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Zosyn Side Effects

Generic name: piperacillin / tazobactam

Medically reviewed by Drugs.com. Last updated on Dec 27, 2023.

Note: This document contains side effect information about piperacillin / tazobactam. Some dosage forms listed on this page may not apply to the brand name Zosyn.

Applies to piperacillin / tazobactam: intravenous powder for solution, intravenous solution.

Serious side effects of Zosyn

Along with its needed effects, piperacillin / tazobactam may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking piperacillin / tazobactam:

More common

Less common

Rare

Incidence not known

Other side effects of Zosyn

Some side effects of piperacillin / tazobactam may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

Rare

For Healthcare Professionals

Applies to piperacillin / tazobactam: intravenous powder for injection, intravenous solution.

General

In general, side effects have been described as transient and mild to moderate. The most common side effects have included diarrhea, rash, erythema, pruritus, vomiting, allergic reactions, nausea, urticaria, superinfection, phlebitis, thrombophlebitis, dyspepsia, and insomnia. In clinical trials, this drug was discontinued in 3.2% of patients due to dermatologic effects (including rash, pruritus), gastrointestinal effects (including diarrhea, nausea, vomiting), and allergic reactions. In nosocomial pneumonia trials, 11% of patients discontinued this drug due to a side effect.[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 20%)

Common (1% to 10%): Constipation, nausea, oral candidiasis, vomiting, dyspepsia, abdominal pain, soft/loose stools

Uncommon (0.1% to 1%): Stomatitis

Rare (0.01% to 0.1%): Pseudomembranous colitis

Frequency not reported: Dry mouth, Clostridioides difficile-associated diarrhea , hiccough, stool changes, enlarged abdomen, flatulence, duodenal ulcer, melena, gastrointestinal hemorrhage, gastritis, ileus, taste perversion, ulcerative stomatitis, colitis, dysphagia, glossitis, fecal incontinence, gastric ulcer, pancreatitis[Ref]

Diarrhea associated with this drug was usually self-limited. There have been case reports of pseudomembranous colitis. The onset of pseudomembranous colitis symptoms has been reported during and after antibacterial therapy.[Ref]

Nervous system

Common (1% to 10%): Headache

Frequency not reported: Dizziness, convulsions, neuromuscular excitability, tremor, vertigo, syncope, central nervous system depression, grand mal convulsion, cerebrovascular accident, somnolence, tinnitus, hypertonia, stupor, deafness, tonic-clonic seizure

Postmarketing reports: Seizures

Piperacillin:

-Frequency not reported: Neurotoxicity, effect of neuromuscular blocking agents enhanced[Ref]

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

Dermatologic

Common (1% to 10%): Rash (including maculopapular, bullous, urticarial), pruritus

Uncommon (0.1% to 1%): Urticaria

Rare (0.01% to 0.1%): Purpura, eruption (including bullous dermatitis)

Frequency not reported: Increased sweating, eczema/eczematoid rash, exanthema, erythematous rash, excoriations, diaphoresis, fungal dermatitis, exanthematous pustulosis, drug-induced petechial rash

Postmarketing reports: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis, exfoliative dermatitis, maculopapular rash

Piperacillin:

-Frequency not reported: Petechial rash/purpura due to thrombocytopenia, exanthematous pustulosis, bullous dermatosis, erythema nodosum, exanthems, exfoliative dermatitis, urticaria, pruritus, vesiculation, Jarisch-Herxheimer reaction, Stevens-Johnson syndrome, purpura, vasculitis[Ref]

A patient with mononucleosis developed a nonallergic rash after using this drug for 3 weeks for osteomyelitis. He had no history of penicillin allergy. His Epstein-Barr virus IgG and IgM antibodies were positive. The rash resolved quickly after discontinuation of the drug.

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

Other

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

Common (1% to 10%): Fever/pyrexia, candidiasis, decreased blood albumin, decreased total protein, increased blood alkaline phosphatase

Uncommon (0.1% to 1%): Flushing, chills

Rare (0.01% to 0.1%): Rigors

Frequency not reported: Transient elevations of alkaline phosphatase, edema, hot flushes, tiredness, pain, generalized edema, peripheral edema, moniliasis, chest pain, back pain, malaise, asthenia, earache, xerosis, decreased drug level, false-positive tests for Aspergillus galactomannan antigenemia

Postmarketing reports: Candida infection, candidal superinfection[Ref]

Renal

Common (1% to 10%): Increased blood creatinine, increased blood urea/BUN

Rare (0.01% to 0.1%): Renal failure, tubulointerstitial nephritis

Frequency not reported: Increased serum creatinine, nephrotoxicity, acute onset of renal dysfunction (with elevated serum creatinine, lumbar pain, rash, fever, arthralgias, eosinophiluria), acute kidney failure, abnormal kidney function

Postmarketing reports: Interstitial nephritis, acute renal injury[Ref]

In a randomized, multicenter, controlled trial in critically ill adults (n=1200), this drug was found to be a risk factor for renal failure and associated with delayed recovery of renal function as compared to other beta-lactam antibacterial agents.

