Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
Zerbaxa was evaluated in Phase 3 comparator-controlled clinical trials of complicated intra-abdominal infections and complicated urinary tract infections (including pyelonephritis) in adult patients.


The most common adverse reactions (≥ 3% in pooled Phase 3 trials of complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis) occurring in patients receiving Zerbaxa were nausea, headache, constipation, diarrhoea, and pyrexia and were generally mild or moderate in severity.

Zerbaxa was evaluated in a Phase 3 comparator-controlled clinical trial of adult patients with hospital-acquired pneumonia, including ventilator-associated pneumonia.

The most common adverse reactions (≥ 5% in a Phase 3 trial of hospital-acquired pneumonia, including ventilator-associated pneumonia) occurring in patients receiving Zerbaxa were diarrhoea, alanine aminotransferase increased, and aspartate aminotransferase increased and were generally mild or moderate in severity.

Tabulated list of adverse reactions

The following adverse reactions have been identified during adult clinical trials with Zerbaxa. Adverse reactions are classified according to MedDRA system organ class and frequency. Frequency categories are derived according to the following conventions: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) (see Table 3).

Table 3: Adverse reactions identified during adult clinical trials with ceftolozane/tazobactam Common                                   Uncommon
System organ class
(≥ 1/100 to < 1/10)                      (≥ 1/1,000 to < 1/100)
Candidiasis including oropharyngeal and vulvovaginal1,
2
Infections and infestations Clostridioides difficile colitis          Clostridioides difficile colitis1, fungal urinary tract infection1,
Clostridioides difficile infection2
Blood and the lymphatic
Thrombocytosis1                          Anaemia1 system disorders
Hyperglycaemia1,
Metabolism and nutrition
Hypokalemia1                             hypomagnesaemia1,
disorders hypophosphataemia1
1        1
Psychiatric disorders        Insomnia , anxiety
Nervous system disorders Headache1, dizziness1                        Ischemic stroke1 Atrial fibrillation1, tachycardia1,
Cardiac disorders angina pectoris1
Vascular disorders           Hypotension1                             Phlebitis1, venous thrombosis1 Respiratory, thoracic, and
Dyspnoea1 mediastinal disorders
Gastritis1, abdominal distension1,
Nausea1, diarrhoea3, constipation1,
Gastrointestinal disorders                                            dyspepsia1, flatulence1, ileus vomiting3, abdominal pain1 paralytic1
Skin and subcutaneous
Rash1                                    Urticaria1 tissue disorders
Renal and urinary
Renal impairment1, renal failure1 disorders
General disorders and administration site          Pyrexia1, infusion site reactions1 conditions


Common                                     Uncommon
System organ class
(≥ 1/100 to < 1/10)                        (≥ 1/1,000 to < 1/100) Alanine aminotransferase increased3,
Coombs test positive3, increased aspartate aminotransferase increased3,
serum gamma-glutamyl transaminases increased2, liver function
Investigations                                                           transpeptidase (GGT)1, increased test abnormal2, blood alkaline serum alkaline phosphatase1,
phosphatase increased2, gamma-
Clostridioides test positive2 glutamyltransferase increased2
1
Specific for the complicated intra-abdominal infections, acute pyelonephritis, and complicated urinary tract infections indications treated with Zerbaxa (1 g / 0.5 g intravenously every 8 hours) for up to 14 days.
2
Specific for the hospital-acquired pneumonia, including ventilator-associated pneumonia indication treated with Zerbaxa (2 g / 1 g intravenously every 8 hours) for up to 14 days.
3
Applies across all indications: complicated intra-abdominal infections, acute pyelonephritis, complicated urinary tract infections, and hospital-acquired pneumonia, including ventilator-associated pneumonia.

Description of selected adverse reactions

Laboratory values
The development of a positive direct Coombs test may occur during treatment with Zerbaxa. The incidence of seroconversion to a positive direct Coombs test was 0.2% in patients receiving Zerbaxa and 0% in patients receiving the comparator in the adult complicated intra-abdominal infections and complicated urinary tract infections clinical trials. The incidence of seroconversion to a positive direct Coombs test was 31.2% in patients receiving Zerbaxa and 3.6% in patients receiving meropenem in the adult hospital-acquired pneumonia, including ventilator-associated pneumonia clinical trial. In clinical studies, there was no evidence of haemolysis in patients who developed a positive direct Coombs test in any treatment group.

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