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Zosyn (Piperacillin / Tazobactam) - Side Effects and Adverse Reactions



Adverse Events From Clinical Trials

During the initial clinical investigations, 2621 patients worldwide were treated with ZOSYN in phase 3 trials. In the key North American 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%).

Adverse local reactions that were reported, irrespective of relationship to therapy with ZOSYN, were phlebitis (1.3%), injection site reaction (0.5%), pain (0.2%), inflammation (0.2%), thrombophlebitis (0.2%), and edema (0.1%).

Based on patients from the North American trials (n=1063), the events with the highest incidence in patients, irrespective of relationship to ZOSYN therapy, were diarrhea (11.3%); headache (7.7%); constipation (7.7%); nausea (6.9%); insomnia (6.6%); rash (4.2%), including maculopapular, bullous, urticarial, and eczematoid; vomiting (3.3%); dyspepsia (3.3%); pruritus (3.1%); stool changes (2.4%); fever (2.4%); agitation (2.1%); pain (1.7%); moniliasis (1.6%); hypertension (1.6%); dizziness (1.4%); abdominal pain (1.3%); chest pain (1.3%); edema (1.2%); anxiety (1.2%); rhinitis (1.2%); and dyspnea (1.1%).

Additional adverse systemic clinical events reported in 1.0% or less of the patients in the initial North American trials are listed below within each body system.

Autonomic nervous system—hypotension, ileus, syncope

Body as a whole—rigors, back pain, malaise

Cardiovascular—tachycardia, including supraventricular and ventricular; bradycardia; arrhythmia, including atrial fibrillation, ventricular fibrillation, cardiac arrest, cardiac failure, circulatory failure, myocardial infarction

Central nervous system—tremor, convulsions, vertigo

Gastrointestinal—melena, flatulence, hemorrhage, gastritis, hiccough, ulcerative stomatitis

Pseudomembranous colitis was reported in one patient during the clinical trials. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. (see WARNINGS.)

Hearing and Vestibular system—tinnitus


Metabolic and Nutritional—symptomatic hypoglycemia, thirst

Musculoskeletal—myalgia, arthralgia

Platelets, Bleeding, Clotting—mesenteric embolism, purpura, epistaxis, pulmonary embolism (see PRECAUTIONS, General.)

Psychiatric—confusion, hallucination, depression

Reproductive, Female—leukorrhea, vaginitis

Respiratory—pharyngitis, pulmonary edema, bronchospasm, coughing

Skin and Appendages—genital pruritus, diaphoresis

Special senses—taste perversion

Urinary—retention, dysuria, oliguria, hematuria, incontinence


Vascular (extracardiac)—flushing

Nosocomial Pneumonia Trials

In a completed study of nosocomial lower respiratory tract infections, 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.

In this study of ZOSYN in combination with an aminoglycoside, adverse events that occurred in more than 1% of patients and were considered by the investigator to be drug-related were: diarrhea (17.6%), fever (2.7%), vomiting (2.7%), urinary tract infection (2.7%), rash (2.3%), abdominal pain (1.8%), generalized edema (1.8%), moniliasis (1.8%), nausea (1.8%), oral moniliasis (1.8%), BUN increased (1.8%), creatinine increased (1.8%), peripheral edema (1.8%), abdomen enlarged (1.4%), headache (1.4%), constipation (1.4%), liver function tests abnormal (1.4%), thrombocythemia (1.4%), excoriations (1.4%), and sweating (1.4%).

Drug-related adverse events reported in 1% or less of patients in the nosocomial pneumonia study of ZOSYN with an aminoglycoside were: acidosis, acute kidney failure, agitation, alkaline phosphatase increased, anemia, asthenia, atrial fibrillation, chest pain, CNS depression, colitis, confusion, convulsion, cough increased, thrombocytopenia, dehydration, depression, diplopia, drug level decreased, dry mouth, dyspepsia, dysphagia, dyspnea, dysuria, eosinophilia, fungal dermatitis, gastritis, glossitis, grand mal convulsion, hematuria, hyperglycemia, hypernatremia, hypertension, hypertonia, hyperventilation, hypochromic anemia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia, hypoxia, ileus, injection site edema, injection site pain, injection site reaction, kidney function abnormal, leukocytosis, leukopenia, local reaction to procedure, melena, pain, prothrombin decreased, pruritus, respiratory disorder, SGOT increased, SGPT increased, sinus bradycardia, somnolence, stomatitis, stupor, tremor, tachycardia, ventricular extrasystoles, and ventricular tachycardia.

