The following changes, observed in rats and macaques receiving the irbesartan/ hydrochlorothiazide combination at 10/ 10 and 90/ 90 mg/ kg/ day, were also seen with one of the two medicinal products alone and/ or were secondary to decreases in blood pressure (no significant toxicologic interactions were observed): kidney changes, characterized by slight increases in serum urea and creatinine, and hyperplasia/ hypertrophy of the juxtaglomerular apparatus, which are a direct consequence of the interaction of irbesartan with the renin-angiotensin system; slight decreases in erythrocyte parameters (erythrocytes, haemoglobin, haematocrit); stomach discoloration, ulcers and focal necrosis of gastric mucosa were observed in few rats in a 6 months toxicity study at irbesartan 90 mg/ kg/ day, hydrochlorothiazide 90 mg/ kg/ day, and irbesartan/ hydrochlorothiazide 10/ 10 mg/ kg/ day.
Los siguientes cambios, observados en ratas y macacos que recibieron dosis de 10/ 10 y 90/ 90 mg/ kg/ día de la combinación irbesartan/ hidroclorotiazida, también se observaron con la administración de uno de los dos medicamentos en monoterapia y/ o fueron secundarios a la reducción de la presión arterial (no se observaron interaciones toxicológicas significativas): cambios renales, caracterizados por ligeros incrementos en los valores de urea y creatinina séricos, e hiperplasia/ hipertrofia del sistema yuxtaglomerular, que es una consecuencia directa de la interacción de irbesartan con el sistema renina-angiotensina;