Pexidartinib

Pexidartinib is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium.

• TURALIO is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. TURALIO is a kinase inhibitor indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

• None. None.contraindicated

Recommended Dosage : 250 mg orally twice daily with a low-fat meal (approximately 11 to 14 grams of total fat). ( 2.1 ) See full prescribing information for dosage modifications due to adverse reactions, renal impairment and hepatic impairment. ( 2.2 , 2.5 , 2.6 ) 2.1 Recommended Dosage The recommended dosage of TURALIO is 250 mg taken orally twice daily with a low-fat meal (approximately 11 to 14 grams of total fat) until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3) ] . Taking TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat) increases pexidartinib concentrations and may increase the risk of adverse reactions, including hepatotoxicity [see Warnings and Precautions (5.1 , 5.4) , Drug Interactions (7.2) , Clinical Pharmacology (12.2 , 12.3) ] . Swallow TURALIO capsules whole. Do not open, break, or chew the capsules. If a patient vomits or misses a dose of TURALIO, instruct the patient to take the next dose at its scheduled time. 2.2 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are provided in Table 1. Table 1: Recommended Dose Reductions for TURALIO for Adverse Reactions Dose Reduction Total Daily Dose Administration of Total Daily Dose with Low-Fat Meal First 375 mg 125 mg in the morning and 250 mg in the evening Second 250 mg 125 mg twice daily Permanently discontinue TURALIO in patients who are unable to tolerate 125 mg orally twice daily. The recommended dosage modifications for adverse reactions are summarized in Table 2.

Embryo-Fetal Toxicity : May cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use an effective non-hormonal method of contraception. ( 5.3 , 7.3 , 8.1 , 8.3 ) Potential Risks Associated with a High-Fat Meal : May increase incidence and severity of adverse reactions, including hepatotoxicity. Avoid taking TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat). ( 2.1 , 5.4 ) 5.1 Hepatotoxicity TURALIO can cause serious and potentially fatal liver injury and is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) [see Warnings and Precautions (5.2) ]. Hepatotoxicity, including liver failure and life-threatening vanishing bile duct syndrome (VBDS), ductopenia, and symptomatic cholestasis (including severe pruritus) can occur in patients treated with TURALIO and can occur despite monitoring and prompt drug cessation. The mechanism of cholestatic hepatotoxicity is unknown and its occurrence cannot be predicted. It is unknown whether liver injury can also occur in the absence of increased transaminases. Of the first 609 patients who received TURALIO under the REMS program, 32 (5.3%) developed a liver injury event of concern (LIEC), defined as any serious liver-related outcome or any liver abnormality that triggers drug discontinuation per the US Prescribing Information [ see Dosage and Administration (2.2) ]. These 32 patients developed liver toxicity within 71 days of the first dose of TURALIO; ten required hospitalization, and two developed VBDS.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ]. Most common adverse reactions (>20%) were increased lactate dehydrogenase, increased aspartate aminotransferase, hair color changes, fatigue, increased alanine aminotransferase, decreased neutrophils, increased cholesterol, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TURALIO 250 mg orally twice daily administered with a low-fat meal has been established based on adequate and well-controlled studies of TURALIO 400 mg orally twice daily administered on an empty stomach and additional pharmacokinetic data that indicate there is no clinically significant difference in the relative exposure between the two dosages [see Clinical Pharmacology (12.3) ]. The safety of TURALIO was evaluated in ENLIVEN [see Clinical Studies (14.1) ] . ENLIVEN excluded patients with ALT, AST, or total bilirubin >1.5 × ULN; and known active or chronic infection with hepatitis B or C virus, or human immunodeficiency virus.

Lactation : Advise not to breastfeed. ( 8.2 ) Renal Impairment : Reduce the dosage for patients with mild to severe renal impairment. ( 2.5 , 8.6 ) Hepatic Impairment : Reduce the dosage for patients with moderate hepatic impairment. ( 2.6 , 8.7 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , TURALIO may cause embryo-fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of TURALIO. Oral administration of pexidartinib to pregnant animals during the period of organogenesis resulted in malformations, post-implantation loss, and abortion at maternal exposures that were approximately equal to the human exposure at the recommended dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Embryo-fetal development studies investigating the administration of pexidartinib during the period of organogenesis were conducted in rats and rabbits.

