Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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)
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%)
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
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.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
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
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