CYP3A4 and Hyponatremia: ContraindicatedHypovolemia▪Gastrointestinal losses: vomiting, diarrhea, and bleeding▪Skin losses: burns and excessive sweating▪Third spacing: acute pancreatitis and small bowel obstruction▪Renal losses: diuretic use, aldosterone deficiency, cerebral salt wasting syndrome, and salt wasting nephropathiesSevere hyponatremia (presence of severe symptoms or PNa < 120 mmol/L)History of hypersensitivity reaction to vasopressin receptor antagonistsAnuriaImpaired thirst mechanismConcomitant use of drugs that increase plasma levels of vasopressin receptor antagonists (i.e., CYP3A4 inhibitors)