Usual Adult Dose for Giant Cell Tumor of Bone

400 mg orally 2 times a day

Use: For symptomatic (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery

Renal Dose Adjustments

Mild (CrCl 60 to 89 mL/min), moderate (CrCl 30 to 59 mL/min), or severe (CrCl 15 to 29 mL/min) renal impairment: 200 mg orally in the morning and 400 mg orally in the evening

Liver Dose Adjustments

• Mild hepatic impairment (total bilirubin less than or equal to upper limit of normal (ULN) with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST): No adjustment recommended.
• Moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) to severe (total bilirubin greater than 3 to 10 x ULN and any AST) hepatic impairment: Dose adjustment(s) may be required; however, no specific guidelines have been suggested.

Dose Adjustments

DOSE REDUCTION RECOMMENDATION:

• First dose reduction: Reduce dose to 600 mg orally daily (200 mg in the morning and 400 mg in the evening).
• Second dose reduction: Reduce dose to 400 mg orally daily (200 mg orally 2 times a day).
• Permanently discontinue therapy in patients who are unable to tolerate 200 mg orally 2 times a day.

• ALT and/or AST greater than 3 to 5 times the upper limit of normal (ULN): Withhold therapy and monitor liver tests weekly; if AST and ALT are less than or equal to 3 x ULN within 4 weeks, resume at reduced dose if AST or ALT is not less than or equal to 3 x ULN in 4 weeks, permanently discontinue therapy.
• ALT and/or AST greater than 5 to 10 x ULN: Withhold therapy and monitor liver tests 2 times a week; if AST and ALT are less than or equal to 3 x ULN within 4 weeks, resume therapy at reduced dose; if AST or ALT is not less than or equal to 3 x ULN in 4 weeks, permanently discontinue therapy.
• ALT or AST greater than 10 x ULN: Permanently discontinue therapy; monitor liver tests 2 times a week until AST or ALT is less than or equal to 5 x ULN, then weekly until less than or equal to 3 x ULN.
• ALP (confirm ALP elevations as liver isozyme fraction) greater than 2 x ULN with GGT greater than 2 x ULN: Permanently discontinue therapy; monitor liver tests 2 times a week until ALP is less than or equal to 5 x ULN, then weekly until less than or equal to 2 x ULN.
• Total bilirubin (TB) greater than ULN to less than 2 x ULN OR direct bilirubin (DB) greater than ULN and less than 1.5 x ULN: Withhold therapy and monitor liver tests 2 times a week. If an alternate cause for increased bilirubin is confirmed and bilirubin is less than ULN within 4 weeks, resume at reduced dose. If bilirubin is not less than ULN in 4 weeks, permanently discontinue therapy.
• TB greater than or equal to 2 x ULN OR DB greater than 1.5 x ULN: Permanently discontinue therapy; monitor liver tests 2 times a week until bilirubin is less than or equal to ULN.

• Any severe or intolerable reaction: Withhold therapy until improvement or resolution; resume therapy at a reduced dose upon improvement or resolution.

• Avoid concomitant use of this drug with strong CYP450 3A inhibitors or UGT inhibitors.
• If concomitant use with a strong CYP450 3A inhibitor or UGT inhibitor cannot be avoided, reduce the pexidartinib dose.
• If concomitant use of a strong CYP450 3A inhibitor or UGT inhibitor is discontinued, increase the pexidartinib dose (after 3 plasma half-lives of the

• Pexidartinib planned dose of 800 mg daily: Reduce dose to 200 mg 2 times a day.
• Pexidartinib planned dose of 600 mg daily: Reduce dose to 200 mg 2 times a day.
• Pexidartinib planned dose of 400 mg daily: Reduce dose to 200 mg once a day.

• Avoid the concomitant use of proton pump inhibitors (PPI) with pexidartinib.
• As an alternative to a PPI, administer pexidartinib 2 hours before or 2 hours after taking a locally-acting antacid, or if using a histamine 2 (H2)-receptor antagonist, administer pexidartinib at least 2 hours before or 10 hours after taking an H2-receptor antagonist.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for pexidartinib. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
HEPATOTOXICITY:

• This drug can cause serious and potentially fatal liver injury.

• Monitor liver function tests prior to initiating this drug and at specified intervals

• Withhold and dose reduce or permanently discontinue therapy based on severity of hepatotoxicity.
• This drug is available only through a restricted program called the TURALIO

• None

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal or snack.
• Capsules should be swallowed whole and not opened, broken, or chewed.
• If a dose is vomited or missed, it should be skipped, and the next dose should be taken at its scheduled time.

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to

• Keep containers closed and do not remove desiccant from bottles.

• Do not breastfeed during therapy and for 1 week after.
• Both males and females of reproductive potential taking this drug may experience impaired fertility.
• Tell your healthcare provider of all concomitant products (including over-the-counter products and supplements) that you are taking.