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Side Effects


PIPRACIL (piperacillin sodium) 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.

Read the Pipracil (piperacillin sodium) Side Effects Center for a complete guide to possible side effects



The mixing of piperacillin with an aminoglycoside in vitro can result in substantial inactivation of the aminoglycoside.


When used in the perioperative period, piperacillin has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Caution is indicated when piperacillin is used perioperatively. In one controlled clinical study, the ureidopenicillins, including piperacillin, were reported to prolong the action of vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the non-depolarizing muscle relaxants could be prolonged in the presence of piperacillin.


The oral combination of probenecid before intramuscular injection of PIPRACIL (piperacillin sodium) produces an increase in piperacillin peak serum level of about 30%.


Coagulation parameters should be tested more frequently and monitored regularly during simultaneous administration of high doses of heparin, oral anticoagulants, or other drugs that may affect the blood coagulation system or the thrombocyte function.


Piperacillin sodium may reduce the excretion of methotrexate. Therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity.

Drug/Laboratory Test Interactions

As with other penicillins, the administration of PIPRACIL (piperacillin sodium) may result in a false-positive reaction for glucose in the urine using a copper-reduction method. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

There have been reports of positive test results using the Bio-Rad Laboratories Platelia AspergillusEIA test in patients receiving piperacillin/tazobactam injection who were subsequently found to be free ofAspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with the Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported.

Therefore, positive test results in patients receiving piperacillin should be interpreted cautiously and confirmed by other diagnostic methods.

Read the Pipracil Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 8/12/2008

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