Xacduro: A Breakthrough Treatment for HABP and VABP

Introduction

Xacduro (sulbactam/durlobactam) is a combination antibiotic injection used to treat hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex in adults. Xacduro is a co-packaged kit containing two components as sterile powders for reconstitution: 1 clear single-dose vial of sulbactam for injection 1 g and 2 amber single-dose vials of durlobactam for injection 0.5 g.

FDA Approval

The FDA approved Xacduro (sulbactam/durlobactam) on May 23, 2023, for the treatment of HABP and VABP caused by susceptible strains of A. baumannii-calcoaceticus complex in patients 18 years of age and older. This approval provides a new treatment option for healthcare providers and patients facing the challenge of treating infections caused by these difficult-to-treat bacteria.

Manufacturer Details

Xacduro vial is manufactured by Allergan plc, a global pharmaceutical company focused on developing and commercializing innovative therapeutics. The medication is supplied as a sterile, lyophilized powder for reconstitution with water for injection, and each mL of reconstituted solution contains sulbactam and durlobactam.

Indication

XACDURO is prescribed for individuals aged 18 and above to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) resulting from susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. These infections typically occur in healthcare settings, such as hospitals, with those on ventilators, with catheters, in ICU, with open surgical wounds, or with prolonged stays.

Mechanism of Action

The mechanism of action of Xacduro lies in the combination of sulbactam and durlobactam. Sulbactam is a beta-lactamase inhibitor that inhibits bacterial penicillin-binding proteins, while durlobactam is a beta-lactamase enzyme that protects sulbactam from being degraded by enzymes produced by A. baumannii. This combination of drugs works synergistically to combat the infection caused by the A. baumannii-calcoaceticus complex.

Dosage Information and Form

The recommended dosage of Xacduro injection is based on creatinine clearance (CLcr) and administered by intravenous infusion over three hours. The dosing frequency varies depending on the patient’s CLcr:

• For patients with CLcr greater than or equal to 130 mL/min: 1500 mg (sulbactam 1 g and durlobactam 1 g) every 6 hours
• For patients with CLcr between 45 and 129 mL/min: 750 mg (sulbactam 1.25 g and durlobactam 1.25 g) every 6 hours
• For patients with CLcr between 30 and 44 mL/min: 500 mg (sulbactam 1.25 g and durlobactam 1.25 g) every 8 hours
• For patients with CLcr between 15 and 29 mL/min: 250 mg (sulbactam 0.625 g and durlobactam 0.625 g) every 12 hours
• For patients with CLcr less than 15 mL/min: 125 mg (sulbactam 0.375 g and durlobactam 0.375 g) every 24 hours

Warning and Precaution

Xacduro injection is contraindicated in individuals with a known history of severe hypersensitivity to its components, such as sulbactam and durlobactam, or other beta-lactam antibacterial drugs. The medication carries a warning regarding hypersensitivity reactions, including serious and occasionally fatal anaphylactic reactions, which have been reported with beta-lactam antibacterial drugs, including Xacduro. If an allergic reaction occurs, discontinuation of Xacduro is recommended. 

Additionally, Clostridioides difficile-Associated Diarrhea (CDAD) has been reported with various systemic antibacterial agents, including Xacduro. It is advised to evaluate the occurrence of diarrhea and take appropriate measures if CDAD is suspected.

Xacduro should not be used to treat infections caused by pathogens other than Acinetobacter species.

Usage Of Xacduro In Specific Population 

• Xacduro’s safety and effectiveness have not been established in pediatric patients under 18. 
• Regarding pregnancy, specific data on Xacduro’s use are unavailable. 
• The presence of durlobactam in human or animal milk is not documented, while sulbactam is found in human milk at low concentrations. No information on Xacduro, sulbactam, or durlobactam effects on the breastfed infant or milk production is available. 
• Considering that Xacduro is substantially excreted by the kidney, dosing adjustments for elderly patients should be made based on renal function, as they are more likely to experience decreased renal function. 

Before taking the medicine inform your doctor if you are pregnant or breastfeeding. 

Side Effects

The most common adverse reactions associated with Xacduro were liver test abnormalities, diarrhea, anemia, and hypokalemia. 

Conclusion

Xacduro is a novel treatment for HABP or VABP caused by susceptible strains of A. baumannii-calcoaceticus complex. Its mechanism involves the synergistic action of sulbactam and durlobactam, inhibiting bacterial penicillin-binding proteins and protecting sulbactam from enzymatic degradation by A. baumannii. Administered through intravenous infusion over three hours, Xacduro is supplied as a sterile, lyophilized powder for reconstitution with water for injection. Healthcare providers should carefully assess the potential risks and benefits of Xacduro for patients with these infections.

FAQ: 

1. Can Xacduro be used in pediatric patients?

The safety and effectiveness of Xacduro in pediatric patients younger than 18 years of age have not been established. Therefore, its use in pediatric patients is not recommended.

2. What are the side effects of Xacduro?

Common side effects of Xacduro may include diarrhea and changes to liver enzyme levels in the blood. It is important to consult a healthcare professional for a comprehensive understanding of potential side effects and their management. 

3. How to store Xacduro?

After preparing the bag, Store the medicine in the refrigerator at a temperature between 36°F to 46°F (2°C to 8°C) until it’s ready for use. Ensure to finish the entire process, from reconstitution to infusion, within 24 hours. Avoid freezing the bag.

4. How to buy Xacduro online?

To buy Xacduro online, contact SANSFRO or similar pharmaceutical procurement firms specializing in medicine importation from the US and Europe. For accurate information tailored to the Indian market, reach out to the dedicated Patient Support Team at (+91) 93157 05373 or help@sansfro.com.  

5. What is the Xacduro cost?

Several factors and product specifications contribute to the pricing of Xacduro. For accurate and current Xacduro cost information in the Indian market, please contact our Patient Support Team at (+91) 93157 05373 or via email at help@sansfro.com. Our team will provide you with the latest and precise cost details for Xacduro. 

Reference:

1. https://www.drugs.com/xacduro.html 
2. https://reference.medscape.com/drug/xacduro-sulbactam-durlobactam-4000348 
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216974Orig1s000Correctedlbl.pdf 
4. https://www.xacduro.com/using-xacduro 
5. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pneumonia-caused-certain-difficult-treat-bacteria