Piperacillin for Injection: Indications, Dosage, Precautions, Adverse Effects
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Piperacillin for Injection - Product Information

Manufacture: Fresenius Kabi USA, LLC
Country: Canada
Condition: Bone infection (Osteomyelitis), Burns, External, Cholangitis, Endometritis, Epididymitis, Gonorrhea (Gonococcal Infection, Uncomplicated), Gonococcal Infection, Joint Infection, Meningitis, Peritonitis, Pneumonia, Pyelonephritis (Kidney Infections), Postoperative Infection, Sepsis, Septicemia, Skin Infection (Skin or Soft Tissue Infection), Skin Infection, bacterial (Bacterial Skin Infection), Skin or Soft Tissue Infection, Surgical Prophylaxis, Streptococcal Infection, Urinary Tract Infection
Class: Antibiotics/antineoplastics, Penicillins
Form: Intravenous (IV), Powder
Ingredients: Sodium piperacillin

Action and Clinical Pharmacology

Piperacillin is a semi-synthetic β-lactam antibiotic which is bactericidal and exerts its antibacterial action by inhibiting both septum and cell-wall synthesis in the bacterial cell.

Piperacillin was shown to have a particularly high affinity for PBP-3 and also a high affinity for PBP-1A, -1B and -2 of Escherichia coli and Pseudomonas. These results indicate that the enzymes involved in septum (PBP-3) and cell wall (PBP-1A, -1B) synthesis and in the maintenance of the shape (PBP-2) of the bacterium are the primary sites of action of piperacillin.

Piperacillin is eliminated primarily (60 ‒ 80%) by glomerular filtration and tubular secretion as unchanged drug in the urine. The mean elimination half-life is 54 minutes after the administration of 2 grams and 63 minutes following 6 grams. The elimination half-life is increased twofold in mild to moderate renal impairment and five- to six-fold in severe renal impairment.

Indications and Clinical Use

Piperacillin for Injection is recommended for the treatment of systemic and local infections due to susceptible strains of gram-negative and gram-positive aerobic and anaerobic bacteria listed below. Because of its broad spectrum activity, Piperacillin for Injection is also suitable for the therapy of mixed infections, and the presumptive therapy of serious infections when piperacillin- sensitive pathogens are suspected as the cause of disease.

  1. Intra-abdominal infections including hepatobiliary and surgical infections caused by Escherichia coli, Pseudomonas aeruginosa, enterococci, Clostridium spp., anaerobic cocci, and Bacteroides spp., including fragilis.
  2. Urinary tract infections (complicated and uncomplicated) caused by Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Proteus mirabilis and enterococci.
  3. Gynecological infections including endometritis and pelvic inflammatory disease, caused by Bacteroides spp., including fragilis, anaerobic cocci, Neisseria gonorrhoeae, and enterococci (Streptococcus faecalis).
  4. Septicemia including bacteremia caused by Escherichia coli, Klebsiella spp., Serratia spp., Proteus mirabilis, pneumoniae, enterococci, Pseudomonas aeruginosa, Bacteroides spp., and anaerobic cocci.
  5. Lower respiratory tract infections caused by Escherichia coli, Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Haemophilus influenzae, Bacteroides species and anaerobic cocci. Although improvement has been noted in patients with cystic fibrosis, lasting bacterial eradication may not be
  6. Skin and skin structure infections caused by Escherichia coli, Klebsiella spp., Serratia spp., Acinetobacter spp., Enterobacter spp., Pseudomonas aeruginosa, indole-positive Proteus spp., Proteus mirabilis, Bacteroides spp., including fragilis, anaerobic cocci and enterococci.
  7. Bone and joint infections caused by Pseudomonas aeruginosa, enterococci, Bacteroides spp., and anaerobic cocci.
  8. Uncomplicated urethritis caused by Neisseria gonorrhoeae.

Appropriate cultures should be made before initiating treatment. Presumptive therapy may be started while awaiting results of susceptibility tests. Treatment should be adjusted, if necessary, when results of these tests become available.

