Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of PIPRACIL and other antibacterial drugs, PIPRACIL should only be used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

PIPRACIL, sterile piperacillin sodium, is a semisynthetic broad-spectrum penicillin for parenteral use derived from D(-)-α-aminobenzylpenicillin. The chemical name of piperacillin sodium is sodium (2S,5R,6R)-6-[(R)-2-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-2-phenylacetamido]-3,-3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate. The chemical formula is C23H26N5NaO7S, and the molecular weight is 539.54. Its structural formula is:

Piperacillin sodium powder is a white to off-white solid having the characteristic appearance of products prepared by freeze-drying. It is freely soluble in water and in alcohol. The pH of an aqueous solution containing 400 milligrams per milliliter ranges from 5.5 to 7.5. One g contains 1.85 mEq (42.5 mg) of sodium (Na+).

Piperacillin is an antibiotic which exerts its bactericidal activity by inhibiting both septum and cell wall synthesis. It is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria. Piperacillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms
Enterococci, including Enterococcus faecalis
Streptococcus pneumoniae
Streptococcus pyogenes

Aerobic gram-negative microorganisms
Acinetobacter species
Enterobacter species
Escherichia coli
Haemophilus influenzae (non-β-lactamase-producing strains)
Klebsiella species
Morganella morganii
Neisseria gonorrhoeae
Proteus mirabilis
Proteus vulgaris
Providencia rettgeri
Pseudomonas aeruginosa
Serratia species

Anaerobic gram-positive microorganisms
Anaerobic cocci
Clostridium species

Anaerobic gram-negative microorganisms
Bacteroides species, including Bacteroides fragilis

The following in vitro data are available, but their clinical significance is unknown.

At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin. However, the safety and effectiveness of piperacillin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-positive microorganisms
Streptococcus agalactiae
Streptococcus bovis
Viridans group streptococci

Aerobic gram-negative microorganisms
Burkholderia cepacia
Citrobacter diversus
Citrobacter freundii
Pseudomonas fluorescens
Stenotrophomonas maltophilia
Yersinia enterocolitica

Anaerobic gram-positive microorganisms
Actinomyces species
Eubacterium species

Anaerobic gram-negative microorganisms
Fusobacterium necrophorum
Fusobacterium nucleatum
Porphyromonas asaccharolytica
Prevotella melaninogenica
Veillonella species

Therapeutic: PIPRACIL is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

Intra-Abdominal Infections including hepatobiliary and surgical infections caused by E. coli, Pseudomonas aeruginosa, enterococci, Clostridium spp., anaerobic cocci, or Bacteroides spp., including B. fragilis.

Urinary Tract Infections caused by E. coli, Klebsiella spp., P. aeruginosa, Proteus spp., including P. mirabilis, or enterococci.

Gynecologic Infections including endometritis, pelvic inflammatory disease, pelvic cellulitis caused by Bacteroides spp., including B. fragilis, anaerobic cocci, Neisseria gonorrhoeae, or enterococci (E. faecalis).

Septicemia including bacteremia caused by E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., P. mirabilis, S. pneumoniae, enterococci, P. aeruginosa, Bacteroides spp., or anaerobic cocci.

Lower RespiratoryTract Infections caused by E. coli, Klebsiella spp., Enterobacter spp., P. aeruginosa, Serratia spp., H. influenzae, Bacteroides spp., or anaerobic cocci. Although improvement has been noted in patients with cystic fibrosis, lasting bacterial eradication may not necessarily be achieved.

Skin and Skin Structure Infections caused by E. coli, Klebsiella spp., Serratia spp., Acinetobacter  spp., Enterobacter spp., P. aeruginosa, Morganella morganii, Providencia rettgeri, Proteus vulgaris, P. mirabilis, Bacteroides spp., including B. fragilis, anaerobic cocci, or enterococci.

Bone and Joint Infections caused by P. aeruginosa, enterococci, Bacteroides spp., or anaerobic cocci.

Uncomplicated Gonococcal Urethritis caused by N. gonorrhoeae.

PIPRACIL has also been shown to be clinically effective for the treatment of infections at various sites caused by Streptococcus species including S. pyogenes and S. pneumoniae; however, infections caused by these organisms are ordinarily treated with more narrow spectrum penicillins. Because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic bacteria, PIPRACIL is particularly useful for the treatment of mixed infections and presumptive therapy prior to the identification of the causative organisms.

Also, PIPRACIL may be administered as single drug therapy in some situations where normally two antibiotics might be employed.

Piperacillin has been successfully used with aminoglycosides, especially in patients with impaired host defenses. Both drugs should be used in full therapeutic doses.

Appropriate cultures should be made for susceptibility testing before initiating therapy and therapy adjusted, if appropriate, once the results are known.

Prophylaxis: PIPRACIL is indicated for prophylactic use in surgery including intra-abdominal (gastrointestinal and biliary) procedures, vaginal hysterectomy, abdominal hysterectomy, and cesarean section. Effective prophylactic use depends on the time of administration; PIPRACIL should be given one-half to one hour before the operation so that effective levels can be achieved in the site prior to the procedure.

