Tolerability

ZAVICEFTA: A safety and tolerability profile similar to ceftazidime alone1
In Phase III clinical trials, the adverse event profile of ZAVICEFTA was similar to that seen with either best available therapy, doripenem or meropenem1–3

  • Overall rates of any AE were low in the ZAVICEFTA and best available therapy groups1–5
  • Rates of all other AE categories were low and balanced across treatment arms1–5
  • Most common (>5%) AEs for ZAVICEFTA were positive Direct Coombs test, nausea and diarrhoea4
  • Nausea and diarrhoea were usually mild or moderate in intensity4
  • No new, significant or unexpected safety concerns were identified in Phase III clinical trials1–3,5

AEs in cIAI and cUTI

Incidence of very common (≥1/10) and common (≥1/100 and <1/10) adverse drug reactions occurring in patients receiving ZAVICEFTA during Phase II and III cIAI and cUTI clinical trials.4

*ZAVICEFTA use may cause development of a positive direct antiglobulin test (DAGT, or Direct Combs test), which may interfere with the crossmatching of blood and/or may cause drug-induced immune haemolytic anaemia. While DAGT seroconversion in patients receiving ZAVICEFTA was very common in clinical studies (the estimated range of seroconversion across Phase III studies was 3.2% to 20.8% in patients with a negative Direct Combs 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. However, the possibility that haemolytic anaemia could occur in association with ZAVICEFTA treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with ZAVICEFTA should be investigated for this possibility.

Special warnings and precautions for use4

Hypersensitivity reactions:

  • Serious and occasionally fatal hypersensitivity reactions are possible. In case of hypersensitivity reactions, treatment with ZAVICEFTA must be discontinued immediately and adequate emergency measures must be initiated
  • 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

Clostridium difficile-associated diarrhoea:

  • C. difficile-associated diarrhoea has been reported with ZAVICEFTA, and can range in severity from mild to life threatening

Abbreviations:
AE, adverse event; CI, confidence interval; cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; DAGT, direct antiglobulin test; HAP, hospital-acquired pneumonia; mMITT, microbiologically modified intention-to-treat; VAP, ventilator-associated pneumonia.

References:

  1. Mazuski JE, et al. Clin Infect Dis 2016;62:1380–9
  2. Carmeli Y, et al. Lancet Infect Dis 2016;16:661–73
  3. Wagenlehner FM, et al. Clin Infect Dis 2016;63:754–62
  4. ZAVICEFTA. Summary of Product Characteristics.
  5. Torres A, et al. Lancet Infect Dis 2017;18:285-95
Prescribing Information
Meronem IV 1g – SPC 
Legal Category: POM.       Basic NHS Cost: 10 vial pack £206.28
Meronem IV 500mg – SPC 
Legal Category: POM.       Basic NHS Cost: 10 vial pack £103.14

 

Piperacillin/tazobactam
Tazocin 2 g/0.25 g Powder for Solution for Infusion – SPC
Legal category: POM.       Basic NHS cost: 1 vial pack £7.65 
Tazocin 4  g/0.5 g Powder for Solution for Infusion – SPC
Legal category: POM.       Basic NHS cost: 1 vial pack £15.17 
 
Tygacil 50 mg Powder for Solution for Infusion – SPC
Legal Category: POM.       Basic NHS Cost: 10 vial pack £323.10
 
ZAVICEFTA® 2 g/0.5 g Powder for Concentrate for Solution for Infusion – SPC
Legal category: POM.       Basic NHS price: 10 vial pack £857.00.

PP-ZVA-GBR-0630.  October 2019