Although in some cases these events were mild to moderate, they at times led to withdrawal from treatment. These events were generally mild to moderate and occurred early in therapy. This represents an incidence of 0.0035 deaths per patient year. As in the general population, the incidence of stone formation among topiramate treated patients was higher in men. Increased fluid intake increases the urinary output, lowering the concentration of substances involved in stone formation.
Hydrat ion is recommended to reduce new stone formation.
The major route of elimination of unchanged topiramate and its metabolites is via the kidney. The relevance of this finding to human carcinogenic risk is uncertain. Topiramate did not demonstrate genotoxic potential when tested in a battery of in vitro and in vivo assays. Topiramate has demonstrated selective developmental toxicity , including teratogenicity in experimental animal studies. Nursing Mothers Topiramate is excreted in the milk of lactating rats.