Version May 2024
Pneumonia, hospital-acquired or ventilator-associated :
Note: Reserve use for patients with A. baumannii-calcoaceticus complex infection.
IV: Sulbactam 1 g/durlobactam 1 g every 6 hours (Ref). Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref).
Note: Estimation of kidney function for the purpose of drug dosing should be done using the Cockcroft-Gault formula.
Altered kidney function:
CrCl 45 to 129 mL/minute: No dosage adjustment necessary.
CrCl 30 to 44 mL/minute: IV: Sulbactam 1 g/durlobactam 1 g every 8 hours.
CrCl 15 to 29 mL/minute: IV: Sulbactam 1 g/durlobactam 1 g every 12 hours.
CrCl <15 mL/minute: IV: Loading dose: Sulbactam 1 g/durlobactam 1 g every 12 hours for 3 doses, then sulbactam 1 g/durlobactam 1 g once daily. Note: For patients whose CrCl declines to <15 mL/minute after therapy has been initiated, administer once daily without loading dose.
Augmented renal clearance (CrCl ≥130 mL/minute): IV: Sulbactam 1 g/durlobactam 1 g every 4 hours.
Hemodialysis, intermittent (thrice weekly): Dialyzable (sulbactam: 41%; durlobactam: 33%): IV: Loading dose: Sulbactam 1 g/durlobactam 1 g every 12 hours for 3 doses, then sulbactam 1 g/durlobactam 1 g once daily; administer after hemodialysis on dialysis days. Note: For patients who require hemodialysis after therapy has been initiated, administer once daily without loading dose.
No dosage adjustment necessary.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Endocrine & metabolic: Hypokalemia (12%)
Gastrointestinal: Diarrhea (17%)
Hematologic & oncologic: Anemia (13%)
Hepatic: Abnormal hepatic function tests (19%)
1% to 10%:
Cardiac: Cardiac arrhythmia (9%)
Gastrointestinal: Constipation (6%)
Hematologic & oncologic: Thrombocytopenia (6%)
Hypersensitivity: Anaphylactic shock (1%)
Renal: Acute kidney injury (6%; including increased serum creatinine, renal failure syndrome, toxic nephrosis)
Severe hypersensitivity to sulbactam, durlobactam, any component of the formulation, or other beta-lactam antibacterial drugs.
Concerns related to adverse effects:
• Hypersensitivity reactions: Hypersensitivity reactions, including serious skin reactions and fatal hypersensitivity (anaphylactic) reactions, have occurred in patients receiving beta-lactams; risk is increased in patients with a history of beta-lactam and/or multiple allergen hypersensitivity. Hypersensitivity reactions to sulbactam and durlobactam have been observed; prior to therapy, obtain history of previous hypersensitivity reactions to all beta-lactams and other allergens. Discontinue therapy and initiate appropriate treatment if signs and symptoms of anaphylaxis or severe hypersensitivity occur.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Xacduro: Sulbactam sodium 1 g and durlobactam sodium 1 g (3 ea)
No
Solution (reconstituted) (Xacduro Intravenous)
1-1 g (per each): $190.00
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IV: Administer by IV infusion over 3 hours; if refrigerated prior to administration, bring to room temperature for 15 to 30 minutes immediately prior to administration.
Pneumonia, hospital-acquired or ventilator-associated: Treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, in patients ≥18 years of age caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.
Limitations of use: Not indicated for the treatment of pneumonia caused by pathogens other than susceptible isolates of A. baumannii-calcoaceticus complex.
Sulbactam and durlobactam may be confused with ampicillin and sulbactam.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
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. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Sulbactam. Management: Recommendations for management of this interaction vary by specific sulbactam-containing product. Coadministration of probenecid with sulbactam/durlobactam is not recommended, but no specific actions are recommended for ampicillin/sulbactam. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Sulbactam crosses the human placenta. Outcome data following maternal use of sulbactam during pregnancy are available following use in combination with ampicillin.
Adverse events were observed in reproduction studies when durlobactam was administered SUBQ to pregnant mice in doses up to 4 times the maximum recommended human dose (MRHD) (based on AUC). Adverse events were not observed in reproduction studies when durlobactam was administered IV to pregnant rats in doses up to 4 times the MRHD.
Sulbactam is present in breast milk; excretion of durlobactam is not known.
A review article notes the exposure of sulbactam to a breastfeeding infant would be ~1% to 2% of a typical adult dose following administration in combination with ampicillin (Foulds 1986).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Monitor for signs of hypersensitivity reaction, including anaphylaxis and serious skin reactions. Regularly monitor kidney function.
Sulbactam is a beta-lactam antibacterial and Ambler class A serine beta-lactamase inhibitor that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins 1 and 3. Durlobactam is a diazabicyclooctane beta-lactamase inhibitor that protects sulbactam from degradation by certain serine beta-lactamases.
Distribution: Sulbactam: Vd: 25.4 ± 11.3 L; Durlobactam: Vd: 30.3 ± 12.9 L.
Protein binding: Sulbactam: 38%; Durlobactam: 10%.
Metabolism: Minimally metabolized.
Half-life elimination: Sulbactam: 2.15 ± 1.16 hours (when given with durlobactam); Durlobactam: 2.52 ± 0.77 hours. Note: Elimination kinetics of both sulbactam and durlobactam are similarly affected in patients with renal impairment; therefore, the blood concentration ratio is expected to remain constant regardless of renal function.
Time to peak: Sulbactam: Tmax: 3.2 ± 0.6 hours; Durlobactam: Tmax: 3.1 ± 0.5 hours (Sagan 2020).
Excretion: Sulbactam: Urine (75% to 85% as unchanged drug); Durlobactam: Urine (78% as unchanged drug).
Altered kidney function: In patients with eGFR ≥60 to <90 mL/minute/1.73 m2, AUCs of both sulbactam and durlobactam increased 1.4-fold. In patients with eGFR ≥30 to <60 mL/minute/1.73 m2, AUC increased 2-fold for sulbactam and 1.9-fold for durlobactam. In patients with eGFR <30 mL/minute/1.73 m2, AUC increased 4.3-fold for sulbactam and 3.7-fold for durlobactam.
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