Pexidartinib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami Ardakani
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Black Box Warning
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Hepatotoxicity
See full prescribing information for complete Boxed Warning.
Pexidartinib can cause serious and potentially fatal liver injury, including acute liver failure and chronic liver injury with fibrosis. Monitor liver tests prior to initiation of Pexidartinib and during treatment. Pexidartinib is available only through a restricted program called the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.
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Overview
Pexidartinib is a Tyrosine Kinase Inhibitor that is FDA approved for the treatment of Tenosynovial Giant Cell Tumor (TGCT).. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Increased liver enzymes (e.g., AST, ALT), Hair color changes, Increased cholesterol levels, Decreased white blood cell counts, Fatigue, Edema, Rash, and Dysgeusia (altered taste). Decreased phosphate levels.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
The recommended dosage is 400 mg (two 200 mg capsules) taken orally twice daily on an empty stomach (at least 1 hour before or 2 hours after a meal or snack).
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Pexidartinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
There is limited information regarding Pexidartinib Contraindications in the drug label.
Warnings
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Hepatotoxicity
See full prescribing information for complete Boxed Warning.
Pexidartinib can cause serious and potentially fatal liver injury, including acute liver failure and chronic liver injury with fibrosis. Monitor liver tests prior to initiation of Pexidartinib and during treatment. Pexidartinib is available only through a restricted program called the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.
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Hepatotoxicity: Pexidartinib can cause serious and potentially fatal liver injury. Monitor liver tests prior to initiation and during treatment.
Embryo-Fetal Toxicity: Pexidartinib can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the final dose.
Adverse Reactions
Clinical Trials Experience
Increased liver enzymes (e.g., AST, ALT) Hair color changes Increased cholesterol levels Decreased white blood cell counts Fatigue Edema Rash Dysgeusia (altered taste) Decreased phosphate levels
Postmarketing Experience
Adverse reactions identified during post-approval use include serious liver injury and hypersensitivity reactions.
Drug Interactions
Strong CYP3A Inhibitors: Concomitant use may increase Pexidartinib plasma concentrations. Avoid concomitant use.
Strong CYP3A Inducers: Concomitant use may decrease Pexidartinib plasma concentrations. Avoid concomitant use.
Acid-Reducing Agents: Avoid concomitant use with proton pump inhibitors. If acid-reducing agents are required, use locally acting antacids or H2 receptor antagonists and separate dosing.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
Pexidartinib can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the final dose.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pexidartinib in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Pexidartinib during labor and delivery.
Nursing Mothers
Advise not to breastfeed during treatment and for 1 week after the final dose.
Pediatric Use
There is no FDA guidance on the use of Pexidartinib in pediatric settings.
Geriatic Use
No overall differences in safety or effectiveness were observed between elderly and younger patients.
Gender
There is no FDA guidance on the use of Pexidartinib with respect to specific gender populations.
Race
There is no FDA guidance on the use of Pexidartinib with respect to specific racial populations.
Renal Impairment
No dosage adjustment is necessary for patients with mild to moderate renal impairment. The effect of severe renal impairment on Pexidartinib pharmacokinetics is unknown.
Hepatic Impairment
Pexidartinib is not recommended for use in patients with pre-existing increased serum transaminases, total bilirubin, or active liver or biliary tract disease.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pexidartinib in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Pexidartinib in patients who are immunocompromised.
Administration and Monitoring
Administration
Pexidartinib is administered orally. Patients should take 400 mg (two 200 mg capsules) twice daily on an empty stomach—at least 1 hour before or 2 hours after meals or snacks. Capsules should be swallowed whole with water, without chewing or crushing. Therapy must be initiated and monitored by a healthcare provider enrolled in the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program due to the risk of hepatotoxicity.
Monitoring
Liver function tests (ALT, AST, and bilirubin) must be performed prior to starting treatment and every week for the first 8 weeks, then every 2 weeks for the next month, and monthly thereafter. Monitor patients for signs and symptoms of hepatotoxicity or any liver-related adverse events. Cholesterol and white blood cell counts should also be monitored periodically. (accessdata.fda.gov)
IV Compatibility
Not applicable, as pexidartinib is administered orally.
Overdosage
Symptoms of overdose may include exaggerated adverse reactions, particularly related to liver function. There is no specific antidote for pexidartinib. In the event of overdose, provide symptomatic and supportive care, including enhanced liver function monitoring.
Pharmacology
There is limited information regarding Pexidartinib Pharmacology in the drug label.
Mechanism of Action
Pexidartinib is a tyrosine kinase inhibitor that targets colony-stimulating factor-1 receptor (CSF1R), a receptor involved in the proliferation and survival of macrophages. By inhibiting CSF1R, pexidartinib reduces the number of tumor-associated macrophages, which play a role in the progression of Tenosynovial Giant Cell Tumor (TGCT).
Structure
There is limited information regarding Pexidartinib Structure in the drug label.
Pharmacodynamics
Pexidartinib reduces macrophage activity in tumor tissue, which is measurable by a reduction in macrophage markers. Prolonged inhibition of CSF1R has shown improvements in patients with symptomatic TGCT.
Pharmacokinetics
Absorption: Peak plasma concentrations (C_max) are reached approximately 2–4 hours after oral administration. Metabolism: Primarily metabolized by CYP3A4. Elimination: Excreted through feces (~65%) and urine (~30%). Half-life: Approximately 25 hours after a single dose.
Nonclinical Toxicology
There is limited information regarding Pexidartinib Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Pexidartinib Clinical Studies in the drug label.
How Supplied
Pexidartinib is supplied as 200 mg capsules, which are opaque white with "PEX200" imprinted on them. It is available in bottles of 60 or 120 capsules.
Storage
Store pexidartinib at 20°C to 25°C (68°F to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and light, and keep the bottle tightly closed.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Patients should be informed to: Take pexidartinib on an empty stomach.
Recognize and immediately report any symptoms of liver toxicity (e.g., yellowing of the skin or eyes, dark urine, fatigue, nausea).
Adhere to scheduled liver function tests as part of the REMS program monitoring.
Use effective contraception during treatment and for 1 month after the last dose.
Precautions with Alcohol
Alcohol consumption may exacerbate liver toxicity and is generally discouraged while taking pexidartinib. Patients should consult their healthcare provider regarding alcohol use during treatment.
Brand Names
Turalio
Look-Alike Drug Names
There is limited information regarding Pexidartinib Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.