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Product Name
Chemical Name
Piperacillin (Sodium)
Therapeutic Category
Pharmacologic Category
Antibiotic, Penicillin
Pharmaceutical Form
Piperacillin (Sodium) 1000mg / 2000mg
Monitoring Parameters
Dosing: Adult
Usual dosage range:
I.M.: 2-3 g/dose every 6-12 hours; maximum: 24 g/24 hours
I.V.: 3-4 g/dose every 4-6 hours; maximum: 24 g/24 hours
Burn wound sepsis: I.V.: 4 g every 4 hours with vancomycin and amikacin
Cholangitis, acute: I.V.: 4 g every 6 hours
Malignant otitis externa: I.V.: 4-6 g every 4-6 hours with tobramycin
Moderate infections: I.M., I.V.: 2-3 g/dose every 6-12 hours (maximum: 2 g I.M./site)
Prosthetic joint (Pseudomonas): I.V.: 3 g every 6 hours with aminoglycoside
Pseudomonas infections: I.V.: 4 g every 4 hours
Severe infections: I.M., I.V.: 3-4 g/dose every 4-6 hours (maximum: 24 g/24 hours)
Urinary tract infections: I.V.: 2-3 g/dose every 6-12 hours
Uncomplicated gonorrhea: I.M.: 2 g in a single dose accompanied by 1 g probenecid 30 minutes prior to injection

Dosing: Pediatric

Usual dosage range: Infants and Children: I.M., I.V.: 200-300 mg/kg/day in divided doses every 4-6 hours
Cystic fibrosis: I.M., I.V.: 350-500 mg/kg/day in divided doses every 4-6 hours

Dosing: Geriatric

Adjust dose for renal impairment:
I.M.: 1-2 g every 8-12 hours
I.V.: 2-4 g every 6-8 hours

Dosing: Renal Impairment

Clcr 10-50 mL/minute: Administer every 6-8 hours.
Clcr <10 mL/minute: Administer every 8 hours.
Moderately dialyzable (20% to 50%)
Continuous arteriovenous or venovenous hemofiltration: Dose as for Clcr 10-50 mL/minute.
Treatment of susceptible infections such as septicemia, acute and chronic respiratory tract infections, skin and soft tissue infections, and urinary tract infections due to susceptible strains of Pseudomonas, Proteus, and Escherichia coli and Enterobacter; active against some streptococci and some anaerobic bacteria; febrile neutropenia (as part of combination regimen)
Adverse Reactions
Frequency not defined.
Central nervous system: Confusion, convulsions, drowsiness, fever, Jarisch-Herxheimer reaction
Dermatologic: Rash, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Electrolyte imbalance, hypokalemia
Hematologic: Abnormal platelet aggregation and prolonged PT (high doses), agranulocytosis, Coombs' reaction (positive), hemolytic anemia, pancytopenia
Local: Thrombophlebitis
Neuromuscular & skeletal: Myoclonus
Renal: Acute interstitial nephritis, acute renal failure
Miscellaneous: Anaphylaxis, hypersensitivity reactions
Hypersensitivity to piperacillin, other beta-lactam antibiotics (penicillins or cephalosporins), or any component of the formulation
Warnings / Precautions Drug
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.
• Bleeding disorders: Particularly in patients with renal impairment, bleeding disorders have been observed; discontinue if thrombocytopenia or bleeding occurs.
• Leukopenia/neutropenia: During prolonged use, leukopenia and neutropenia have been reported.
• 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:
• Cystic fibrosis: An increased frequency of fever and rash has been reported in patients with cystic fibrosis.
• Renal impairment: Use with caution in patients with renal impairment, due to sodium load and adverse effects (anemia, neuropsychological changes); dosage adjustment recommended.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk D: Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
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
Probenecid: May increase the serum concentration of Penicillins. 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. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Pregnancy Implications
Adverse events have not been observed in animal studies; therefore, piperacillin is classified as pregnancy category B. Piperacillin crosses the placenta and distributes into the amniotic fluid. Due to pregnancy induced physiologic changes, some pharmacokinetic parameters of piperacillin may be altered. At term, the apparent volume of distribution of piperacillin is increased and peak concentrations are significantly lower. Total clearance is normal to increased at term. These changes continue into the early postpartum period.
Enters breast milk/compatible
Breast-Feeding Considerations
Small amounts of piperacillin are excreted in breast milk. The manufacturer recommends that caution be exercised when administering piperacillin to nursing women. Other penicillins are considered safe for use during breast-feeding. Nondose-related effects could include modification of bowel flora.
Dietary Considerations
Sodium content of 1 g: 1.85 mEq
Mechanism of Action
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
Absorption: I.M.: 70% to 80%
Protein binding: ~16%
Bioavailability: Not well absorbed when given orally
Half-life elimination (dose dependent; prolonged with moderately severe renal or hepatic impairment):
Neonates: 1-5 days old: 3.6 hours; >6 days old: 2.1-2.7 hours
Children: 1-6 months: 0.79 hour; 6 months to 12 years: 0.39-0.5 hour
Adults: 36-80 minutes
Time to peak, serum: I.M.: 30-50 minutes
Excretion: Primarily urine; partially feces
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