The recommended dose in patients with varying degrees of renal function is presented in Table 1.

Patients receiving continuous renal replacement therapy (CRRT) need a higher dose than patients on haemodialysis. For patients receiving continuous renal replacement therapy, the dose should be adjusted guided by the CRRT clearance (CLCRRT in mL/min).

For patients with changing renal function, serum creatinine concentrations and eGFR should be monitored at least daily and the dose of EXBLIFEP adjusted accordingly. For patients with Hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP), infusion time should be 4 hours regardless of the renal impairment status.

125 g thereafter (every 24 hours but after the haemodialysis session on haemodialysis days). 2). Paediatric population The safety and efficacy in children below 18 years of age has not yet been established. No data are available. 4 Method of administration EXBLIFEP is administered via intravenous infusion.

6.

9%). 2% (1/516). Tabulated list of adverse reactions The following adverse reactions have been reported with cefepime alone during clinical studies or post marketing surveillance and/or identified during Phase 2 or/and Phase 3 studies with cefepime- enmetazobactam.

Adverse reactions are classified according to System Organ Class, frequency, preferred term using MedDRA terminology. 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) and not known (frequency cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 2. Frequency of adverse reactions by system organ class System organ class Frequency MedDRA preferred term (PT) Infections and infestations Uncommon Clostridioides difficile associated diarrhoea (CDAD), oral candidiasisa, vaginal infection 7 System organ class Frequency MedDRA preferred term (PT) Rare Candida infectiona Blood and lymphatic system disorders Very common Coombs test positivea Common Prothrombin time prolongeda, partial thromboplastin time prolongeda, anaemiaa, eosinophiliaa Uncommon Thrombocytopenia, leukopeniaa, neutropeniaa Not known Aplastic anaemiab, haemolytic anaemiab, agranulocytosisa Immune system disorders Rare Anaphylactic reactiona, angioedemaa, dermatitis allergic Not known Anaphylactic shocka Metabolism and nutrition disorders Not known Urine glucose false positivea Psychiatric disorders Not known Confusional statea, hallucinationa Nervous system disorders Common Headache Uncommon Dizziness Rare Convulsiona, paraesthesiaa, dysgeusia Not known Comaa, stupora, encephalopathya, altered state of consciousnessa, myoclonusa Vascular disorders Common Infusion site phlebitis Rare Vasodilationa Not known Haemorrhageb, Respiratory, thoracic and mediastinal disorders Rare Dyspnoeaa Gastrointestinal disorders Common Diarrhoea Uncommon Pseudomembranous colitis, colitis, vomiting, nausea, Rare Abdominal pain, constipation Hepatobiliary disorders Common Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Alkaline phosphatase increased Skin and subcutaneous tissue disorders Common Rash Uncommon Erythema, urticaria, pruritus Not known Toxic epidermal necrolysisb, Stevens- Johnson syndromeb, erythema multiformeb 8 System organ class Frequency MedDRA preferred term (PT) Renal and urinary disorders Uncommon Blood urea increased, blood creatinine increased Not known Renal failurea, toxic nephropathyb Reproductive system and breast disorders Rare Vulvovaginal pruritus General disorders and administration site condition Common Infusion site reaction, injection site pain, injection site inflammation Uncommon Pyrexiaa, infusion site inflammation Rare Chillsa Investigations Common Amylase increased, lipase increased, lactate dehydrogenase increased a: Adverse reactions reported only with cefepime alone.

8). Patients who have a history of hypersensitivity to other beta-lactam antibiotics may also be hypersensitive to cefepime-enmetazobactam. 3). Cefepime-enmetazobactan should be administered with caution to patients with a history of asthma or allergic diathesis.

The patient must be carefully monitored during the first administration. If an allergic reaction occurs, treatment must be discontinued immediately and adequate emergency measures must be initiated. 2). Reversible encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures (including nonconvulsive status epilepticus), and/or renal failure have been reported with cefepime/enmetazobactam when the dose has not been reduced in patients with renal impairment.

In some cases, neurotoxicity was reported in patients with renal impairment despite dose adjustments. Renal function should be monitored carefully if medicinal products with nephrotoxic potential, such as aminoglycosides and potent diuretics, are administered concomitantly with cefepime- enmetazobactam.

Clostridioides difficile associated diarrhoea (CDAD) CDAD has been reported with cefepime-enmetazobactam, and may range in severity from mild diarrhoea to fatal colitis. CDAD must be considered in patients who present with diarrhoea during or subsequent to the administration of cefepime-enmetazobactam.

Discontinuation of therapy with cefepime-enmetazobactam and the use of supportive measures together with the administration of specific treatment for C. difficile should be considered. Medicinal products that inhibit peristalsis should not be given.

5 Non-susceptible organisms The use of cefepime-enmetazobactam may result in overgrowth of non-susceptible organisms, which may require interruption of treatment or other appropriate measures. Elderly No dose adjustment based on age is required.

1. - Hypersensitivity to any cephalosporin antibacterial agent. , penicillins, carbapenems or monobactams).