sulbactam/durlobactam (Rx)

Brand and Other Names:Xacduro

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injection, powder for reconstitution

  • Copackaged kit containing each component in separate vials
  • Sulbactam: 1g/vial (1 clear, single-dose vial/kit), PLUS
  • Durlobactam: 0.5g/vial (2 amber, single-dose vials/kit)

Acinetobacter baumannii-calcoaceticus Infection

Indicated for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (ABC)

2 g (1 g sulbactam and 1 g durlobactam) IV q6hr infused over 3 hr

Recommended duration of treatment is 7-14 days; adjust duration of therapy to patient’s clinical status

Dosage Modifications

Renal impairment

  • Monitor renal function regularly
  • CrCl ≥130 mL/min: Increase dose frequency to q4hr
  • CrCl 45-129 mL/min: Maintain dose frequency at q6hr
  • CrCl 30-44 mL/min: Decrease dose frequency to q8hr
  • CrCl 15-29 mL/min: Decrease dose frequency to q12hr
  • CrCl <15 mL/min
    • Initial: Give q12hr x 3 doses (ie, 0, 12, and 24 hr), followed by q24hr after third dose
    • Patients taking sulbactam/durlobactam and CrCl declines to <15 mL/min: Decrease dose frequency to q24hr
    • Patients on hemodialysis: Administer dose after dialysis session has ended

Hepatic impairment

  • Dosage adjustments are not necessary
  • Hepatic impairment is not expected to alter the elimination as neither sulbactam nor durlobactam undergo substantial hepatic metabolism/excretion

Dosing Considerations

Limitation of use: Not indicated for HABP/VABP caused by pathogens other than susceptible isolates of ABC

To reduce development of drug-resistant bacteria and maintain effectiveness, use only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria

Safety and efficacy not established

Drug is substantially excreted by the kidney, and elderly patients are more likely to have decreased renal function

Adjust dosing regimen for elderly patients based on renal function

Next:

Interactions

Interaction Checker

and sulbactam/durlobactam

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (25)

              • clarithromycin

                clarithromycin will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • crofelemer

                crofelemer will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • cyclosporine

                cyclosporine will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • eluxadoline

                eluxadoline will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • encorafenib

                encorafenib will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • erythromycin base

                erythromycin base will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • erythromycin ethylsuccinate

                erythromycin ethylsuccinate will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • erythromycin lactobionate

                erythromycin lactobionate will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • erythromycin stearate

                erythromycin stearate will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • fostemsavir

                fostemsavir will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • gemfibrozil

                gemfibrozil will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • glecaprevir/pibrentasvir

                glecaprevir/pibrentasvir will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • grapefruit

                grapefruit will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • leniolisib

                leniolisib will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • microbiota oral

                sulbactam/durlobactam decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .

              • pazopanib

                pazopanib will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • rifampin

                rifampin will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • rifamycin

                rifamycin will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • ritonavir

                ritonavir will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • sofosbuvir/velpatasvir

                sofosbuvir/velpatasvir will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • tacrolimus

                tacrolimus will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • telmisartan

                telmisartan will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • trofinetide

                trofinetide will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • verapamil

                verapamil will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              • voxilaprevir

                voxilaprevir will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

              Monitor Closely (1)

              • pretomanid

                pretomanid will increase the level or effect of sulbactam/durlobactam by Other (see comment). Use Caution/Monitor. Increase monitoring for drug-related adverse effects if pretomanid is coadministered with sensitive OATP1B3 substrates.

              Minor (0)

                Previous
                Next:

                Adverse Effects

                >10%

                Liver test abnormalities (19%)

                Diarrhea (17%)

                Anemia (13%)

                Hypokalemia (12%)

                1-10%

                Arrhythmia (9%)

                Acute kidney injury (6%)

                Thrombocytopenia (6%)

                Constipation (6%)

                Previous
                Next:

                Warnings

                Contraindications

                History of known severe hypersensitivity to sulbactam and durlobactam, or other beta-lactam antibacterial drugs

                Cautions

                Hypersensitivity

                • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions reported in patients receiving beta-lactam antibacterial drugs
                • These reactions are more likely to occur in individuals with history of beta-lactam hypersensitivity and/or a history of sensitivity to multiple allergens

                Clostridioides difficile-associated diarrhea (CDAD)

                • CDAD reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis
                • Treatment with antibacterial agents alters normal flora of colon, leading to C difficile overgrowth that produces toxins A and B, which contribute to CDAD development
                • Hypertoxin-producing C difficile strains cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
                • Consider CDAD if diarrhea occurs following antibacterial drug use
                • Careful medical history is necessary, since CDAD has been reported to occur over 2 months after antibacterial administration; if severe watery or bloody diarrhea develops, patient should contact their healthcare provider
                • If CDAD is suspected or confirmed, assess the risk/benefit of continuing treatment
                • Institute appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C difficile, and surgical evaluation, as clinically indicated

