Zavicefta

4). 1). 5 g Every 8 hours 2 hours Duration of treatment should be in accordance with the site of infection. 5 g Every 8 hours 2 hours Guided by the severity of the infection, the pathogen(s) and the patient’s clinical and bacteriological progress5 1 CrCL estimated using the Cockcroft-Gault formula.

2 To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process. 3 To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.

4 The total duration shown may include intravenous Zavicefta followed by appropriate oral therapy. 5 There is very limited experience with the use of Zavicefta for more than 14 days. 1). 5 g Every 8 hours 2 hours cIAI: 5 – 14 days cUTI4: 5 – 14 days HAP/VAP: 7 – 14 days LTO: Guided by the severity of the infection, the pathogen(s) and the patient’s clinical and bacteriologi cal progress5 Every 8 hours 2 hours 3 months to < 6 months6 40 mg/kg/10 mg/kg Every 8 hours 2 hours 1 CrCL estimated using the Schwartz bedside formula.

2 To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process. 3 To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.

4 The total treatment duration shown may include intravenous Zavicefta followed by appropriate oral therapy. 5 There is very limited experience with the use of Zavicefta for more than 14 days. 2). 6). 8 Paediatric patients studied from 3 to 12 months of age were full term (≥37 weeks gestation).

5 mg/kg Every 8 hours 2 hours 31 to ≤ 44 weeks PMA7 20 mg/kg/5 mg/kg 26 to < 31 weeks PMA7,8 20 mg/kg/5 mg/kg Every 12 hours 2 hours 1 To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process.

2 To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process. 3 The total treatment duration shown may include intravenous Zavicefta followed by appropriate oral therapy.

Summary of the safety profile In seven Phase 2 and Phase 3 clinical trials, 2024 adults were treated with Zavicefta. The most common adverse reactions occurring in ≥5% of patients treated with Zavicefta were Coombs direct test positive, nausea, and diarrhoea.

Nausea and diarrhoea were usually mild or moderate in intensity. Tabulated list of adverse reactions The following adverse reactions have been reported with ceftazidime alone and/or identified during the Phase 2 and Phase 3 trials with Zavicefta.

Adverse reactions are classified according to frequency and System Organ Class. Frequency categories are derived from adverse reactions and/or potentially clinically significant laboratory abnormalities, and are defined according to the following conventions: Very common (≥1/10) Common (≥1/100 and <1/10) Uncommon (≥1/1,000 and <1/100) Rare (≥1/10,000 and <1/1000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) 12 Table 7: Frequency of adverse reactions by system organ class System organ class Very common Common Uncommon Very rare Not known Infections and infestations Candidiasis (including Vulvovaginal candidiasis and Oral candidiasis) Clostridioides difficile colitis Pseudomembranous colitis Blood and lymphatic system disorders Coombs direct test positive Eosinophilia Thrombocytosis Thrombocytopenia Neutropenia Leukopenia Lymphocytosis Agranulocytosis Haemolytic anaemia Immune system disorders Anaphylactic reaction Nervous system disorders Headache Dizziness Paraesthesia Cardiac disorders Kounis syndromea,* Gastrointestinal disorders Diarrhoea Abdominal pain Nausea Vomiting Dysgeusia Hepatobiliary disorders Alanine aminotransferase increased Aspartate aminotransferase increased Blood alkaline phosphatase increased Gamma- glutamyltransferase increased Blood lactate dehydrogenase Increased Jaundice Skin and subcutaneous tissue disorders Rash maculo- papular Urticaria Pruritus Toxic epidermal necrolysis Stevens- Johnson syndrome 13 System organ class Very common Common Uncommon Very rare Not known Erythema multiforme Angioedema Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Acute generalised exanthematous pustulosis (AGEP)* Renal and urinary disorders Blood creatinine increased Blood urea increased Acute kidney injury Tubuloint erstitial nephritis General disorders and administration site conditions Infusion site thrombosis Infusion site phlebitis Pyrexia * ADR identified post-marketing.

8). In case of hypersensitivity reactions, treatment with Zavicefta must be discontinued immediately and adequate emergency measures must be initiated. 8). Before beginning treatment, it should be established whether the patient has a history of hypersensitivity reactions to ceftazidime, to other cephalosporins or to any other type of β-lactam antibacterial agent.

Caution should be used if ceftazidime/avibactam is given to patients with a history of non-severe hypersensitivity to penicillins, monobactams or carbapenems. 8). Patients should be advised of the signs and symptoms and monitored closely for skin reactions.

If signs and symptoms suggestive of these reactions appear, Zavicefta should be withdrawn immediately, and an alternative treatment considered. If the patient has developed a serious reaction such as SJS, TEN, DRESS or AGEP with the use of ceftazidime, treatment with Zavicefta must not be restarted in this patient at any time.

Clostridioides difficile - associated diarrhoea Clostridioides difficile - associated diarrhoea has been reported with ceftazidime/avibactam, and can range in severity from mild to life-threatening. 8). Discontinuation of therapy with Zavicefta and the administration of specific treatment for Clostridioides difficile should be considered.

Medicinal products that inhibit peristalsis should not be given. 2). Neurological sequelae, including tremor, myoclonus, non-convulsive status epilepticus, convulsion, encephalopathy and coma, have occasionally been reported with ceftazidime when the dose has not been reduced in patients with renal impairment.

In patients with renal impairment, close monitoring of estimated creatinine clearance is advised. In some patients, the creatinine clearance estimated from serum creatinine can change quickly, especially early in the course of treatment for the infection.

g. furosemide) may adversely affect renal function. 8). 8% in patients with a negative Coombs test at baseline and at least one follow-up test), there was no evidence of haemolysis in patients who developed a positive DAGT on treatment.

1. Hypersensitivity to any cephalosporin antibacterial agent. g. g. penicillins, monobactams or carbapenems). 75 mg/kg Every 12 hours 8