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Piperacillin Side Effects

Medically reviewed by Drugs.com. Last updated on Sep 10, 2023.

Applies to piperacillin: injectable powder for injection.

General

This drug was generally well tolerated. Local side effects (after IV or IM injection) were most common.[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, loose stools

Frequency not reported: Nausea, vomiting, bloody diarrhea, pseudomembranous colitis, Clostridium difficile-associated diarrhea[Ref]

The onset of pseudomembranous colitis symptoms has been reported during or after antimicrobial therapy.[Ref]

Dermatologic

Common (1% to 10%): Rash, pruritus

Frequency not reported: Vesicular eruptions/vesiculation, erythema multiforme, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, drug reactions with eosinophilia and systemic symptoms (DRESS), petechial rash/purpura, exanthematous pustulosis, bullous dermatosis, erythema nodosum, exanthems, exfoliative dermatitis, Jarisch-Herxheimer reaction[Ref]

An increased incidence of rash has been reported in cystic fibrosis patients.

DRESS has been reported, particularly with piperacillin-tazobactam.

Petechial rash or purpura due to thrombocytopenia has been reported.[Ref]

Local

Common (1% to 10%): Thrombophlebitis, injection site pain, injection site induration, injection site erythema

Frequency not reported: Ecchymosis, deep vein thrombosis, hematomas[Ref]

Thrombophlebitis was more likely when insufficiently diluted solution was injected into the vein.[Ref]

Other

Common (1% to 10%): Drug fever

Frequency not reported: Fever, edema, fatigue, decreased serum potassium levels, superinfection (including candidiasis), hemorrhagic manifestations[Ref]

An increased incidence of fever has been reported in cystic fibrosis patients.

Patients with liver disease or those receiving cytotoxic therapy or diuretics have reported decreased serum potassium levels with high doses of this drug.[Ref]

Hypersensitivity

Frequency not reported: Anaphylactic/anaphylactoid reactions (some leading to shock and fatalities)[Ref]

Hematologic

Frequency not reported: Agranulocytosis, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, eosinophilia, bleeding disorders, positive Coombs tests, hemorrhage/bleeding, decreased prothrombin time, platelet dysfunction, prolonged bleeding times[Ref]

Risk factors for reversible leukopenia (neutropenia) included prolonged therapy with high doses or concomitant drugs that cause this effect.[Ref]

Nervous system

Frequency not reported: Headache, dizziness, seizures/convulsions, prolonged muscle relaxation, paralysis, neurotoxicity, encephalopathy, neuromuscular excitability[Ref]

Neuromuscular excitability and convulsions have been reported when higher than recommended doses were given IV.[Ref]

Renal

Frequency not reported: Elevated serum creatinine, elevated BUN, interstitial nephritis, renal failure[Ref]

Drug-induced interstitial nephritis is a rare but potentially serious side effect of all penicillins.[Ref]

Hepatic

Frequency not reported: Elevated liver enzymes (LDH, AST, ALT), hyperbilirubinemia, hepatotoxicity, cholestatic hepatitis[Ref]

Metabolic

Frequency not reported: Hypokalemia, electrolyte disturbances, acid-base disturbances[Ref]

Respiratory

Frequency not reported: Epistaxis

References

1. Cerner Multum, Inc. Canadian Product Information. 2015.

2. Winston DJ, Murphy W, Young LS, Hewitt WL. Piperacillin therapy for serious bacterial infections. Am J Med. 1980;69:255-61.

3. Lutz B, Mogabgab W, Holmes B, et al. Clinical evaluation of the therapeutic efficacy and tolerability of piperacillin. Antimicrob Agents Chemother. 1982;22:10-4.

4. Eliopoulos GM, Moellering RC. Azlocillin, mezlocillin, and piperacillin: new broad-spectrum penicillins. Ann Intern Med. 1982;97:755-60.

5. Link AS, Jr. Efficacy and safety of ticarcillin plus clavulanic acid and piperacillin in patients with lower respiratory tract infections. Am J Med. 1985;79:86-7.

6. Mandell GL. In vitro microbiology and pharmacokinetics of piperacillin. Clin Ther. 1985;7:37-44.

7. Product Information. Pipracil (piperacillin). Lederle Laboratories. 2001;PROD.

8. Ramakrishnan K, Scheid DC. Diagnosis and management of acute pyelonephritis in adults. Am Fam Physician. 2005;71:933-42.

9. Abate G, Godbole K, Springston C. Piperacillin/tazobactam-induced petechial rash. Ann Pharmacother. 2010;44:1345-6.

10. Strandvik B. Adverse reactions to piperacillin in patients with cystic fibrosis. Lancet. 1984;06/16/84:1362.

11. Stead RJ, Kennedy HG, Hodson ME, Batten JC. Adverse reactions to piperacillin in cystic fibrosis. Lancet. 1984;04/14/84:857.

12. Pleasants RA, Walker TR, Samuelson WM. Allergic reactions to parenteral beta-lactam antibiotics in patients with cystic fibrosis. Chest. 1994;106:1124-8.

13. Cabanas R, Munoz L, LopezSerrano C, Contreras J, Padial A, Caballero T, MorenoAncillo A, Barranco P. Hypersensitivity to piperacillin. Allergy. 1998;53:819-20.

14. Moore M, McNamara TR, Johnson J. Elevated bleeding time and epistaxis associated with piperacillin therapy. South Med J. 1985;78:363.

15. Kirkwood CF, Lasezkay GM. Neutropenia associated with mezlocillin and piperacillin. Drug Intell Clin Pharm. 1985;19:112-4.

16. Lee M, Stobnicki M, Sharifi R. Hemorrhagic complications of piperacillin therapy. J Urol. 1986;136:454-5.

17. Bressler RB, Huston DP. Piperacillin-induced anemia and leukopenia. South Med J. 1986;79:255-6.

18. Fass RJ, Copelan EA, Brandt JT, Moeschberger ML, Ashton JJ. Platelet-mediated bleeding caused by broad-spectrum penicillins. J Infect Dis. 1987;155:1242-8.

19. Gentry LO, Jemsek JG, Natelson EA. Effects of sodium piperacillin on platelet function in normal volunteers. Antimicrob Agents Chemother. 1981;19:532-3.

20. Singh N, Yu VL, Mieles LA, Wagener MM. Beta-lactam antibiotic-induced leukopenia in severe hepatic dysfunction: risk factors and implications for dosing in patients with liver disease. Am J Med. 1993;94:251-6.

21. Yan MT, Chu HY, Chau T, Lin SH. Profound thrombocytopenia associated with piperacillin in a hemodialysis patient. Clin Nephrol. 2009;72:240-3.

22. Mackie K, Pavlin EG. Recurrent paralysis following piperacillin administration. Anesthesiology. 1990;72:561-3.

23. Parkmatsumoto YC, Tazawa T. Piperacillin-induced encephalopathy. J Neurol Sci. 1996;140:141-2.

24. Malanga CJ, Kokontis L, Mauzy S. Piperacillin-induced seizures. Clin Pediatr (Phila). 1997;36:475-6.

Further information

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Some side effects may not be reported. You may report them to the FDA.

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