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.

MANAGEMENT: The use of idelalisib with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; amiodarone; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; methotrexate; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; tetracyclines; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients treated with idelalisib should 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. 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.

GENERALLY AVOID: Due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of vorasidenib, smoking tobacco during treatment with vorasidenib may decrease its plasma concentrations and anti-tumor effect. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Patient should be advised to avoid smoking tobacco during treatment with vorasidenib because it may reduce efficacy of the therapy.