Comprehensive Analysis of Strong Opioid Side Effects in Palliative Care Using the SIDER Database

<b>Background/Objectives</b>: There exist multiple opioid-based treatments in palliative care, each with distinct side effect profiles. When adverse events occur, switching opioids can help maintain effective pain management. However, owing to limited clinical evidence, no comprehensive guidelines exist for opioid switching. This study employed the Side Effect Resource (SIDER) database, which aggregates adverse event data from clinical trials and package inserts, to analyze the side effects of five commonly used "strong opioids" in palliative care in Japan, namely morphine, fentanyl, oxycodone, hydromorphone, and tapentadol. <b>Methods</b>: Data on the names and incidence of adverse events for each opioid were extracted from SIDER 4.1, developed by the Max Delbrück Center for Molecular Medicine. Cluster analysis and principal component analysis were performed to interpret the data. <b>Results</b>: The key side effects of opioids were nausea, vomiting, constipation, and drowsiness. Fentanyl was more frequently associated with nausea and vomiting but less frequently with constipation and drowsiness. Tapentadol caused nausea relatively more frequently and constipation less frequently. Oxycodone was prominently linked to drowsiness, whereas morphine was frequently associated with constipation and drowsiness. Hydromorphone was associated with higher rates of constipation and vomiting but lower incidences of nausea and drowsiness. <b>Conclusions</b>: All side effects characterizing the opioids were related to μ-opioid receptor stimulation, although the present study findings highlight differences in the frequency of specific side effects among the opioids. These results provide objective insights that can guide opioid switching in response to adverse effects.