DAPTOMYCIN NORIDEM

Clinical studies in patients employed infusion of daptomycin over at least 30 minutes. There is no clinical experience in patients with the administration of daptomycin as an injection over 2 minutes. This mode of administration was only studied in healthy subjects.

2). 1). - cSSTI with concurrent SAB: Daptomycin Noridem 6 mg/kg is administered once every 24 hours. See below for dose adjustments in patients with renal impairment. The duration of therapy may need to be longer than 14 days in accordance with the perceived risk of complications in the individual patient.

- Known or suspected RIE due to Staphylococcus aureus: Daptomycin Noridem 6 mg/kg is administered once every 24 hours. See below for dose adjustments in patients with renal impairment. The duration of therapy should be in accordance with available official recommendations.

6). Daptomycin Noridem should not be used more frequently than once a day. 4). Renal impairment Daptomycin is eliminated primarily by the kidney. Due to limited clinical experience (see table and footnotes below) daptomycin should only be used in adult patients with any degree of renal impairment (CrCl < 80 mL/min) when it is considered that the expected clinical benefit outweighs the potential risk.

2). The dosage regimen for daptomycin in paediatric patients with renal impairment has not been established. Dose adjustments in adult patients with renal impairment by indication and creatinine clearance. 2). No data are available in patients with severe hepatic impairment (Child-Pugh Class C).

Therefore, caution should be exercised if Daptomycin Noridem is given to such patients. 4). Paediatric population (1 to 17 years of age) The recommended dosage regimens for paediatric patients based on age and indication are shown below.

1 < 30 mL/min 6 mg/kg every 48 hours (1, 2) cSSTI = complicated skin and soft-tissue infections; SAB = S. 2). (2) The same dose adjustments, which are based on pharmacokinetic data in volunteers including PK modelling results, are recommended for adult patients on haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).

2). Indication cSSTI without SAB cSSTI associated with SAB Age group Dosage Regimen Duration of therapy Dosage Regimen Duration of therapy 12 to 17 years 5 mg/kg once every 24 hours infused over 30 minutes 7 mg/kg once every 24 hours infused over 30 minutes 7 to 11 years 7 mg/kg once every 24 hours infused over 30 minutes 9 mg/kg once every 24 hours infused over 30 minutes 2 to 6 years 9 mg/kg once every 24 hours infused over 60 minutes 12 mg/kg once every 24 hours infused over 60 minutes 1 to < 2 years 10 mg/kg once every 24 hours infused over 60 minutes Up to 14 Days 12 mg/kg once every 24 hours infused over 60 minutes (1) cSSTI = complicated skin and soft-tissue infections; SAB = S.

Summary of the safety profile In clinical studies, 2,011 adult subjects received daptomycin. Within these trials, 1,221 subjects received a daily dose of 4 mg/kg, of whom 1,108 were patients and 113 were healthy volunteers; 460 subjects received a daily dose of 6 mg/kg, of whom 304 were patients and 156 were healthy volunteers.

In paediatric studies, 372 patients received daptomycin, of whom 61 received a single dose and 311 received a therapeutic regimen for cSSTI or SAB (daily doses ranged from 4 mg/kg to 12 mg/kg). , considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported at similar frequencies for daptomycin and comparator regimens.

The most frequently reported adverse reactions (frequency common (≥ 1/100 to < 1/10)) are: Fungal infections, urinary tract infection, candida infection, anaemia, anxiety, insomnia, dizziness, headache, hypertension, hypotension, gastrointestinal and abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating and distension, liver function tests abnormal (increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP)), rash, pruritus, limb pain, serum creatine phosphokinase (CPK) increased, infusion site reactions, pyrexia, asthenia.

Less frequently reported, but more serious, adverse reactions include hypersensitivity reactions, eosinophilic pneumonia, (occasionally presenting as organising pneumonia), drug reaction with eosinophilia and systemic symptoms (DRESS), angioedema and rhabdomyolysis.

Tabulated list of adverse reactions The following adverse reactions were reported during therapy and during follow-up with frequencies corresponding to 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); not known (cannot be estimated from the available data): Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

General If a focus of infection other than cSSTI or RIE is identified after initiation of Daptomycin Noridem therapy consideration should be given to instituting alternative antibacterial therapy that has been demonstrated to be efficacious in the treatment of the specific type of infection(s) present.

Anaphylaxis/hypersensitivity reactions Anaphylaxis/hypersensitivity reactions have been reported with daptomycin. If an allergic reaction to Daptomycin Noridem occurs, discontinue use and institute appropriate therapy. Pneumonia It has been demonstrated in clinical studies that daptomycin is not effective in the treatment of pneumonia.

Daptomycin Noridem is therefore not indicated for the treatment of pneumonia. 1). The safety and efficacy of daptomycin in children and adolescents aged below 18 years with right-sided infective endocarditis (RIE) due to Staphylococcus aureus have not been established.

The efficacy of daptomycin in patients with prosthetic valve infections or with left- sided infective endocarditis due to Staphylococcus aureus has not been demonstrated. g. debridement, removal of prosthetic devices, valve replacement surgery) without delay.

Enterococcal infections There is insufficient evidence to be able to draw any conclusions regarding the possible clinical efficacy of daptomycin against infections due to enterococci, including Enterococcus faecalis and Enterococcus faecium.

In addition, dose regimens of daptomycin that might be appropriate for the treatment of enterococcal infections, with or without bacteraemia, have not been identified. Failures with daptomycin in the treatment of enterococcal infections that were mostly accompanied by bacteraemia have been reported.

1). Non-susceptible micro-organisms The use of antibacterials may promote the overgrowth of non-susceptible micro- organisms. If superinfection occurs during therapy, appropriate measures should be taken. 8). If CDAD is suspected or confirmed, Daptomycin Noridem may need to be discontinued and appropriate treatment instituted as clinically indicated.

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