Ceftaroline fosamil

The dose should be adjusted when creatinine clearance (CrCL) is ≤50 mL/min, as shown in the tables below. The recommended durations of treatment are the same as for patients with CrCL >50 mL/min.

Dose recommendations for children and adolescents are based on pharmacokinetic (PK) modelling.

There is insufficient information to recommend dosage adjustments in adolescents aged from 12 to <18 years with bodyweight <33 kg and in children aged from 2 to 12 years with End-stage renal disease (ESRD).

There is insufficient information to recommend dosage adjustments in children aged from 2 months to <2 years with moderate or severe renal impairment or ESRD.

Dosage in adults and adolescents (aged from 12 to <18 years with bodyweight ≥33 kg) with CrCL ≤50 mL/min:

^a Calculated using the Cockcroft-Gault formula.
^b Zinforo should be administered after haemodialysis on haemodialysis days.
^c Based on pharmacokinetic and pharmacodynamic analyses the recommended dose regimen for treatment of cSSTI due to S. aureus for which the ceftaroline MIC is 2 or 4 mg/L is the dose recommended in the table by renal function category administered every 8 hours using 2 hour infusions.

Dosage in children aged from 2 to <12 years with CrCL ≤50 mL/min and adolescents aged from 12 to <18 years with bodyweight <33 kg and CrCL ≤50 mL/min:

^a Calculated using the Schwartz formula.
^b The dose recommendations are applicable to treatment of S. aureus for which the ceftaroline MIC is ≤1 mg/L.
^c Dose is based on CrCL. CrCL should be closely monitored and the dose adjusted according to changing renal function.
^d The dose administered every 8 hours should not exceed 300 mg.
^e The dose administered every 8 hours should not exceed 200 mg.

Antibacterial-associated colitis and pseudomembranous colitis have been reported with ceftaroline fosamil and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of ceftaroline fosamil. In such circumstance, the discontinuation of therapy with ceftaroline fosamil and the use of supportive measures together with the administration of specific treatment for Clostridium difficile should be considered.

Serious and occasionally fatal hypersensitivity reactions are possible.

Patients who have a history of hypersensitivity to cephalosporins, penicillins or other beta-lactam antibacterials may also be hypersensitive to ceftaroline fosamil. Ceftaroline should be used with caution in patients with a history of non-severe hypersensitivity reactions to any other beta-lactam antibiotics (e.g. penicillins or carbapenems). If a severe allergic reaction occurs during treament with ceftaroline fosamil, the medicinal product should be discontinued and appropriate measures taken.

The development of a positive direct antiglobulin test (DAGT) may occur during treatment with cephalosporins. The incidence of DAGT seroconversion in patients receiving ceftaroline fosamil was 11.2% in the five pooled pivotal studies with administration every 12 hours (600 mg administered over 60 minutes every 12 hours) and 32.3% in a study in patients receiving ceftaroline fosamil every 8 hours (600 mg administered over 120 minutes every 8 hours).

The development of a positive direct antiglobulin test (DAGT) may occur during treatment with cephalosporins. The incidence of DAGT seroconversion in patients receiving ceftaroline fosamil was 11.2% in the five pooled pivotal studies with administration every 12 hours (600 mg administered over 60 minutes every 12 hours) and 32.3% in a study in patients receiving ceftaroline fosamil every 8 hours (600 mg administered over 120 minutes every 8 hours). In clinical studies there was no evidence of haemolysis in patients who developed a positive DAGT on treatment. However, the possibility that haemolytic anaemia may occur in association with cephalosporins including ceftaroline fosamil treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with ceftaroline fosamil should be investigated for this possibility.

There are no or limited amount of data from the use of ceftaroline fosamil in pregnant women. Animal studies conducted in rat and rabbit do not indicate harmful effects with respect to reproductive toxicity at exposures similar to therapeutic concentrations. Following administration throughout pregnancy and lactation in the rat, there was no effect on pup birth weight or growth, although minor changes in foetal weight and delayed ossification of the interparietal bone were observed when ceftaroline fosamil was administered during organogenesis.

As a precautionary measure, it is preferable to avoid the use of ceftaroline fosamil during pregnancy unless the clinical condition of the woman requires treatment with an antibiotic with ceftaroline fosamil’s antibacterial profile.

It is unknown whether ceftaroline fosamil is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ceftaroline fosamil therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

The effects of ceftaroline fosamil on fertility on humans have not been studied. Animal studies with ceftaroline fosamil do not indicate harmful effects with respect to fertility.

Undesirable effects e.g. dizziness may occur and this may have an effect on the ability to drive and use of machines.