No

Antibiotic, Penicillin

Treatment of infections of lower respiratory tract, urinary tract, skin and skin structures, gynecologic, bone and joint infections, and septicemia caused by susceptible organisms. Tazobactam expands activity of piperacillin to include beta-lactamase producing strains of S. aureus, H. influenzae, Bacteroides, and other gram-negative bacteria.

B

Breast-feeding/lactation: Use by the breast-feeding mother may result in diarrhea, candidiasis, or allergic response in the infant

Hypersensitivity to penicillins, beta-lactamase inhibitors, or any component

Due to sodium load and to the adverse effects of high serum concentrations of penicillins, dosage modification is required in patients with impaired or underdeveloped renal function; use with caution in patients with seizures or in patients with history of beta-lactam allergy; safety and efficacy have not been established in children <12 years of age

>10%: Gastrointestinal: Diarrhea (11.3%)

1% to 10%:

Cardiovascular: Hypertension (1.6%)

Central nervous system: Insomnia (6.7%), headache (7% to 8%), agitation (2%), fever (2.4%), dizziness (1.4%)

Dermatologic: Rash (4%), pruritus (3%)

Gastrointestinal: Constipation (7% to 8%), nausea (6.9%), vomiting/dyspepsia (3.3%)

Respiratory: Rhinitis/dyspnea (~1%)

Miscellaneous: Serum sickness-like reaction

<1%: Hypotension, edema, confusion, pseudomembranous colitis, bronchospasm

Several laboratory abnormalities have rarely been associated with piperacillin/tazobactam including reversible eosinophilia, and neutropenia (associated most often with prolonged therapy), positive direct Coombs' test, prolonged PT and PTT, transient elevations of LFT, increases in creatinine

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 dysfunction

Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed

Decreased effect: Tetracyclines may decrease penicillin effectiveness; aminoglycosides physical inactivation of aminoglycosides in the presence of high concentrations of piperacillin and potential toxicity in patients with mild to moderate renal dysfunction; decreased efficacy of oral contraceptives is possible

Increased effect:

Probenecid may increase penicillin levels

Neuromuscular blockers may increase duration of blockade

Aminoglycosides synergistic efficacy

Heparin with high-dose parenteral penicillins may result in increased risk of bleeding

Store at controlled room temperature; after reconstitution, solution is stable in NS or D₅W for 24 hours at room temperature and 7 days when refrigerated; use single dose vials immediately after reconstitution (discard unused portions after 24 hours at room temperature and 48 hours if refrigerated)

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. Tazobactam inhibits many beta-lactamases, including staphylococcal penicillinase and Richmond and Sykes types II, III, IV, and V, including extended spectrum enzymes; it has only limited activity against class I beta-lactamases other than class Ic types.

Both AUC and peak concentrations are dose proportional

Metabolism: Piperacillin: 6% to 9%; Tazobactam: ~26%

Protein binding: Piperacillin: ~26% to 33%; Tazobactam: 31% to 32%

Half-life: Piperacillin: 1 hour; Metabolite: 1-1.5 hours; Tazobactam: 0.7-0.9 hour

Elimination: Both piperacillin and tazobactam are directly proportional to renal function

Piperacillin: 50% to 70% eliminated unchanged in urine, 10% to 20% excreted in bile

Tazobactam: Found in urine at 24 hours, with 26% as the inactive metabolite

Hemodialysis removes 30% to 40% of piperacillin and tazobactam; peritoneal dialysis removes 11% to 21% of tazobactam and 6% of piperacillin; hepatic impairment does not affect the kinetics of piperacillin or tazobactam significantly

Children <12 years: Not recommended due to lack of data

Children >12 years and Adults:

Severe infections: I.V.: Piperacillin/tazobactam 4/0.5 g every 8 hours or 3/0.375 g every 6 hours

Moderate infections: I.M.: Piperacillin/tazobactam 2/0.25 g every 6-8 hours; treatment should be continued for greater than or equal to 7-10 days depending on severity of disease (Note: I.M. route not FDA-approved)

Dosing interval in renal impairment:

