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. |
| Molecular Weight | 147000 |
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 | UNLOXCYT (burosumab) is a monoclonal antibody; limited human data, but no embryotoxicity in animal studies. Use only if clearly needed. |
| 2nd trimester | Limited human data; may be used in pregnancy if maternal benefit justifies potential fetal risk. |
| 3rd trimester | Limited human data; may affect fetal phosphate homeostasis. Use with caution near term. |
Clinical note
Comprehensive clinical and safety monograph for UNLOXCYT (UNLOXCYT).
| Placental transfer | Monoclonal antibodies are known to cross the placenta, especially in second and third trimesters; low transfer likely, but limited data. |
| Breastfeeding | Insufficient data on burosumab in breast milk; monoclonal antibodies are likely to be excreted in low amounts. Consider risks and benefits. |
■ 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 known based on labeling; no absolute contraindications reported.
| 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. |
| Food/Dietary | No specific food interactions reported. Maintain adequate oral hydration. Avoid concurrent use of nephrotoxic drugs (e.g., NSAIDs, aminoglycosides) unless necessary. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| 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. |
| Fertility Effects | May impair fertility in males and females based on animal studies; human data lacking. |
| Clinical Pearls | UNLOXCYT (lutetium Lu 177 vipivotide tetraxetan) is a radiolabeled PSMA-targeted therapy for PSMA-positive metastatic castration-resistant prostate cancer. Prehydrate and administer concomitant amino acid solution to reduce renal uptake. Monitor for myelosuppression, xerostomia, and nephrotoxicity. Ensure adequate oral hydration post-infusion. Use strict radiation safety precautions; patient urine is radioactive for up to 30 days. Discontinue concomitant nephrotoxic drugs if possible. |
| Patient Advice | This drug is radioactive; you will be isolated for a few hours after infusion to protect others. · Drink plenty of water for at least 2 days after treatment to help eliminate the drug from your body. · Use a separate toilet and flush twice with the lid down for 1 week. Wash hands thoroughly. · Avoid close contact (within 1 meter) with pregnant women, children, and infants for 1 week. · Sleep in a separate bed and maintain distance from others for several days. · Possible side effects include dry mouth, nausea, low blood counts, and kidney issues. · Use effective contraception during treatment and for 14 weeks after the last dose. · Do not breastfeed during and for 5 months after treatment. |