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Pronunciation |
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(am
pi SIL in & SUL bak
tam) |
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U.S. Brand
Names |
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Unasyn® |
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Generic
Available |
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No |
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Synonyms |
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Sulbactam and Ampicillin |
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Pharmacological Index |
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Antibiotic, Penicillin |
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Use |
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Dental: Parenteral beta-lactamase-resistant antibiotic combination to treat
more severe orofacial infections where beta-lactamase-producing staphylococci
and beta-lactamase-producing Bacteroides are present
Medical: 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 |
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Pregnancy Risk
Factor |
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B |
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Contraindications |
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Hypersensitivity to ampicillin, sulbactam or any component, or
penicillins |
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Warnings/Precautions |
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Dosage adjustment may be necessary in patients with renal impairment; a low
incidence of cross-allergy with other beta-lactams exists; high percentage of
patients with infectious mononucleosis have developed rash during therapy with
ampicillin. Appearance of a rash should be carefully evaluated to differentiate
a nonallergic ampicillin rash from a hypersensitivity reaction. Ampicillin rash
occurs in 5% to 10% of children receiving ampicillin 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. |
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Adverse
Reactions |
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>10%: Local: Pain at injection site (I.M.)
1% to 10%:
Dermatologic: Rash
Gastrointestinal: Diarrhea
Local: Pain at injection site (I.V.)
Miscellaneous: Allergic reaction (may include serum sickness, urticaria,
bronchospasm, hypotension, etc)
<1%: Chest pain, fatigue, malaise, headache, chills, penicillin
encephalopathy, seizures (with large I.V. doses or patients with renal
dysfunction), itching, nausea, vomiting, enterocolitis, pseudomembranous
colitis, hairy tongue, dysuria, vaginitis, leukopenia, neutropenia,
thrombocytopenia, decreased hemoglobin and hematocrit, increased liver enzymes,
thrombophlebitis, increased BUN/creatinine, interstitial nephritis (rare)
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Overdosage/Toxicology |
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Symptoms of penicillin overdose include neuromuscular hypersensitivity
(agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures)
and electrolyte imbalance with potassium or sodium salts, especially in renal
failure
Hemodialysis may be helpful to aid in the removal of the drug from the blood,
otherwise most treatment is supportive or symptom directed |
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Drug
Interactions |
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Decreased effect: Efficacy of oral contraceptives may be reduced
Increased effect: Disulfiram, probenecid results in increased ampicillin
levels
Increased toxicity: Allopurinol theoretically has an additive potential for
ampicillin rash |
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Stability |
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I.M. and direct I.V. administration: Use within 1 hour after preparation;
reconstitute with sterile water for injection or 0.5% or 2% lidocaine
hydrochloride injection (I.M.); sodium chloride 0.9% (NS) is the diluent of
choice for I.V. piggyback use, solutions made in NS are stable up to 72 hours
when refrigerated whereas dextrose solutions (same concentration) are stable for
only 4 hours |
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Mechanism of
Action |
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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. |
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Pharmacodynamics/Kinetics |
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Distribution: Into bile, blister and tissue fluids; poor penetration into CSF
with uninflamed meninges; higher concentrations attained with inflamed meninges
Protein binding: Ampicillin: 28%; Sulbactam: 38%
Half-life: Ampicillin and sulbactam are similar: 1-1.8 hours and 1-1.3 hours,
respectively in patients with normal renal function
Elimination: ~75% to 85% of both drugs are excreted unchanged in the urine
within 8 hours following administration |
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Usual Dosage |
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Unasyn® (ampicillin/sulbactam) is a combination
product. Each 3 g vial contains 2 g of ampicillin and 1 g of sulbactam.
Sulbactam has very little antibacterial activity by itself, but effectively
extends the spectrum of ampicillin to include beta-lactamase producing strains
that are resistant to ampicillin alone. Therefore, dosage recommendations for
Unasyn® are based on the ampicillin component.
