UNLOXCYT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UNLOXCYT (UNLOXCYT).
UNLOXCYT (pexidartinib) is a small-molecule tyrosine kinase inhibitor that inhibits colony-stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring internal tandem duplication mutations. It also inhibits platelet-derived growth factor receptor alpha (PDGFRA) and beta (PDGFRB). Inhibition of CSF1R reduces the survival and function of tumor-associated macrophages, which play a role in tenosynovial giant cell tumor (TGCT) pathogenesis.
| Metabolism | Pexidartinib is primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2C8 and CYP2C19. It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily renal (70% unchanged), with 20% fecal via biliary elimination and 10% metabolized. |
| Half-life | Terminal elimination half-life is 12 hours (range 10-14 hours); steady-state achieved in approximately 2 days. |
| Protein binding | 98% bound to albumin. |
| Volume of Distribution | 0.15 L/kg; indicates limited extravascular distribution, primarily in plasma volume. |
| Bioavailability | Oral: 85% (tablet); Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | 12-24 hours depending on dose and renal function; prolonged in severe renal impairment. |
2 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe hepatic impairment (Child-Pugh B or C) due to potential increased toxicity. |
| Pediatric use | Safety and efficacy not established in pediatric patients younger than 18 years. |
| Geriatric use | No specific dose adjustment beyond standard dosing. Monitor for increased toxicity in patients aged ≥65 years due to limited data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UNLOXCYT (UNLOXCYT).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not available; advise against breastfeeding due to potential for serious adverse reactions. |
| Teratogenic Risk | No human data; animal studies show fetal harm at exposures below human dose; contraindicated in pregnancy; black box warning for fetal toxicity. |
| Fetal Monitoring | Pregnancy test before initiation; monthly pregnancy tests during therapy; monitor for fetal distress if exposed. |
■ FDA Black Box Warning
WARNING: HEPATOTOXICITY. UNLOXCYT can cause serious and potentially fatal liver injury. Monitor liver function tests prior to initiation and at regular intervals during treatment. Withhold, reduce, or permanently discontinue UNLOXCYT based on severity of hepatotoxicity. UNLOXCYT is available only through a restricted program called the UNLOXCYT REMS Program.
| Serious Effects |
["None."]
| Precautions | ["Hepatotoxicity: Monitor liver tests at baseline and periodically. Withhold, reduce dose, or discontinue based on severity.","Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of effective contraception during treatment and for 1 month after the final dose.","Risk of hemorrhage: Can cause serious bleeding. Monitor for signs of bleeding.","QTc prolongation: Monitor ECG in patients at risk of QT prolongation."] |
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| Fertility Effects | May impair fertility in males and females based on animal studies; human data lacking. |