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Zosyn Side Effects

Generic Name: piperacillin / tazobactam

Note: This page contains side effects data for the generic drug piperacillin / tazobactam. It is possible that some of the dosage forms included below may not apply to the brand name Zosyn.

For the Consumer

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

As well as its needed effects, piperacillin / tazobactam may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking piperacillin / tazobactam, check with your doctor or nurse immediately:

More common:
  • Diarrhea
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
Rare
  • 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

Minor Side Effects

Some piperacillin / tazobactam side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned 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
Rare
  • 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

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

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

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

Dermatologic

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

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]

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%): 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]

Renal

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]

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]

Hematologic

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

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, cholestatic 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

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]

Uncommon (0.1% to 1%): Anaphylaxis
Frequency not reported: 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]

Psychiatric

Common (1% to 10%): Insomnia
Frequency not reported: Hallucination, anxiety, confusion, aggressive reaction (combative), depression, agitation[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%): 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

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

Respiratory

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]

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

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

9. 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 43 (2006): 447-59

10. 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 83 (1994): 280-6

11. Mandell GL "In vitro microbiology and pharmacokinetics of piperacillin." Clin Ther 7 (1985): 37-44

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24. 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 69 (2012): 1109

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It is possible that some side effects of Zosyn may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

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