AVYCAZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVYCAZ (AVYCAZ).
AVYCAZ is a combination of ceftazidime, a cephalosporin beta-lactam antibiotic, and avibactam, a non-beta-lactam beta-lactamase inhibitor. Ceftazidime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis. Avibactam protects ceftazidime from degradation by certain beta-lactamases, including Ambler class A, class C, and some class D enzymes.
| Metabolism | Ceftazidime is primarily excreted unchanged by the kidneys via glomerular filtration. Avibactam is also primarily eliminated renally and undergoes minimal metabolism. The metabolism of both components is not significantly mediated by cytochrome P450 enzymes. |
| Excretion | Ceftazidime: primarily renal (80-90% unchanged); avibactam: primarily renal (85-95% unchanged). Fecal excretion <1%. |
| Half-life | Ceftazidime: ~2.8 hours; avibactam: ~2.7 hours. Extended in renal impairment (e.g., CrCl <50 mL/min requires dose adjustment). |
| Protein binding | Ceftazidime: ~10% bound to albumin; avibactam: ~8% bound to human plasma proteins. |
| Volume of Distribution | Ceftazidime: ~0.19 L/kg; avibactam: ~0.29 L/kg. Indicates extensive distribution into extracellular fluid. |
| Bioavailability | IV only; bioavailability is 100%. |
| Onset of Action | IV: Onset within 1-2 hours after start of infusion based on PK/PD target attainment for sensitive organisms. |
| Duration of Action | Dosing interval 8 hours; bactericidal activity persists for 8-12 hours post-dose. Clinical duration depends on infection site and MIC. |
1 vial (ceftazidime 2g and avibactam 0.5g) IV over 2 hours every 8 hours.
| Dosage form | POWDER |
| Renal impairment | CrCl 31-50 mL/min: 1 vial IV q8h; CrCl 16-30 mL/min: 1 vial IV q12h; CrCl 6-15 mL/min: 1 vial IV q24h; CrCl ≤5 mL/min: 1 vial IV q48h. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric patients under 18 years of age. |
| Geriatric use | Dose based on renal function, as per adult renal adjustment; no specific age-related adjustments. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVYCAZ (AVYCAZ).
| Breastfeeding | Ceftazidime is excreted in human milk in low concentrations; avibactam excretion is unknown. The M/P ratio for ceftazidime is approximately 0.02. Caution is advised due to potential disruption of infant gut flora. Consider benefits of breastfeeding versus risk of infant exposure. |
| Teratogenic Risk | AVYCAZ (ceftazidime-avibactam) is classified as FDA Pregnancy Category B. Animal reproduction studies in rats and rabbits at doses up to 1.6 times the human dose revealed no evidence of fetal harm. However, there are no adequate and well-controlled studies in pregnant women. Ceftazidime crosses the placenta. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
No black box warning for AVYCAZ.
| Serious Effects |
["Known hypersensitivity to ceftazidime, avibactam, or other cephalosporins","Severe hypersensitivity (e.g., anaphylaxis) to any other beta-lactam antibacterial agents"]
| Precautions | ["Hypersensitivity: Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-lactam antibiotics.","Clostridioides difficile-associated diarrhea (CDAD): Has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis.","Direct Coombs test seroconversion: Positive direct Coombs test may develop during treatment, potentially interfering with crossmatching.","Central nervous system (CNS) adverse reactions: Including seizures, encephalopathy, and myoclonus have been reported, particularly in patients with renal impairment or higher doses.","Renal impairment: Dose adjustment required based on creatinine clearance.","Hepatotoxicity: Elevations of liver enzymes have been observed.","Nephrotoxicity: Concurrent use with nephrotoxic agents may increase risk."] |
| Food/Dietary |
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| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal renal function and for adverse effects such as Clostridioides difficile diarrhea. In neonates exposed in utero, observe for signs of hypersensitivity or gastrointestinal disturbances. |
| Fertility Effects | No human data on fertility effects. Animal studies showed no impairment of fertility in rats at doses up to 1.6 times the human dose. |
| No significant food interactions. However, alcohol should be avoided due to potential disulfiram-like reaction (nausea, vomiting, flushing, headache). |
| Clinical Pearls | AVYCAZ (ceftazidime-avibactam) is a beta-lactam/beta-lactamase inhibitor combination active against ESBLs, KPC, and OXA-48 carbapenemases. It is not active against metallo-beta-lactamases (e.g., NDM, VIM). Dose adjustment required for creatinine clearance <50 mL/min. Monitor for hypersensitivity reactions, including anaphylaxis. Can cause positive direct Coombs test without hemolysis. |
| Patient Advice | Take exactly as prescribed; complete full course even if feeling better. · Inform your doctor if you have kidney disease; blood tests may be needed to adjust dose. · Report any signs of allergic reaction (rash, hives, difficulty breathing, swelling). · May cause diarrhea; tell your doctor if severe or persistent. · Avoid alcohol during treatment and for 72 hours after last dose due to possible disulfiram-like reaction. |