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Home > Drugs > Beta-lactamase inhibitors > Piperacillin and tazobactam > Piperacillin and tazobactam Side Effects
Beta-lactamase inhibitors

Piperacillin / tazobactam Side Effects

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

Serious side effects

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

  • 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
  • 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
  • trouble breathing

Rare

  • Agitation
  • bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
  • 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, cramps, 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
  • stomach cramps, pain, or tenderness
  • 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
  • black, tarry stools
  • blistering, peeling, or loosening of the skin
  • bloody or cloudy urine
  • high fever
  • joint or muscle pain
  • light-colored stools
  • loss of bladder control
  • mental status changes
  • muscle spasm or jerking of all extremities
  • pale skin
  • red irritated eyes
  • red skin lesions, often with a purple center
  • seizures
  • shakiness and unsteady walk, unsteadiness, trembling, or other problems with muscle control or coordination
  • sudden loss of consciousness
  • swelling of the feet or lower legs
  • swollen, painful, or tender lymph glands in the neck, armpit, or groin
  • trouble breathing
  • upper right abdominal or stomach pain
  • yellow eyes or skin

Other side effects

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

  • Constipation
  • 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

Rare

  • Body aches or pain
  • change in taste or bad unusual or unpleasant (after) taste
  • feeling of constant movement of self or surroundings
  • sensation of spinning
  • severe sleepiness
  • 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%): Stomatitis

Rare (0.01% to 0.1%): Pseudomembranous colitis

Frequency not reported: Dry mouth, Clostridioides 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

Postmarketing reports: Seizures

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%): Urticaria

Rare (0.01% to 0.1%): Purpura, 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%): Flushing, chills

Rare (0.01% to 0.1%): Rigors

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

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

Rare (0.01% to 0.1%): Renal failure, tubulointerstitial nephritis

Frequency not reported: Increased serum creatinine, nephrotoxicity, 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]

In a randomized, multicenter, controlled trial in critically ill adults (n=1200), this drug was found to be a risk factor for renal failure and associated with delayed recovery of renal function as compared to other beta-lactam antibacterial agents.

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]

Hematologic

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%): Leukopenia, neutropenia, prolonged prothrombin time

Rare (0.01% to 0.1%): Anemia, eosinophilia, 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]

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

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

Frequency not reported: Anaphylaxis, 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]

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]

Psychiatric

Common (1% to 10%): Insomnia

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

Postmarketing reports: Delirium[Ref]

Metabolic

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

Frequency not reported: Hypoglycemia, 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]

Hypokalemia has been reported when high doses of piperacillin were administered to patients with liver disease and patients using cytotoxic therapy or diuretics.[Ref]

Respiratory

Rare (0.01% to 0.1%): 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]

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