In a previous nosocomial pneumonia study conducted with a dosing regimen of 3.375 g given every 4 hours with an aminoglycoside, the following adverse events, irrespective of drug relationship, were observed: diarrhea (20%); constipation (8.4%); agitation (7.1%); nausea (5.8%); headache (4.5%); insomnia (4.5%); oral thrush (3.9%); erythematous rash (3.9%); anxiety (3.2%); fever (3.2%); pain (3.2%); pruritus (3.2%); hiccough (2.6%); vomiting (2.6%); dyspepsia (1.9%); edema (1.9%); fluid overload (1.9%); stool changes (1.9%); anorexia (1.3%); cardiac arrest (1.3%); confusion (1.3%); diaphoresis (1.3%); duodenal ulcer (1.3%); flatulence (1.3%); hypertension (1.3%); hypotension (1.3%); inflammation at injection site (1.3%); pleural effusion (1.3%); pneumothorax (1.3%); rash, not otherwise specified (1.3%); supraventricular tachycardia (1.3%); thrombophlebitis (1.3%); and urinary incontinence (1.3%).

Adverse events irrespective of drug relationship observed in 1% or less of patients in the above study with ZOSYN and an aminoglycoside included: aggressive reaction (combative), angina, asthenia, atelectasis, balanoposthitis, cerebrovascular accident, chest pain, conjunctivitis, deafness, dyspnea, earache, ecchymosis, fecal incontinence, gastric ulcer, gout, hemoptysis, hypoxia, pancreatitis, perineal irritation/pain, urinary tract infection with trichomonas, vitamin B12 deficiency anemia, xerosis, and yeast in urine.


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.

In this study, adverse events that were reported in more than 1% of patients, irrespective of relationship to therapy with ZOSYN, were: diarrhea (7.0%), fever (4.8%), vomiting (3.7%), local reaction (3.3%), abscess (2.2%), sepsis (2.2%), abdominal pain (1.8%), infection (1.8%), bloody diarrhea (1.1%), pharyngitis (1.5%), constipation (1.1%), and SGOT increase (1.1%).

Adverse events reported in 1% or less of pediatric patients receiving ZOSYN are consistent with adverse events reported in adults.

Additional controlled studies in pediatric patients showed a similar safety profile as that described above.

Post-Marketing Experience

Additional adverse events reported from worldwide marketing experience with ZOSYN, occurring under circumstances where causal relationship to ZOSYN is uncertain:

Gastrointestinal—hepatitis, cholestatic jaundice

Hematologic—hemolytic anemia, anemia, thrombocytosis, agranulocytosis, pancytopenia

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

Infections––candidal superinfections

Renal—interstitial nephritis, renal failure

Skin and Appendages—erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

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

Adverse Laboratory Events (Seen During Clinical Trials)

Of the studies 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, without regard to drug relationship, include:

Hematologic—decreases in hemoglobin and hematocrit, thrombocytopenia, increases in platelet count, eosinophilia, leukopenia, neutropenia. The leukopenia/neutropenia associated with ZOSYN administration appears to be reversible and most frequently associated with prolonged administration, i.e., ≥ 21 days of therapy. 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

Urinalysis—proteinuria, hematuria, pyuria

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.

The following adverse reaction has also been reported for PIPRACIL® (piperacillin for injection):

Skeletal—prolonged muscle relaxation (see PRECAUTIONS, Drug Interactions.)

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


Below is a sample of reports where side effects / adverse reactions may be related to Zosyn. The information is not vetted and should not be considered as verified clinical evidence.

Possible Zosyn side effects / adverse reactions in 84 year old male

Reported by a physician from Japan on 2011-10-07

Patient: 84 year old male

Reactions: Blood Bilirubin Increased, Jaundice, Alanine Aminotransferase Increased, Aspartate Aminotransferase Increased, Liver Disorder

Adverse event resulted in: hospitalization

Suspect drug(s):
Doripenem Monohydrate
    Indication: Pneumonia
    Start date: 2011-09-02
    End date: 2011-09-08

    Indication: Pneumonia
    Start date: 2011-09-08
    End date: 2011-09-15

    Indication: Pneumonia
    Start date: 2011-08-31
    End date: 2011-09-01

Possible Zosyn side effects / adverse reactions in 86 year old male

Reported by a pharmacist from Japan on 2011-10-13

Patient: 86 year old male weighing 54.0 kg (118.8 pounds)

Reactions: Renal Failure Acute

Adverse event resulted in: hospitalization

Suspect drug(s):

Other drugs received by patient: Candesartan Cilexetil; Lasix; Slow-K; Lendormin; Allopurinol; Valproate Sodium

Possible Zosyn side effects / adverse reactions in 69 year old female

Reported by a pharmacist from Japan on 2011-10-13

Patient: 69 year old female weighing 39.0 kg (85.8 pounds)

Reactions: Pneumonia Aspiration, Cardiac Failure, Hepatic Enzyme Increased

Adverse event resulted in: death

Suspect drug(s):
    Indication: Pneumonia

    Dosage: 1.5 g, 2x/day
    Indication: Pneumonia
    Start date: 2011-07-21
    End date: 2011-07-26

    Dosage: 4.5 g, 2x/day
    Indication: Pyrexia
    Start date: 2011-06-27
    End date: 2011-07-10

Other drugs received by patient: Bisolvon; Strong NEO-Minophagen C; Intrafat; Humulin R; Tathion; TPN Electrolytes IN Plastic Container; Liveres; Nicardipine HCL

See index of all Zosyn side effect reports >>

Drug label data at the top of this Page last updated: 2013-07-15

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