(P-274) Detecting Drug-drug Interaction Signal of Concomitant Use of Tramadol and SSRI Using Korea Adverse Event Reporting System Database

Background: Tramadol is a commonly prescribed opioid analgesic and patients who use opioid consistently are more liable to take antidepressants such as selective serotonin reuptake inhibitor (SSRI). There were no studies on drug-drug interaction (DDI) between tramadol and SSRI using Korea adverse events reporting system (KAERS) database.

Objectives: To present the number of adverse events (AEs) reports by concomitant use of tramadol and SSRI and detect signals of AEs of DDI using KAERS database.

Methods: We used the KAERS database which is a nationwide database of AEs reports from 2015 to 2019. Concomitant use was defined as the simultaneous reports of tramadol (WHO-ATC, N02AX02) and SSRI (N06AB) by report number without considering the timing of administration. Ω Shrinkage Measure Model and Chi-Square Statistics Model were used to calculate the criteria for detecting AEs signal resulting from the concomitant use of tramadol and SSRI. We defined signal using three indices: Ω025 (frequentist) > 0, Ω025 (Bayesian) > 0, ꭓ > 2. Detected signals were confirmed whether listed on the drug label in Korea, Micromedex, and SIDER.

Results: Among the total of 2,372,147 drug-adverse event pairs were reported from 2015 to 2019, 57 were associated with concomitant use of tramadol and SSRI, 61,883 were associated with only tramadol, and 5,036 were associated with only SSRI. Fourteen AEs of 35 AEs on reports of concomitant use were detected as signals. 8 signals satisfied one index, 3 signals satisfied two indices, and 3 signals satisfied all indices. Of the 14 detected signals, 4 signals, including GI neoplasm benign, graft-versus-host disease, drug reaction paradoxical, incorrect dose prescribed, were not listed on drug label in Korea, Micromedex, and SIDER.

Conclusions: This study showed that using spontaneous reports 14 DDI signals were detected, including 4 signals previously not established. Further study of DDI associated with new signals using other databases is needed.