Ceftazidime and Avibactam
Medically reviewed on August 12, 2018
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- Avibactam and Ceftazidime
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Avycaz: Ceftazidime 2 g and avibactam 0.5 g (1 ea)
Brand Names: U.S.
- Cephalosporin Combination
Ceftazidime inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Avibactam inactivates some beta-lactamases and protects ceftazidime from degradation.
Vd: Ceftazidime: 17 L; Avibactam: 22.2 L
Ceftazidime: ~80% to 90% of dose eliminated as unchanged drug; Avibactam: Not metabolized
Ceftazidime: Urine (~80% to 90% as unchanged drug); Avibactam: Urine (97%)
Ceftazidime: 2.76 hours; Avibactam: 2.71 hours
Ceftazidime: <10%; Avibactam: 5.7% to 8.2%
Special Populations: Renal Function Impairment
Half-life increases in patients with impaired renal function; AUC of avibactam increases 2.6-fold, 3.8-fold, and 7-fold in patients with mild, moderate or severe renal impairment, respectively.
Use: Labeled Indications
Intra-abdominal infections, complicated: Treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age, in combination with metronidazole, caused by Citrobacter freundii complex, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.
Pneumonia, hospital-acquired and ventilator-associated: Treatment of hospital-acquired bacterial pneumonia and ventilator-associated (HAP/VAP) bacterial pneumonia in adult patients caused by ceftazidime/avibactam-susceptible K. pneumoniae, E. cloacae, E. coli, Serratia marcescens, P. mirabilis, P. aeruginosa, and Haemophilus influenzae.
Urinary tract infections, complicated (including pyelonephritis): Treatment of complicated urinary tract infections (cUTI) (including pyelonephritis) in patients ≥18 years of age, caused by C. freundii complex, E. cloacae, E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa.
Known serious hypersensitivity to ceftazidime, avibactam, other cephalosporins, or any component of the formulation
Note: Dosage recommendations are expressed as total grams of the ceftazidime/avibactam combination.
Intra-abdominal infections, complicated: IV: 2.5 g every 8 hours in combination with metronidazole for 5 to 14 days
Pneumonia, hospital-acquired and ventilator-associated (HAP/VAP): IV: 2.5 g every 8 hours for 7 to 14 days
Urinary tract infections, complicated (including pyelonephritis): IV: 2.5 g every 8 hours for 7 to 14 days
Refer to adult dosing.
Dosing: Renal Impairment
Note: Estimation of renal function for the purpose of drug dosing should be done using the Cockcroft-Gault formula. Dosage recommendations are expressed as total grams of the ceftazidime/avibactam combination:
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 31 to 50 mL/minute: 1.25 g every 8 hours
CrCl 16 to 30 mL/minute: 0.94 g every 12 hours
CrCl 6 to 15 mL/minute: 0.94 g every 24 hours
CrCl ≤5 mL/minute: 0.94 g every 48 hours
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Administer after hemodialysis on dialysis days; base dose upon patient's estimated renal function (eg, CrCl 6 to 15 mL/minute or CrCl ≤5 mL/minute). Approximately 55% (based on a ceftazidime 1 g dose and avibactam 100 mg dose) is removed following a 4-hour dialysis session.
Dosing: Hepatic Impairment
No dosage adjustment necessary.
IV: Reconstitute vial with 10 mL of NS, D5W, SWFI or other compatible solution listed in the manufacturer’s labeling (resulting approximate concentration: ceftazidime 167 mg/mL and avibactam 42 mg/mL) and further dilute in 50 to 250 mL of a compatible IV infusion fluid; mix gently. Solution ranges in color from clear to light yellow.
IV: Administer by intermittent infusion over 2 hours.
Vials: Store intact vials at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light. After reconstitution, contents of the vial should be transferred within 30 minutes to an infusion bag for further dilution.
Intermittent IV infusion: Admixed solutions in NS, D5W, LR, or any combination of dextrose and sodium chloride injection containing up to dextrose 2.5% and sodium chloride 0.45% are stable up to 12 hours at room temperature and 24 hours at 2°C to 8°C (36°F to 46°F). Use solutions previously stored at 2°C to 8°C (36°F to 46°F) within 12 hours of subsequent storage at room temperature.
Aminoglycosides: Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Chloramphenicol (Systemic): May diminish the therapeutic effect of CefTAZidime. Management: Consider using a different combination of antimicrobials, especially if bactericidal activity is desired. If these agents are combined, monitor for reduced antimicrobial effectiveness and/or therapeutic failure. Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Probenecid: May increase the serum concentration of Avibactam. Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy
Tolvaptan: May increase the serum concentration of OAT3 Substrates. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Ceftazidime: Positive direct Coomb. False-positive reaction for urine glucose with certain methods; use glucose tests based on enzymatic glucose oxidase reactions.
Also see ceftazidime monograph.
>10%: Hematologic & oncologic: Positive direct coombs test (3% to 21%; no hemolytic anemia reactions reported)
1% to 10%:
Dermatologic: Pruritus (2%)
Gastrointestinal: Vomiting (≥5%), diarrhea (3%), nausea (3%), constipation (2%), upper abdominal pain (1%)
<1%, postmarketing, and/or case reports: Acute renal failure, anxiety, candidiasis, Clostridium difficile associated diarrhea, dysgeusia, hypokalemia, increased gamma-glutamyl transferase, increased serum ALT, increased serum AST, injection site phlebitis, leukopenia, maculopapular rash, nephrolithiasis, renal insufficiency, skin rash, thrombocytopenia, thrombocythemia, urticaria
Concerns related to adverse effects:
• Hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam drugs. Before initiating therapy, carefully investigate previous penicillin, cephalosporin, or carbapenem hypersensitivity. Use caution if given to a patient with a penicillin or other beta-lactam allergy; cross sensitivity has been established. If an allergic reaction occurs, discontinue and institute appropriate management.
• Neurotoxicity: Severe neurological reactions have been reported with ceftazidime, including asterixis, coma, encephalopathy, myoclonus, neuromuscular excitability, seizures, and nonconvulsive status epilepticus. Risk may be increased in the presence of renal impairment; ensure dose adjusted for renal function. Discontinue therapy if patient develops neurotoxicity.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Renal impairment: In a complicated intra-abdominal infection clinical trial, patients with a creatinine clearance (CrCl) of 30 to 50 mL/minute had lower clinical cure rates than those with CrCl >50 mL/minute; however, these patients received a daily dose that was 33% lower than what is currently recommended for patients with this degree of renal impairment. Decreased clinical response was not seen in patients with a baseline CrCl of 30 to 50 mL/minute in complicated UTI clinical trials. Monitor renal function at baseline and at least daily in patients with changing renal function. Adjust the dose accordingly.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitor for signs of anaphylaxis during first dose. Monitor renal function at baseline in all patients, and at least daily in patients with changing renal function.
Adverse events have not been observed in animal reproduction studies conducted with ceftazidime; adverse events have been observed in some animal reproduction studies conducted with avibactam.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, nausea, or vomiting. Have patient report immediately to prescriber seizures, muscle rigidity, tremors, abnormal movements, confusion, hallucinations, passing out, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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Other brands: Avycaz