Unasyn - Drug Monograph

Introduction

Unasyn (ampicillin sodium/sulbactam sodium) is an intravenous antibiotic combination medication used for the treatment of moderate to severe infections. It combines a broad-spectrum penicillin (ampicillin) with a beta-lactamase inhibitor (sulbactam) to extend its antimicrobial coverage against beta-lactamase-producing organisms that would otherwise be resistant to ampicillin alone.

Mechanism of Action

Unasyn exerts its bactericidal effects through two complementary mechanisms:

• Ampicillin: A beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death
• Sulbactam: A beta-lactamase inhibitor that irreversibly binds to and inactivates certain beta-lactamase enzymes produced by resistant bacteria, protecting ampicillin from degradation

This combination provides enhanced activity against beta-lactamase-producing strains of Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Klebsiella species, Bacteroides species, and other anaerobic organisms.

Indications

FDA-approved indications for Unasyn include:

• Skin and skin structure infections
• Intra-abdominal infections
• Gynecological infections
• Bacterial septicemia

It is particularly effective against mixed aerobic-anaerobic infections and is commonly used in hospital settings for surgical prophylaxis and treatment of complicated infections.

Dosage and Administration

• Adults: 1.5-3g (ampicillin 1-2g/sulbactam 0.5-1g) IV every 6 hours
• Maximum daily dose: 12g (8g ampicillin/4g sulbactam)

• Renal impairment:

- CrCl 15-29 mL/min: Administer every 12 hours - CrCl 5-14 mL/min: Administer every 24 hours

• Hepatic impairment: No specific dosage adjustment recommended
• Elderly: Consider renal function adjustments
• Pediatrics: 100-200 mg ampicillin/50-100 mg sulbactam per kg/day in divided doses every 6 hours

• IV infusion over 15-30 minutes
• Reconstitute with appropriate diluent (sterile water, NaCl 0.9%)
• Stable for 2-8 hours at room temperature or 72 hours refrigerated

Pharmacokinetics

• Widely distributed into body tissues and fluids
• Crosses placenta and enters breast milk
• Poor CSF penetration unless meninges are inflamed
• Protein binding: Ampicillin 15-25%, Sulbactam 38%

• Minimal hepatic metabolism
• Both components undergo some hydrolysis

• Primarily renal excretion (75-85% unchanged)
• Half-life: Approximately 1 hour (prolonged in renal impairment)
• Dialyzable: Yes (hemodialysis removes both components)

Contraindications

• History of hypersensitivity to penicillins, beta-lactamase inhibitors, or other beta-lactam antibiotics
• Patients with a history of ampicillin-associated cholestatic jaundice/hepatic dysfunction

Warnings and Precautions

• Clostridium difficile-associated diarrhea (may range from mild to life-threatening)
• Superinfections with fungal or bacterial pathogens
• Hematologic effects (leukopenia, neutropenia, thrombocytopenia)
• Hepatic dysfunction and monitoring of liver enzymes
• Seizure potential in patients with renal impairment or when given in high doses
• Potassium content: 3.0 mEq sodium per gram of Unasyn

Drug Interactions

• Probenecid: Decreases renal tubular secretion of ampicillin → increased levels
• Allopurinol: Increased risk of skin rash
• Oral contraceptives: May decrease efficacy
• Warfarin: May potentiate anticoagulant effect
• Methotrexate: May decrease methotrexate clearance
• Aminoglycosides: Physical incompatibility (do not mix in same solution)

Adverse Effects

• Diarrhea (6-9%)
• Injection site reactions (3%)
• Rash (2-4%)
• Nausea/vomiting (1-2%)

• Anaphylaxis (<0.01%)
• Clostridium difficile-associated diarrhea
• Hematologic abnormalities (neutropenia, thrombocytopenia)
• Hepatic enzyme elevations
• Interstitial nephritis
• Seizures (with high doses or renal impairment)

Monitoring Parameters

• Signs and symptoms of infection (fever, WBC count)
• Renal function (BUN, creatinine)
• Liver function tests (AST, ALT, alkaline phosphatase)
• Complete blood count with differential
• Signs of hypersensitivity reactions
• Diarrhea assessment (possible C. difficile)
• Serum electrolytes in patients receiving high doses
• Culture and sensitivity results when available

Patient Education

• Report any signs of allergic reaction (rash, itching, swelling, difficulty breathing)
• Complete full course of therapy even if feeling better
• Report severe diarrhea or abdominal pain immediately
• Inform all healthcare providers of Unasyn use
• Notify provider if pregnant, planning pregnancy, or breastfeeding
• Understand that this medication is administered only intravenously in healthcare settings
• Report unusual bleeding or bruising

References

1. Unasyn® [package insert]. New York, NY: Pfizer Inc; 2021. 2. Gilbert DN, Chambers HF, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed; 2022. 3. Lexicomp Online. Ampicillin/Sulbactam. Wolters Kluwer Clinical Drug Information; 2023. 4. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed; 2023. 5. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed; 2020. 6. Trissel LA. Handbook on Injectable Drugs. 20th ed. American Society of Health-System Pharmacists; 2021.