Symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery.
Acts as a tyrosine kinase inhibitor that selectively inhibits the colony-stimulating factor 1 receptor (CSF1R) which slows proliferation of tumor cells in the synovium.
Reduction in tumor size and improvement in joint movement.
Absorption: High-fat food increases drug exposure by 100% and delays absorption.
Distribution: Extensively distributed to extravascular tissues.
Protein Binding: >99%.
Metabolism and Excretion: Primarily metabolized by 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)
|PO||unknown||2.5 hr||12 hr|
- Pre-existing liver enzyme elevations or active liver or biliary tract disease
- Severe hepatic impairment
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Mild, moderate, or severe 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.
Adverse Reactions/Side Effects
CNS: dysgeusia, amnesia, attention disturbances, confusion, memory impairment
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: HEPATOTOXICITY, constipation, vomiting, dry mouth, stomatitis
GU: ↓ fertility
Hemat: NEUTROPENIA, anemia, lymphocytopenia, thrombocytopenia
Metabolic: ↓ appetite, hypercholesterolemia
Neuro: peripheral neuropathy
Misc: fatigue, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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.
St. John's wort may ↓ levels and effectiveness; avoid concurrent use.
Grapefruit or grapefruit juice may ↑ levels and risk of toxicity; if concurrent use cannot be avoided, ↓ pexidartinib dose.
PO (Adults): 400 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of strong or moderate CYP3A inhibitors or UGT inhibitors– If originally taking pexidartinib 600 mg/day or 800 mg/day, ↓ dose to 200 mg twice daily; if originally taking pexidartinib 400 mg/day, ↓ dose to 200 mg once daily.
PO (Adults): CCr 15–89 mL/min– 200 mg every morning and 400 mg every evening until disease progression or unacceptable toxicity.
PO (Adults): Moderate hepatic impairment (total bilirubin 1.51–3x ULN not due to Gilbert's syndrome)– 200 mg twice daily until disease progression or unacceptable toxicity.
Capsules: 200 mg
Monitor for signs and symptoms of liver toxicity (yellowing of your skin and whites of eyes, dark urine, loss of appetite, right upper abdominal pain or tenderness, feeling overly tired, nausea, vomiting, fever, rash, itching) during therapy.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
- Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), before starting therapy, weekly for first 8 wk, every 2 wk for next mo and every 3 mo thereafter. If AST and ALT >3–5 × ULN, hold dose and monitor liver tests weekly. If AST and ALT ≤3 × ULN within 4 wk, resume at reduced dose. If AST or ALT >3 × ULN in 4 wk, permanently discontinue therapy. If AST and ALT >5–10 × ULN, hold dose and monitor liver tests twice weekly. If AST and ALT ≤3 × ULN within 4 wk, resume at reduced dose. If AST or ALT >3 × ULN in 4 wk, permanently discontinue pexidartinib. If AST and ALT >10 × ULN, permanently discontinue pexidartinib. Monitor liver tests twice weekly until AST or ALT ≤5 times ULN, then weekly until ≤3 × ULN. If ALP and GGT >2 × ULN, discontinue therapy permanently. Monitor liver tests twice weekly, until ALP ≤5 × ULN, then weekly until ≤2 × ULN. If total bilirubin ↑ >ULN to <2 × ULN or direct bilirubin >ULN and <1.5 × ULN, hold dose and monitor liver tests twice weekly. If an alternate cause for ↑ bilirubin is confirmed and bilirubin <ULN within 4 wk, resume at reduced dose. If bilirubin is >ULN in 4 wk, permanently discontinue pexidartinib. If total bilirubin ≥2 × ULN or direct bilirubin >1.5 × ULN, discontinue therapy permanently. Monitor liver tests twice weekly until bilirubin ≤ULN. Rechallenge with a reduced dose of pexidartinib may result in a recurrence of ↑ AST, ALT, bilirubin, or ALP. Monitor liver tests weekly for 1st mo after rechallenge.
- May cause ↑LDH and cholesterol and ↓serum phosphate.
- May cause ↓ neutrophils, lymphocytes, hemoglobin, and platelets.
- REMS: Pexidartinib is only available through a restricted program: Turalio REMS. Prescribers must enroll and complete training. Patient must sign enrollment form for inclusion in a patient registry. Pharmacies must be certified and only dispense to authorized patients. Information is available at www.turalioREMS.com or 1-833-887-2546.
- Dose reduction schedule: First dose reduction, 600 mg daily taken as 200 mg in morning and 400 mg in evening. Second dose reduction, 400 mg daily taken as 200 mg twice daily. If patient unable to tolerate 200 mg twice daily, discontinue pexidartinib permanently.
- PO Administer twice daily on an empty stomach, at least 1 hr before or 2 hr after a meal or snack. DNC: Swallow capsules whole; do not open, break, or chew.
- If antacids or H2 antagonists are needed, administer pexidartinib 2 hr before or 2 hr after antacids. Administer pexidartinib at least 2 hr before or 10 hr after H2 antagonists.
- Instruct patient to take pexidartinib on an empty stomach, 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 H2 antagonists.
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 women 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.
Reduction in tumor size and improvement in joint movement.