Table 3.

Dose Modifications for Hepatotoxicity

Adverse Reaction	Severity	Dose Modification
Hepatotoxicity
Increased ALT and/or AST	Greater than 3 to 5 times ULN	Hold and monitor LFTs weekly Resume at reduced dose if ALT and AST are <3 x ULN within 4 weeks If >3 x ULN in 4 weeks, permanently discontinue
	Greater than 5 to 10 times ULN	Hold and monitor LFTs twice weekly Resume at reduced dose if ALT and AST are <3 x ULN within 4 weeks If >3 x ULN in 4 weeks, permanently discontinue
	Greater than 10 times ULN	Permanently discontinue pexidartinib Monitor LFTs twice weekly until AST/ALT <5 x ULN then weekly until ≤3 x ULN
Increased ALPa and GGT	ALP greater than 2 times ULN with GGT greater than 2 times ULN	Permanently discontinue pexidartinib Monitor LFTs twice weekly until ALP ≤5 x ULN, then weekly until ≤2 x ULN
Increased bilirubin	TB greater than ULN to less than 2 times ULN or DB greater than ULN and less than 1.5 times ULN	Hold and monitor LFTs twice weekly Resume at reduced dose if another source of elevated bilirubin is confirmed and bilirubin < ULN within 4 weeks If >ULN in 4 weeks, permanently discontinue
	TB greater or equal to 2 times ULN or DB greater than 1.5 times ULN	Permanently discontinue pexidartinib Monitor LFTs twice weekly until bilirubin ≤ULN
Any	Severe or intolerable	Withhold until improvement or resolution Resume at a reduced dose upon improvement or resolution

Note: ^aConfirm ALP elevations as liver isozyme fraction.

Abbreviations: ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; DB, direct bilirubin; GGT, gamma-glutamyl transferase; TB, total bilirubin; ULN, upper limit of normal; LFT, liver function test.