Medication Guide App

Piperacillin / tazobactam Side Effects

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

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

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. In clinical trials, piperacillin-tazobactam was discontinued in 3.2% of patients due to dermatologic effects (including rash and pruritus; 1.3%), gastrointestinal effects (including diarrhea, nausea, and vomiting; 0.9%), and allergic reactions (0.5%). In nosocomial pneumonia trials, 11% of patients discontinued piperacillin-tazobactam due to a side effect.[Ref]

Gastrointestinal

Diarrhea associated with piperacillin-tazobactam was usually self-limited. There were case reports of pseudomembranous colitis in patients receiving piperacillin-tazobactam. 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 (up to 8.4%), nausea (up to 6.9%), oral candidiasis (3.9%), vomiting (up to 3.3%), dyspepsia (up to 3.3%), abdominal pain (up to 1.8%)
Uncommon (0.1% to 1%): Pseudomembranous colitis (1% or less), stomatitis (1% or less)
Frequency not reported: Oral thrush/moniliasis, hiccough, stool changes, enlarged abdomen, flatulence, anorexia, duodenal ulcer, melena, gastrointestinal hemorrhage, gastritis, ileus, taste perversion, ulcerative stomatitis, colitis, dry mouth, dysphagia, glossitis, fecal incontinence, gastric ulcer, pancreatitis, Clostridium difficile-associated diarrhea[Ref]

Nervous system

Neurotoxicity has been reported with piperacillin.

Piperacillin may have neuromuscular blocking properties, and has been noted to enhance the effect of neuromuscular blocking agents.[Ref]

Common (1% to 10%): Headache (up to 7.7%), insomnia (up to 6.6%)
Frequency not reported: Agitation, dizziness, tremor, convulsions, vertigo, syncope, central nervous system depression, grand mal convulsion, cerebrovascular accident, somnolence, tinnitus, hypertonia, stupor, deafness, tonic-clonic seizure, neurotoxicity, effect of neuromuscular blocking agents enhanced[Ref]

Dermatologic

A patient with mononucleosis developed a nonallergic rash after 3 weeks of treatment with piperacillin-tazobactam 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 piperacillin-tazobactam.

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

Petechial rash or purpura due to thrombocytopenia, exanthematous pustulosis, bullous dermatosis, erythema nodosum, exanthems, exfoliative dermatitis, urticaria, pruritus, vesiculation, Jarisch-Herxheimer reaction, Stevens-Johnson syndrome, purpura, and vasculitis have been reported with piperacillin.[Ref]

Common (1% to 10%): Rash (including maculopapular, bullous, and urticarial; up to 4.2%), pruritus (up to 3.2%)
Frequency not reported: Erythematous rash, excoriations, sweating, diaphoresis, fungal dermatitis, exanthemous pustulosis, drug-induced petechial rash, eczematoid rash, petechial rash or purpura due to thrombocytopenia, bullous dermatosis, erythema nodosum, exanthems, exfoliative dermatitis, urticaria, vesiculation, Jarisch-Herxheimer reaction, purpura, vasculitis
Postmarketing reports: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis[Ref]

Other

Piperacillin therapy has been associated with an increased incidence of fever in patients with cystic fibrosis.[Ref]

Common (1% to 10%): Fever (up to 3.2%), candidiasis (up to 1.8%)
Uncommon (0.1% to 1%): Rigors (1% or less), flushing (1% or less)
Frequency not reported: Pain, edema, generalized edema, peripheral edema, moniliasis, chest pain, back pain, malaise, asthenia, earache, xerosis, decreased drug level, false-positive tests for Aspergillus galactomannan antigenemia, Candidal superinfections[Ref]

Renal

A 51-year-old woman developed an acute onset of renal dysfunction after 6 days of therapy with piperacillin-tazobactam. The patient also had an elevated serum creatinine, lumbar pain, rash, fever, arthralgias, and eosinophiluria. The piperacillin-tazobactam was discontinued and the patient's symptoms improved to baseline after 21 days of prednisone.[Ref]

Common (1% to 10%): Increased blood creatinine (1.8%), increased blood urea nitrogen (1.8%)
Uncommon (0.1% to 1%): Renal failure (1% or less)
Frequency not reported: Increased serum creatinine, acute onset of renal dysfunction (with elevated serum creatinine, lumbar pain, rash, fever, arthralgias, and eosinophiluria), acute kidney failure, abnormal kidney function
Postmarketing reports: Interstitial nephritis[Ref]

Hematologic

Common (1% to 10%): Thrombocythemia (1.4%)
Uncommon (0.1% to 1%): Anemia (1% or less), thrombocytopenia (1% or less), eosinophilia (1% or less), purpura (1% or less)
Rare (less than 0.1%): Reversible bone marrow suppression
Frequency not reported: Leukopenia, hypochromic anemia, leukocytosis, decreased prothrombin, ecchymosis, decreased hemoglobin and hematocrit, increased platelet count, neutropenia, positive direct Coombs' test, prolonged prothrombin time, prolonged partial thromboplastin time, prolonged bleeding time, thrombocytosis, vitamin B12 deficiency anemia, bleeding disorders
Postmarketing reports: Hemolytic anemia, agranulocytosis, pancytopenia[Ref]

Reversible bone marrow suppression was rare and usually limited to prolonged therapy with piperacillin.

