ZOSYN INJECTION SIDE EFFECTS
- Generic Name: piperacillin and tazobactam pharmacy bulk vial
- Brand Name: Zosyn Injection
SIDE EFFECTS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
During the initial clinical investigations, 2621 patients worldwide were treated with ZOSYN in phase 3 trials. In the key North American monotherapy 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, ZOSYN 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%).
Table 1: Adverse Reactions from ZOSYN Monotherapy Clinical Trials
| System Organ Class Adverse Reaction |
| Gastrointestinal disorders |
| Diarrhea (11.3%) |
| Constipation (7.7%) |
| Nausea (6.9%) |
| Vomiting (3.3%) |
| Dyspepsia (3.3%) |
| Abdominal pain (1.3%) |
| General disorders and administration site conditions |
| Fever (2.4%) |
| Injection site reaction ( ≤ 1%) |
| Rigors ( ≤ 1%) |
| Immune system disorders |
| Anaphylaxis ( ≤ 1%) |
| Infections and infestations |
| Candidiasis (1.6%) |
| Pseudomembranous colitis ( ≤ 1%) |
| Metabolism and nutrition disorders |
| Hypoglycemia ( ≤ 1%) |
| Musculoskeletal and connective tissue disorders |
| Myalgia( ≤ 1%) |
| Arthralgia ( ≤ 1%) |
| Nervous system disorders |
| Headache (7.7%) |
| Psychiatric disorders |
| Insomnia (6.6%) |
| Skin and subcutaneous tissue disorders |
| Rash (4.2%, including maculopapular, bullous, and urticarial) |
| Pruritus (3.1%) |
| Purpura ( ≤ 1%) |
| Vascular disorders |
| Phlebitis (1.3%) |
| Thrombophlebitis ( ≤ 1%) |
| Hypotension ( ≤ 1%) |
| Flushing ( ≤ 1%) |
| Respiratory, thoracic and mediastinal disorders |
| Epistaxis ( ≤ 1%) |
Nosocomial Pneumonia Trials
Two trials of nosocomial lower respiratory tract infections were conducted. In one study, 222 patients were treated with ZOSYN 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 q6h) 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 (11.0%) 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. The second trial used a dosing regimen of 3.375 g given every 4 hours with an aminoglycoside.
Table 2: Adverse Reactions from ZOSYN Plus Aminoglycoside Clinical Trials*
| System Organ Class Adverse Reaction |
| Blood and lymphatic system disorders |
| Thrombocythemia (1.4%) |
| Anemia ( ≤ 1%) |
| Thrombocytopenia ( ≤ 1%) |
| Eosinophilia ( ≤ 1%) |
| Gastrointestinal disorders |
| Diarrhea (20%) |
| Constipation (8.4%) |
| Nausea (5.8%) |
| Vomiting (2.7%) |
| Dyspepsia (1.9%) |
| Abdominal pain (1.8%) |
| Stomatitis ( ≤ 1%) |
| General disorders and administration site conditions |
| Fever (3.2%) |
| Injection site reaction ( ≤ 1%) |
| Infections and infestations |
| Oral candidiasis (3.9%) |
| Candidiasis (1.8%) |
| Investigations |
| BUN increased (1.8%) |
| Blood creatinine increased (1.8%) |
| Liver function test abnormal (1.4%) |
| Alkaline phosphatase increased ( ≤ 1%) |
| Aspartate aminotransferase increased ( ≤ 1%) |
| Alanine aminotransferase increased ( ≤ 1%) |
| Metabolism and nutrition disorders |
| Hypoglycemia ( ≤ 1%) |
| Hypokalemia ( ≤ 1%) |
| Nervous system disorders |
| Headache (4.5%) |
| Psychiatric disorders |
| Insomnia (4.5%) |
| Renal and urinary disorders |
| Renal failure ( ≤ 1%) |
| Skin and subcutaneous tissue disorders |
| Rash (3.9%) |
| Pruritus (3.2%) |
| Vascular disorders |
| Thrombophlebitis (1.3%) |
| Hypotension (1.3%) |
| *For adverse drug reactions that appeared in both studies the higher frequency is presented. |
Pediatrics
Studies of ZOSYN 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 intraabdominal infections (including appendicitis and/or peritonitis), 273 patients were treated with ZOSYN (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 ZOSYN group and 73 (27.1%) in the cefotaxime/metronidazole group. Six patients (2.2%) in the ZOSYN group and 5 patients (1.9%) in the cefotaxime/metronidazole group discontinued due to an adverse event.
Adverse Laboratory Events (Seen During Clinical Trials)
Of the trials reported, including that of nosocomial lower respiratory tract infections in which a higher dose of ZOSYN was used in combination with an aminoglycoside, changes in laboratory parameters include:
Hematologic – decreases in hemoglobin and hematocrit, thrombocytopenia, increases in platelet count, eosinophilia, leukopenia, neutropenia. 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
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.
Post-Marketing Experience
In addition to the adverse drug reactions identified in clinical trials in Table 3 and Table 4, the following adverse reactions have been identified during post-approval use of ZOSYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hepatobiliary – hepatitis, jaundice
Hematologic – hemolytic anemia, agranulocytosis, pancytopenia
Immune – hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock)
Renal – interstitial nephritis
Respiratory – eosinophilic pneumonia
Skin and Appendages – erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), dermatitis exfoliative
Additional Experience With piperacillin
The following adverse reaction has also been reported for piperacillin for injection:
Skeletal – prolonged muscle relaxation.
Post-marketing experience with ZOSYN in pediatric patients suggests a similar safety profile to that seen in adults.
SRC: NLM .