Drug-drug interaction signals between carbonic anhydrase inhibitors and vitamin D preparations in urinary tract stones: disproportionality analysis evaluation from Japanese spontaneous reports of adverse events

Carbonic anhydrase inhibitors used as antiepileptic drugs promote calcium phosphate stones. Patients with epilepsy often receive vitamin D concurrently, which may increase urinary calcium and stone formation. We analyzed drug-drug interactions to determine if vitamin D contribute to renal and urinary tract stone disease associated with carbonic anhydrase inhibitors. The Japanese Adverse Drug Event Report (JADER) was used to detect signals of the additive effects of vitamin D on carbonic anhydrase inhibitor-associated renal and urinary tract stone disease. Disproportionality analysis and Ω shrinkage measure were used to detect renal and urinary tract stone disease signals when carbonic anhydrase inhibitors were used with vitamin D. We found 61 cases of carbonic anhydrase inhibitor-related renal and urinary tract stone disease. When carbonic anhydrase inhibitors were combined with vitamin D preparations, a significant positive signal was observed for renal and urinary tract stone disease exclusively (aROR 59.85, 95% CI 29.04–123.36, p < 0.001), compared to that with carbonic anhydrase inhibitor (aROR 12.99; 95% CI 9.69–17.41; p < 0.001) or vitamin D alone (aROR 8.68, 95% CI 6.98–10.79, p < 0.001). A significant positive signal was also detected for the Ω shrinkage measure (Ω025 = 0.429). Vitamin D preparations may adversely affect renal and urinary tract stone disease when used with carbonic anhydrase inhibitors, and the hypothesis should be further investigated in future research.