Pexidartinib Dosage

Medically reviewed by Drugs.com. Last updated on Oct 29, 2024.

Usual Adult Dose for Giant Cell Tumor of Bone

250 mg orally 2 times a day

Treatment duration: Until disease progression or unacceptable toxicity

Comments:

• Take with a low-fat meal (approximately 11 to 14 grams of total fat).
• Taking with a high-fat meal increases the drug's concentrations and may increase the risk of adverse reactions, including hepatotoxicity.

Use: For symptomatic tenosynovial giant cell tumor 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 dysfunction: 125 mg orally in the morning and 250 mg orally in the evening with a low-fat meal

Liver Dose Adjustments

• Mild hepatic dysfunction (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 hepatic dysfunction: (total bilirubin greater than 1.5 to 3 x ULN and any AST): 125 mg twice a day with a low-fat meal
• Severe hepatic dysfunction (total bilirubin greater than 3 to 10 x ULN and any AST): Unknown

HEPATOTOXICITY:

• 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.

Dose Adjustments

RECOMMENDED DOSE REDUCTIONS FOR ADVERSE REACTIONS:

• First dose reduction: Total daily dose of 375 mg; 125 mg in the morning and 250 mg in the evening with a low-fat meal
• Second dose reduction: Total daily dose 250 mg; 125 mg twice daily with a low-fat meal
• Permanently discontinue in patients unable to tolerate 125 mg orally twice a day

ADVERSE REACTIONS OR OTHER LABORATORY ABNORMALITIES:

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

CONCOMITANT USE OF STRONG CYP450 3A INHIBITORS OR URIDINE 5-DIPHOSPHATE GLUCURONOSYLTRANSFERASES (UGT) INHIBITORS:

• 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 dose:
• Total dose 500 mg daily: Reduce dose to 125 mg 2 times a day.
• Total dose of 375 mg daily: Reduce dose to 125 mg 2 times a day.
• Total dose of 250 mg daily: Reduce dose to 125 mg once a day.

• If concomitant use of a moderate or strong CYP450 3A inhibitor or UGT inhibitor is discontinued, increase the dose of this drug (after 3 plasma half-lives of the moderate or strong CYP450 3A inhibitor or UGT inhibitor) to the dose that was used before starting the inhibitor.

CONCOMITANT USE OF ACID-REDUCING AGENTS:

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

Precautions

The US FDA requires a medication guide to assure safe use. For additional information go to: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for pexidartinib. It includes communication plan, elements to assure safe use, and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
HEPATOTOXICITY:

• This drug can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome.

Recommendations:

• Monitor liver function tests prior to initiating this drug and at specified intervals during therapy.
• Withhold and dose reduce or permanently discontinue therapy based on severity of hepatotoxicity.
• Monitoring and prompt treatment discontinuation may not eliminate the risk of serious and potentially fatal liver injury.
• This drug is available only through a restricted program called the TURALIO REMS Program.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• 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.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).
• Keep containers closed and do not remove desiccant from bottles.

General:

• Report suspected adverse reactions to Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Monitoring:

• Liver tests prior to and during treatment

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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