Safety profile of piperacillin/tazobactam in phase I and III clinical studies.

The safety of piperacillin/tazobactam was investigated in Phase I and Phase III clinical studies. In 22 Phase I pharmacokinetic studies, 242 healthy subjects and 232 patients were given single and multiple doses of piperacillin/tazobactam, piperacillin alone, tazobactam alone, and/or placebo. Interaction with tobramycin and vancomycin was also studied. Of 1201 patients enrolled in Phase III trials, 944 received piperacillin 4 g plus tazobactam 500 mg every 8 h for lower respiratory tract infections, complicated urinary tract infections, skin and soft tissue infections, and intra-abdominal infections, or piperacillin 2 g plus tazobactam 500 mg 8 hourly for less severe infections; 90 patients received imipenem/cilastatin as a comparative regimen. Piperacillin 4 g and tazobactam 500 mg were also administered every 6 h with an aminoglycoside to 167 patients with pulmonary infection or neutropenia and bacterial infection. In all trials, piperacillin/tazobactam was found to be safe and well tolerated. One death was deemed possibly drug-related. Thirty-eight patients were withdrawn from the trials because of adverse experiences, most often diarrhoea and allergic skin reactions. The commonest laboratory abnormalities related to liver function. The safety of piperacillin/tazobactam appears similar to that of other beta-lactam/beta-lactamase inhibitor combinations.