XACDURO Dosage & Rx Info | Uses, Side Effects

Xacduro Generic Name & Formulations

Legal Class

General Description

Sulbactam 1g + durlobactam 0.5g (co-packaged); pwd for IV inj after reconstitution and dilution; preservative-free.

Pharmacological Class

Beta-lactam antibacterial/beta-lactamase inhibitor + beta-lactamase inhibitor.

How Supplied

Kit—1 (sulbactam 1g + durlobactam 2×0.5g single-dose vials)

Storage

Stored refrigerated at 2°C to 8°C (36°F to 46°F); brief exposure to
8°C to 15°C (46°F to 59°F) permitted [see USP Controlled Cold Temperature]. Do not freeze. Store prepared Xacduro solution in the refrigerator.

Manufacturer

Entasis Therapeutics Ltd.

Generic Availability

Mechanism of Action

Sulbactam is a beta-lactam antibacterial and Ambler Class A serine beta-lactamase inhibitor that has bactericidal activity due to its inhibition of Acinetobacter baumannii-calcoaceticus complex (ABC) penicillin-binding proteins PBP1 and PBP3, which are essential enzymes required for bacterial cell wall synthesis.

Durlobactam is a diazabicyclooctane non-beta-lactam, beta-lactamase inhibitor, that protects sulbactam from degradation by certain serine-beta-lactamases. Durlobactam alone does not have antibacterial activity against ABC isolates.

Xacduro Indications

Indications

Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Acinetobacter baumanii-calcoaceticus complex.

Limitations of Use

Not for HABP/VABP caused by pathogens other than susceptible isolates of Acinetobacter baumanii-calcoaceticus complex.

Xacduro Dosage and Administration

Adult

Give by IV infusion over 3hrs. Treatment duration: 7–14 days. Base dose on renal function. ≥18yrs: CrCl ≥130mL/min: 1g/1g every 4hrs; CrCl 45–129mL/min: 1g/1g every 6hrs; CrCl 30–44mL/min: 1g/1g every 8hrs; CrCl 15–29mL/min: 1g/1g every 12hrs; CrCl <15mL/min: 1g/1g every 12hrs for first 3 doses, followed by every 24hrs; those on hemodialysis, give dose after session.

Children

<18yrs: not established.

Xacduro Contraindications

Contraindications

Other β-lactam antibacterial allergy.

Xacduro Boxed Warnings

Not Applicable

Xacduro Warnings/Precautions

Warnings/Precautions

History of beta-lactam hypersensitivity and/or sensitivity to multiple allergens. Discontinue if allergic reactions occur. If C.diff-associated diarrhea (CDAD) suspected or confirmed, assess risk/benefit of continuing treatment. Give appropriate fluid/electrolyte management, protein supplementation, antibacterial treatment, surgical evaluation as indicated. Pregnancy. Nursing mothers. Elderly: monitor renal function.

Xacduro Pharmacokinetics

Distribution

Plasma protein bound: 38% (sulbactam); 10% (durlobactam).

Elimination

Renal. Half-life: 2.15 ± 1.16 hours (sulbactam), 2.52 ± 0.77 hours (durlobactam).

Xacduro Interactions

Interactions

May be potentiated by OAT1 inhibitors (eg, probenecid): avoid concomitant use.

Xacduro Adverse Reactions

Adverse Reactions

Liver test abnormalities, diarrhea, anemia, hypokalemia; hypersensitivty reactions, C. difficile-associated diarrhea.

Xacduro Clinical Trials

Clinical Trials

The approval was based data from the phase 3 ATTACK trial (ClinicalTrials.gov Identifier: NCT03894046), which evaluated Xacduro vs colistin in patients with documented A baumannii hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia; the majority of patients had pneumonia as the baseline infection.

Xacduro was found to be statistically noninferior to colistin for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections. The mortality rate was 19.0% (12/63) in the Xacduro arm and 32.3% (20/62) in the colistin arm (treatment difference, -13.2%; 95% CI, -30.0, 3.5).

Additionally, a statistically significant difference in clinical cure rates was observed; 61.9% with Xacduro vs 40.3% with colistin. Clinical cure was defined as complete resolution or significant improvement of signs and symptoms that were present at baseline and no new symptoms, such that no additional gram-negative antimicrobial therapy was warranted.

Xacduro Note