Mixed Infections

Piperacillin has also been shown to be clinically effective for the treatment of infections at various sites caused by streptococcus species, including Group A β-hemolytic Streptococcus and Streptococcus pneumoniae. While infections caused solely by these organisms are ordinarily treated with narrower spectrum penicillins, mixed infections involving the above, and other organisms susceptible to piperacillin, may be effectively treated by the latter.

Piperacillin for Injection may be administered as single drug therapy in some situations where normally two antibiotics might be employed.


The efficacy of piperacillin has been demonstrated in infections produced by organisms resistant to other penicillins, some aminoglycosides and cephalosporins.

Combined Therapy with Other Antibiotics

In vitro synergism has been shown between piperacillin and some aminoglycosides in some bacterial strains. Piperacillin has been used clinically with aminoglycosides, especially in patients with impaired host defenses. Both drugs were used in full therapeutic doses.

Piperacillin for Injection can be used safely in combination with penicillinase-resistant penicillins, e.g., oxacillin, in mixed infections when β-lactamase-positive Staphylococcus aureus is isolated along with piperacillin-susceptible organisms.

Piperacillin for Injection may be administered concomitantly with a cephalosporin, provided that an additive or synergistic antibacterial action of the two antibiotics is ascertained through in vitro tests. Based on in vitro data, cefoxitin should not be given with piperacillin when infections caused by organisms producing inducible β-lactamases are suspected or confirmed.


A history of allergic reactions to any of the penicillins and/or cephalosporins.

Piperacillin for Injection when reconstituted with Lidocaine for intramuscular use is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.


Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with penicillins. These reactions are more apt to occur in persons with a history of sensitivity to multiple allergens.

Cross-sensitivity of patients to penicillins and cephalosporins has been reported. Before initiating therapy with Piperacillin for Injection, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins and other allergens.

If an allergic reaction occurs, the antibiotic should be discontinued. The usual agents (antihistamines, pressor amines and corticosteroids) should be readily available.


Antibiotic-associated pseudomembranous colitis has been reported with nearly all antibacterial agents, including piperacillin, and may range in severity from mild to life-threatening. It is important to consider this diagnosis if significant diarrhea or colitis occurs during therapy. Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, management with fluids and electrolytes, protein supplementation and treatment with an oral antibacterial drug effective against Clostridium difficile (e.g., oral vancomycin) should be considered.


While Piperacillin for Injection possesses the characteristic low toxicity of the penicillin group of antibiotics, it is advisable to check periodically for organ dysfunction (including renal, hepatic and hematopoietic) during prolonged therapy.

Bleeding manifestations have occurred in some patients receiving β-lactam antibiotics including piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure.

If bleeding manifestations or significant leukopenia occur, Piperacillin for Injection should be discontinued and appropriate therapy instituted.

The possibility of the emergence of resistant organisms and the development of superinfections should be kept in mind, particularly during prolonged treatment. If this occurs, appropriate measures should be taken.

As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses of Piperacillin for Injection are given intravenously.

Since piperacillin is excreted not only renally but also by the biliary route, it can be used at reduced dosage (see DOSAGE AND ADMINISTRATION) in patients with severely restricted kidney function and in those who have had nephrotoxic reactions to other drugs.

Piperacillin for Injection is a monosodium compound containing 1.85 milliequivalents (42.5 mg) of Na+ per gram based on molecular weight (see PHARMACEUTICAL INFORMATION).

This should be considered when treating patients requiring restricted salt intake. Periodic electrolyte determinations should be made in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves, receiving cytotoxic therapy or diuretics. Electrolyte and cardiac status should also be monitored during prolonged treatment in patients with impaired cardiac function.

Antimicrobials used in high doses for short periods to treat gonorrhea may mask or delay the symptoms of incubating syphilis. Therefore, prior to treatment, patients with gonorrhea should also be evaluated for syphilis. Specimens for dark field examination should be obtained from patients with any suspected primary lesion, and serologic tests should be performed. In all cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of 4 months.

