Balance Disorder as a Potential Cause of Fall in Patients Taking Enzalutamide

Introduction: Balance disorder related to enzalutamide was reported by an oncologist in Montenegro. Enzalutamide is an androgen-receptor inhibitor approved for prostate cancer treatment. Various nervous system disorders were recognized in clinical trials [1] but balance disorder is not a listed adverse drug reaction (ADR) for enzalutamide. Falls and fractures are listed as very common ADRs in the EU Summary of Product Characteristics (SmPC) [2]. Aim: To investigate a potential signal and to assess balance disorder as a potential cause of fall in patients taking enzalutamide. Methods: This combination was analysed during the Signal Detection and Causality Assessment Training Course, Uppsala Monitoring Centre, May 2023. Data analysis, based on case reports from participants' country specific data, was performed in VigiBase, the WHO global database of suspected ADRs. A literature search was performed and product information reviewed. Results: As of 12 May 2023, 520 cases of enzalutamide and balance disorder (MedDRA PT) were found in VigiBase (de-duplicated data set). The Information Component (IC025) value was 1.8 indicating statistically disproportionate reporting. A similar PT, dysstasia, was reported in 105 cases, IC 025 value: All of the 620 cases were selected. In 523 (84.3%) reports enzalutamide was the only suspected drug. In 134 (21.6%) reports fall was co-reported (Table 1) and 264 (42.6%) reports were related to elderly patients (> 75 years). For further analysis, cases with co-reported fatigue, asthenia, decreased appetite, muscular weakness and arthralgia as potential causes of fall were excluded and 241 cases remained. Out of these, fall was co-reported in 38 (15.8%) of reports and 99 (41.1%) reports were related to elderly patients (>75 years). Discussion: Dizziness/vertigo are listed in the FDA product label [3] but are not mentioned in the EU SmPC [2]. Fall is an important identified risk related to enzalutamide [4]. In the PLATO study, 1.57% participants receiving enzalutamide 160 mg experienced balance disorder versus 0.80% receiving enzalutamide 160mg+abiraterone 1000mg+ prednisone 10mg and 0.00% receiving placebo+abiraterone 1000mg+ prednisone 10mg [5]. Disproportionality in VigiBase was also noticed for a newer anti-androgen apalutamide and balance disorder (IC025 value: 1.0). Conclusion: Detailed analysis is needed to assess the potential causal relationship between balance disorder and enzalutamide. Patients should be informed about the