A 51-year-old woman developed an acute onset of renal dysfunction after 6 days of therapy with this drug. The patient also had an elevated serum creatinine, lumbar pain, rash, fever, arthralgias, and eosinophiluria. The drug was discontinued and the patient's symptoms improved to baseline after 21 days of prednisone.[Ref]

Hematologic

Common (1% to 10%): Thrombocythemia, thrombocytopenia, positive direct Coombs test, prolonged activated partial thromboplastin time

Uncommon (0.1% to 1%): Leukopenia, neutropenia, prolonged prothrombin time

Rare (0.01% to 0.1%): Anemia, eosinophilia, agranulocytosis, bleeding manifestations, prolonged bleeding time

Very rare (less than 0.01%): Disturbed thrombocyte function, prolonged partial thromboplastin time

Frequency not reported: Decreased hemoglobin, decreased hematocrit, increased platelet count, hypochromic anemia, leukocytosis, decreased prothrombin, ecchymosis, vitamin B12 deficiency anemia

Postmarketing reports: Hemolytic anemia, pancytopenia, thrombocytosis

Piperacillin:

-Rare (0.01% to 0.1%): Reversible bone marrow suppression

-Frequency not reported: Bleeding disorders, neutropenia, thrombocytopenia, hemolytic anemia[Ref]

Leukopenia/neutropenia was frequently associated with prolonged therapy (i.e., 21 days or longer) and appeared to be reversible. Leukopenia has been reported in 23% of patients with liver disease receiving beta-lactam antibiotics.

Reversible bone marrow suppression was rare and usually limited to prolonged therapy with piperacillin.[Ref]

Hepatic

Common (1% to 10%): Abnormal liver function test, increased AST, increased ALT

Uncommon (0.1% to 1%): Increased blood bilirubin

Rare (0.01% to 0.1%): Increased GGT

Frequency not reported: Transient elevations of AST, transient elevations of ALT, transient elevations of bilirubin

Postmarketing reports: Hepatitis, jaundice

Piperacillin:

-Frequency not reported: Hepatotoxicity[Ref]

Cardiovascular

Common (1% to 10%): Phlebitis, thrombophlebitis, hypotension

Frequency not reported: Cardiac arrest, supraventricular tachycardia, tachycardia, ventricular tachycardia, bradycardia, arrhythmia, atrial fibrillation, ventricular fibrillation, cardiac failure, circulatory failure, myocardial infarction, hypertension, angina, sinus bradycardia, ventricular extrasystoles, mesenteric embolism[Ref]

Hypersensitivity

Frequency not reported: Anaphylaxis, allergic reactions

Postmarketing reports: Hypersensitivity, anaphylactic reaction, anaphylactoid reaction, anaphylactic shock, anaphylactoid shock

Piperacillin:

-Frequency not reported: Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (resulting in shock and fatalities)[Ref]

Hypersensitivity reactions have generally included urticarial rash, but rare reports of severe reactions (including anaphylaxis, Stevens-Johnson syndrome, dyspnea, hypotension, and edema) have been reported. Hypersensitivity reactions (including fever, rash, and eosinophilia) have been reported.[Ref]

Psychiatric

Common (1% to 10%): Insomnia

Frequency not reported: Hallucination, anxiety, confusion, aggressive reaction (combative), depression, agitation

Postmarketing reports: Delirium[Ref]

Metabolic

Hypokalemia has been reported when high doses of piperacillin were administered to patients with liver disease and patients using cytotoxic therapy or diuretics.[Ref]

Uncommon (0.1% to 1%): Hypokalemia, decreased blood glucose

Frequency not reported: Hypoglycemia, electrolyte abnormalities (e.g., increased and decreased sodium, potassium, calcium), hyperglycemia, symptomatic hypoglycemia, thirst, anorexia, acidosis, dehydration, gout, hypernatremia, hyponatremia, hypophosphatemia, hypomagnesemia, fluid overload

Piperacillin:

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

Respiratory

Rare (0.01% to 0.1%): Epistaxis

Frequency not reported: Pleural effusion, pneumothorax, rhinitis, dyspnea, pharyngitis, pulmonary edema, bronchospasm, coughing, pulmonary embolism, hyperventilation, respiratory disorder, increased cough, atelectasis, hemoptysis, hypoxia

Postmarketing reports: Eosinophilic pneumonia[Ref]

