ampicillin sodium and sulbactam sodium
Unasyn

Pharmacologic classification: aminopenicillin/beta-lactamase inhibitor combination
Therapeutic classification: antibiotic
Pregnancy risk category B


Available forms
Available by prescription only
Injection: vials and piggyback vials containing 1.5 g (1 g ampicillin sodium with 500 mg sulbactam sodium) and 3 g (2 g ampicillin sodium with 1 g sulbactam sodium)

Indications and dosages
 Skin and skin-structure infections, intra-abdominal and gynecologic infections caused by susceptible gram-positive bacteria, gram-negative bacteria, beta-lactamase-producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella (including K. pneumoniae), Proteus mirabilis, Bacteroides (including B. fragilis), Enterobacter, Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis, and Acinetobacter calcoaceticus. Adults: 1.5 to 3 g I.M. or I.V. q 6 hours. Don’t exceed 4 g daily of sulbactam sodium.
 Skin and skin-structure infections caused by susceptible organisms. Children who weigh less than 88 lb (40 kg): Same as adult dose.
Children age 1 and older who weigh less than 40 kg: 300 mg/kg I.V. daily in divided doses q 6 hours not to exceed 14 days of therapy.
≡ Dosage adjustment. For adults with renal impairment, give the usually recommended doses, but less frequently, as shown in below.

Creatinine clearance (ml/min) Half-life (hours) Recommended interval

15-29 5 12 hr
5-14 9 24 hr

Pharmacodynamics
Antibiotic action: Ampicillin is bactericidal; it adheres to bacterial penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. Sulbactam inhibits beta-lactamase, an enzyme produced by ampicillin-resistant bacteria that degrades ampicillin.

Pharmacokinetics
Absorption: Well absorbed after I.M. administration.
Distribution: Both distributed into pleural, peritoneal, and synovial fluids, lungs, prostate, liver, and gallbladder; they also penetrate middle ear effusions, maxillary sinus and bronchial secretions, tonsils, and sputum. Ampicillin readily crosses the placental barrier; it’s minimally protein-bound at 15% to 25%; sulbactam is about 38% bound.
Metabolism: Both are metabolized only partially; only 15% to 25% of both are metabolized.
Excretion: Both are excreted in the urine by renal tubular secretion and glomerular filtration. They’re also excreted in breast milk. Elimination half-life is 1 to 11/2 hours; in patients with extensive renal impairment, half-life can be as long as 10 to 24 hours.

Route Onset Peak Duration
I.V. Immediate Immediately after infusion Unknown
I.M. Unknown Unknown Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other penicillins. Use cautiously in patients with maculopapular rash.

Interactions
Drug-drug. Allopurinol: May increase risk of rash. Monitor patient closely.
Aminoglycosides: The ampicillin component may cause in vitro inactivation of aminoglycosides if these antibiotics are mixed in the same infusion container. Don’t mix together.
Anticoagulants: Large doses of I.V. penicillins can increase bleeding risks of anticoagulants because of prolongation of bleeding times. Monitor PT and INR.
Probenecid: Decreases excretion of both ampicillin and sulbactam. Monitor patient for toxicity.

Adverse reactions
CV: thrombophlebitis.
GI: nausea, vomiting, diarrhea, glossitis, stomatitis, gastritis, black "hairy" tongue, enterocolitis, pseudomembranous colitis.
Hematologic: anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, agranulocytosis.
Other: hypersensitivity reactions (erythematous maculopapular rash, urticaria, anaphylaxis), overgrowth of nonsusceptible organisms, pain at injection site, vein irritation.

Effects on lab test results
• May increase BUN, creatinine, ALT, AST, alkaline phosphatase, bilirubin, LDH, CK, and GGT levels.
• May increase eosinophil count. May decrease hemoglobin and platelet, WBC, and granulocyte counts.

Overdose and treatment
Neurologic adverse reactions, including seizures, are likely.
 Treatment is supportive. Ampicillin and sulbactam are likely to be removed by hemodialysis.

Special considerations
• Ampicillin alters results of urine glucose tests that use cupric sulfate (Benedict’s reagent or Clinitest). Make urine glucose determinations with glucose oxidase methods (Chemstrip uG, Diastix, or glucose enzymatic test strip).
• For I.V. use, reconstitute powder in piggyback units to desired concentrations with sterile water for injection, normal saline solution, D5W, lactated Ringer’s injection, 1/6 M sodium lactate injection, D5W in half-normal saline solution, or 10% invert sugar.
 ALERT Give I.V. drug by slow injection over at least 10 to 15 minutes or infuse in greater dilutions with 50 to 100 ml of a compatible diluent over 15 to 30 minutes to avoid risk for seizures.
• For I.M. injection, reconstitute with sterile water for injection, or 0.5% or 2% lidocaine hydrochloride injection. To obtain 375 mg/ml solutions (250 mg ampicillin/125 mg sulbactam/ml), add contents of the 1.5-g vial to 3.2 ml of diluent to produce 4 ml withdrawal volume; add 3-g vial to 6.4 ml of diluent to produce 8 ml withdrawal volume.
• Reconstituted solutions are stable for varying periods (from 2 to 72 hours) depending on diluent used. Refer to package insert for specific information. For patients on sodium restriction, note that a 1.5-g dose of ampicillin sodium/sulbactam sodium yields 5 mEq of sodium.
• Store powder below 86° F (30° C).
• Test for Clostridium difficile in patients with persistent diarrhea.
• Monitor patient for overgrowth of nonsusceptible organisms.
Pregnant patients
• Safety in pregnant women hasn’t been established.
• Transient decreases in serum estradiol, conjugated estrone, conjugated estriol, and estriol glucuronide may occur.
Breast-feeding patients
• Drug appears in breast milk. Because safety in breast-feeding women hasn’t been established, recommend a different feeding method during therapy.
Pediatric patients
• Safety in children younger than age 1 hasn’t been established. Safety and efficacy for use in children for treatment of skin and skin structure infections have been established. Not for use to treat other infections or for I.M. use.
Geriatric patients
• Because of diminished renal tubular secretion in geriatric patients, half-life of drug may be prolonged.

Patient education
• Tell patient to report a rash, fever, or chills. A rash is the most frequent allergic reaction.
• Advise patient to report discomfort at insertion site.
• Warn patient that I.M. injection may cause pain at the injection site.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use