Characteristics of Hypocalcemia-related Reports in the JADER Database: A Pharmacovigilance Study

Drug-induced hypocalcemia is a clinically important electrolyte disorder. Several medications are known to induce hypocalcemia; however, a comprehensive evaluation across therapeutic classes remains limited. Therefore, this study aimed to characterize drug-induced hypocalcemia using data from the Japanese Adverse Drug Event Report (JADER) database.

This retrospective pharmacovigilance study was conducted using JADER reports from April 2004 to February 2026. Hypocalcemia-related reports were identified using the preferred terms "hypocalcemia," "hypocalcemic seizure," and "blood calcium decreased." Reporting odds ratios (RORs) and 95% confidence intervals (CIs) were calculated for suspected drugs and second-level Anatomical Therapeutic Chemical (ATC) classifications. Concomitant adverse events were also evaluated.

In total, 1,448 hypocalcemia-related reports were identified. Denosumab (n=595) and zoledronic acid (n=213) were the most frequently reported suspected drugs and demonstrated strong reporting signals (ROR 185.20 and 46.57, respectively). Among the ATC classifications, Drugs for Treatment of Bone Diseases (M05) showed the strongest signal (ROR=84.23). Concomitant adverse events were present in 50.9% of the reports, with hypomagnesemia being the most common electrolyte abnormality (14.5%). Antineoplastic agents and drugs for acid-related disorders were also frequently recorded in the reports.

Hypocalcemia-related reports were identified across multiple therapeutic classes, particularly bone-modifying agents. Concomitant electrolyte abnormalities, particularly hypomagnesemia, were frequently reported. Overall, these findings provide a comprehensive overview of drug-induced hypocalcemia and support the importance of comprehensive electrolyte monitoring in clinical practice.