TURALIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TURALIO (TURALIO).
TURALIO (pexidartinib) is a small molecule kinase inhibitor that inhibits colony-stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) bearing internal tandem duplication mutations. Inhibition of CSF1R reduces survival and differentiation of macrophages and osteoclasts, which are involved in tenosynovial giant cell tumor (TGCT) pathogenesis.
| Metabolism | Pexidartinib is primarily metabolized by CYP3A4, with minor contributions from CYP2C19 and CYP2C9. |
| Excretion | Following oral administration of pexidartinib, 65.1% of the dose is eliminated in feces (31.3% as unchanged drug) and 26.5% in urine (1.5% as unchanged). |
| Half-life | Terminal elimination half-life is approximately 14.2 hours in the central compartment, with a prolonged terminal phase half-life of approximately 24.6 hours due to enterohepatic recycling. Steady state is achieved within 7 days. |
| Protein binding | 99.5% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution is approximately 300 L (4.3 L/kg based on 70 kg), indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Absolute oral bioavailability is approximately 47% (range 35–60%); food increases AUC by up to 100% and Cmax by 2-fold, with high-fat meals causing the greatest increase. |
| Onset of Action | Clinical response (tumor regression) may be observed within 8–12 weeks of initiating therapy; peak plasma concentrations occur 2–4 hours post-dose. |
| Duration of Action | Trough concentrations remain above the IC50 for CSF1R for the entire 12-hour dosing interval; the drug effect persists throughout the dosing interval and for several days after discontinuation due to tissue retention. |
| Molecular Weight | 437.5 |
200 mg orally twice daily on a continuous daily dosing schedule until disease progression or unacceptable toxicity.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce to 200 mg orally once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included limited number of patients ≥65 years, with no overall differences in safety or efficacy observed. |
| 1st trimester | Contraindicated during first trimester due to risk of embryofetal toxicity and teratogenicity based on its mechanism of action as a CSF1R inhibitor. |
| 2nd trimester | Contraindicated during second trimester due to potential adverse effects on fetal development and growth restriction. |
| 3rd trimester | Contraindicated during third trimester as CSF1R inhibition may impair fetal immune development and cause fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for TURALIO (TURALIO).
| Placental transfer | Likely transferred across the placenta as a small molecule (molecular weight 437.5 Da); animal studies show embryofetal toxicity, suggesting placental passage. |
| Breastfeeding | It is not known whether TURALIO is excreted in human milk. However, due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 1 week after the final dose. |
■ FDA Black Box Warning
WARNING: SERIOUS AND POTENTIALLY FATAL LIVER INJURY. TURALIO can cause serious and potentially fatal liver injury. Monitor liver function tests before and during treatment. Withhold, reduce dose, or permanently discontinue based on severity. TURALIO is available only through a Risk Evaluation and Mitigation Strategy (REMS) program.
| Serious Effects |
PregnancyHypersensitivity to pexidartinib or any excipients
| Precautions | Hepatotoxicity: Monitor liver function tests. Embryo-fetal toxicity: Can cause fetal harm. Lactation: Advise not to breastfeed. Risk of wound healing complications: Withhold for 5 half-lives before elective surgery. Risk of gastrointestinal perforation. Risk of QT prolongation. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase pexidartinib levels. Take with or without food, but take with a meal if gastrointestinal upset occurs. |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Pexidartinib is embryotoxic and teratogenic in animals. Based on its mechanism of action (CSF1R, KIT, and FLT3 inhibition), there is a potential risk of fetal harm. Avoid use during pregnancy. If used, advise of potential risks. First trimester: highest risk of major malformations. Second and third trimesters: risk of impaired fetal growth and development. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) every 2 weeks for first 8 weeks, then monthly. Monitor for edema, pancreatitis, and respiratory symptoms. In pregnant patients, monitor fetal growth via ultrasound and consider serial growth scans. |
| Fertility Effects | Based on animal studies, pexidartinib may impair male and female fertility. Effects on human fertility unknown. May cause structural damage to reproductive organs (e.g., testicular toxicity). |
| Clinical Pearls | TURALIO (pexidartinib) is a CSF1R inhibitor indicated for tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations not amenable to surgery. Monitor for hepatotoxicity; baseline and periodic liver function tests required. Do not initiate if transaminases >3x ULN or bilirubin >1.5x ULN. Discontinue permanently for elevated transaminases with bilirubin >2x ULN or for any evidence of severe liver injury. Also monitor for edema, fatigue, and febrile neutropenia. Use in pregnancy only if benefit outweighs risk; effective contraception required for females of reproductive potential. |
| Patient Advice | Take TURALIO exactly as prescribed, usually twice daily with or without food. · Do not drink grapefruit juice or eat grapefruit while taking this medication. · You will need regular blood tests to check your liver function before and during treatment. · Report any signs of liver problems: yellowing of skin or eyes, dark urine, severe fatigue, right upper abdominal pain, or easy bruising/bleeding. · Use effective birth control during treatment and for at least 2 weeks after the last dose if you are able to become pregnant. · Do not breastfeed while taking TURALIO and for at least 2 weeks after the last dose. · Avoid activities requiring mental alertness until you know how the drug affects you, as it may cause dizziness or fatigue. · Tell your doctor about all medications you take, including over-the-counter drugs and herbal supplements. |