openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 1 · 1 matching rows.
adverse reactions
ADVERSE REACTIONS Adverse Events From Clinical Trials During the initial clinical investigations, 2621 patients worldwide were treated with piperacillin and tazobactam for injection 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, piperacillin and tazobactam 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 piperacillin and tazobactam, 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 piperacillin and tazobactam 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% 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 Hypersensitivity —anaphylaxis 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 Vision —photophobia Vascular (extracardiac) —flushing Nosocomial Pneumonia Trials In a completed study of nosocomial lower respiratory tract infections, 222 patients were treated with piperacillin and tazobactam 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 q 6 h) 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%) 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 piperacillin and tazobactam in combination with an aminoglycoside, adverse events that occurred in more than 1% 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 piperacillin and tazobactam 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 piperacillin and tazobactam 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 B 12 deficiency anemia, xerosis, and yeast in urine. Pediatrics Studies of piperacillin and tazobactam 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 piperacillin and tazobactam (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 piperacillin and tazobactam group and 73 (27.1%) in the cefotaxime/metronidazole group. Six patients (2.2%) in the piperacillin and tazobactam 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 piperacillin and tazobactam were: diarrhea (7%), 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 piperacillin and tazobactam 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 piperacillin and tazobactam, occurring under circumstances where causal relationship to piperacillin and tazobactam 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 piperacillin and tazobactam 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 piperacillin and tazobactam for injection 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 piperacillin and tazobactam 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 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. To report SUSPECTED ADVERSE EVENTS, contact FDA at 1-800-FDA-1088 or www.fda.gov .