Zavicefta Ceftazidime and Avibactam Sodium for Injection

1. Indications and Usage
Complicated Urinary Tract Infections (cUTI): Including complicated pyelonephritis.
Complicated Intra-abdominal Infections (cIAI): Used in combination with metronidazole.
Hospital-acquired and Ventilator-associated Pneumonia (HAP/VAP): For bacterial pathogens.
Limited Treatment Options: Treatment of adult patients with limited treatment options caused by susceptible Gram-negative pathogens, including Enterobacterales (e.g., carbapenem-resistant strains) and Pseudomonas aeruginosa.
2. Dosage and Administration
Route of Administration: For Intravenous (IV) Infusion ONLY.
Recommended Dosage: 2.5 g (2.0 g ceftazidime and 0.5 g avibactam) administered every 8 hours.
Critical Administration Instructions:
Infusion Time: Administer over approximately 2 hours to maximize pharmacodynamic targets.
Preparation: Reconstitute with Sterile Water for Injection, then further dilute in 0.9% Sodium Chloride or 5% Dextrose.
Compatibility: Do not mix with other drugs, including Vancomycin, in the same IV line or infusion bag. Flush the IV line between medications.
3. Mechanism of Action
Ceftazidime: A third-generation cephalosporin that binds to penicillin-binding protein 3 (PBP3) to inhibit bacterial cell wall synthesis. It is highly stable against many AmpC β-lactamases.
Avibactam: A novel non-β-lactam β-lactamase inhibitor that reversibly inhibits Class A (e.g., KPC) and Class D (e.g., OXA-48) β-lactamases, as well as some Class C enzymes.
Synergy: This combination restores ceftazidime’s activity against multidrug-resistant Enterobacterales and Pseudomonas aeruginosa that produce these enzymes.
4. Safety and Warnings
Hypersensitivity: Serious allergic reactions, including anaphylaxis, have been reported. Caution is advised in patients with a history of hypersensitivity to other β-lactams.
Neurotoxicity: Seizures and other CNS adverse reactions have been reported. Dose adjustment is necessary in patients with renal impairment.
Clostridioides difficile: Use may lead to C. difficile-associated diarrhea (CDAD), which can range from mild diarrhea to fatal colitis.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Nausea, diarrhea, constipation, headache, hypokalemia, insomnia, and infusion site reactions.
Clinical Research Highlights: Phase 3 clinical programs (e.g., ATTRACT, ADEPT) demonstrated non-inferiority to meropenem in cUTI and cIAI, with a favorable safety profile compared to colistin-based regimens.
6. Drug Interactions
Probenecid: May decrease the total clearance of ceftazidime and increase serum concentrations.
Nephrotoxic Agents: Concomitant use with other nephrotoxic drugs (e.g., aminoglycosides, polymyxins) requires careful monitoring of renal function.
Vancomycin: Incompatibility exists when mixed; sequential administration requires thorough IV line flushing.
7. Pharmaceutical Information
Chemical Composition: Active Ingredients: Ceftazidime and Avibactam Sodium.
Appearance: White to pale yellow lyophilized powder or cake.
Packaging: Single-use vial (2.5 g calculated as ceftazidime 2.0 g and avibactam 0.5 g).
Storage: Store in the original carton at controlled room temperature (20°C to 25°C).