The use of some penicillins (ampicillin, amoxicillin) has been associated with morbilliform rashes in some cases of infectious mononucleosis. Piperacillin for Injection should therefore be used with caution in the treatment of infections caused by susceptible organisms in patients with infectious mononucleosis.

As with other semisynthetic penicillins, Piperacillin for Injection therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

Because of chemical instability, Piperacillin for Injection should not be used for intravenous administration with solutions containing only sodium bicarbonate (see INCOMPATIBILITY section).

Piperacillin for Injection should not be added to blood products.

Drug Interactions

The mixing of Piperacillin for Injection with an aminoglycoside in vitro can result in substantial inactivation of the aminoglycoside.

Concurrent administration of probenecid results in higher and more prolonged serum levels of piperacillin.

Whenever Piperacillin for Injection is administered concurrently with another antibiotic, the drugs should not be mixed in the same solution but must be administered separately.

Piperacillin, when used clinically in the early postoperative period, has been implicated in the prolongation of the neuromuscular blockage of vecuronium. In a controlled clinical study, the ureidopenicillins including piperacillin have been reported to prolong the action of vecuronium. Caution is indicated when piperacillin is used perioperatively with vecuronium and similar neuromuscular blocking agents.

Usage During Pregnancy or Lactation

Although reproduction studies in mice and rats performed at doses up to 4 times the human dose have shown no evidence of impaired fertility or harm to the fetus, safety of piperacillin use in pregnant women has not been determined. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. It has been found to cross the placenta in rats.

Caution should be exercised when Piperacillin for Injection is administered to nursing mothers. It is excreted in low concentrations in milk.

Pediatric Use

Dosage for children under the age of 12 has not been established.

Adverse Reactions

Piperacillin 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 adult clinical trials thrombophlebitis was noted in 2.5% of patients. It is more likely to occur when an insufficiently diluted solution is injected into the vein.

Pain, erythema, and/or induration at the injection site occurred in 1% of patients. Less frequent reactions, including ecchymosis, deep vein thrombosis and hematomas, have also occurred.

Hypersensitivity Reactions

Rash and/or pruritus was noted in 2.3% of patients. Drug fever was 2% (Note: The incidence of rash and fever is higher in patients with cystic fibrosis). Other less frequent findings included vesicular eruptions, positive Coombs’ tests. Anaphylactoid reactions have been reported rarely (see WARNINGS). Other dermatologic manifestations such as erythema multiforme, Stevens- Johnson Syndrome and Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS) have been reported rarely. DRESS has notably been reported when piperacillin was used in combination with tazobactam.


Diarrhea and loose stools were noted in 3% of patients. Other less frequent reactions included vomiting, nausea and bloody diarrhea. Pseudomembranous colitis has been reported rarely.


Increases in liver enzymes (LDH, SGOT, SGPT), hyperbilirubinemia. Rarely, cholestatic hepatitis.


Elevations of creatinine or BUN and rarely interstitial nephritis.

Central Nervous System

Headache, dizziness, fatigue. Convulsions with high doses.

Hemic and Lymphatic

Reversible leukopenia, neutropenia, thrombocytopenia and/or eosinophilia, bleeding and decreases in prothrombin time 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 rarely to demonstrate a decrease in serum potassium concentrations with high doses of piperacillin.


Rarely, prolonged muscle relaxation.


Superinfection, including candidiasis, and hemorrhagic manifestations.

Symptoms and Treatment of Overdosage

Other than general supportive treatment, no specific antidote is known. Excessive serum levels of piperacillin may be reduced by hemodialysis. As with other penicillins, neuromuscular excitability or convulsions have occurred following large intravenous doses. General supportive measures, including administration of phenytoin and barbiturates or other anticonvulsant drugs may be considered. Daily doses of piperacillin of at least 24 g have been administered to humans without observation of adverse effects.

