Piperacillin And Tazobactam Side Effects

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity Adverse Reactions [see Warnings and Precautions ( 5.1 )] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.2 )] • Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions ( 5.3 )] • Rhabdomyolysis [ see Warnings and Precautions (5.4) ] • Hematologic Adverse Reactions [see Warnings and Precautions ( 5.5 )] • Central Nervous System Adverse Reactions [see Warnings and Precautions ( 5.6 )] • Nephrotoxicity in Critically Ill Patients [see Warnings and Precautions ( 5.7 )] • Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions ( 5.9 )] The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache and insomnia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact WG Critical Care, LLC at 1-866-562-4708 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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.

Clinical Trials in Adult Patients During the initial clinical investigations, 2621 patients worldwide were treated with piperacillin and tazobactam 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, 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 Reactions from Piperacillin and Tazobactam 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 piperacillin and tazobactam for injection 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 every 6 hours) in combination with an aminoglycoside.