                Drug-resistant bacteria

                • Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit and increases risk of developing drug-resistant bacteria

                Drug interaction overview

                • Organic anion transporter 1 (OAT1) substrate
                • OAT1 inhibitors
                  • Avoid coadministration
                  • OAT1 inhibitors may increase plasma concentrations of sulbactam/durlobactam
                Previous
                Next:

                Pregnancy & Lactation

                Pregnancy

                There are no available data on use of sulbactam plus durlobactam in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

                Sulbactam: Available published data from case reports and case series with sulbactam use in combination with ampicillin during pregnancy over many decades have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

                Durlobactam: No human data are available

                Animal studies

                • Sulbactam: Reproduction studies performed in mice, rats, and rabbits at doses up to 10 times the human dose have revealed no evidence of harm to the fetus
                • Durlobactam: Administration to pregnant mice and rats during organogenesis showed no drug-induced fetal malformations, but an increased incidence of skeletal variations was observed in mice at 2 and 4 times the maximum recommended human dose

                Lactation

                There are no data on presence of durlobactam in human or animal milk

                Sulbactam is present in human milk in low concentrations

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

                Previous
                Next:

                Pharmacology

                Mechanism of Action

                Sulbactam: Beta-lactam antibiotic and Ambler class A serine beta-lactamase inhibitor; elicits 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: 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

                Absorption

                Peak plasma concentration

                • Sulbactam: 32.4 mcg/mL
                • Durlobactam: 29.2 mcg/mL

                AUC

                • Sulbactam: 515 mcg⋅hr/mL
                • Durlobactam: 471 mcg⋅hr/mL

                Distribution

                Protein bound

                • Sulbactam: 38%
                • Durlobactam: 10%

                Vd (steady state)

                • Sulbactam: 25.4 L
                • Durlobactam: 30.3 L

                Metabolism

                Minimally metabolized

                Elimination

                Half-life

                • Sulbactam: 2.15 hr
                • Durlobactam: 2.52 hr

                Clearance

                • Sulbactam: 11.6 L/hr
                • Durlobactam: 9.96 L/hr

                Excretion

                • Sulbactam: Urine, 75-85% unchanged
                • Durlobactam: Urine, 78% unchanged
                Previous
                Next:

                Administration

                IV Incompatibilities

                Do not mix with other drugs or physically add to solutions containing other drugs

                IV Compatibilities

                0.9% NaCl

                IV Preparation

                Reconstitution

                • Reconstituted solutions are NOT for direct injection and must be diluted before IV infusion
                • Dilution must occur within 1 hr of reconstitution
                • Sulbactam
                  • Add 5 mL sterile water for injection to 1-g vial and gently shake to dissolve
                  • Resulting concentration is 1 g/5 mL
                  • Solution should appear clear, colorless to slightly yellow
                • Durlobactam
                  • Add 2.5 mL sterile water for injection to each 0.5-g vial and gently shake to dissolve
                  • Resulting concentration is 0.5 g/2.5 mL per vial
                  • Solution should appear clear, light yellow to orange

                Further dilution

                • Prepare required dose by withdrawing 5 mL of reconstituted sulbactam and 5 mL (2.5 mL from each vial) of reconstituted durlobactam
                • Add withdrawn volume of both sulbactam and durlobactam to 100-mL infusion bag of 0.9% NaCl
                • Discard unused portion
                • Inspected visually for particulate matter and discoloration
                • Prepared solution should appear clear, light yellow to orange, and free of particulates
                • Discard if solution is cloudy or contains particulates

                IV Administration

                Bring prepared solution to ambient room temperature (over 15-30 minutes) before infusion

                Administer all doses by IV infusion over 3 hr

                Storage

                Vials do not contain bacteriostatic preservative

                Unopened vials

                • Refrigerate at 2-8ºC (36-46ºF); brief exposure to 8-15ºC (46-59ºF) permitted
                • Do not freeze

                Prepared solution

                • Refrigerate at 2-8ºC (36-46ºF) until administration
                • Do not exceed 24 hr between time starting reconstitution of powders and completion of infusion
                • Discard unused portion
                Previous
                Next:

                Images

                No images available for this drug.
                Previous
                Next:

                Patient Handout

                A Patient Handout is not currently available for this monograph.
                Previous
                Next:

                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
                Email to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Email Forms to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Previous
                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.