XACDURO (COPACKAGED)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XACDURO (COPACKAGED) (XACDURO (COPACKAGED)).
Sulbactam-durlobactam: Sulbactam is a beta-lactamase inhibitor and also binds to penicillin-binding proteins (PBPs) of Acinetobacter baumannii, inhibiting cell wall synthesis. Durlobactam is a beta-lactamase inhibitor that protects sulbactam from degradation by certain beta-lactamases, including class A, C, and D serine beta-lactamases.
| Metabolism | Sulbactam: Not extensively metabolized. Durlobactam: Not extensively metabolized. Both are primarily excreted unchanged in urine. No significant hepatic metabolism. |
| Excretion | Renal excretion of unchanged drug: sulbactam ~80%, durlobactam ~90% within 24 hours. Biliary/fecal elimination: minimal (<1%). |
| Half-life | Sulbactam: ~1 hour; durlobactam: ~2 hours. In patients with moderate to severe renal impairment, half-life may be prolonged up to 3-4 times, requiring dose adjustment. |
| Protein binding | Sulbactam: ~38% bound to human serum albumin; durlobactam: ~7% bound to human serum albumin. |
| Volume of Distribution | Sulbactam: ~0.2 L/kg; durlobactam: ~0.3 L/kg. Vd approximates extracellular fluid volume, indicating limited tissue penetration but adequate for bloodstream infections. |
| Bioavailability | Not applicable; XACDURO is administered intravenously only, thus bioavailability is 100% via IV route. |
| Onset of Action | Intravenous administration: onset of antibacterial effect within 1-2 hours post-infusion, based on time to achieve therapeutic plasma concentrations above MIC. |
| Duration of Action | Duration of antibacterial effect approximately 6-8 hours, supporting every 6-hour dosing regimen. Clinical cure rates assessed at test-of-cure visit (7-14 days post-therapy). |
XACDURO (ceftazidime-avibactam) 2.5 g (ceftazidime 2 g + avibactam 0.5 g) intravenously over 2 hours every 8 hours.
| Dosage form | POWDER |
| Renal impairment | For CrCl (calculated using Cockcroft-Gault) 31-50 mL/min: 1.25 g IV every 8 hours; CrCl 16-30 mL/min: 0.94 g IV every 12 hours; CrCl 6-15 mL/min: 0.94 g IV every 24 hours; CrCl ≤5 mL/min: 0.94 g IV every 48 hours. For patients on hemodialysis, administer after dialysis on dialysis days. |
| 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 | For pediatric patients aged 3 months to <18 years: Ceftazidime-avibactam 50 mg/kg (ceftazidime 40 mg/kg + avibactam 10 mg/kg) IV over 2 hours every 8 hours, up to a maximum of 2.5 g per dose. For neonates and infants <3 months: Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment based on age alone; dose adjustment based on renal function as per renal adjustment guidelines. Elderly patients often have decreased renal function; monitor CrCl and adjust accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XACDURO (COPACKAGED) (XACDURO (COPACKAGED)).
| Breastfeeding | It is not known whether sulbactam or durlobactam are excreted in human milk. Sulbactam is excreted in the milk of lactating rats. No data on M/P ratio. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | There are no adequate and well-controlled studies of XACDURO in pregnant women. In animal reproduction studies, intravenous administration of sulbactam-durlobactam to pregnant rats and rabbits during organogenesis resulted in fetal malformations at doses 0.5 times (rats) and 0.2 times (rabbits) the human clinical dose based on AUC. Therefore, XACDURO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester: potential for major malformations; second and third trimesters: potential for growth restriction and central nervous system effects. |
■ FDA Black Box Warning
There is no black box warning for XACDURO.
| Serious Effects |
["Known hypersensitivity to sulbactam, durlobactam, or any component of the product.","History of severe allergic reaction to beta-lactam antibiotics (e.g., penicillins, cephalosporins, carbapenems)."]
| Precautions | ["Hypersensitivity reactions including anaphylaxis and serious skin reactions have been reported.","Clostridioides difficile-associated diarrhea (CDAD) may occur.","Use in patients with renal impairment: Dose adjustment required based on creatinine clearance.","Potential for development of drug-resistant bacteria."] |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN, urine output) during therapy as XACDURO is primarily renally excreted. Consider fetal monitoring (ultrasound for growth and anatomy) if used in pregnant women. No specific maternal-fetal monitoring requirements are established; however, standard pregnancy monitoring is recommended. |
| Fertility Effects | Animal studies have not been conducted to evaluate the effects of XACDURO on fertility. Subcutaneous administration of durlobactam to rats at doses up to 300 mg/kg/day (approximately 2.4 times the human clinical dose based on AUC) did not impair male or female fertility. No fertility data are available for sulbactam alone or the combination. |