Local

Common (1% to 10%): Injection site reaction

Uncommon (0.1% to 1%): Injection site pain, injection site inflammation

Frequency not reported: Injection site edema, local reaction to procedure[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Myalgia/muscle pain, arthralgia

Frequency not reported: Muscular weakness, prolonged muscle relaxation

Piperacillin:

-Frequency not reported: Prolonged muscle relaxation[Ref]

Genitourinary

Frequency not reported: Urinary tract infection, urinary incontinence, genital pruritus, balanoposthitis, leukorrhea, vaginitis, perineal irritation/pain, urinary retention, dysuria, oliguria, hematuria, urinary incontinence, urinary tract infection with trichomonas, yeast in urine, proteinuria, pyuria[Ref]

Ocular

Frequency not reported: Photophobia, diplopia, conjunctivitis[Ref]

References

1. Product Information. Zosyn (piperacillin-tazobactam). Lederle Laboratories. 2001;PROD.

2. Cerner Multum, Inc. UK Summary of Product Characteristics.

3. Cerner Multum, Inc. Australian Product Information.

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

5. 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.

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

7. 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.

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

9. Wise R. The efficacy and safety of piperacillin / tazobactam in the therapy of bacteraemia. J Antimicrob Chemother. 1993;31:97-104.

10. Mouton Y, Leroy O, Beuscart C, Chidiac C, Senneville E, Ajana F, Lecocq P. Efficacy, safety and tolerance of parenteral piperacillin / tazobactam in the treatment of patients with lower respiratory tract infections. J Antimicrob Chemother. 1993;31:87-95.

11. Kuye O, Teal J, DeVries VG, Morrow CA, Tally FP. Safety profile of piperacillin / tazobactam in phase I and III clinical studies. J Antimicrob Chemother. 1993;31:113-24.

12. Tassler H, Cullmann W, Elhardt D. Therapy of soft tissue infections with piperacillin / tazobactam. J Antimicrob Chemother. 1993;31:105-12.

13. Sweet RL, Roy S, Faro S, Obrien WF, Sanfilippo JS, Seidlin M, Mcgregor JA, Pastorek JA, Auger P, Summitt RL, Murray G, San. Piperacillin and tazobactam versus clindamycin and gentamicin in the treatment of hospitalized women with pelvic infection. Obstet Gynecol. 1994;83:280-6.

14. Wilcox MH, Freeman J, Fawley W, et al. Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea. J Antimicrob Chemother. 2004;54:168-72.

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

16. Schmitt DV, Leitner E, Welte T, Lode H. Piperacillin/Tazobactam vs Imipenem/Cilastatin in the Treatment of Nosocomial Pneumonia-a Double Blind Prospective Multicentre Study. Infection. 2006;34:127-34.

17. Bow EJ, Rotstein C, Noskin GA, et al. A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies. Clin Infect Dis. 2006;43:447-59.

18. Lau WK, Mercer D, Itani KM, et al. A Randomized, Open-Label, Comparative Study of Piperacillin/Tazobactam Administered by Continuous Infusion vs. Intermittent Infusion for the Treatment of Hospitalized Patients with Complicated Intra-Abdominal Infection. Antimicrob Agents Chemother. 2006.

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

20. Bassilios N, Restoux A, Vincent F, Rondeau E, Sraer JD. Piperacillin/Tazobactam inducing seizures in a hemodialysed patient. Clin Nephrol. 2002;58:327-8.

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

22. LeClaire AC, Martin CA, Hoven AD. Rash associated with piperacillin / tazobactam administration in infectious mononucleosis. Ann Pharmacother. 2004;38:996-8.

23. Grieco T, Cantisani C, Innocenzi D, Bottoni U, Calvieri S. Acute generalized exanthematous pustulosis caused by piperacillin / tazobactam. J Am Acad Dermatol. 2005;52:732-3.

24. Pill MW, O'Neill CV, Chapman MM, Singh AK. Suspected acute interstitial nephritis induced by piperacillin-tazobactam. Pharmacotherapy. 1997;17:166-9.

25. Liu TJ, Lam JP. Piperacillin-tazobactam-induced acute interstitial nephritis with possible meropenem cross-sensitivity in a patient with osteomyelitis. Am J Health Syst Pharm. 2012;69:1109.

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

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

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

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

30. 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.

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32. 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.

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36. Thickett KM, Wildman MJ, Fegan CD, Stableforth DE. Haemolytic anaemia following treatment with piperacillin in a patient with cystic fibrosis. J Antimicrob Chemother. 1999;43:435-6.

37. Peralta FG, Sanchez MB, Roiz MP, Pena MA, Tejero MA, Arjona R. Incidence of Neutropenia during Treatment of Bone-Related Infections with Piperacillin-Tazobactam. Clin Infect Dis. 2003;37:1568-72.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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