Important potential risks not reflected in Japanese drug labeling: implications for risk management plan termination

Abstract Background Risk management plans (RMPs) support lifecycle management of drug-related risks. In Japan, however, their use in clinical practice remains limited, and healthcare professionals often rely on the package insert for safety information. After RMP termination at re-examination, healthcare professionals may no longer readily identify unresolved risks absent from the package insert through either the package insert or the Pharmaceuticals and Medical Devices Agency (PMDA) RMP source. Objectives We investigated the extent to which important potential risks in RMPs are reflected in the package insert and considered the implications of RMP termination when such risks remain undocumented. Methods We analyzed RMPs publicly available as of May 2023 using data from the PMDA website. For each important potential risk, we examined whether it was documented in the package insert and summarized the results descriptively by risk type. Results Among 772 important potential risks in 330 RMPs, 134 (17.4%) were not documented in the package insert. Non-documentation proportions were relatively high for “Infections and infestations” (32.7%), “Gastrointestinal disorders” (32.4%), and “Neoplasms benign, malignant and unspecified (incl cysts and polyps)” (28.4%), whereas a relatively low proportion was observed for “Vascular disorders” (2.3%). Conclusion Some important potential risks in active Japanese RMPs were not documented in the package insert. This may create gaps in risk communication after RMP termination, although clinical outcomes and patient harm were not assessed. Allowing RMP continuation beyond re-examination when necessary may help maintain awareness of unresolved safety concerns.