Pexidartinib

Pexidartinib is a prescription medication used for the treatment of tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

• Pexidartinib is available under the following different brand names: Turalio

Common side effects of Pexidartinib include:

• abnormal liver function tests
• high cholesterol
• low blood cell counts
• puffy eyes
• changes in the color of the hair
• rash
• decreased or altered sense of taste

Serious side effects of Pexidartinib include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• dark urine
• yellowing of the skin or eyes (jaundice)
• right-sided upper stomach pain
• loss of appetite
• nausea
• vomiting
• fever
• tiredness
• itching

Rare side effects of Pexidartinib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 125 mg

Tenosynovial Giant Cell Tumor

Adult dosage

• 250 mg orally twice a day with a low-fat meal (~11-14 g total fat); continue until disease progression or unacceptable toxicity
• Taking with a high-fat meal (~55-65 g total fat) increases pexidartinib concentrations and may increase the risk of adverse reactions, including hepatotoxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pexidartinib has severe interactions with the following drugs:
  • lonafarnib
  • mavacamten
  • pacritinib
• Pexidartinib has serious interactions with at least 180 drugs.
• Pexidartinib has moderate interactions with at least 21 drugs.
• Pexidartinib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pexidartinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pexidartinib?”

Cautions

• 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; the mechanism of cholestatic hepatotoxicity is unknown and its occurrence cannot be predicted
  • It is unknown whether the liver injury occurs in the absence of increased transaminases
  • Administration with food increases drug exposure by 100% and may increase the 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
• Risks associated with a high-fat meal
  • Taking with a high-fat meal increases pexidartinib concentrations, which may increase the incidence and severity of adverse reactions, including hepatotoxicity
  • Instruct patients to take the drug with a low-fat meal
  • Consider referring patients to a dietician as deemed necessary
• 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
  • Further information is available at www.turalioREMS.com or 1-833-887-2546
• Drug interaction overview
  • The substrate of CYP3A4 and UGT1A4; is also known to cause hepatoxicity
    • Moderate CYP3A inducer
      • Hepatotoxic agents
      • Avoid coadministration of pexidartinib with other products known to cause hepatoxicity in patients with increased serum transaminases, total bilirubin, or direct bilirubin (above ULN) or active liver or biliary tract disease, owing to increased risk of hepatoxicity
  • Strong or moderate CYP3A inhibitors or UGT inhibitors
    • Avoid coadministration
    • Strong CYP3A inhibitors increase pexidartinib plasma concentrations and potentially increase the incidence and severity of adverse reactions
    • Reduce pexidartinib dose according to recommendations
  • Strong CYP3A inducers
    • Avoid coadministration
    • Strong CYP3A inducers decrease pexidartinib plasma levels, which may decrease pexidartinib efficacy
  • CYP3A substrates
    • Pexidartinib decreases the concentration of CYP3A substrates, which may reduce the efficacy of these substrates
    • Avoid coadministration with hormonal contraceptives
    • Avoid coadministration with CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures; if coadministration is unavoidable, increase the CYP3A substrate dosage in accordance with the prescribing information
  • Acid-reducing agents
    • Avoid coadministration with proton pump inhibitors (PPIs)
    • PPIs decrease pexidartinib plasma concentrations, which may decrease pexidartinib efficacy
    • Alternatively, may use a locally-acting antacid or H2-receptor antagonist

Pregnancy and Lactation

• 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 miscarriages related to use in pregnant women
• Pregnancy testing
  • Verify pregnancy status in females of reproductive potential before initiating treatment
• Contraception
  • Females of reproductive potential: Use effective nonhormonal contraception during treatment and for 1 month after the final dose; therapy can render hormonal contraceptives ineffective
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after the final dose
• Infertility
  • Based on findings from animal studies, treatment may impair both male and female fertility
• Lactation
  • No data is available on the presence of pexidartinib or its metabolites in either human or animal milk or its effects on a breastfed child or milk production
  • Advise females not to breastfeed during treatment and for at least 1 week after the final dose