The prophylactic use of piperacillin should be stopped within 24 hours, since continuing administration of any antibiotic increases the possibility of adverse reactions, but in the majority of surgical procedures, does not reduce the incidence of subsequent infections. If there are signs of infection, specimens for culture and susceptibility testing should be obtained for identification of the causative microorganism so that appropriate therapy can be instituted.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of PIPRACIL and other antibacterial drugs, PIPRACILshould only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

PIPRACIL is contraindicated in patients with a history of allergic reactions to any of the betalactams, including penicillins and/or cephalosporins.

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC/ANAPHYLACTOID) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH PIPRACIL, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, PIPRACIL SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC/ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including PIPRACIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PIPRACIL is generally well tolerated. The most common adverse reactions have been local in nature, following intravenous or intramuscular injection. The following adverse reactions may occur:

Local Reactions: In clinical trials thrombophlebitis was noted in 4% of patients. Pain, erythema, and/or induration at the injection site occurred in 2% of patients. Less frequent reactions including ecchymosis, deep vein thrombosis, and hematomas have also occurred.

Gastrointestinal: Diarrhea and loose stools were noted in 2% of patients. Other less frequent reactions included vomiting, nausea, increases in liver enzymes (LDH, AST, ALT), hyperbilirubinemia, cholestatic hepatitis, bloody diarrhea, and pseudomembranous colitis. The onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS.)

Hypersensitivity Reactions: Anaphylactic/anaphylactoid reactions (some leading to shock and fatalities) have been reported. (See WARNINGS.)

Rash was noted in 1% of patients. Other less frequent findings included pruritus, vesicular eruptions, and positive Coombs tests.

Other dermatologic manifestations, such as erythema multiforme, urticaria, toxic epidermal necrolysis and Stevens-Johnson syndrome, have been reported.

Renal: Elevations of creatinine or BUN, renal failure and interstitial nephritis have been reported.

Central Nervous System: Headache, dizziness, fatigue, and seizures have been reported.

Hemic and Lymphatic: Hemolytic anemia, agranulocytosis, pancytopenia, prolonged bleeding time, reversible leukopenia, neutropenia, thrombocytopenia, and/or eosinophilia have been reported. As with other β-lactam antibiotics, reversible leukopenia (neutropenia) is more apt to occur in patients receiving prolonged therapy at high dosages or in association with drugs known to cause this reaction.

Serum Electrolytes: Individuals with liver disease or individuals receiving cytotoxic therapy or diuretics were reported to demonstrate a decrease in serum potassium concentrations with high doses of piperacillin. Hypokalemia has been reported.

Skeletal: Prolonged muscle relaxation (see PRECAUTIONS, Drug Interactions).

Other: Fever, superinfection, including candidiasis; hemorrhagic manifestations have been reported.

Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

There is no specific information on overdose with PIPRACIL. Other penicillin-class drugs in overdosage, however, have the potential to cause neuromuscular hyperirritability or convulsive seizures. In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. Piperacillin can be removed by hemodialysis but not peritoneal dialysis.

PIPRACIL may be administered by the intramuscular route (see NOTE) or intravenously as a three- to five-minute intravenous injection or as a 20- to 30-minute infusion. The usual dosage of PIPRACIL for serious infections is 3 to 4 g given every four to six hours as a 20- to 30-minute infusion. For serious infections, the intravenous route should be used.

PIPRACIL should not be mixed with an aminoglycoside in a syringe or infusion bottle since this can result in inactivation of the aminoglycoside.

The maximum daily dose for adults is usually 24 g/day, although higher doses have been used.

Intramuscular injections (see NOTE) should be limited to 2 g per injection site. This route of administration has been used primarily in the treatment of patients with uncomplicated gonorrhea and urinary tract infections.

The average duration of PIPRACIL treatment is from seven to ten days, except in the treatment of gynecologic infections, which is from three to ten days; the duration should be guided by the patient's clinical and bacteriological progress. For most acute infections, treatment should be continued for at least 48 to 72 hours after the patient becomes asymptomatic. Antibiotic therapy for S. pyogenes infections should be maintained for at least ten days to reduce the risk of rheumatic fever.

When PIPRACIL is given concurrently with aminoglycosides, both drugs should be used in full therapeutic doses.

PIPRACIL® (piperacillin for injection) is available in vials containing freeze-dried piperacillin sodium powder equivalent to two, three, and four g of piperacillin. One g of piperacillin (as a monosodium salt) contains 1.85 mEq (42.5 mg) of sodium.

Product Numbers
2 gram/Vial-10 per box-NDC 0206-3879-16
3 gram/Vial-10 per box-NDC 0206-3882-55
4 gram/Vial-10 per box-NDC 0206-3880-25

Store at controlled room temperature 20°C-25°C(68°F-77°F).

1National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically – Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January, 2000.

2National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing – Eleventh Informational Supplement. NCCLS Document M100-S11, Vol. 21, No. 1, NCCLS, Wayne, PA, January, 2001.

3National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests – Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA, January, 2000.

4National Committee for Clinical Laboratory Standards. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria – Fifth Edition. Approved Standard NCCLS Document M11-A5, Vol. 21, No. 2, NCCLS, Wayne, PA, March, 2001.

Wyeth®

Wyeth Pharmaceuticals Inc.
Philadelphia, PA 19101

W10440C007
ET01
Rev 03/07