Dosing and uses of Unasyn (ampicillin-sulbactam)
Adult dosage forms and strengths
powder for solution
- 1.5g (ampicillin 1g/sulbactam 0.5g)
- 3g (ampicillin 2g/sulbactam 1g)
- 15g (ampicillin 10g/sulbactam 5g)
Gynecologic Infections
1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6hr; not to exceed 12 g/day
Intra-Abdominal Infections
1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6hr; not to exceed 12 g/day
Skin & Skin Structure Infections
1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6hr; not to exceed 12 g/day
Orbital Cellulitis
3 g (2 g ampicillin + 1 g sulbactam) IV q6hr
Pelvic Inflammatory Disease
3 g (2 g ampicillin + 1 g sulbactam) IV q6hr
Pneumonia
Aspiration or community acquired: 1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV q6hr for 5 or more days
Hospital acquired: 3 g IV q6hr for 5 or more days
Urinary Tract Infections
Pyelonephritis: 3 g (2 g ampicillin + 1 g sulbactam) IV q6hr for 14 days
Acute Bacterial Rhinosinusitis (Off-label)
Severe infection requiring hospitalization
1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV q6hr for 5-7 days
Endocarditis (Off-label)
Enterococcus infection resistant to penicillin/susceptible to aminoglycosides: 3 g (2 g ampicillin + 1 g sulbactam) IV q6hr for 6 weeks if not aminoglycoside resistant; >6 weeks if aminoglycoside resistant
HACEK infection: 3 g (2 g ampicillin + 1 g sulbactam) IV q6hr for 4 weeks
Dosing Modifications
Renal impairment
- CrCl 5-14 mL/min/1.73 m²: 1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV q24hr
- CrCl 15-29 mL/min/1.73 m²: 3 g (2 g ampicillin + 1 g sulbactam) IV q12hr
- CrCl ≥ 30 mL/min/1.73 m²: No dose adjustment necessary
Pediatric dosage forms and strengths
powder for solution
- 1.5g (ampicillin 1g/sulbactam 0.5g)
- 3g (ampicillin 2g/sulbactam 1g)
- 15g (ampicillin 10g/sulbactam 5g)
Skin Infections
>1 year (<40 kg): 200 mg/kg/day IV divided q6hr; not to exceed 14 days of therapy
>1 year (>40 kg): 1.5 g (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) q6hr; not to exceed 12 g/day
Epiglottitis
Children and adolescents: 100-200 mg ampicillin/kg/day IV divided q6hr
Mild/Moderate Infection
>1 month-1 year: 100-150 mg ampicillin/kg/day IV/IM divided q6hr
>1 year: 100-200 mg ampicillin/kg/day IV/IM divided q6hr
Meningitis/Severe Infections
>1 month-1 year: 200-300 mg ampicillin/kg/day IV/IM divided q6hr
>1 year: 200-400 mg ampicillin/kg/day IV/IM divided q6hr
Peritonsillar and Retropharyngeal Abscess
Children and adolescents: 200 mg ampicillin/kg/day IV divided q6hr
Unasyn (ampicillin-sulbactam) adverse (side) effects
>10%
IM injection site pain (16%)
1-10%
Diarrhea (3%)
IV injection site pain (3%)
Thrombophlebitis (3%)
Rash ( < 2%)
<1%
Abdominal distention
Black, "hairy" tongue
Candidiasis
Chest pain
Chills
Dysuria
Edema
Epistaxis
Erythema
Fatigue
Flatulence
Glossitis
Headache
Itching
Malaise
Mucosal bleeding
Nausea
Pseudomembranous colitis
Seizure
Tightness in throat
Thrombocytopenia
Urine retention
Vomiting
Warnings
Contraindications
Hypersensitivity to drug or components
Patients with previous history of cholestatic jaundice/hepatic dysfunction associated with ampicillin sulbactam
Cautions
Use caution in patients with allergy to cephalosporins and carbapenems
Adjust dose in renal failure
Prolonged use is associated with fungal or bacterial superinfection
Hepatic dysfunction, including hepatitis and cholestatic jaundice reported; hepatic toxicity is usually reversible; however, deaths have occurred; monitor hepatic function at regular intervals in patients with hepatic impairment
A generalized dull red maculopapular rash may occur in 5-10% of children 3-14 days after initiating therapy; carefully evaluate the rash to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; it normally begins on the trunk and spreads over most of the body; it may be most intense at pressure areas, elbows, and knees
Hepatotoxicity reported; monitor hepatic function at regular intervals in patients with hepatic impairment
A high percentage of patients with infectious mononucleosis have developed rash during therapy; therapy is not recommended in these patients
Pregnancy and lactation
Pregnancy category: B
Lactation: Excreted in breast milk; use caution
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 of Unasyn (ampicillin-sulbactam)
Mechanism of action
Drug combination of beta-lactamase inhibitor with ampicillin; interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms; alternative to amoxicillin when unable to take medication orally; covers skin, enteric flora, and anaerobes; not ideal for nosocomial pathogens.
Absorption
Ampicillin
- Bioavailability: 30-40%
- Peak plasma time: 1-2 hr (oral)
Distribution
Ampicillin
- Protein bound: 15-25%
- Blister and tissue fluids, bile, and CSF with inflamed meninges
Sulbactam
- Protein bound: 38%
- Bile, blister, and tissue fluids
Metabolism
Ampicillin and sulbactam
- Liver
Elimination
Ampicillin
- Half-life: 1-1.8 hr (normal renal function); 7-20 hr (anuria/end-stage renal disease)
- Excretion: Urine (90% within 24 hr)
Sulbactam
- Half-life: 1-1.3 hr
- Excretion: Urine (75-85%)
Administration
IV Incompatibilities
Additive: Aminoglycosides, ciprofloxacin
Y-site: Aminoglycosides, amiodarone, amphotericin B cholesteryl sulfate, ciprofloxacin, cisatracurium(?), diltiazem(?), idarubicin, nicardipine, ondansetron, sargramostim
IV Compatibilities
Solution: Ns
Additive: Aztreonam
Y-site: Amifostine, aztreonam, bivalirudin, cefepime, dexmedetomidine, docetaxel, enalaprilat, etoposide PO4, famotidine, fenoldopam, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, Hextend, insulin, linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa, vancomycin
IV/IM Preparation
Reconstitute with SWI or 0.5% or 2% lidocaine injection (IM) to obtain a 250 mg ampicillin-125 mg sulbactam/mL solution
IM: Use within 1 hr after preparation
IV: Further dilute to 3-45 mg/mL with appropriate diluent
Use NS for IV piggyback
IV: Use within 8 hr after preparation
IV/IM Administration
Administer around-the-clock to promote less variation in peak and trough serum levels
Slow IV injection over at least 10-15 min or infusion over 15-30 min
IM: Deep into large muscle mass
Storage
Store intact vials <30°C
