UNASYN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UNASYN (UNASYN).
Ampicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs); sulbactam is a beta-lactamase inhibitor that prevents degradation of ampicillin by beta-lactamases.
| Metabolism | Ampicillin is primarily excreted unchanged in urine; sulbactam is also excreted renally with minimal hepatic metabolism. |
| Excretion | Renal: ampicillin (~75-90% unchanged) and sulbactam (~75-85% unchanged); biliary/fecal: minimal (<5% for each component). |
| Half-life | Ampicillin: ~1 hour (normal renal function); sulbactam: ~1-1.4 hours (normal renal function); prolonged in renal impairment (ampicillin up to 20 hours, sulbactam up to 10-15 hours in anuria). |
| Protein binding | Ampicillin: ~20% bound to albumin; sulbactam: ~38% bound to albumin. |
| Volume of Distribution | Ampicillin: 0.3-0.4 L/kg; sulbactam: 0.2-0.4 L/kg; distributes well into extracellular fluid and tissues (e.g., pleural fluid, bile, middle ear). |
| Bioavailability | IM: ~100% (both components); oral: not applicable (only parenteral formulation). |
| Onset of Action | IV: immediate (within minutes); IM: rapid (peak levels in 30-60 minutes). |
| Duration of Action | IV/IM: approximately 6-8 hours (requires q6h dosing for serious infections). |
| Molecular Weight | Ampicillin: 349.4 Da; Sulbactam: 255.2 Da (combination: average 302.3 Da as a mixture) |
3 g (ampicillin 2 g + sulbactam 1 g) IV every 6 hours; total daily dose of sulbactam not to exceed 4 g.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 15-29 mL/min: 1.5 g (ampicillin 1 g + sulbactam 0.5 g) IV every 12 hours; CrCl 5-14 mL/min: 1.5 g IV every 24 hours; hemodialysis: administer after dialysis. |
| Liver impairment | No adjustment required for mild-to-moderate hepatic impairment; not studied in severe hepatic disease. |
| Pediatric use | Children ≥1 year: 300 mg/kg/day (ampicillin 200 mg/kg + sulbactam 100 mg/kg) IV divided every 6 hours; neonates and infants <1 year: not established. |
| Geriatric use | Dose based on renal function; monitor for neurotoxicity; max daily sulbactam dose 4 g. |
| 1st trimester | Ampicillin/sulbactam crosses the placenta. Animal studies show no evidence of harm, but no adequate human studies in first trimester. Use only if clearly needed. |
| 2nd trimester | Safe in second trimester; no known teratogenic risk. Monitor for maternal diarrhea or rash. |
| 3rd trimester | Safe; theoretical risk of kernicterus in newborn if given near delivery due to bilirubin displacement by ampicillin, but clinical significance low. Use if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for UNASYN (UNASYN).
| Placental transfer | Both ampicillin and sulbactam cross the placenta readily. Fetal serum concentrations reach 50-100% of maternal levels. |
| Breastfeeding | Ampicillin and sulbactam are excreted into breast milk in low concentrations. Ampicillin levels in milk are less than 0.1% of maternal weight-adjusted dose; sulbactam levels are similar. Considered compatible with breastfeeding; may cause diarrhea or allergic reaction in infant. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Hypersensitivity to penicillins or beta-lactam antibacterialsHistory of cholestatic jaundice or hepatic impairment associated with ampicillin/sulbactamInfections caused by penicillinase-producing organisms (unless susceptible)Epstein-Barr virus infection (increased risk of rash)
| Precautions | Serious hypersensitivity reactions (anaphylaxis) especially in penicillin-allergic patients, Clostridium difficile-associated diarrhea (CDAD), Seizures with high doses or renal impairment, Hepatotoxicity (elevated liver enzymes, hepatitis), Renal impairment: dose adjustment required, Superinfection with prolonged use, Blood dyscrasias (neutropenia, thrombocytopenia) |
| Food/Dietary | No specific food interactions. Alcohol may increase risk of disulfiram-like reaction (rare). Maintain adequate hydration. |
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| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | UNASYN (ampicillin/sulbactam) is classified as Pregnancy Category B. No evidence of teratogenicity in animal studies. Adequate human studies are lacking; use only if clearly needed. Risk of neonatal kernicterus if administered near term due to bilirubin displacement. |
| Fetal Monitoring | Monitor maternal renal function, signs of hypersensitivity, and diarrhea. Fetal monitoring for bradycardia or distress not routinely required unless maternal adverse effects occur. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. |
| Clinical Pearls | UNASYN (ampicillin/sulbactam) is a beta-lactam/beta-lactamase inhibitor combination. It is active against MSSA, Streptococcus spp., Enterobacteriaceae (including ESBL-producing strains only if inoculum effect considered but sulbactam does not inhibit AmpC or carbapenemases), and anaerobes including Bacteroides fragilis. It does not cover MRSA, Pseudomonas aeruginosa, or Enterococcus faecium. Dosage adjustment required for renal impairment (CrCl <30 mL/min: extend interval to q12h). Note: sulbactam has intrinsic anti-Acinetobacter activity. For skin and soft tissue infections, pelvic infections, and intra-abdominal infections. Incompatible with aminoglycosides; avoid mixing in same IV line. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop early even if you feel better. · This medication is given by injection; report any severe diarrhea, rash, or difficulty breathing immediately. · If you develop watery or bloody diarrhea, do not take anti-diarrhea medicine; contact your doctor. · Complete the full course to prevent antibiotic resistance. · Tell your healthcare provider about all medications you take, especially blood thinners, methotrexate, or probenecid. |