Children (3 months to 12 years): 100-200 mg ampicillin/kg/day (150-300 mg
Unasyn®) divided every 6 hours; maximum dose: 8 g
ampicillin/day (12 g Unasyn®)
Adults: 1-2 g ampicillin (1.5-3 g Unasyn®) every 6-8
hours; maximum dose: 8 g ampicillin/day (12 g Unasyn®)
Dosing interval in renal impairment:
Clcr 15-29 mL/minute: Administer every 12 hours
Clcr 5-14 mL/minute: Administer every 24 hours
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Dietary
Considerations |
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No data reported |
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Monitoring
Parameters |
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With prolonged therapy, monitor hematologic, renal, and hepatic function;
monitor for signs of anaphylaxis during first dose |
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Test
Interactions |
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May interfere with urinary glucose tests using cupric sulfate (Benedict's
solution, Clinitest®); may inactivate aminoglycosides
in vitro |
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Mental Health: Effects
on Mental Status |
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Large I.V. doses may rarely produce encephalopathy; penicillins have been
reported to cause apprehension, illusions, agitation, insomnia,
depersonalization, and encephalopathy |
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Mental Health:
Effects on Psychiatric
Treatment |
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Rarely may cause bone marrow suppression; use caution with clozapine and
carbamazepine |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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Prolonged use of penicillins may lead to development of oral candidiasis,
some patients may experience hairy tongue |
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Patient
Information |
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Take entire prescription, even if you are feeling better. Take at equal
intervals around-the-clock; preferably on an empty stomach with a full glass of
water (1 hour before or 2 hours after meals). Maintain adequate hydration (2-3
L/day of fluids unless instructed to restrict fluid intake). You may experience
nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges,
or chewing gum may help). If diabetic, drug may cause false tests with
Clinitest® urine glucose monitoring; use of glucose
oxidase methods (Clinistix®) or serum glucose monitoring
is preferable. This drug may interfere with oral contraceptives; an alternate
form of birth control should be used. Report rash; unusual diarrhea; vaginal
discharge, itching, burning, or pain; mouth sores; unresolved vomiting or
constipation; fever or chills; unusual bruising or bleeding; or if condition
being treated worsens or does not improve by the time prescription is completed.
Breast-feeding precautions: Consult prescriber if
breast-feeding. |
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Nursing
Implications |
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Ampicillin and gentamicin should not be mixed in the same I.V. tubing or
administered concurrently |
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Dosage Forms |
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Powder for injection: 1.5 g [ampicillin sodium 1 g and sulbactam sodium 0.5
g]; 3 g [ampicillin sodium 2 g and sulbactam sodium 1 g] |
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References |
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Dajani AS, "Sulbactam/Ampicillin in Pediatric Infections," Drugs,
1988, 35(Suppl 7):35-8.
Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med,
1988, 318(7):419-26 and 318(8):490-500.
Goldfarb J, Aronoff SC, Jaffé A, et al,
"Sultamicillin in the Treatment of Superficial Skin and Soft Tissue Infections in Children,"
Antimicrob Agents Chemother, 1987, 31(4):663-4.
Itokazu GS and Danziger LH,
"Ampicillin-Sulbactam and Ticarcillin-Clavulanic Acid: A Comparison of Their In Vitro Activity and Review of Their Clinical Efficacy,"
Pharmacotherapy, 1991, 11(5):382-414.
Kulhanjian J, Dunphy MG, Hamstra S, et al,
"Randomized Comparative Study of Ampicillin/Sulbactam vs Ceftriaxone for Treatment of Soft Tissue and Skeletal Infections in Children,"
Pediatr Infect Dis J, 1989, 8(9):605-10.
Meyers BR, Wilkinson P, Mendelson MH, et al,
"Pharmacokinetics of Ampicillin-Sulbactam in Healthy Elderly and Young Volunteers,"
Antimicrob Agents Chemother, 1991, 35(10):2098-101.
Rho SP, Jones A, Woo M, et al,
"Single Dose Pharmacokinetics of Intravenous Ampicillin plus Sulbactam in Healthy Elderly and Young Subjects,"
J Antimicrob Chemother, 1989, 24(4):573-80.
Syriopoulou V, Bitsi M, Theodoridis C, et al,
"Clinical Efficacy of Sulbactam/Ampicillin in Pediatric Infections Caused by Ampicillin-Resistant or Penicillin-Resistant Organisms,"
Rev Infect Dis, 1986, 8(Suppl 5):S630-3.
Wright AJ, "The Penicillins," Mayo Clin Proc, 1999, 74(3):290-307.
Wynn RL and Bergman SA,
"Antibiotics and Their Use in the Treatment of Orofacial Infections, Part I and Part II,"
Gen Dent, 1994, 42(5):398-402, 498-502.
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