Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most common adverse reactions occurring in ≥ 3% of approximately 3,242 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                                  thrombocytopenia
, prothrombin time (PT) prolonged,
activated partial thromboplastin time (aPTT) prolonged,
international normalized ratio
(INR) increased
Immune                     Rash,           Anaphylaxis system                     pruritus        hypersensitivity disorders                                  (e.g. urticaria, lip and face swelling)
(see sections 4.3 and 4.4)



System            Very           Common            Uncommon               Rare                   Not known organ class       common
Nervous                          Headache,         Encephalopathy*,+ system                           dizziness disorders

Vascular                         Phlebitis disorders

Respiratory,                                                                                     Eosinophilic thoracic and                                                                                     pneumonia* mediastinal disorders

Gastrointestin                   Diarrhoea,
al disorders                     nausea,
vomiting,
abdominal pain

Hepatobiliary                    Increased disorders                        transaminase s
Renal and                                          Blood creatinine urinary                                            increased disorders


General                          Pyrexia,
disorders and                    infusion site administratio                    reactions n site                           (erythema,
conditions                       phlebitis,
pain)

Investigations    Coombs
Direct Test
Positive
(see section 4.4
)
*
Adverse Drug Reaction (ADR) identified post-marketing.
+
Risk of encephalopathy is higher in patients with renal impairment in whom the dose of ceftaroline has not been appropriately reduced (see sections 4.2 and 4.9).



Description of selected adverse reactions
Severe Cutaneous Adverse Reactions
SCARs (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis) have been reported with beta-lactam antibiotics, including cephalosporins (see section 4.4).

Kounis Syndrome
Acute coronary syndrome associated with an allergic reaction (Kounis syndrome) has been reported with other beta-lactam antibiotics.

Rash
Rash was observed at a common frequency in both the pooled Phase III studies in cSSTI with administration of Zinforo every 12 hours (600 mg administered over 60 minutes every 12 hours) and the study in cSSTI with administration every 8 hours (600 mg administered over 120 minutes every 8 hours). However, the frequency of rash in the subgroup of Asian patients receiving Zinforo every 8 hours was very common (18.5%).

Paediatric population

The safety assessment in paediatric patients is based on the safety data from 2 trials in which 227 patients aged from 2 months to 17 years with cSSTI or CAP received Zinforo. Overall, the safety profile in these 227 patients was similar to that observed in the adult population.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il