- March 15, 2022
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Brand Name :
Turalio
Synonyms :
pexidartinib
Class :
Antineoplastic agents and Tyrosinase Kinase Inhibitors; CSF1R Inhibitors
Dosage forms & Strengths
Capsule
200mg
pexidartinib is indicated in the treatment of tenosynovial giant cell tumor
A dose of 400 mg is administered twice daily on an empty stomach
The medication is continued until the disease is reduced to acceptable toxicity
Dose Adjustments
In case of adverse reactions, the dose is modified or reduced
The pattern of dose reduction goes like this
First dose reduction: 200 mg in the morning and 200 mg in the afternoon
Second dose reduction: 200 mg twice daily
In case the patient is unable to tolerate 200 mg twice daily, discontinue the treatment
The safety and efficacy of pexidartinib are not found for pediatric dosing
Refer to the adult dosing
pexidartinib decreases the effect or level of lonafarnib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
pexidartinib decreases the effect or level of mavacamten by altering the intestinal/hepatic CYP3A4 enzyme metabolism
pexidartinib decreases the effect or level of pacritinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
pexidartinib: they may diminish the serum concentration of antacids
pexidartinib: they may diminish the serum concentration of antacids
pexidartinib: they may diminish the serum concentration of antacids
pexidartinib: they may diminish the serum concentration of antacids
pexidartinib: they may diminish the serum concentration of antacids
CYP3A4 inducers decrease the concentration of abemaciclib in serum
CYP3A4 inducers decrease the concentration of avapritinib in serum
CYP3A4 inducers decrease the concentration of bosutinib in serum
CYP3A4 inducers decrease the concentration of cobimetinib in serum
CYP3A4 inducers decrease the concentration of daridorexant in serum
CYP3A4 inducers decrease the concentration of encorafenib in serum
CYP3A4 inducers decrease the concentration of flibanserin in serum
it may increase the concentration of pexidartinib in serum
CYP3A4 inducers decrease the concentration of active metabolites of infigratinib in serum
CYP3A4 inducers decrease the concentration of neratinib in serum
CYP3A4 inducers decrease the concentration of olaparib in serum
CYP3A4 inducers decrease the concentration of pemigatinib in serum
CYP3A4 inducers decrease the concentration of selumetinib in serum
CYP3A4 inducers decrease the concentration of tazemetostat in serum
CYP3A4 inducers decrease the concentration of velpatasvir in serum
CYP3A4 inducers decrease the concentration of vorapaxar in serum
CYP3A4 inducers decrease the concentration of zanubrutinib in serum
pexidartinib: they may diminish the serum cocentration of hormonal contraceptives
pexidartinib: they may diminish the serum cocentration of hormonal contraceptives
pexidartinib: they may diminish the serum cocentration of hormonal contraceptives
pexidartinib: they may diminish the serum cocentration of hormonal contraceptives
It may diminish the effect when combined with lumateperone by affecting CYP3A4 metabolism
It may enhance when combined with vitamin D
Might lead to a reduction in the concentration serum of Hormonal Contraceptives
Might lead to a reduction in the concentration serum of Hormonal Contraceptives
Might lead to a reduction in the concentration serum of Hormonal Contraceptives
Could potentially reduce the concentration serum of hormonal contraceptives
Could potentially reduce the concentration serum of hormonal contraceptives
when both drugs are combined, there may be an increased risk or severity of adverse effects
may enhance hepatotoxic effects of pexidartinib
the effect of pexidartinib is decreased by lorlatinib, by altering intestinal or hepatic CYP3A4 enzyme metabolism
CYP3A strong enhancers of the small intestine may reduce the bioavailability of pexidartinib
they both increase the effect of each other when used simultaneously
pexidartinib and oxymetholone increase the effect of each other
pexidartinib and danazol both increase the effect of each other
pexidartinib and fluoxymesterone both increase the effect of each other
pexidartinib and methyltestosterone both increase the effect of each other
oxandrolone and pexidartinib both increase the effect of each other
pexidartinib and methyltestosterone both increase the effect of each other
it decreases the concentration of hormonal contraceptives in serum
lansoprazole amoxicillin and clarithromycin
when amoxicillin combines with pexidartinib it decreases the effects of action of drug and results in hepatotoxicity
amoxicillin and clavulanate potassium
when amoxicillin combines with pexidartinib it decreases the effects of action of drug and results in hepatotoxicity
omeprazole amoxicillin and clarithromycin
when both drugs are combined, there may be a decreased effect of the drug's action by antagonism effect
when both drugs are combined, there may be a decreased effect of the drug's action by antagonism effect
pexidartinib and testolactone both increase the effect of each other
may diminish the serum concentration of Hormonal Contraceptives
etonogestrel/ethinyl estradiol
may diminish the serum concentration of Hormonal Contraceptives
pexidartinib and methyltestosterone both increase the effect of each other
aluminum hydroxide decreases the effect or level of pexidartinib by inhibiting gastrointestinal absorption
pexidartinib decreases the effect or level of atogepant by altering the intestinal or hepatic CYP3A4 enzyme metabolism
pexidartinib decreases the effect or level of belumosudil by altering the intestinal or hepatic CYP3A4 enzyme metabolism
calcium carbonate decreases the effect or level of pexidartinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
cenobamate decreases the effect or level of pexidartinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
elagolix decreases the effect or level of pexidartinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
pexidartinib decreases the effect or level of isavuconazonium sulfate by altering the intestinal or hepatic CYP3A4 enzyme metabolism
istradefylline increases the effect or level of pexidartinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
decreases the effect or level of pexidartinib by inhibiting gastrointestinal absorption
decreases the effect or level of pexidartinib by inhibiting gastrointestinal absorption
increases the effect or level of pexidartinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
decreases the effect or level of pexidartinib by inhibiting gastrointestinal absorption
pexidartinib decreases the effect or level of tivozanib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
Actions and Spectrum:
pexidartinib is a tyrosine kinase inhibitor that selectively targets colony-stimulating factor 1 receptor (CSF1R), a protein involved in the growth and survival of certain types of cells, including tumor-associated macrophages. By inhibiting CSF1R, pexidartinib can disrupt tumor-associated macrophages’ activity and potentially slow tumor growth.
