Zinforo · 4.8 Undesirable effects · 1

HOS-095960 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile The most common adverse reactions occurring in ≥ 3% of approximately 3242 patients treated with Zinforo in clinical studies were diarrhoea, headache, nausea, and pruritus, and were generally mild or moderate in severity. Clostridium difficile-associated disease (CDAD) and severe hypersensitivity reactions may also occur. A greater incidence of rash in Asian patients (see below) and a greater incidence of DAGT seroconversion (see section 4.4) were observed in a study of adult patients with cSSTI conducted with Zinforo 600 mg administered over 120 minutes every 8 hours. Tabulated list of adverse reactions The following adverse reactions have been identified during clinical trials and post-marketing experience with Zinforo. Adverse reactions are classified according to System Organ Class and frequency. Frequency categories are derived according to the following conventions: 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), not known (cannot be estimated from the available data). Table 5 Frequency of adverse reactions by system organ class from clinical trials and post- marketing experience System Very Common Uncommon Rare Not known organ class common Infections and Clostridium infestations difficile colitis (see section 4.4) Blood and Anaemia, Agranulocytosis* lymphatic leucopenia, , eosinophilia* system neutropenia*, disorders thrombocytopeni a, prothrombin time (PT) prolonged, activated partial thromboplastin time (aPTT) prolonged, international normalized ratio (INR) increased Immune Rash, pruritus Anaphylaxis, system

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HOS-095956 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Hypersensitivity to the cephalosporin class of antibacterials. Immediate and severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or carbapenems).

HOS-095955 · has-indication-information · PDF-Seite 2

Zinforo is indicated for the treatment of the following infections in neonates, infants, children, adolescents and adults (see sections 4.4 and 5.1): • Complicated skin and soft tissue infections (cSSTI) • Community-acquired pneumonia (CAP) Consideration should be given to official guidance on the appropriate use of antibacterial agents.

HOS-095958 · has-interaction-information · PDF-Seite 7

No clinical drug-drug interaction studies have been conducted with ceftaroline fosamil. The interaction potential of ceftaroline or ceftaroline fosamil on medicinal products metabolised by CYP450 enzymes is expected to be low since they are not inhibitors nor inducers of CYP450 enzymes in vitro. Ceftaroline or ceftaroline fosamil are not metabolised by CYP450 enzymes in vitro, therefore co-administered CYP450 inducers or inhibitors are unlikely to influence the pharmacokinetics of ceftaroline. Ceftaroline is neither a substrate, nor an inhibitor of renal uptake transporters (OCT2, OAT1, and OAT3) in vitro. Therefore, interactions of ceftaroline with medicinal products that are substrates or inhibitors (e.g. probenecid) of these transporters would not be expected. Paediatric population As with adults, the interaction potential is expected to be low in paediatrics.

HOS-095959 · has-pregnancy-information · PDF-Seite 7

Pregnancy 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 (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Zinforo during pregnancy unless the clinical condition of the woman requires treatment with an antibiotic with Zinforo’s antibacterial profile. Breast-feeding It is unknown whether ceftaroline fosamil or ceftaroline 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 Zinforo 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 (see section 5.3). 7

HOS-095957 · has-warning-information · PDF-Seite 5

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) and drug reaction with eosinophilia and systemic symptoms (DRESS) which can be life-threatening or fatal, have been reported in association with ceftaroline treatment (see section 4.8). Acute generalised exanthematous pustulosis (AGEP) has been reported in association with beta-lactam antibiotics (including cephalosporins) treatment. 5 Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, ceftaroline should be withdrawn immediately, and an alternative treatment considered. If the patient has developed a severe skin reaction such as SJS, TEN or DRESS with the use of ceftaroline, treatment with ceftaroline must not be restarted in this patient at any time. 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

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