Side Effects of Ceftazidime-Avibactam
Ceftazidime-avibactam is generally well tolerated with a safety profile similar to ceftazidime alone, with most adverse events being mild to moderate in severity. 1
Common Adverse Events
The most frequently reported side effects include:
- Gastrointestinal disorders occur in 13-18% of patients, including diarrhea (1 in 78 patients), nausea (1 in 156), vomiting (1 in 500), and abdominal pain (1 in 416) 1
- Local injection site reactions affect fewer than 2% of patients, manifesting as phlebitis and inflammation at the IV site (1 in 69 patients) 1
- Hypersensitivity reactions occur in approximately 2% of patients, presenting as pruritus, rash, and fever 1
Serious but Rare Adverse Events
While uncommon, clinicians must remain vigilant for:
- Severe skin reactions including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have been reported with cephalosporins including ceftazidime 1
- Anaphylaxis with bronchospasm and/or hypotension occurs very rarely 1
- Clostridioides difficile infection may develop during or after treatment, with pseudomembranous colitis symptoms potentially occurring even after therapy completion 1
Neurological Complications
- Central nervous system reactions (fewer than 1%) include headache, dizziness, and paresthesia 1
- Seizures have been reported, particularly in renally impaired patients receiving unadjusted doses 1
- Encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia can occur in patients with renal impairment who do not receive appropriate dose adjustments 1
Hematologic and Laboratory Abnormalities
- Eosinophilia occurs in approximately 1 in 13 patients 1
- Positive Coombs test without hemolysis develops in 1 in 23 patients, though rare cases of hemolytic anemia have been reported 1
- Transient hepatic enzyme elevations affect 1 in 15-23 patients (AST, ALT, LDH, GGT, alkaline phosphatase) 1
- Transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia, and lymphocytosis occur very rarely 1
- Transient elevations in blood urea nitrogen and serum creatinine are observed occasionally 1
Clinical Trial Safety Data
- In the REPRISE trial, 31% of ceftazidime-avibactam patients experienced adverse events compared to 39% in the best available therapy (carbapenem) group, with most being mild or moderate 2
- Real-world data from 203 patients showed potential drug-related adverse effects in only 8.4%, including acute kidney injury (10 cases), C. difficile infection (3 cases), rash (2 cases), and single cases of gastrointestinal intolerance and neutropenia 3
- No new safety concerns were identified in phase 3 trials, and the combination demonstrated excellent safety and tolerability with few serious drug-related adverse events 2, 4, 5
Critical Pitfall to Avoid
Always adjust dosing in patients with creatinine clearance ≤50 mL/min to prevent neurological complications, as encephalopathy and seizures are associated with unadjusted dosing in renal impairment 1, 6