Avapritinib Disease Interactions

Exposure to avapritinib is increased in patients with severe hepatic impairment and a lower starting dose is recommended for all indications. No dose adjustment is recommended for patients with mild (total bilirubin at the upper limit of normal [ULN] or less and AST greater than ULN, or total bilirubin greater than 1 to 1.5 x ULN and any AST) or moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment.

Serious and fatal intracranial hemorrhage has been reported in patients treated with avapritinib. Patient conditions and risk factors for intracranial hemorrhage include a history of vascular aneurysm, intracranial hemorrhage or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. In patients with advanced systemic mastocytosis (AdvSM), ensure platelet counts are performed prior to treatment, and then as recommended during therapy. Do not initiate treatment in patients with AdvSM if platelet counts are less than 50 x 10(9)/L.

The effect of severe renal impairment (CrCl 15 to 29 mL/min) or end-stage renal disease (CrCl <15 mL/min) on the pharmacokinetics of avapritinib is unknown, and the recommended dose of avapritinib has not been established for these patients. No dose adjustment is recommended for patients with mild or moderate renal impairment (CrCl) 30 to 89 mL/min estimated by Cockcroft-Gault].