For treatment of hypersensitivity reactions, see WARNINGS.

Dosage and Administration


Piperacillin for Injection may be administered intramuscularly or intravenously (either in a 3 to 5 minute injection or by infusion). Dosage and route of administration should be determined by the severity of the infection and condition of the patient.

The usual dosage of Piperacillin for Injection for serious infections is 3 to 4 g given every 4 to 6 hours as a 20 to 30 minute infusion. For serious infections the intravenous route should be used.

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

Dosage Recommendations
Type of InfectionUsual Total Daily
Frequency of
Serious infections such as septicemia, nosocomial pneumonia, intra-abdominal infections, aerobic and anaerobic gynecologic infections, and skin and soft tissue infections.12 ‒ 18 g i.v.
(200 ‒ 300 mg/kg)
Every 4 to 6 hours
Complicated urinary tract infections8 ‒ 16 g i.v.
(125 ‒ 200 mg/kg)
Every 6 to 8 hours
Uncomplicated urinary tract infections and most community-acquired pneumonia6 ‒ 8 g i.m. or i.v.
(100 – 125 mg/kg)
Every 6 to 12 hours
Uncomplicated gonococcal urethritis2 g i.m.*Single dose

* One gram of probenecid given orally ½ hour prior to injection.

Dosage in Renal Impairment (Adults)
Degree of
CreatinineUrinary Tract
Urinary Tract
Clearance (mL/min.)Serum Level (mg %)
Mild> 401.5 ‒ 3.0N/A **N/A **N/A **
Moderate20 ‒ 403.1 ‒ 5.0N/A **9 g/day(3 g q 8 h)12 g/day(4 g q 8 h)
Severe< 20> 56 g/day (3 g q 12 h)6 g/day(3 g q 12 h)8 g/day(4 g q 12 h)
Patients on Hemodialysis***    6 g/day(2 g q 8 h)

** N/A: No adjustment necessary

*** Hemodialysis removes 30 ‒ 50% of the drug in 4 hours; an additional dose of 1 g of Piperacillin for Injection should be administered following each dialysis period. For patients with renal failure, hepatic insufficiency or biliary tract obstruction measurement of serum levels of Piperacillin for Injection will provide additional guidance for adjusting dosage.

Infants and Children

Dosages in infants and children under 12 years of age have not been established.

Duration of Therapy

The average duration of Piperacillin for Injection treatment is from 7 to 10 days, except in the treatment of gynecologic infections, in which it is from 3 to 10 days; the duration should be guided by the patient's clinical and bacteriological progress. Some infections such as osteomyelitis may require significantly longer periods of therapy. For most acute infections, treatment should be continued for at least 48 to 72 hours after the patient becomes asymptomatic. Antibiotic therapy for Group A β-hemolytic streptococcal infections should be maintained for at least 10 days to reduce the risk of rheumatic fever or glomerulonephritis.


Intramuscular Injection

Intramuscular injections 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. Injection should be given into the upper outer quadrant of the buttock (i.e., gluteus maximus).

When indicated by clinical and bacteriological findings, intramuscular administration of 6 to 8 g daily of Piperacillin for Injection, in divided doses, may be utilized for initiation of therapy. In addition, intramuscular administration of the drug may be considered for maintenance therapy after clinical and bacteriological improvement has been obtained with intravenous Piperacillin for Injection treatment.

The deltoid area should be used only if well-developed, and then only with caution to avoid radial nerve injury. Intramuscular injections should not be made into the lower or mid-third of the upper arm.

Intravenous Injection (Bolus)

Reconstituted solution should be injected slowly over a 3 to 5 minute period to help avoid vein irritation.

Intravenous Infusion

Infusion should be carried out over a period of about 20 ‒ 40 minutes or intermittent infusion over a 30 minute to 2 hour period. During infusion it is desirable to discontinue the primary intravenous solution.