Dosage & Administration
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Turalio Prescribing Information
WARNING: HEPATOTOXICITY
See full prescribing information for complete boxed warning.
- TURALIO can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome.
- Monitor liver tests prior to initiation of TURALIO and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue TURALIO based on severity of hepatotoxicity. Monitoring and prompt cessation of TURALIO may not eliminate the risk of serious and potentially fatal liver injury.
- TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program.
TURALIO 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.
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 | ||
| ||
| Hepatotoxicity [see Warnings and Precautions (5.1)] | ||
| Increased ALT and/or AST | Greater than 3 to 5 times ULN |
|
| Greater than 5 to 10 times ULN |
| |
| 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 |
| |
| Adverse Reactions or Other Laboratory Abnormalities [see Adverse Reactions (6.1)] | ||
| Any | Severe or intolerable |
|
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 | ||
| ||
| 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).
Capsules: 125 mg, size 1 with white opaque body and powder blue opaque cap with black print "DSC521"
Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], TURALIO may cause embryo-fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of TURALIO. Oral administration of pexidartinib to pregnant animals during the period of organogenesis resulted in malformations, post-implantation loss, and abortion at maternal exposures that were approximately equal to the human exposure at the recommended dose (see Data). Advise pregnant women of the potential risk to a fetus.
In the U.S. 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.
Data
Animal Data
Embryo-fetal development studies investigating the administration of pexidartinib during the period of organogenesis were conducted in rats and rabbits. In rats, pexidartinib resulted in increased post-implantation loss and fetal malformations including localized fetal edema, absence of kidney and ureter, abnormalities of the reproductive tract, and developmental variations including misshapen kidney, decreased skeletal ossification and higher mean litter proportions of slightly or moderately malaligned sternebrae at doses of 40 mg/kg (approximately equal to the human exposure at the recommended dose). In rabbits, administration of pexidartinib resulted in increased post-implantation loss, abortion, and fetal malformations including absence of kidney or ureter, rudimentary, misshapen or malpositioned kidney, rib abnormalities, and skeletal variations of accessory skull bones at doses of 60 mg/kg (approximately equal to the human exposure at the recommended dose).
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
TURALIO may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to the initiation of TURALIO [see Use in Specific Populations (8.1)].
Contraception
Females
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with TURALIO and for 1 month after the final dose. Counsel patients to use non-hormonal method(s) of contraception, since TURALIO can render hormonal contraceptives ineffective [see Drug Interactions (7.3), Nonclinical Toxicology (13.1)].
Males
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TURALIO and for 1 week after the final dose [see Nonclinical Toxicology (13.1)].
Infertility
Based on findings from animal studies, TURALIO may impair both male and female fertility [see Nonclinical Toxicology (13.1)].
Pediatric Use
The safety and effectiveness 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 from younger subjects.
Renal Impairment
Reduce the dosage when administering TURALIO to patients with mild to severe renal impairment (CLcr 15 to 89 mL/min, estimated by Cockcroft-Gault [C-G]) [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].
Hepatic Impairment
No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] with AST > ULN or total bilirubin >1 to 1.5 × ULN with any AST) [see Clinical Pharmacology (12.3)].
Reduce the dosage of TURALIO for patients with moderate hepatic impairment (total bilirubin >1.5 to 3 × ULN, not due to Gilbert's syndrome, with any AST) [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].
TURALIO has not been studied in patients with severe hepatic impairment (total bilirubin >3 to 10 × ULN and any AST).
None.