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Zosyn Side Effects

Generic Name: piperacillin / tazobactam

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

For the Consumer

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

Side effects requiring immediate medical attention

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

  • Bladder pain
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • blurred vision
  • burning upper abdominal or stomach pain
  • changes in urination
  • chest pain
  • confusion
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fever or sweating
  • headache
  • inflammation or swelling at the injection site
  • lower back or side pain
  • nausea or vomiting
  • pain, tenderness, or swelling of the foot or leg
  • pain, warmth, or burning in the fingers, toes, and legs
  • problems with vision or hearing
  • skin rash
  • slow or fast heartbeat
  • troubled breathing


  • Abdominal or stomach cramps, pain, or tenderness
  • agitation
  • bone pain
  • bruising
  • chills
  • cold sweats
  • cough
  • deep or fast breathing with dizziness
  • depression
  • diarrhea, watery and severe, which may also be bloody
  • drowsiness
  • dry mouth
  • hives
  • hostility
  • itching of the vagina or genital area
  • lethargy
  • muscle pain or cramps
  • muscle stiffness or twitching
  • nightmares
  • numbness or tingling in the hands, feet, or lips
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • sore throat
  • sores, ulcers, or white spots on the lips, tongue, or inside the mouth
  • swollen glands
  • temporary blindness
  • thick, white vaginal discharge with no odor or with a mild odor
  • total body jerking
  • unexplained weight loss
  • unusual bleeding or bruising

Incidence not known

  • Back or leg pain
  • blistering, peeling, or loosening of the skin
  • high fever
  • joint or muscle pain
  • red skin lesions, often with a purple center
  • yellow eyes or skin

Side effects not requiring immediate medical attention

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

  • Difficulty having a bowel movement (stool)
  • trouble sleeping

Less common

  • Acid or sour stomach
  • cracks in the skin at the corners of the mouth
  • hiccup
  • irritation and redness of the skin
  • runny nose
  • sneezing
  • stuffy nose
  • white patches in the mouth or on the tongue


  • Body aches or pain
  • burning feeling in the chest or stomach
  • change in taste or bad unusual or unpleasant (after) taste
  • feeling of constant movement of self or surroundings
  • sensation of spinning
  • severe sleepiness
  • tenderness in stomach area
  • vision changes
  • voice changes

For Healthcare Professionals

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


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]


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]

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%): Pseudomembranous colitis, stomatitis

Frequency not reported: Dry mouth, Clostridium 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]

Nervous system

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

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


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

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

Uncommon (0.1% to 1%): Purpura, urticaria

Rare (0.01% to 0.1%): 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


-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]


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%): Rigors, flushing, chills

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]


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

Uncommon (0.1% to 1%): Renal failure

Rare (0.01% to 0.1%): Tubulointerstitial nephritis

Frequency not reported: Increased serum creatinine, 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]

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]


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]

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

Uncommon (0.1% to 1%): Anemia, eosinophilia, leukopenia, neutropenia, prolonged prothrombin time

Rare (0.01% to 0.1%): 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


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

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


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, cholestatic jaundice


-Frequency not reported: Hepatotoxicity[Ref]


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]


Uncommon (0.1% to 1%): Anaphylaxis

Frequency not reported: Allergic reactions

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


-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]


Common (1% to 10%): Insomnia

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


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

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


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

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%): 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]


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]


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

Frequency not reported: Muscular weakness, prolonged muscle relaxation


-Frequency not reported: Prolonged muscle relaxation[Ref]


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]


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


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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.