Metabolism

The pharmacokinetics of TURALIO was evaluated following single doses in healthy subjects and following multiple doses in patients as summarized in Table 9. Table 9: TURALIO Exposure and Pharmacokinetic Parameters General Information Steady state exposure [Mean (SD)] Pexidartinib 400 mg twice daily on an empty stomach (similar exposure to that of the recommended dosage) C max 8625 (2746) ng/mL AUC 0-12h 77465 (24975) ng∙h/mL Dose proportionality Pexidartinib exposure (C max and AUC 0-INF ) increased linearly over the single oral dose range of 200 to 2400 mg administered on an empty stomach (0.5…

Due to the high plasma protein binding, TURALIO is not expected to be dialyzable [see Clinical Pharmacology (12.3) ] .

• Aug 2, 2019NDANDA211810Daiichi Sankyo Inc

1. 1Product Dose Omission Issue26438%
2. 2Fatigue24936%
3. 3Hair Colour Changes23534%
4. 4Nausea13920%
5. 5Pruritus11216%
6. 6Off Label Use10415%
7. 7Rash8612%
8. 8Therapy Cessation8112%
9. 9Pain7310%
10. 10Headache7210%
11. 11Product Dose Omission In Error699.8%
12. 12Diarrhoea659.3%
13. 13Product Use Issue628.8%
14. 14Arthralgia598.4%
15. 15No Adverse Event568.0%

The 10 most recently updated of 30 ClinicalTrials.gov registrations naming Pexidartinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...
  Recruiting · Phase 1 · Interventional · 54 enrolled · National Cancer Institute (NCI)
  NCT02390752updated 2026-06-08
• I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
  Recruiting · Phase 2 · Interventional · 5,000 enrolled · QuantumLeap Healthcare Collaborative
  NCT01042379updated 2026-05-06
• A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan
  Active not recruiting · Phase 2 · Interventional · 9 enrolled · Daiichi Sankyo Co., Ltd.
  NCT04703322updated 2026-03-04
• A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma
  Completed · Interventional · 6 enrolled · Daiichi Sankyo Co., Ltd.
  NCT02975700updated 2026-01-13
• A Long-term Study Evaluating Hepatotoxicity Associated With TURALIO™ (Pexidartinib) Treatment
  Recruiting · Observational · 30 enrolled · Daiichi Sankyo
  NCT04635111updated 2025-10-06
• A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT
  Active not recruiting · Phase 3 · Interventional · 40 enrolled · Daiichi Sankyo Co., Ltd.
  NCT04488822updated 2025-09-09
• PLX3397 Plus Sirolimus in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors
  Terminated · Phase 1 · Phase 2 · Interventional · 39 enrolled · Gulam Manji
  NCT02584647updated 2025-03-21
• CGT9486 (Formerly Known as PLX9486) as a Single Agent and in Combination With PLX3397 (Pexidartinib) or Sunitinib in Participants With Advanced Solid Tumors
  Completed · Phase 1 · Phase 2 · Interventional · 51 enrolled · Cogent Biosciences, Inc.
  NCT02401815updated 2025-02-14
• Study to Evaluate Discontinuation and Re-Treatment in Participants With Tenosynovial Giant Cell Tumor (TGCT) Previously Treated With Pexidartinib
  Completed · Phase 4 · Interventional · 32 enrolled · Daiichi Sankyo
  NCT04526704updated 2024-12-30
• Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
  Completed · Phase 3 · Interventional · 120 enrolled · Daiichi Sankyo
  NCT02371369updated 2022-05-11

Frequently asked questions

How does Pexidartinib work?

Pexidartinib is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium.

What is Pexidartinib used for?

According to FDA labeling, Pexidartinib carries indications including: TURALIO is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. TURALIO is a kinase inhibitor indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pexidartinib?

Pexidartinib is classified as Other protein kinase inhibitors, Kinase Inhibitor, Colony Stimulating Factor Receptor Type 1 (CSF-1R) Inhibitors, Cytochrome P450 2B6 Inhibitors, Cytochrome P450 3A Inducers, Kinase Inhibitors, Tyrosine Kinase Inhibitors, UGT1A1 Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Pexidartinib?

Pexidartinib is marketed under brand names including Turalio.

What are the contraindications for Pexidartinib?

Pexidartinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.