Ceftazidime + Avibactam

Ceftazidime + Avibactam is a combination antibiotic used to treat serious gram-negative bacterial infections. It is effective in complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI) including pyelonephritis, and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Ceftazidime is a third-generation cephalosporin antibiotic that inhibits bacterial cell wall synthesis, and avibactam is a beta-lactamase inhibitor that protects ceftazidime from degradation by beta-lactamase enzymes. It is administered as an intravenous infusion under the supervision of a healthcare professional.

• Complicated Intra-abdominal Infections (cIAI)
• Complicated Urinary Tract Infections (cUTI) including Pyelonephritis
• Hospital-acquired Bacterial Pneumonia (HABP)
• Ventilator-associated Bacterial Pneumonia (VABP)

Ceftazidime inhibits bacterial peptidoglycan cell wall synthesis following binding to penicillin binding proteins (PBPs), which leads to bacterial cell lysis and death. Avibactam is a non β-lactam, β-lactamase inhibitor that acts by forming a covalent adduct with the enzyme that is stable to hydrolysis. It inhibits both Ambler class A and class C β-lactamases and some class D enzymes, including extended-spectrum β-lactamases (ESBLs), KPC and OXA-48 carbapenemases, and AmpC enzymes. Avibactam does not inhibit class B enzymes (metallo-β-lactamases) and is not able to inhibit many class D enzymes.

Ceftazidime: Third-generation cephalosporin with broad-spectrum gram-negative activity, including Pseudomonas; arrests bacterial growth by binding to 1 or more penicillin-binding proteins, and thereby inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell-wall synthesis and inhibiting cell-wall biosynthesis.

Avibactam: Diazabicyclooctanone, non-beta-lactam, beta-lactamase inhibitor; alone has no antibacterial activity at clinically relevant doses; when combined with ceftazidime, avibactam protects ceftazidime from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum of ceftazidime to include many gram-negative bacteria normally not susceptible to ceftazidime.

Adult Dose (CrCl >50 mL/min):

Pediatric Dose (3 months-18 years):

Renal Dose:

Hemodialysis patients: Administer after hemodialysis on hemodialysis days.

Reconstitution: Reconstitute powder with 10 mL of one of the following solutions: Sterile water for injection, 0.9% NaCl, D5W, combinations of dextrose and sodium chloride containing up to 2.5% dextrose and 0.45% NaCl, Lactated Ringer injection. Upon constitution, solution may be held for no longer than 30 minutes before transferring and further diluting in a suitable infusion bag.

Reconstituted solution results in ~0.167 g/mL of ceftazidime and ~0.042 g/mL avibactam. Further dilute with the same diluent used for reconstitution (except sterile water for injection), to achieve a total volume of 50-250 mL before infusion.

Volume to withdraw from constituted vial for further dilution: 2.5 g: 12 mL; 1.25 g: 6 mL; 0.94 g: 4.5 mL. Mix gently and ensure contents are dissolved completely.

Administration: Infuse IV over 2 hours.

If you miss a dose of Ceftazidime + Avibactam, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Common Side Effects (≥5%):

• Diarrhea (8%)
• Nausea (7%)
• Vomiting (5%)
• Headache (3%)
• Dizziness (2%)
• Abdominal pain (1%)
• Constipation (2%)
• Pruritus (2%)

Other Side Effects: Thrombocytopenia, leukopenia, injection site phlebitis, candidiasis, increased liver enzymes, hypokalemia, acute kidney injury, rash, urticaria, anxiety.

• Serious and occasionally fatal anaphylactic reactions and serious skin reactions have been reported with beta-lactam antibacterials; caution in patients with history of allergy to cephalosporins, penicillins, or carbapenems.
• Clostridium difficile associated diarrhea (CDAD) has been associated with nearly all systemic antibacterials; severity may range from mild diarrhea to fatal colitis; may occur >2 months following antibacterial use.
• Seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with ceftazidime, especially in the setting of renal impairment; adjust dose according to CrCl.
• Decreased efficacy in adult cIAI patients with baseline CrCl of 30-50 mL/min; monitor CrCl at least daily in patients with changing renal function and adjust dose accordingly.

• Known serious hypersensitivity to avibactam, ceftazidime, or other cephalosporins.

Clinical interaction study of this IV infusion or avibactam alone with probenecid has not been conducted; co-administration with probenecid is not recommended.

Information on alcohol consumption with Ceftazidime + Avibactam is not available.

There are no adequate and well-controlled studies of ceftazidime/avibactam, ceftazidime, or avibactam in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed.

Ceftazidime is excreted in human milk in low concentrations. Unknown whether avibactam is excreted into human milk, although avibactam was shown to be excreted in the milk of rats. No information is available on the effects of ceftazidime and avibactam on the breastfed child or on milk production.

Pediatric dose (3 months-18 years): 2-18 years: 62.5 mg/kg (max 2.5 g) 8 hourly; 6 months-2 years: 62.5 mg/kg 8 hourly; 3-6 months: 50 mg/kg 8 hourly. Safety and efficacy not established in patients <3 months.

Limited information is available on dose adjustment for elderly patients.

Renal Impairment:

Hemodialysis patients: Administer after hemodialysis on hemodialysis days.

Hepatic Impairment: No dose adjustment required for liver disease.

Information on Ceftazidime + Avibactam overdosage is not available.

Store at temperature not exceeding 25°C in a dry place. Protect from light & moisture.

Ceftazidime + Avibactam