Drug Detail:Turalio (Pexidartinib [ pex-i-dar-ti-nib ])
Generic Name: PEXIDARTINIB HYDROCHLORIDE 125mg
Dosage Form: capsule
Drug Class: Multikinase inhibitors
Recommended Dosage
The recommended dosage of TURALIO is 250 mg taken orally twice daily with a low-fat meal (approximately 11 to 14 grams of total fat) until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3)]. Taking TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat) increases pexidartinib concentrations and may increase the risk of adverse reactions, including hepatotoxicity [see Warnings and Precautions (5.1, 5.4), Drug Interactions (7.2), Clinical Pharmacology (12.2, 12.3)].
Swallow TURALIO capsules whole. Do not open, break, or chew the capsules.
If a patient vomits or misses a dose of TURALIO, instruct the patient to take the next dose at its scheduled time.
Dosage Modifications for Adverse Reactions
The recommended dose reductions for adverse reactions are provided in Table 1.
| Dose Reduction | Total Daily Dose | Administration of Total Daily Dose with Low-Fat Meal |
|---|---|---|
| First | 375 mg | 125 mg in the morning and 250 mg in the evening |
| Second | 250 mg | 125 mg twice daily |
Permanently discontinue TURALIO in patients who are unable to tolerate 125 mg orally twice daily.
The recommended dosage modifications for adverse reactions are summarized in Table 2.
| Adverse Reaction | Severity | TURALIO Dosage Modifications |
|---|---|---|
| ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; DB = direct bilirubin; GGT = gamma-glutamyl transferase; TB = total bilirubin; ULN = upper limit of normal | ||
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| Hepatotoxicity [see Warnings and Precautions (5.1)] | ||
| Increased ALT and/or AST | Greater than 3 to 5 times ULN |
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| Greater than 5 to 10 times ULN |
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| Greater than 10 times ULN |
|
|
| Increased ALP* and GGT | ALP greater than 2 times ULN with GGT greater than 2 times ULN |
|
| Increased bilirubin | TB greater than ULN to less than 2 times ULN or DB greater than ULN and less than 1.5 times ULN |
|
| TB greater or equal to 2 times ULN or DB greater than 1.5 times ULN |
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| Adverse Reactions or Other Laboratory Abnormalities [see Adverse Reactions (6.1)] | ||
| Any | Severe or intolerable |
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Concomitant Use of Moderate or Strong CYP3A Inhibitors or UGT Inhibitors
Avoid concomitant use of TURALIO with moderate or strong CYP3A inhibitors or UGT inhibitors during treatment with TURALIO. If concomitant use with a moderate or strong CYP3A inhibitor or UGT inhibitor cannot be avoided, reduce the TURALIO dose according to the recommendations in Table 3.
If concomitant use of a moderate or strong CYP3A inhibitor or UGT inhibitor is discontinued, increase the TURALIO dose (after 3 plasma half-lives of the moderate or strong CYP3A inhibitor or UGT inhibitor) to the dose that was used before starting the inhibitor [see Clinical Pharmacology (12.3)].
| Total Daily Dose* | Modified Total Daily Dose for Concomitant Use with Moderate or Strong CYP3A Inhibitors or UGT Inhibitors | Dosing Schedule for Modified Total Daily Dose for Use with Moderate or Strong CYP3A Inhibitors or UGT Inhibitors |
|---|---|---|
| Administer with Low-Fat Meal | ||
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| 500 mg | 250 mg | 125 mg twice daily |
| 375 mg | 250 mg | 125 mg twice daily |
| 250 mg | 125 mg | 125 mg once daily |
Concomitant Use of Acid-Reducing Agents
Avoid the concomitant use of proton pump inhibitors (PPI) while taking TURALIO. As an alternative to a PPI, administer TURALIO 2 hours before or 2 hours after taking a locally-acting antacid, or if using a histamine 2 (H2)-receptor antagonist, administer TURALIO at least 2 hours before or 10 hours after taking an H2-receptor antagonist [see Clinical Pharmacology (12.3)].
Dosage Modification for Renal Impairment
The recommended dosage of TURALIO for patients with mild to severe renal impairment (creatinine clearance [CLcr] 15 to 89 mL/min estimated by Cockcroft-Gault using actual body weight) is 125 mg in the morning and 250 mg in the evening with a low-fat meal [see Clinical Pharmacology (12.3)].
Dosage Modification for Hepatic Impairment
The recommended dosage of TURALIO for patients with moderate hepatic impairment (total bilirubin >1.5 to 3 × upper limit of normal (ULN), not due to Gilbert's syndrome, with any AST) is 125 mg twice daily with a low-fat meal [see Clinical Pharmacology (12.3)]. TURALIO has not been studied in patients with severe hepatic impairment (total bilirubin >3 to 10 × ULN and any AST).
