Drug Interaction Report

GENERALLY AVOID: Coadministration of idelalisib with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. The use of idelalisib has been associated with elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 5 times the upper limit of normal. Serious and fatal hepatotoxicity occurred in 14% of patients treated with idelalisib in premarketing trials. Liver enzyme elevations were generally observed within the first 12 weeks of treatment and were reversible with dose interruption. Following treatment resumption at a lower dose, 26% of patients had recurrence of ALT and AST elevations.

GENERALLY AVOID: The risk and/or severity of diarrhea may be increased when idelalisib is used with other agents that cause diarrhea. In premarketing trials, serious and fatal diarrhea or colitis (Grade 3 or higher) occurred in 14% of patients receiving idelalisib. Diarrhea may occur at any time and responds poorly to antimotility agents. The median time to resolution across trials ranged from one week to one month following interruption of idelalisib therapy and, in some instances, use of corticosteroids. Serious and fatal intestinal perforation has also been reported with idelalisib. At the time of perforation, some patients had moderate to severe diarrhea.

MANAGEMENT: The use of idelalisib with other agents that can induce hepatotoxicity and/or diarrhea should be avoided whenever possible. Patients treated with idelalisib should be monitored for development of severe diarrhea or colitis and have serum ALT, AST, and bilirubin measured prior to initiation of treatment and regularly during treatment in accordance with the product labeling, and the dosing adjusted or interrupted as necessary. Permanent discontinuation of idelalisib is recommended in those who experience recurrent hepatotoxicity following dosage reduction and/or life-threatening diarrhea or intestinal perforation. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Patients should also contact their physician immediately if the number of bowel movements per day increases by six or more, or if they have new or worsening abdominal pain, chills, fever, nausea, or vomiting.