About TURALIO

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CSF-1

Colony-stimulating factor 1

Overexpression of the colony-stimulating factor 1 receptor (CSF-1R) ligand promotes cell proliferation and accumulation in the synovium.1 The neoplastic cells drive a tumor landscape composed primarily of inflammatory cells.2

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CSF-1R

Colony-stimulating factor 1 receptor

Pexidartinib is a small-molecule tyrosine kinase inhibitor that targets CSF-1R, KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation.1

In vitro, pexidartinib inhibited the proliferation of cell lines dependent on CSF-1R and ligand-induced autophosphorylation of CSF-1R.1

Pexidartinib also inhibited the proliferation of a CSF-1R–dependent cell line in vivo.1

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CSF-1, colony-stimulating factor 1; CSF-1R, colony-stimulating factor 1 receptor.

Dosage and administration1

Important administration instructions

Administer TURALIO on an empty stomach, with no food or snack at least 2 hours before or at least 1 hour after medication.

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Recommended dosage

The recommended dose of TURALIO is 400 mg taken twice daily until disease progression or unacceptable toxicity.

TURALIO capsules should be swallowed whole. Capsules should not be opened, broken, or chewed.

If patients vomit or miss a dose of TURALIO, instruct them to take the next dose at its scheduled time.

Overdosage

Due to the high plasma protein binding, TURALIO is not expected to be dialyzable.

Dosage modifications for adverse reactions

Recommended TURALIO dose reductions for adverse reactions

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Permanently discontinue TURALIO in patients who are unable to tolerate 200 mg orally twice daily.

Dosage modifications

Dose reductions or interruptions occurred in 38% of patients who received TURALIO, most frequently (occurring in >1 patient) due to increased ALT (13%), increased AST (13%), nausea (8%), increased ALP (7%), vomiting (4.9%), increased bilirubin (3.3%), increased gamma-glutamyl transferase (3.3%), dizziness (3.3%), and abdominal pain (3.3%).

Recommended TURALIO dosage modifications for adverse reactions

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ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ARs, adverse reactions; GGT, gamma-glutamyltransferase; ULN, upper limit of normal.

aConfirm ALP elevations as liver isozyme fraction.

Warnings and precautions1

arrow-up Hepatotoxicity

Hepatotoxicity

TURALIO can cause serious and potentially fatal liver injury and is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).

Hepatotoxicity with ductopenia and cholestasis has occurred in patients treated with TURALIO. Across 768 patients who received TURALIO in clinical trials, there were 2 irreversible cases of cholestatic liver injury. One patient with advanced cancer and ongoing liver toxicity died and one patient required a liver transplant. The 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.

In ENLIVEN, 3 of 61 patients (5%) who received TURALIO developed signs of serious liver injury, defined as 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 ALP was ≥2 × ULN. ALT, AST, and total bilirubin improved to <2 × ULN in these patients 1 to 7 months after discontinuing TURALIO.

Avoid TURALIO in patients with preexisting increased serum transaminases, total bilirubin, or direct bilirubin (>ULN) and in patients with active liver or biliary tract disease including increased ALP. Taking TURALIO with food increases drug exposure by 100% and may increase the risk of hepatotoxicity. Administer TURALIO on an empty stomach, either 1 hour before or 2 hours after a meal or snack.

Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and GGT, prior to initiation of TURALIO, weekly for the first 8 weeks, every 2 weeks for the next month, and every 3 months thereafter.

Withhold and dose reduce or permanently discontinue TURALIO based on the severity of the hepatotoxicity. Rechallenging with a reduced dose of TURALIO may result in a recurrence of increased serum transaminases, bilirubin, and ALP. Monitor liver tests, including direct bilirubin, weekly for the first month after rechallenge.

arrow-up TURALIO REMS

TURALIO REMS

TURALIO is available only through a restricted program under a REMS, because of the risk of hepatotoxicity. Notable requirements of the TURALIO REMS 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 dispense only to patients who are authorized (enrolled in the REMS patient registry) to receive TURALIO.

Further information is available at turalioREMS.com or 1-833-887-2546.

To become a certified prescriber, please visit turalioREMS.com.

arrow-up Embryo-fetal toxicity

Embryo-fetal toxicity

Based on animal studies and its mechanism of action, TURALIO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TURALIO and for 1 month after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TURALIO and for 1 week after the final dose.

Drug interactions1

Use with hepatotoxic drugs: TURALIO can cause hepatotoxicity. In patients with increased serum transaminases, total bilirubin, or direct bilirubin (>ULN), or active liver or biliary tract disease, avoid coadministration of TURALIO with other products known to cause hepatotoxicity.

Clinically important drug interactions with TURALIO

Drug interactions Drug interactions

CYP3A, cytochrome P450, family 3, subfamily A; H2, histamine 2; PPIs, proton pump inhibitors; UGT, uridine diphosphate glucuronosyltransferase.

Please click here for full Prescribing Information, including Boxed WARNING, and click here for Medication Guide.

Use in specific populations1

Pregnancy

Risk summary
Based on findings from animal studies and its mechanism of action, TURALIO may cause embryo-fetal harm when administered to pregnant women. The available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of TURALIO. Advise pregnant women of the potential risk to a fetus.

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

Risk summary
There are no data on the presence of pexidartinib or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with TURALIO and for at least 1 week after the final dose.

Females and males of reproductive potential

Pregnancy testing
Verify pregnancy status in females of reproductive potential prior to the initiation of TURALIO.

Contraception
TURALIO may cause embryo-fetal harm when administered to a pregnant woman.

Females: Advise females of reproductive potential to use effective contraception during treatment with TURALIO and for 1 month after their final dose.

Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TURALIO and for 1 week after their final dose.

Infertility

Based on findings from animal studies, TURALIO may impair both male and female fertility.

Pediatric use

The safety and efficacy of TURALIO in pediatric patients have not been established.

Geriatric use

Clinical studies of TURALIO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.

Renal impairment

Reduce the dose when administering TURALIO to patients with mild to severe renal impairment (CrCl 15 to 89 mL/min, estimated by Cockcroft-Gault [C-G]).

Hepatic impairment

No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin <ULN with AST >ULN or total bilirubin >1 to 1.5 times ULN with any AST).

The recommended dose of TURALIO has not been established for patients with moderate (total bilirubin >1.5 to 3 times ULN and any AST) to severe (total bilirubin >3 to 10 times ULN and any AST) hepatic impairment.

Prescribing TURALIO Due to the risk of hepatotoxicity, TURALIO is available only through a restricted program called TURALIO REMS. In order to prescribe TURALIO, a healthcare provider must become certified.