Ampicillin and sulbactam

U.S. BRAND NAMES — Unasyn®

PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin

DOSING: ADULTS — Doses expressed as ampicillin/sulbactam combination.

Susceptible infections: I.M., I.V.: 1.5-3 g every 6 hours (maximum: Unasyn® 12 g)

Amnionitis, cholangitis, diverticulitis, endometritis, endophthalmitis, epididymitis/orchitis, liver abscess, osteomyelitis (diabetic foot), peritonitis: I.V.: 3 g every 6 hours

Endocarditis: I.V.: 3 g every 6 hours with gentamicin or vancomycin for 4-6 weeks

Orbital cellulitis: I.V.: 1.5 g every 6 hours

Parapharyngeal space infections: I.V.: 3 g every 6 hours

Pasteurella multocida(human, canine/feline bites): I.V.: 1.5-3 g every 6 hours

Pelvic inflammatory disease: I.V.: 3 g every 6 hours with doxycycline

Peritonitis (CAPD): Intraperitoneal:
Anuric, intermittent: 3 g every 12 hours
Anuric, continuous: Loading dose: 1.5 g; maintenance dose: 150 mg

Pneumonia:
Aspiration, community-acquired: I.V.: 1.5-3 g every 6 hours
Hospital-acquired: I.V.: 3 g every 6 hours

Urinary tract infections, pyelonephritis: I.V.: 3 g every 6 hours for 14 days

DOSING: PEDIATRIC

(For additional information see "Ampicillin and sulbactam: Pediatric drug information")
Susceptible infections: Children ≥ 1 year: I.V.: 100-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®). Note: The American Academy of Pediatrics recommends a dose of up to 300 mg/kg/day for severe infection in infants >1 month of age.

Epiglottitis: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day divided in 4 doses

Mild-to-moderate infections: Children ≥ 1 year: I.V.: 100-200 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)

Peritonsillar and retropharyngeal abscess: Children ≥ 1 year: I.V.: 50 mg ampicillin/kg/dose every 6 hours

Severe infections: Children ≥ 1 year: I.V.: 200-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr 15-29 mL/minute: Administer every 12 hours

Clcr 5-14 mL/minute: Administer every 24 hours

Hemodialysis: Give dose after hemodialysis

Continuous ambulatory peritoneal dialysis (CAPD): 3 g every 24 hours

Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:
CVVH: 3 g every 12 hours
CVVHD/CVVHDF: 3 g every 8 hours

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]; 15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g]
Unasyn®:
1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]
3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]
15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g)]

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]
Unasyn®: 1.5 g [ampicillin 1 g and sulbactam 0.5 g]; 3 g [ampicillin 2 g and sulbactam 1 g]; 15 g [ampicillin 10 g and sulbactam 5 g]; 15 g [ampicillin 10 g and sulbactam 5 g

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Administer by slow injection over 10-15 minutes or I.V. over 15-30 minutes. Ampicillin and gentamicin should not be mixed in the same I.V. tubing.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.

COMPATIBILITY — Stable in NS; variable stability (consult detailed reference) in D51/2NS, D5W, LR.

Y-site administration: Compatible: Amifostine, aztreonam, cefepime, docetaxel, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, insulin (regular), linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, ondansetron, sargramostim. Variable (consult detailed reference): Cisatracurium, diltiazem, vancomycin.

Compatibility when admixed: Compatible: Aztreonam. Incompatible: Aminoglycosides.

USE — Treatment of susceptible bacterial infections involved with skin and skin structure, intra-abdominal infections, gynecological infections; spectrum is that of ampicillin plus organisms producing beta-lactamases such as S. aureus, H. influenzae, E. coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes

ADVERSE REACTIONS SIGNIFICANT — Also see Ampicillin.

>10%: Local: Pain at injection site (I.M.)

1% to 10%:
Dermatologic: Rash
Gastrointestinal: Diarrhea
Local: Pain at injection site (I.V.), thrombophlebitis
Miscellaneous: Allergic reaction (may include serum sickness, urticaria, bronchospasm, hypotension, etc)

<1% (Limited to important or life-threatening): Abdominal distension, candidiasis, chest pain, chills, dysuria, edema, epistaxis, erythema, facial swelling, fatigue, flatulence, glossitis, hairy tongue, headache, interstitial nephritis, itching, liver enzymes increased, malaise, mucosal bleeding, nausea, pseudomembranous colitis, seizure, substernal pain, throat tightness, thrombocytopenia, urine retention, vomiting

CONTRAINDICATIONS — Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns: Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.

Special populations: Pediatrics: Safety and efficacy have not been established in children <1 year of age.

DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy

Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification

Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, ampicillin/sulbactam is classified as pregnancy category B. Both ampicillin and sulbactam cross the placenta. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details).

LACTATION — Enters breast milk/use caution

BREAST-FEEDING CONSIDERATIONS — Ampicillin and sulbactam are both excreted into breast milk in low concentrations. The manufacturer recommends that caution be used if administering to lactating women. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant. The maternal dose of sulbactam does not need altered in the postpartum period. Also refer to the Ampicillin monograph.

DIETARY CONSIDERATIONS — Sodium content of 1.5 g injection: 115 mg (5 mEq)

MONITORING PARAMETERS — With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose

CANADIAN BRAND NAMES — Unasyn®

INTERNATIONAL BRAND NAMES — Ampibactan (VE); Amplisul (EC); Ansulina (TW); Baccillin (KP); Bactacin (KP); Bactesyn (ID); Easyn (MY); Picyn (ID); Prixin (PY); Rukasyn (KP); Sulbaccin (TH); Sulbacin (IN, KP, MY, PH); Sultamicilina (AR); Ubacillin (KP); Ubactam (KP); Unacid (DE); Unacim (FR); Unasyn (AE, AT, BF, BH, BJ, BR, CI, CL, CN, CO, CR, CY, CZ, EC, EE, EG, ET, GH, GM, GN, GT, HK, HN, ID, IL, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NI, OM, PA, PE, PH, QA, SA, SC, SD, SL, SN, SV, SY, TN, TW, TZ, UG, YE, ZA, ZM, ZW); Unasyna (AR, UY)

MECHANISM OF ACTION — The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase-producing organisms; inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

PHARMACODYNAMICS / KINETICS
Ampicillin: See Ampicillin.

Sulbactam:
Distribution: Bile, blister, and tissue fluids
Protein binding: 38%
Half-life elimination: Normal renal function: 1-1.3 hours
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours