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Pexidartinib

Medically reviewed by Drugs.com. Last updated on Jun 29, 2020.

Pronunciation

(pex i DAR ti nib)

Index Terms

  • Pexidartinib Hydrochloride
  • PLX3397

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Turalio: 200 mg

Brand Names: U.S.

  • Turalio

Pharmacologic Category

  • Antineoplastic Agent, Tyrosine Kinase Inhibitor

Pharmacology

Pexidartinib is a tyrosine kinase inhibitor with selective and strong inhibitory activity against the colony-stimulating factor 1 receptor (CSF1R); pexidartinib also inhibits KIT and FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (Tap 2019). Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium. Pexidartinib inhibits proliferation of a CSF1R dependent cell line

Distribution

Vz/F: 187 L

Metabolism

Oxidation via CYP3A4 and glucuronidation via UGT1A4 (glucuronidation forms inactive N-glucuronide metabolite)

Excretion

Feces (65%; 44% as unchanged drug); Urine (27% as metabolites); Clearance: 5.1 L/hour

Time to Peak

2.5 hours

Half-Life Elimination

26.6 hours

Protein Binding

>99%; to albumin and alpha-1 acid glycoprotein

Special Populations: Renal Function Impairment

Mild, moderate, and severe impairment (CrCl 15 to 89 mL/minute) increased pexidartinib exposure by ~30%, compared to normal renal function (CrCl ≥90 mL/minute).

Use: Labeled Indications

Tenosynovial giant cell tumor: Treatment of symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery in adults.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Tenosynovial giant cell tumor: Oral: 400 mg twice daily until disease progression or unacceptable toxicity (Tap 2019).

Dosage adjustment for concomitant therapy:Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Missed dose: If a dose is missed or vomited, administer the next dose at its scheduled time.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Recommended pexidartinib dosage reduction levels:

Initial (usual dose): 400 mg twice daily (total of 800 mg/day).

First dose reduction level: 200 mg in the morning and 400 mg in the evening (total of 600 mg/day).

Second dose reduction level: 200 mg twice daily (total of 400 mg/day).

Permanently discontinue if unable to tolerate 200 mg twice daily.

Severe or intolerable adverse reactions or lab abnormalities (other than hepatic): Withhold pexidartinib until improvement or resolution. Resume pexidartinib at a reduced dose upon improvement or resolution.

Administration

Oral: Administer on an empty stomach, ≥1 hour before or 2 hours after a meal or snack. Swallow capsules whole; do not open, break or chew.

Acid-reducing agents: Administer pexidartinib 2 hours before or 2 hours after locally-acting antacids; administer pexidartinib ≥2 hours before or 10 hours after a H2-receptor antagonist. Avoid concomitant administration of pexidartinib with proton pump inhibitors.

Dietary Considerations

Avoid grapefruit juice.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep container(s) closed; do not remove desiccant from bottles.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abiraterone Acetate. Monitor therapy

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Monitor therapy

Alfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Alfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Consider therapy modification

Antacids: May decrease the serum concentration of Pexidartinib. Management: Administer pexidartinib 2 hours before or after antacids. Consider therapy modification

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Monitor therapy

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Avoid combination

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy

Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Monitor therapy

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Consider therapy modification

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Monitor therapy

Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Avoid combination

Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Pexidartinib. Exceptions: St John's Wort. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Pexidartinib. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with moderate CYP3A4 inhibitors if possible. If combined, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily. Exceptions: Grapefruit Juice. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily Consider therapy modification

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Exceptions: Apixaban; Bromperidol; Rivaroxaban. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dapsone (Systemic). Monitor therapy

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

Doravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Doravirine. Monitor therapy

Elbasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir. Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Monitor therapy

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Avoid combination

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Avoid combination

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Monitor therapy

Etravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etravirine. Monitor therapy

Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Monitor therapy

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Avoid combination

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Consider therapy modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grapefruit Juice: May increase the serum concentration of Pexidartinib. Avoid combination

Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Consider therapy modification

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Pexidartinib. Management: Administer pexidartinib 2 hours before or 10 hours after histamine H2 receptor antagonists. Consider therapy modification

Hormonal Contraceptives: Pexidartinib may decrease the serum concentration of Hormonal Contraceptives. Management: Use an effective non-hormonal form of contraception. Avoid combination

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Monitor therapy

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Monitor therapy

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Avoid combination

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Monitor therapy

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Avoid combination

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

Lurbinectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurbinectedin. Avoid combination

Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Monitor therapy

Meperidine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Monitor therapy

Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Monitor therapy

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Monitor therapy

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Avoid combination

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Monitor perampanel response closely, particularly with changes to CYP3A4 inducer therapy. Consider therapy modification

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Avoid combination

Pitolisant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pitolisant. Monitor therapy

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Avoid combination

Proton Pump Inhibitors: May decrease the serum concentration of Pexidartinib. Management: If acid-reduction is needed, consider administering an antacid 2 hours before or after pexidartinib, or administer pexidartinib 2 hours before or 10 hours after an H2 receptor antagonist. Avoid combination

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Avoid combination

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Avoid combination

Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Sirolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus. Monitor therapy

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

St John's Wort: May decrease the serum concentration of Pexidartinib. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Avoid combination

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Consider therapy modification

UGT1A4 Inhibitors: May increase the serum concentration of Pexidartinib. Management: Avoid use of UGT1A4 inhibitors and pexidartinib. If combined use is required, reduce the pexidartinib dose. If receving pexidartinib 800 mg or 600 mg daily, reduce to 200 mg twice daily. If receiving 400 mg per day, reduce to 200 mg once daily. Consider therapy modification

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Monitor therapy

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Monitor therapy

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Monitor therapy

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Avoid combination

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (20%), hypertension (15%)

Central nervous system: Fatigue (64%)

Dermatologic: Hair discoloration (67%), skin rash (28%), pruritus (18%)

Endocrine & metabolic: Increased lactate dehydrogenase (92%), increased serum cholesterol (44%), decreased serum phosphate (25%)

Gastrointestinal: Dysgeusia (26%), vomiting (20%), decreased appetite (16%), constipation (12%)

Hematologic & oncologic: Decreased neutrophils (44%; grade ≥3: 3%), lymphocytopenia (38%; grade ≥3: 2%), decreased hemoglobin (30%), thrombocytopenia (15%)

Hepatic: Increased serum aspartate aminotransferase (61%), increased serum alanine aminotransferase (31%), increased serum alkaline phosphatase (31%)

Ophthalmic: Swelling of eye (30%)

1% to 10%:

Central nervous system: Neuropathy (10%), cognitive dysfunction

Dermatologic: Alopecia, dyschromia

Gastrointestinal: Cholangitis, oral mucosa ulcer, stomatitis, xerostomia

Hepatic: Hepatotoxicity (5% to <10%), increased serum bilirubin (3%), hepatic disease

Ophthalmic: Blurred vision, decreased visual acuity, diplopia, photophobia

Miscellaneous: Fever

Frequency not defined:

Central nervous system: Dizziness

Endocrine & metabolic: Increased gamma-glutamyl transferase

Gastrointestinal: Abdominal pain, nausea

ALERT: U.S. Boxed Warning

Hepatotoxicity:

Pexidartinib can cause serious and potentially fatal liver injury. Monitor liver tests prior to initiation of pexidartinib and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue pexidartinib based on severity of hepatotoxicity.

Pexidartinib is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: [US Boxed Warning]: Pexidartinib can cause serious and potentially fatal liver injury. Monitor liver function prior to pexidartinib initiation and during treatment. Based on the severity, hepatotoxicity may require treatment interruption, dose reduction, and/or permanent discontinuation. Hepatotoxicity with ductopenia and cholestasis has occurred, including rare irreversible cases of cholestatic liver injury (which were fatal or required liver transplantation). The occurrence of pexidartinib-related cholestatic hepatoxicity cannot be predicted, and the mechanism of hepatotoxicity is unknown. It is not known if liver injury occurs in the absence of transaminase elevations. A small percentage of patients in a clinical study who received pexidartinib developed signs of serious liver injury (ALT or AST ≥3 × ULN with total bilirubin ≥2 × ULN). In these patients, peak ALT ranged from 6 to 9 × ULN, peak total bilirubin ranged from 2.5 to 15 × ULN, and alkaline phosphatase was ≥2 × ULN. ALT, AST and total bilirubin improved to <2 × ULN at 1 to 7 months after discontinuing pexidartinib. Avoid pexidartinib in patients with preexisting increased serum transaminases, total bilirubin or direct bilirubin (> ULN), or active liver or biliary tract disease (including increased alkaline phosphatase). Monitor liver function tests (including AST, ALT, total bilirubin, direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase [GGT]) prior to pexidartinib initiation, weekly for the first 8 weeks, every 2 weeks for the next month, and then every 3 months thereafter. Hepatotoxicity may require treatment interruption, dose reduction, and/or permanent discontinuation (based on the severity). Rechallenge with a reduced pexidartinib dose may result in a recurrence of increased transaminases, bilirubin, or alkaline phosphatase; following rechallenge, monitor liver function tests weekly for the first month. Administer pexidartinib on an empty stomach (1 hour before or 2 hours after a meal or snack), as administration with food increases exposure by up to 100% and may increase the risk of hepatotoxicity. Avoid concurrent administration of other hepatotoxic medications in patients with elevated transaminases, elevated total or direct bilirubin (> ULN), or active liver or biliary tract disease.

Disease-related concerns:

• Renal impairment: Dose reduction recommended in patients with renal impairment.

Concurrent drug therapy issues:

• Acid-reducing agents: Avoid concomitant administration of pexidartinib with proton pump inhibitors. A locally-acting antacid or a histamine 2 (H2)-receptor antagonist may be alternatively utilized. Administer pexidartinib 2 hours before or 2 hours after local antacids. Administer pexidartinib ≥2 hours before or 10 hours after a H2-receptor antagonist.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions

• REMS program: [US Boxed Warning]: Pexidartinib is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program. Information is available at www.turalioREMS.com or 1-833-887-2546.

Monitoring Parameters

Monitor liver function tests (including AST, ALT, total bilirubin, direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase [GGT]) prior to pexidartinib initiation, weekly for the first 8 weeks, every 2 weeks for the next month and then every 3 months thereafter; following rechallenge, monitor liver function tests weekly for the first month. Monitor renal function. Evaluate pregnancy status prior to treatment initiation (in females of reproductive potential). Monitor for signs/symptoms of liver injury. Monitor adherence.

Reproductive Considerations

Evaluate pregnancy status prior to treatment initiation in females of reproductive potential. Females of reproductive potential should use effective nonhormonal contraception during treatment and for 1 month after the last pexidartinib dose. Males with a female partner of reproductive potential should use effective contraception during treatment and for 1 week after the last pexidartinib dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to pexidartinib may cause fetal harm.

Patient Education

What is this drug used for?

• It is used to treat a type of cancer called tenosynovial giant cell tumor (TGCT).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hair discoloration

• Change in taste

• Vomiting

• Constipation

• Lack of appetite

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe headache

• Dizziness

• Passing out

• Vision changes

• Low phosphate like vision changes, confusion, mood changes, muscle pain, muscle weakness, shortness of breath, trouble breathing, or trouble swallowing

• Swelling of arms or legs

• Swelling in or around the eyes

• Burning or numbness feeling

• Infection

• Bruising

• Bleeding

• Severe loss of strength and energy

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.