What are the side effects of Zosyn (Piperacillin/Tazobactam)?

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Last updated: February 28, 2025View editorial policy

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From the Guidelines

Zosyn (piperacillin-tazobactam) can cause several side effects, including common ones like diarrhea, headache, and nausea, as well as more serious but less common side effects like allergic reactions and seizures, as reported in various studies 1.

Common Side Effects

  • Diarrhea
  • Headache
  • Fever
  • Nausea
  • Vomiting
  • Constipation
  • Rash
  • Insomnia Some patients may also experience injection site reactions, such as pain, inflammation, or phlebitis, where the IV is placed 1.

Serious Side Effects

  • Allergic reactions (hives, itching, swelling, difficulty breathing)
  • Severe skin reactions
  • Unusual bleeding or bruising
  • Yellowing of the eyes or skin (jaundice)
  • Seizures
  • Clostridium difficile-associated diarrhea It is essential for patients to contact their healthcare provider immediately if they experience severe diarrhea, significant rash, difficulty breathing, or other concerning symptoms while taking Zosyn 1. These side effects occur because Zosyn is a potent antibiotic that works by inhibiting bacterial cell wall synthesis, but this mechanism can also affect normal body processes 1. Patients with a history of penicillin allergy should inform their doctor before receiving Zosyn as cross-reactivity may occur 1.

Special Considerations

  • Patients with kidney problems or those taking other medications that affect kidney function should be closely monitored while taking Zosyn 1.
  • Blood cell counts should also be monitored in patients taking Zosyn, as it can affect the production of blood cells 1.

From the FDA Drug Label

The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache and insomnia. Table 6: Adverse Reactions from Piperacillin and Tazobactam for Injection Monotherapy Clinical Trials System Organ Class Adverse Reaction Gastrointestinal disorders Diarrhea (11.3%) Constipation (7.7%) Nausea (6.9%) Vomiting (3.3%) Dyspepsia (3.3%) Abdominal pain (1.3%) General disorders and administration site conditions Fever (2.4%) Injection site reaction (≤1%) Rigors (≤1%) Immune system disorders Anaphylaxis (≤1%) Infections and infestations Candidiasis (1.6%) Pseudomembranous colitis (≤1%) Metabolism and nutrition disorders Hypoglycemia (≤1%) Musculoskeletal and connective tissue disorders Myalgia (≤1%) Arthralgia (≤1%) Nervous system disorders Headache (7.7%) Psychiatric disorders Insomnia (6.6%) Skin and subcutaneous tissue disorders Rash (4.2%, including maculopapular, bullous, and urticarial) Pruritus (3.1%) Purpura (≤1%) Vascular disorders Phlebitis (1.3%) Thrombophlebitis (≤1%) Hypotension (≤1%) Flushing (≤1%) Respiratory, thoracic and mediastinal disorders Epistaxis (≤1%) Table 7: Adverse Reactions from Piperacillin and Tazobactam for Injection Plus Aminoglycoside Clinical Trials System Organ Class Adverse Reaction Blood and lymphatic system disorders Thrombocythemia (1.4%) Anemia (≤1%) Thrombocytopenia (≤1%) Eosinophilia (≤1%) Gastrointestinal disorders Diarrhea (20%) Constipation (8.4%) Nausea (5.8%) Vomiting (2.7%) Dyspepsia (1.9%) Abdominal pain (1.8%) Stomatitis (≤1%) General disorders and administration site conditions Fever (3.2%) Injection site reaction (≤1%) Infections and infestations Oral candidiasis (3.9%) Candidiasis (1.8%) Investigations BUN increased (1.8%) Blood creatinine increased (1.8%) Liver function test abnormal (1.4%) Alkaline phosphatase increased (≤1%) Aspartate aminotransferase increased (≤1%) Alanine aminotransferase increased (≤1%) Metabolism and nutrition disorders Hypoglycemia (≤1%) Hypokalemia (≤1%) Nervous system disorders Headache (4.5%) Psychiatric disorders Insomnia (4.5%) Renal and urinary disorders Renal failure (≤1%) Skin and subcutaneous tissue disorders Rash (3.9%) Pruritus (3.2%) Vascular disorders Thrombophlebitis (1.3%) Hypotension (1.3%)

The side effects of Zosyn (Piperacillin/Tazobactam) include:

  • Gastrointestinal disorders:
    • Diarrhea (11.3% to 20%)
    • Constipation (7.7% to 8.4%)
    • Nausea (5.8% to 6.9%)
    • Vomiting (2.7% to 3.3%)
    • Dyspepsia (1.9% to 3.3%)
    • Abdominal pain (1.3% to 1.8%)
  • General disorders and administration site conditions:
    • Fever (2.4% to 3.2%)
    • Injection site reaction (≤1%)
  • Immune system disorders:
    • Anaphylaxis (≤1%)
  • Infections and infestations:
    • Candidiasis (1.6% to 1.8%)
    • Pseudomembranous colitis (≤1%)
  • Metabolism and nutrition disorders:
    • Hypoglycemia (≤1%)
  • Musculoskeletal and connective tissue disorders:
    • Myalgia (≤1%)
    • Arthralgia (≤1%)
  • Nervous system disorders:
    • Headache (4.5% to 7.7%)
  • Psychiatric disorders:
    • Insomnia (4.5% to 6.6%)
  • Skin and subcutaneous tissue disorders:
    • Rash (3.9% to 4.2%)
    • Pruritus (3.1% to 3.2%)
  • Vascular disorders:
    • Phlebitis (1.3%)
    • Thrombophlebitis (≤1%)
    • Hypotension (≤1%)
    • Flushing (≤1%) 2

From the Research

Side Effects of Zosyn (Piperacillin/Tazobactam)

The side effects of Zosyn (Piperacillin/Tazobactam) include:

  • Gastrointestinal symptoms, most commonly diarrhea 3, 4
  • Skin reactions 3
  • Fever, hematologic abnormalities, and transaminitis, particularly with prolonged courses of therapy 5
  • Pulmonary infiltrates with eosinophilia, a rare but potentially serious adverse reaction 6
  • Other adverse events, such as nausea, vomiting, and rash, which are common with piperacillin 6

Adverse Event Incidence

The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given in combination with an aminoglycoside than when given as monotherapy 3. Additionally, prolonged courses of piperacillin-tazobactam have been associated with a significantly higher occurrence of adverse events in pediatric patients 5.

Special Considerations

Piperacillin/tazobactam is generally well tolerated, but physicians should be aware of the potential for rare but serious adverse reactions, such as pulmonary infiltrates with eosinophilia 6. Patients who develop a febrile illness associated with a prolonged course of piperacillin-tazobactam therapy should be evaluated for adverse events related to the drug 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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