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.

Bleeding disorders, neutropenia, thrombocytopenia, and hemolytic anemia have been reported with piperacillin.[Ref]

Hepatic

Hepatotoxicity has been reported with piperacillin.[Ref]

Common (1% to 10%): Abnormal liver function test (1.4%)
Uncommon (0.1% to 1%): Increased aspartate aminotransferase (1% or less), increased alanine aminotransferase (1% or less)
Frequency not reported: Transient elevations of AST (SGOT), transient elevations of ALT (SGPT), transient elevations of bilirubin, increased gamma-glutamyltransferase, cholestatic jaundice, hepatotoxicity
Postmarketing reports: Hepatitis, jaundice[Ref]

Cardiovascular

Common (1% to 10%): Phlebitis (1.3%), thrombophlebitis (up to 1.3%), hypotension (up to 1.3%)
Frequency not reported: Hypertension, cardiac arrest, supraventricular tachycardia, tachycardia, ventricular tachycardia, bradycardia, arrhythmia, atrial fibrillation, ventricular fibrillation, cardiac failure, circulatory failure, myocardial infarction, 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.

Hypersensitivity reactions and anaphylactic/anaphylactoid reactions (resulting in shock and fatalities) have been reported with piperacillin.[Ref]

Uncommon (0.1% to 1%): Anaphylaxis (1% or less)
Frequency not reported: Allergic reactions
Postmarketing reports: Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock)[Ref]

Metabolic

Uncommon (0.1% to 1%): Hypoglycemia (1% or less), hypokalemia (1% or less), increased alkaline phosphatase (1% or less)
Frequency not reported: Transient elevations of alkaline phosphatase, symptomatic hypoglycemia, thirst, acidosis, dehydration, gout, hypernatremia, hypokalemia, hyponatremia, hypophosphatemia, hyperglycemia, decreased total protein or albumin, hypomagnesemia, abnormalities in electrolytes (e.g., increased and decreased sodium, potassium, and calcium), decreased blood glucose, fluid overload, electrolyte disturbances, acid-base disturbances[Ref]

Electrolyte and acid-base disturbances have been reported with piperacillin.[Ref]

Respiratory

Uncommon (0.1% to 1%): Epistaxis (1% or less)
Frequency not reported: Pleural effusion, pneumothorax, rhinitis, dyspnea, pharyngitis, pulmonary edema, bronchospasm, coughing, pulmonary embolism, hyperventilation, respiratory disorder, increased cough, atelectasis, hemoptysis, hypoxia[Ref]

Local

Uncommon (0.1% to 1%): Injection site reaction (1% or less)
Frequency not reported: Injection site edema, injection site pain, inflammation at injection site, local reaction to procedure[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Myalgia (1% or less), arthralgia (1% or less)
Frequency not reported: Prolonged muscle relaxation[Ref]

Prolonged muscle relaxation has been reported with piperacillin.[Ref]

Psychiatric

Frequency not reported: Anxiety, confusion, hallucination, aggressive reaction (combative), depression[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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2. Lau WK, Mercer D, Itani KM, et al. "A Randomized, Open-Label, Comparative Study of Piperacillin/Tazobactam Administered by Continuous Infusion vs. Intermittent Infusion for the Treatment of Hospitalized Patients with Complicated Intra-Abdominal Infection." Antimicrob Agents Chemother (2006):

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6. 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

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8. 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

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13. Wilcox MH, Freeman J, Fawley W, et al. "Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea." J Antimicrob Chemother 54 (2004): 168-72

14. Wise R "The efficacy and safety of piperacillin / tazobactam in the therapy of bacteraemia." J Antimicrob Chemother 31 (1993): 97-104

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19. Bassilios N, Restoux A, Vincent F, Rondeau E, Sraer JD "Piperacillin/Tazobactam inducing seizures in a hemodialysed patient." Clin Nephrol 58 (2002): 327-8

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21. Grieco T, Cantisani C, Innocenzi D, Bottoni U, Calvieri S "Acute generalized exanthematous pustulosis caused by piperacillin / tazobactam." J Am Acad Dermatol 52 (2005): 732-3

22. 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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