pexidartinib

Contraindicated in:

Pre-existing liver enzyme elevations or active liver or biliary tract disease;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment (↓ dose);
Moderate hepatic impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, peripheral edema

Derm: hair color changes, pruritus, rash, alopecia, skin pigmentation changes

EENT: eye edema, blurred vision, diplopia, photophobia

F and E: hypophosphatemia

GI: constipation, vomiting, dry mouth, HEPATOTOXICITY, stomatitis

GU: ↓fertility

Hemat: anemia, lymphocytopenia, thrombocytopenia, NEUTROPENIA

Metab: ↓appetite, hypercholesterolemia

Neuro: dysgeusia, fatigue, peripheral neuropathy, amnesia, amnesia, attention disturbances, confusion, memory impairment

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Hepatotoxic drugs can ↑ risk of hepatotoxicity; avoid concurrent use.
Strong CYP3A inhibitors, including itraconazole, and moderate CYP3A inhibitors, including fluconazole, may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use cannot be avoided, ↓ pexidartinib dose.
Strong CYP3A inducers may ↓ levels and effectiveness; avoid concurrent use.
UGT inhibitors may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use cannot be avoided, ↓ pexidartinib dose.
Proton pump inhibitors may ↓ levels and effectiveness; avoid concurrent use; as alternative, administer pexidartinib 2 hr before or after taking an antacid or ≥2 hr before or 10 hr after taking an H₂ antagonist.
May ↓ levels and effectiveness of CYP3A substrates, including hormonal contraceptives; avoid concurrent use with hormonal contraceptives; avoid concurrent use with other CYP3A substrates; if concurrent use unavoidable, ↑ dose of CYP3A substrate.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit or grapefruit juice may ↑ levels and risk of toxicity; if concurrent use cannot be avoided, ↓ pexidartinib dose.
High-fat meals↑ levels and risk of toxicity; avoid concurrent use; take each dose with low-fat meal.

Availability ⬆ ⬇

Capsules: 125 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 250 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of strong or moderate CYP3A inhibitors or UGT inhibitors: If originally taking pexidartinib 500 mg/day or 375 mg/day, ↓ dose to 125 mg twice daily; if originally taking pexidartinib 250 mg/day, ↓ dose to 125 mg once daily.

Renal Impairment

PO (Adults ): CCr 15–89 mL/min: 125 mg every morning and 250 mg every evening until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment (total bilirubin 1.51–3 times upper limit of normal [ULN] not due to Gilbert's syndrome): 125 mg twice daily until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as a tyrosine kinase inhibitor that selectively inhibits the colony-stimulating factor 1 receptor, which slows proliferation of tumor cells in the synovium.

Therapeutic effects:

Reduction in tumor size and improvement in joint movement.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: High-fat food ↑ drug exposure by 100% and delays absorption.

Distribution: Extensively distributed to extravascular tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the CYP3A4 isoenzyme and through glucuronidation (via UGT1A4); inactive metabolite formed via glucuronidation. 65% excreted via feces (44% as unchanged drug), 27% excreted in urine as metabolites.

Half-Life: 26.6 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2.5 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take pexidartinib with a low-fat meal, as directed. If a dose is missed or patient vomits after dose, omit dose and take next dose at scheduled time. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
REMS: Inform patient of the Turalio REMS program and requirements.
Caution patient to avoid grapefruit juice during therapy.
Advise patient to take pexidartinib 2 hr before or 2 hr after antacids and at least 2 hr before or 10 hr after H₂antagonists.
Advise patient to notify health care professional immediately if signs and symptoms of liver toxicity occur.
Inform patient that pexidartinib may cause a change in hair color and a loss of taste or changes in the way things taste.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, herbal products, especially St. John's wort.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective nonhormonal contraception during and for 1 mo after last dose and to avoid breastfeeding during and for 1 wk after last dose. Advise males with female partners of reproductive potential to use effective nonhormonal contraception during and for 1 wk after last dose of pexidartinib. May impair male and female fertility.
Emphasize the need for regular lab tests to monitor for side effects.

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Indications ⬇

Contraind./Precautions ⬆ ⬇