Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 4/25/2022
Zosyn Side Effects Center

What Is Zosyn?

Zosyn (piperacillin and tazobactam for injection) is a combination of two antibiotics used to treat many different infections caused by bacteria, such as urinary tract infections, bone and joint infections, severe vaginal infections, stomach infections, skin infections, and pneumonia. Zosyn is available in generic form.

What Are Side Effects of Zosyn?

Common side effects of Zosyn include:

  • injection site reactions like
    • swelling,
    • redness,
    • pain,
    • soreness or
    • irritation;
  • dizziness,
  • agitation,
  • trouble sleeping (insomnia),
  • nausea,
  • vomiting,
  • stomach pain or upset,
  • diarrhea,
  • constipation,
  • headache,
  • runny nose,
  • anxiety,
  • skin rash or
  • itching, or
  • vaginal discharge or itching.

Tell your doctor if you have serious side effects of Zosyn including muscle cramps or spasms, swelling of the arms/legs/hands/feet, easy bruising or bleeding, chest pain, confusion, new signs of infection (such as fever, persistent sore throat), severe abdominal or stomach pain, slow/fast/irregular heartbeat, persistent nausea or vomiting, seizures, extreme tiredness, dark or cloudy urine, change in the amount of urine, yellowing eyes or skin, or serious skin reactions (rash, peeling, sores, or blisters).

Dosage for Zosyn

The usual total daily dose of Zosyn for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam).

What Drugs, Substances, or Supplements Interact with Zosyn?

Zosyn may interact with probenecid, antibiotics, blood thinners, or any other medication used to prevent blood clots. Tell your doctor all medications you use.

Zosyn During Pregnancy and Breastfeeding

During pregnancy, Zosyn should be used only when prescribed. This medication may pass into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Zosyn (piperacillin and tazobactam for injection, USP) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


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Zosyn Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Call your doctor at once if you have:

  • severe stomach pain, diarrhea that is watery or bloody (even if it occurs months after your last dose);
  • confusion;
  • muscle twitching or stiffness, trouble walking;
  • a seizure;
  • low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing; or
  • low potassium level--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

  • diarrhea, constipation;
  • nausea;
  • headache; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zosyn (Piperacillin and Tazobactam Injection)


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Zosyn Professional Information


Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

During the initial clinical investigations, 2621 patients worldwide were treated with ZOSYN in phase 3 trials. In the key North American monotherapy clinical trials (n=830 patients), 90% of the adverse events reported were mild to moderate in severity and transient in nature. However, in 3.2% of the patients treated worldwide, ZOSYN was discontinued because of adverse events primarily involving the skin (1.3%), including rash and pruritus; the gastrointestinal system (0.9%), including diarrhea, nausea, and vomiting; and allergic reactions (0.5%).

Table 3: Adverse Reactions from ZOSYN 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%)

Nosocomial Pneumonia Trials

Two trials of nosocomial lower respiratory tract infections were conducted. In one study, 222 patients were treated with ZOSYN in a dosing regimen of 4.5 g every 6 hours in combination with an aminoglycoside and 215 patients were treated with imipenem/cilastatin (500 mg/500 mg q6h) in combination with an aminoglycoside. In this trial, treatment-emergent adverse events were reported by 402 patients, 204 (91.9%) in the piperacillin/tazobactam group and 198 (92.1%) in the imipenem/cilastatin group. Twenty-five (11.0%) patients in the piperacillin/tazobactam group and 14 (6.5%) in the imipenem/cilastatin group (p > 0.05) discontinued treatment due to an adverse event.

The second trial used a dosing regimen of 3.375 g given every 4 hours with an aminoglycoside.

Table 4: Adverse Reactions from ZOSYN Plus Aminoglycoside Clinical Trialsa

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%)
  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%)
a For adverse drug reactions that appeared in both studies the higher frequency is presented.

Other Trials


In a randomized, multicenter, controlled trial in 1200 adult critically ill patients, piperacillin/tazobactam was found to be a risk factor for renal failure (odds ratio 1.7, 95% CI 1.18 to 2.43), and associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs.1 [see WARNINGS AND PRECAUTIONS].


Studies of ZOSYN in pediatric patients suggest a similar safety profile to that seen in adults. In a prospective, randomized, comparative, open-label clinical trial of pediatric patients with severe intra-abdominal infections (including appendicitis and/or peritonitis), 273 patients were treated with ZOSYN (112.5 mg/kg every 8 hours) and 269 patients were treated with cefotaxime (50 mg/kg) plus metronidazole (7.5 mg/kg) every 8 hours. In this trial, treatment-emergent adverse events were reported by 146 patients, 73 (26.7%) in the ZOSYN group and 73 (27.1%) in the cefotaxime/metronidazole group. Six patients (2.2%) in the ZOSYN group and 5 patients (1.9%) in the cefotaxime/metronidazole group discontinued due to an adverse event.

Adverse Laboratory Events (Seen During Clinical Trials)

Of the trials reported, including that of nosocomial lower respiratory tract infections in which a higher dose of ZOSYN was used in combination with an aminoglycoside, changes in laboratory parameters include:

Hematologic - decreases in hemoglobin and hematocrit, thrombocytopenia, increases in platelet count, eosinophilia, leukopenia, neutropenia. These patients were withdrawn from therapy; some had accompanying systemic symptoms (e.g., fever, rigors, chills)

Coagulation - positive direct Coombs' test, prolonged prothrombin time, prolonged partial thromboplastin time

Hepatic - transient elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, bilirubin

Renal - increases in serum creatinine, blood urea nitrogen

Additional laboratory events include abnormalities in electrolytes (i.e., increases and decreases in sodium, potassium, and calcium), hyperglycemia, decreases in total protein or albumin, blood glucose decreased, gamma-glutamyltransferase increased, hypokalemia, and bleeding time prolonged.

Postmarketing Experience

In addition to the adverse drug reactions identified in clinical trials in Table 3 and Table 4, the following adverse reactions have been identified during post-approval use of ZOSYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary - hepatitis, jaundice

Hematologic - hemolytic anemia, agranulocytosis, pancytopenia

Immune - hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock)

Renal - interstitial nephritis

Nervous system disorders - seizure

Psychiatric disorders - delirium

Respiratory - eosinophilic pneumonia

Skin and Appendages - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, (DRESS), acute generalized exanthematous pustulosis (AGEP), dermatitis exfoliative

Additional Experience With Piperacillin

The following adverse reaction has also been reported for piperacillin for injection:

Skeletal - prolonged muscle relaxation [see DRUG INTERACTIONS].

Postmarketing experience with ZOSYN in pediatric patients suggests a similar safety profile to that seen in adults.

Read the entire FDA prescribing information for Zosyn (Piperacillin and Tazobactam Injection)

© Zosyn Patient Information is supplied by Cerner Multum, Inc. and Zosyn Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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