sulbactam/durlobactam

REMS

Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of
Acinetobacter baumannii-calcoaceticus
complex.

Action ⬆ ⬇

Sulbactam is a beta-lactam antibiotic and a beta-lactamase inhibitor that inhibits Acinetobacter baumannii-calcoaceticus complex penicillin-binding proteins. Durlobactam is a beta-lactamase inhibitor that protects sulbactam from being degraded by certain serine-beta-lactamases.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-negative pathogen:
- Acinetobacter baumannii-calcoaceticus complex.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Undergoes minimal metabolism. Primarily excreted by the kidneys, with 75–85% of sulbactam and 78% of durlobactam being excreted as unchanged drug.

Half-Life: Sulbactam: 2–3 hr; Durlobactam: 2–3 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	6 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to sulbactam, durlobactam, or any beta-lactam antibiotic.

Use Cautiously in:

Renal impairment (↓ dose if CCr <45 mL/min);
CCr ≥130 mL/min;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: Consider age-related in renal function in determining dose in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmia

F and E: hypokalemia

GI: ↑liver enzymes, diarrhea, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation

GU: acute kidney injury

Hemat: anemia, thrombocytopenia

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Probenecid may ↓ renal excretion and ↑ levels of sulbactam; concurrent use not recommended.

Route/Dosage ⬆ ⬇

IV (Adults ): CCr 45–129 mL/min: Sulbactam 1 g/durlobactam 1 g every 6 hr for 7–14 days. CCr ≥130 mL/min: Sulbactam 1 g/durlobactam 1 g every 4 hr for 7–14 days.

Renal Impairment

IV (Adults ): CCr 30–44 mL/min: Sulbactam 1 g/durlobactam 1 g every 8 hr for 7–14 days. CCr 15–29 mL/min: Sulbactam 1 g/durlobactam 1 g every 12 hr for 7–14 days. CCr <15 mL/min (at baseline before initiating therapy): Sulbactam 1 g/durlobactam 1 g every 12 hr for first 3 doses, then sulbactam 1 g/durlobactam 1 g every 24 hr to complete a total treatment course of 7–14 days. CCr <15 mL/min (after initiating therapy): Sulbactam 1 g/durlobactam 1 g every 24 hr for 7–14 days.

Availability ⬆ ⬇

Lyophilized powder for injection: sulbactam 1 g/vial + durlobactam 0.5 g/vial (2 vials supplied)

Assessment ⬆ ⬇

Assess patient for infection (vital signs, wound appearance, sputum, urine, stool, and WBCs) at beginning and throughout therapy.
Obtain a history before initiating therapy to determine previous use of, and reactions to, penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity before therapy. First dose may be given before receiving results.
Monitor for signs and symptoms of hypersensitivity (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify health care professional immediately if these occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Monitor bowel function. Report diarrhea, abdominal cramping, fever, and bloody stools to health care professional promptly as a sign of CDAD. May begin up to several mo following cessation of therapy
Monitor for rash; may lead to severe skin reactions.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Xacdurokit includes one clear single-dose vial of sulbactam 1 g and two amber single-dose vials of durlobactam 0.5 g as sterile powders. Reconstitution: Reconstitute sulbactam 1 g 5 mL of sterile water for injection and gently shake to dissolve. Solution is clear, colorless to slightly yellow; do not use solutions that are cloudy, discolored, or contain particulate matter. Dilution must occur within 1 hr of reconstitution. Reconstitute durlobactam 0.5 g single-dose vial with 2.5 mL of sterile water for injection and gently shake to dissolve. Solution is clear, light yellow to orange; do not use solutions that are cloudy, discolored, or contain particulate matter. Dilution must occur within 1 hour of reconstitution. To prepare Xacduro dose, withdraw 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 a 100 mL bag of 0.9% NaCl. Discard unused portion. Store solution in refrigerator. Allow solutions to reach room temperature over 15–30 min before administering. Solutions are stable for 24 hr if refrigerated.
Rate: Infuse over 3 hr.

Patient/Family Teaching ⬆ ⬇

Explain purpose of Xacduro to patient.
Advise patient to report rash, signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools), and allergy.
Caution patient to notify health care professional if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several wk after discontinuation of medication.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Instruct the patient to notify health care professional if symptoms do not improve.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