Indication and Usage
TURALIO® (pexidartinib) is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.
Warnings and Precautions
TURALIO can cause serious and potentially fatal liver injury and is available only through a restricted program called the TURALIO 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.
In ENLIVEN, 3 of 61 (5%) patients who received TURALIO developed signs of serious liver injury, defined as ALT or AST ≥3 × ULN with total bilirubin ≥2 × ULN. ALT, AST and total bilirubin improved to <2 × ULN in these patients 1 to 7 months after discontinuing TURALIO.
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. Please see Adverse Reactions.
Avoid TURALIO in patients with preexisting increased serum transaminases, total bilirubin, or direct bilirubin (>upper limit of normal [ULN]) or patients with active liver or biliary tract disease including increased alkaline phosphatase (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 aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, ALP, and gamma-glutamyl transferase (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, or ALP. Monitor liver tests weekly for the first month after rechallenge.
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:
Further information is available at turalioREMS.com or by calling 1-833-887-2546.
Based on animal studies and its mechanism of action, TURALIO may cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective nonhormonal method of contraception, since TURALIO can render hormonal contraceptives ineffective, 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.
The safety of TURALIO was evaluated in ENLIVEN, in which patients received TURALIO without food at a dose of 400 mg in the morning and 600 mg in the evening orally for 2 weeks followed by 400 mg orally twice daily until disease progression or unacceptable toxicity.
Serious adverse reactions were reported in 13% of patients who received TURALIO. The most frequent serious adverse reactions (occurring in >1 patient) included abnormal liver tests (3.3%) and hepatotoxicity (3.3%).
Permanent discontinuation due to adverse reactions occurred in 13% of patients who received TURALIO. The most frequent adverse reactions (occurring in >1 patient) requiring permanent discontinuation included increased ALT (4.9%), increased AST (4.9%), and hepatotoxicity (3.3%).
Dose reductions or interruptions occurred in 38% of patients who received TURALIO. The most frequent adverse reactions (occurring in >1 patient) requiring a dosage reduction or interruption were increased ALT (13%), increased AST (13%), nausea (8%), increased ALP (7%), vomiting (4.9%), increased bilirubin (3.3%), increased GGT (3.3%), dizziness (3.3%), and abdominal pain (3.3%).
The most common adverse reactions for all grades (>20%) were increased lactate dehydrogenase (92%), increased AST (88%), hair color changes (67%), fatigue (64%), increased ALT (64%), decreased neutrophils (44%), increased cholesterol (44%), increased ALP (39%), decreased lymphocytes (38%), eye edema (30%), decreased hemoglobin (30%), rash (28%), dysgeusia (26%), and decreased phosphate (25%).
Clinically relevant adverse reactions occurring in <10% of patients were blurred vision, photophobia, diplopia, reduced visual acuity, dry mouth, stomatitis, mouth ulceration, pyrexia, cholangitis, hepatotoxicity, liver disorder, cognitive disorders (memory impairment, amnesia, confusional state, disturbance in attention, and attention deficit/hyperactivity disorder), alopecia, and skin pigment changes (hypopigmentation, depigmentation, discoloration, and hyperpigmentation).
Use in Specific Populations
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc, at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.
Please click here for full Prescribing Information, including Boxed WARNING, and click here for Medication Guide.