Electrolyte Disorders Associated with Piperacillin/Tazobactam: A Pharmacovigilance Study Using the FAERS Database

Abstract

Electrolyte disorders (EDs) can disrupt normal bodily functions and lead to life-threatening complications. We evaluated whether piperacillin–tazobactam (TZP), a widely used antibiotic for moderate-to-severe infections, is associated with electrolyte imbalances via a disproportionality analysis of a self-reporting pharmacovigilance database. We searched The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 2004 to 2018 for EDs related to TZP and calculated three data-mining indices—the proportional reporting ratio (PRR), the reporting odds ratio (ROR), and the information component (IC)—compared to all other drugs. Signals were defined when one of the three criteria of the indices was met. For the signals detected in the initial analysis, further disproportionality analyses in relation to other penicillins were conducted using the same method. A total of 9829 reports related to TZP with 36,207 TZP–adverse event pairs were retrieved. Among 10 EDs, hypokalemia was detected as the only significant signal (PRR 2.61; ROR 2.61, 95% CI: 2.17–3.14; IC 95% lower CI: 1.11) compared to all other drugs. Compared with other penicillins, hypokalemia remained a significant signal for TZP using IC (95% lower CI: 0.26). In conclusion, TZP was significantly associated with hypokalemia.

Real-World Data in Pharmacovigilance Database Provides a New Perspective for Understanding the Risk of Clostridium difficile Infection Associated with Antibacterial Drug Exposure

“…In pharmacovigilance practice, according to finding disproportionality between drug usage and adverse events (AEs) occurrence in the pharmacovigilance databases, these real-world AEs data can provide a reference for identifying the potential culprit drugs of specific AE, optimizing the drug selection for individual patients and exploring the interaction between drugs [17]. In terms of exploring the safety profile of antibiotics by using the pharmacovigilance database, Seo, H. and Kim, E. elaborated on the risk characteristics of electrolyte disorders associated with piperacillin/tazobactam and detected the significant signal of hypokalemia for piperacillin/tazobactam compared with other penicillins [18]; Patek, T.M. et al investigated acute kidney injury reports related to antibiotics in the FDA Adverse Event Reporting System (FAERS) database and found 14 classes of antibiotics that were significantly associated with acute kidney injury [19].…”