TURALIO Dosage & Rx Info | Uses, Side Effects

Turalio Generic Name & Formulations

Legal Class

General Description

Pexidartinib (as HCl) 125mg; caps.

Pharmacological Class

Kinase inhibitor.

How Supplied

Caps—28, 120

Manufacturer

Daiichi Sankyo

Generic Availability

Mechanism of Action

Pexidartinib targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium. In vitro, pexidartinib inhibited proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R. Pexidartinib also inhibited the proliferation of a CSF1R dependent cell line in vivo.

Turalio Indications

Indications

In adults with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.

Turalio Dosage and Administration

Adult

Swallow whole. Take with a low-fat meal (~11–14g of total fat). 250mg twice daily until disease progression or unacceptable toxicity. Mild to severe renal impairment (CrCl 15–89mL/min): 125mg in the AM and 250mg in the PM. Moderate hepatic impairment (total bilirubin >1.5–3×ULN, not due to Gilbert’s syndrome, with any AST): 125mg twice daily. Dose modifications for adverse reactions, concomitant moderate or strong CYP3A or UGT inhibitors, acid-reducing agents: see full labeling.

Children

Not established.

Turalio Contraindications

Not Applicable

Turalio Boxed Warnings

Boxed Warning

Hepatotoxicity.

Turalio Warnings/Precautions

Warnings/Precautions

Risk of liver injury (may be fatal). Avoid in patients with pre-existing increased serum transaminases, total/direct bilirubin >ULN, or active liver or biliary tract disease, including increased ALP. Monitor LFTs prior to initiation, weekly for the first 8 weeks, every 2 weeks for the next month, and then every 3 months thereafter. Withhold and reduce dose or permanently discontinue based on severity of hepatotoxicity. Severe hepatic impairment (total bilirubin >3–10×ULN and any AST): not studied. Embryo-fetal toxicity. Advise use of effective contraception during and for 1 month (females; use non-hormonal method) or for 1 week (males w. female partners) after last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after last dose).

REMS

YES

Turalio Pharmacokinetics

Absorption

T_max: 2.5 hours.

Distribution

Apparent volume of distribution: 187 L. Plasma protein bound: >99%.

Metabolism

CYP3A4, UGT1A4.

Elimination

Fecal (65%), renal (27%). Half-life: 26.6 hours. Apparent clearance: 5.1 L/h.

Turalio Interactions

Interactions

Avoid coadministration with a high-fat meal (~55–65g of total fat). Avoid concomitant other products known to cause hepatotoxicity. May be potentiated by moderate or strong CYP3A (including grapefruit or grapefruit juice) or UGT inhibitors; avoid; if unavoidable, reduce Turalio dose. Antagonized by strong CYP3A inducers (including St. John's wort) or proton pump inhibitors (alternatively, can use antacids or H₂-blockers); avoid. Antagonizes CYP3A substrates (eg, hormonal contraceptives, others); avoid; if unavoidable, increase substrate dose.

Turalio Adverse Reactions

Adverse Reactions

Increased lactate dehydrogenase, hair color changes, fatigue, increased AST, decreased neutrophils, increased cholesterol, decreased lymphocytes, eye edema, increased ALP, increased ALT, decreased hemoglobin, rash, dysgeusia, decreased phosphate.

Turalio Clinical Trials

See Literature

Turalio Note