Cl_cr 20-40 mL/minute: Administer 2/0.25 g every 6 hours

Cl_cr <20 mL/minute: Administer 2/0.25 g every 8 hours

Hemodialysis: Administer 2/0.25 g every 8 hours with an additional dose of 0.75 g after each dialysis

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose as for Cl_cr 10-50 mL/minute

LFTs, creatinine, BUN, CBC with differential, serum electrolytes, urinalysis, PT, PTT; monitor for signs of anaphylaxis during first dose

Positive Coombs' [direct] test 3.8%, ALT, AST, bilirubin, and LDH

May cause insomnia, dizziness or agitation; may rarely cause confusion; penicillins reported to cause apprehension, illusions, hallucinations, depersonalization, agitation, encephalopathy, and insomnia

None reported

No information available to require special precautions

Prolonged use of penicillins may lead to development of oral candidiasis

This medication will be administered I.V. or I.M. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce nausea or dry mouth. Important to maintain good oral and vaginal hygiene to reduce incidence of opportunistic infection. Diabetics should use serum glucose testing while receiving this medication. 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 persistent diarrhea, fever, chills, unhealed sores, bloody urine or stool, muscle pain, mouth sores, or difficulty breathing, or skin rash. Breast-feeding precautions: Consult prescriber if breast-feeding.

Discontinue primary infusion, if possible, during infusion and administer aminoglycosides separately from Zosyn™

Injection: Piperacillin sodium 2 g and tazobactam sodium 0.25 g; piperacillin sodium 3 g and tazobactam sodium 0.375 g; piperacillin sodium 4 g and tazobactam sodium 0.5 g (vials at an 8:1 ratio of piperacillin sodium/tazobactam sodium)

Bryson HM and Brogden RN, "Piperacillin/Tazobactam. A Review of its Antibacterial Activity, Pharmacokinetic Properties, and Therapeutic Potential," Drugs, 1994, 47(3):506-35.

Chung KC, Moon YS, Chin A, et al, "Compatibility of Ondansetron Hydrochloride and Piperacillin Sodium-Tazobactam Sodium During Simulated Y-Site Administration," Am J Health Syst Pharm, 1995, 52(14):1554-6.

Jhee SS, Kern JW, Burm JP, et al, "Piperacillin-Tazobactam Pharmacokinetics in Patients With Intra-abdominal Infections," Pharmacotherapy, 1995, 15(4):472-8.

Johnson CA, Halstenson CE, Kelloway JS, et al, "Single-Dose Pharmacokinetics of Piperacillin and Tazobactam in Patients With Renal Disease," Clin Pharmacol Ther, 1992, 51(1):32-41.

"Piperacillin/Tazobactam," Med Lett Drugs Ther, 1994, 36(914):7-9.

Reed MD, Goldfarb J, Yamashita T, et al, "Single-Dose Pharmacokinetics of Piperacillin and Tazobactam in Infants and Children," Antimicrob Agents Chemother, 1994, 38(12):2817-26.

Sanders WE Jr and Sanders CC, "Piperacillin/Tazobactam: A Critical Review of the Evolving Clinical Literature," Clin Infect Dis, 1996, 22(1):107-23.

Schoonover LL, Occhipinti DJ, Rodvold KA, et al, "Piperacillin/Tazobactam: A New Beta-Lactam/Beta-Lactamase Inhibitor Combination," Ann Pharmacother, 1995, 29(5):501-14.

Sorgel F and Kinzig M, "The Chemistry, Pharmacokinetics and Tissue Distribution of Piperacillin/Tazobactam," J Antimicrob Chemother, 1993, 31(Suppl A):39-60.

van der Werf TS, Mulder PO, Zijlstra JG, et al, "Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients With Renal Failure, Treated With Continuous Veno-Venous Hemofiltration (CVVH)," Intens Care Med, 1997, 23(8):873-7.

Wickerts CJ, Asaba H, Gunnarsson B, et al, "Combined Carbon Hemoperfusion and Hemodialysis in Treatment of Penicillin Intoxication," Br Med J, 1980, 280(6226):1254-5.