Prof. Chung-Ang University Seoul, Republic of Korea
Background: Electrolyte imbalances can cause a variety of medical problems depending on the involved electrolytes and severity. Piperacillin/tazobactam (TZP) is the most widely prescribed safe antibiotic agent for moderate-to-severe infections, but TZP-associated electrolyte disorders (EDs), have been widely reported.Objectives: To detect signals of TZP-associated EDs in relation to all other drugs, a disproportionality analysis using a self-reporting real-world database was conducted. Initially detected EDs were analyzed to identify their meaningful association with TZP compared to other penicillins (PCNs). Also, factors affecting EDs were explored.
Methods: For EDs related to TZP (2004~2018), the US Food and Drug Administration Adverse Event Reporting System (FAERS) and three data-mining indices—the proportional reporting ratio (PRR), the reporting odds ratio (ROR), and the information component (IC)—compared to all other drugs. If one of the three criteria of the indices was met, then signals were defined. Focusing on the signals detected in the first analysis, further disproportionality analyses compare to other penicillins were conducted under the same pathway.
Results: During the target period, a total of 11,933,093 spontaneous reports with 217,011,136 drug–adverse events (AEs) were available on FAERS database. The final drug–AEs amounted to 64,606,404 from 10,014,903 reports and a total of 8829 reports related to TZP with 30,207 TZP–AEs were retrieved. Among 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. These results will provide valuable real-world TZD-AEs and improving their safe use. Through this long-period study used the FAERS database, which includes worldwide reports, we can guarantee the representativeness of the international population.
Conclusions: In this first study to evaluate TZP-related EDs using a pharmacovigilance database, a disproportionality analysis using the FAERS database and found that hypokalemia was the only signal of TZP-related EDs. Even though the presence of other ED-related reports, unexpected signals of EDs for TZP were not detected.Compared with other penicillins, TZP was significantly associated with hypokalemia.