In addition to its role in TGCT, pexidartinib has shown promise in treating other types of cancer, including glioblastoma and diffuse intrinsic pontine glioma (DIPG), highly aggressive brain tumors. pexidartinib has also been studied as a potential treatment for rheumatoid arthritis, characterized by the infiltration of macrophages into the joints.
Frequency defined:
>10%
Increased LDH
Hair color changes
Fatigue
Increased AST
Increased cholesterol
Decreased neutrophils
Decreased lymphocytes
Increased ALT
Increased ALP
Eye edema
Decreased hemoglobin
Rash
Dysgeusia
Peripheral edema
Vomiting
Pruritus
Decreased appetite
Decreased platelets
Increased AST
Hypertension
Increased ALT
Constipation
Blurred vision
1-10%
Neuropathy
Photophobia
Diplopia
Reduced visual acuity
Dry mouth
Stomatitis
Mouth ulceration
Pyrexia
Cholangitis
Hepatotoxicity
Liver disorder
Cognitive disorders
Alopecia
Increased cholesterol
Decreased phosphate
Increased ALP
Increased bilirubin
Black-Box Warning:
pexidartinib can cause severe and potentially fatal liver injury, so it is important to monitor liver function tests before and during treatment. If liver toxicity is detected, the dose of pexidartinib may need to be reduced, or the drug may need to be temporarily or permanently discontinued, depending on the severity of the hepatotoxicity.
To ensure the safe use of pexidartinib, the FDA has mandated a restricted program called the Turalio Risk Evaluation and Mitigation Strategy (REMS). This program is designed to ensure that the benefits of pexidartinib outweigh its risks.
It includes the mandatory enrollment of prescribers and pharmacies, patient education materials, and ongoing safety data monitoring. REMS aims to minimize the risk of liver toxicity associated with pexidartinib while providing access to this necessary therapy for patients with TGCT.
Contraindication/Caution:
Pregnancy consideration: The drug is toxic and unsafe for pregnant women and the developing fetus.
Breastfeeding warnings: No data on the excretion of pexidartinib in breast milk is available. Because of possible serious effects, women are advised to breastfeed one week after the last dose of pexidartinib.
Pregnancy category:
Pharmacology:
pexidartinib selectively binds to and inhibits the activity of CSF1R, thereby blocking the signaling pathway that promotes the growth and survival of these cells. It reduces the number of macrophages and osteoclasts in the body, which can help reduce inflammation and bone resorption.
Pharmacodynamics:
pexidartinib has been shown to selectively inhibit the proliferation and survival of CSF1R-dependent cell lines in vitro and to reduce the number of macrophages and osteoclasts in vivo in animal models. In addition to its effects on CSF1R, pexidartinib has also been shown to inhibit the activity of KIT, a receptor tyrosine kinase often overexpressed in certain types of cancer.
Pharmacokinetics:
Absorption
The peak plasma concentration is achieved in 2.5 hours
The peak plasma concentration is 8625 ng/mL
The area under the curve is 77,465 ng h/mL
The time to achieve steady state is 7 days
Distribution
The volume of distribution is 187 L
Bound protein is more than 99%
Human serum albumin is around 99.9% and alpha-1 acid glycoprotein: 89.9%
Metabolism
Primary pathway
CYP3A4 oxidizes the drug, and glucuronidation occurs by UGT1A4
N-glucuronide metabolite
UGT1A4 forms the major inactive metabolite
Elimination and Excretion
The half-life is 26.6 hours
The rate of clearance is 5.1 L/hr
The drug is excreted 65% in feces and 27% in urine as metabolites (>/=10% as N-glucuronide)
Administration:
pexidartinib is a prescription medication used for the treatment of symptomatic tenosynovial giant cell tumor (TGCT) in adults. It is available in capsule form and should be taken orally with or without food. The usual recommended dose is 400 mg (4 capsules) twice daily until disease progression or unacceptable toxicity occurs.
Before starting pexidartinib treatment, patients should undergo liver function tests, complete blood counts, and monitoring for hypertension. Patients with severe hepatic impairment should not take pexidartinib, and those with mild to moderate hepatic impairment should be monitored closely during treatment.
Patient information leaflet
Generic Name: pexidartinib (Rx)
Pronounced: PEX-i-DAR-ti-nib
Why do we use pexidartinib?
pexidartinib is a medication that is used to treat a rare type of cancer called tenosynovial giant cell tumor (TGCT), which can develop in the joints, tendons, and synovial tissue. TGCT is a benign tumor that can cause pain, stiffness, and limited mobility, and can also cause damage to surrounding tissue if left untreated.
pexidartinib works by inhibiting a specific enzyme called CSF1R, which plays a key role in the development and survival of the tumor cells. By blocking this enzyme, pexidartinib can reduce the growth and spread of the tumor, and improve the symptoms associated with TGCT.
pexidartinib is typically used in cases where the tumor cannot be removed surgically or when it has spread to other parts of the body. It is usually administered orally in the form of capsules, and treatment may last for several months or longer depending on the individual case.
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