Pexidartinib
Indications
Pexidartinib is used for:
Tenosynovial Giant Cell Tumor
Adult Dose
Tenosynovial Giant Cell Tumor
Indicated for adults with tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery
400 mg PO BID on an empty stomach until disease progression or unacceptable toxicity
Hepatic impairment
Mild (TB ULN or TB >1-1.5x ULN with any AST): No dosage adjustment required
Moderate or severe: Not established;
Child Dose
Renal Dose
Renal impairment
Mild-to-severe (CrCl 15-89 mL/min): 200 mg in AM and 400 mg in evening
Administration
Oral Administration
Administer on empty stomach, at least 1 hr before or 2 hr after a meal or snack
Swallow capsule whole; do not open, break, or chew
Contra Indications
Precautions
Based on animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
Hepatoxicity
Hepatotoxicity with ductopenia and cholestasis occurred; mechanism of cholestatic hepatotoxicity is unknown and its occurrence cannot be predicted
It is unknown whether liver injury occurs in the absence of increased transaminases
Administration with food increases drug exposure by 100% and may increase risk of hepatotoxicity
Monitor liver tests before initiating treatment, weekly for the first 8 weeks, every 2 weeks for the next month, and every 3 months thereafter
REMS program
Available only through a restricted program under a REMS, owing to the risk of hepatoxicity
Requirements of the program include the following:
Prescribers must be certified with the program by enrolling and completing training
Patients must complete and sign an enrollment form for inclusion in a patient registry
Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive pexidartinib
Pregnancy-Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, embryofetal harm may occur when administered to a pregnant woman
Available human data do not establish the presence or absence of major birth defects or miscarriage related to use in pregnant women
Animal data
Oral administration of pexidartinib to pregnant animals during organogenesis resulted in malformations, postimplantation loss, and abortion at maternal exposures that were approximately equal to the human exposure at the recommended dose of 800 mg
Advise pregnant women of the potential risk to a fetus
Pregnancy testing
Verify pregnancy status in females of reproductive potential before initiating treatment
Contraception
Embryofetal harm may occur when administered to a pregnant woman
Females of reproductive potential: Use effective contraception during treatment and for 1 month after final dose
Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after final dose
Infertility
Based on findings from animal studies, treatment may impair both male and female fertility
Lactation
There are no data on presence of pexidartinib or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production
Owing to the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after final dose
Interactions
Adverse Effects
Side effects of Pexidartinib :
All grades of severity listed unless otherwise indicated
>10%
Increased LDH (92%)
Hair color changes (67%)
Fatigue (64%)
Increased AST, Grade 1 (61%)
Increased cholesterol (44%)
Decreased neutrophils (44%)
Decreased lymphocytes (38%)
Increased ALT (31%)
Increased ALP (31%)
Eye edema (30%)
Decreased hemoglobin (30%)
Rash (28%)
Dysgeusia (26%)
Peripheral edema (20%)
Vomiting (20%)
Pruritus (18%)
Decreased appetite (16%)
Decreased platelets (15%)
Increased AST, Grade 2 (15%)
Hypertension (15%)
Increased ALT, Grade 2 (13%)
Constipation (12%)
Blurred vision (>10%)
>10% (Grade >3)
Increased ALT (20%)
Increased AST (12%)
Mechanism of Action
Orally bioavailable inhibitor of colony-stimulator factor 1 receptor (CSF1R), a tyrosine kinase receptor; also elicits potential antineoplastic, macrophage checkpoint-inhibitory, and immunomodulating activities
Targets and binds to CSF1R expressed on monocytes, macrophages, and osteoclasts, and inhibits the binding of the CSF1R ligands colony-stimulating factor-1 and interleukin-34, to CSF1R; this prevents CSF1R activation and CSF1R-mediated signaling in these cells
The described actions block production of inflammatory mediators by macrophages and monocytes and reduce inflammation, thereby inhibiting immunomodulating activity by macrophages and enhancing T-cell infiltration and antitumor T-cell immune responses, which inhibits tumor cell proliferation