Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Hypersensitivity reactions
Serious and occasionally fatal hypersensitivity reactions are possible (see sections 4.3 and 4.8).

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in association with beta-lactam antibiotics (including cephalosporins) treatment

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 or SCAR occurs during treatment with Zinforo, the medicinal product should be discontinued and appropriate measures taken.

With other beta-lactam antibiotics there have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction, see section 4.8).

Clostridium difficile-associated diarrhoea
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 (see section 4.8). 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.

Non-susceptible organisms
Superinfections may occur during or following treatment with Zinforo.

Patients with pre-existing seizure disorder
Seizures have occurred in toxicology studies at 7-25 times human ceftaroline Cmax levels (see section 5.3). Clinical study experience with ceftaroline fosamil in patients with pre-existing seizure disorders is very limited. Therefore, Zinforo should be used with caution in this patient population.

Direct antiglobulin test (Coombs test) seroconversion and potential risk of haemolytic anaemia 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), (see section 4.8). 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 Zinforo treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with Zinforo should be investigated for this possibility.

Limitations of the clinical data
There is no experience with ceftaroline in the treatment of CAP in the following patient groups: the immunocompromised, patients with severe sepsis/septic shock, severe underlying lung disease (e.g.
cystic fibrosis, see section 5.2),, those with PORT Risk Class V, and/or CAP requiring ventilation at 

presentation, CAP due to methicillin-resistant S. aureus or patients requiring intensive care. Caution is advised when treating such patients.

There is no experience with ceftaroline in the treatment of cSSTI in the following patient groups: the immunocompromised, patients with severe sepsis/septic shock, necrotizing fasciitis, perirectal abscess and patients with third degree and extensive burns. There is limited experience in treating patients with diabetic foot infections. Caution is advised when treating such patients.

Effects on Driving

4.7   Effects on ability to drive and use machines


Undesirable effects e.g. dizziness may occur and this may have an effect on the ability to drive and use of machines (see section 4.8).