New NDC and dose for TURALIO (pexidartinib) – 11/7/22

[et_pb_section fb_built=”1″ _builder_version=”4.18.0″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”et_body_layout”][et_pb_row _builder_version=”4.19.4″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”et_body_layout”][et_pb_column type=”4_4″ _builder_version=”4.19.4″ _module_preset=”default” global_colors_info=”{}” theme_builder_area=”et_body_layout”][et_pb_code _builder_version=”4.19.4″ _module_preset=”default” hover_enabled=”0″ global_colors_info=”{}” theme_builder_area=”et_body_layout” sticky_enabled=”0″]New NDC and dose for TURALIO® (pexidartinib) (see Prescribing Information and Boxed WARNING) 96 DSI041-TUR-A-02
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TURALIO® New Dosing Regimen
Approved in the U.S.
 
The dosing change is being made due to the known effects food has on the absorption of TURALIO and the potential for drug overexposure that could happen if a patient takes the TURALIO 200 mg capsule with a meal rather than on an empty stomach. Taking the 400 mg dose of TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat) increases the concentration of TURALIO in the body and may increase the risk of adverse reactions, including hepatotoxicity.
 
Therefore, as a post-marketing requirement issued by the FDA, Daiichi Sankyo conducted pharmacokinetic studies to further evaluate the effects of food when taking TURALIO. These studies demonstrated that lowering the dose of TURALIO and taking it with a low-fat meal helps to minimize the potential for drug overexposure in the event a patient did not carefully follow the dietary recommendations when taking the 200 mg capsule of TURALIO. Existing patients should continue to take the 200 mg capsule on an empty stomach until the new dosage is available and contact their healthcare providers with any questions.
 
 
Dosing Change for TURALIO
 
The 200 mg capsule recommended dosage of TURALIO is 400 mg (2 x 200 mg) taken orally twice daily for a maximum dose of 800 mg per day. TURALIO 200 mg capsules must be taken on an empty stomach, at least 1 hour before or 2 hours after a meal or snack
 
The 125 mg capsule recommended dosage of TURALIO is 250 mg (2 x 125 mg) taken orally twice daily for a maximum dose of 500 mg per day. TURALIO 125 mg capsules must be taken with a low-fat meal containing approximately 11-14 grams of total fat
 
 
To allot adequate time to educate patients and healthcare providers about the upcoming change, Daiichi Sankyo, Inc. will discontinue the 200 mg TURALIO capsules and introduce the 125 mg capsules on February 1, 2023.
 
The 125 mg capsules will be available in 120-count bottles (NDC 65597–407–20). Please update your systems to reflect the new dose and NDC to minimize patient disruption.
 
Please review the Important Safety Information, including Boxed WARNING, below and the full Prescribing Information and Medication Guide here.
 
Indication and Important Safety Information
 
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.
 
 
     
WARNING: HEPATOTOXICITY
 
TURALIO can cause serious and potentially fatal liver injury.
 
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.
 
TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program.
 
 
 
Contraindications
 
None.
 
Warnings and Precautions
 
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 occurred in patients treated with TURALIO. Across 768 patients who received TURALIO in clinical trials, there were two 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 (5%) patients who received TURALIO developed signs of serious liver injury, defined as ALT or AST ≥3 × upper limit of normal (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 alkaline phosphatase (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); or active liver or biliary tract disease, including increased ALP. Monitor liver tests, including AST, 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. Rechallenge 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 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 by calling 1-833-887-2546.
 
Embryo-fetal toxicity
 
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.
 
Adverse Reactions
 
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).
 
Drug Interactions
 
Use with hepatotoxic products: 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.
 
Moderate or strong CYP3A inhibitors: Concomitant use of a moderate or strong CYP3A inhibitor may increase pexidartinib concentrations. Reduce TURALIO dosage if concomitant use of moderate or strong CYP3A inhibitors cannot be avoided.
 
Strong CYP3A inducers: Concomitant use of a strong CYP3A inducer decreases pexidartinib concentrations. Avoid concomitant use of strong CYP3A inducers.
 
Uridine diphosphate glucuronosyltransferase (UGT) inhibitors: Concomitant use of a UGT inhibitor increases pexidartinib concentrations. Reduce TURALIO dosage if concomitant use of UGT inhibitors cannot be avoided.
 
Acid-reducing agents: Concomitant use of a proton pump inhibitor (PPI) decreases pexidartinib concentrations. Avoid concomitant use of PPIs. Use histamine-2 receptor antagonists or antacids if needed.
 
CYP3A substrates: TURALIO is a moderate CYP3A inducer. Concomitant use of TURALIO decreases concentrations of CYP3A substrates. Avoid coadministration of TURALIO with hormonal contraceptives and other CYP3A substrates where minimal concentration changes may lead to serious therapeutic failure. Increase the CYP3A substrate dosage in accordance with approved product labeling if concomitant use is unavoidable.
 
Use in Specific Populations
 
Pregnancy: TURALIO may cause embryo-fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus.
 
Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women to not breastfeed during treatment with TURALIO and for at least 1 week after the final dose.
 
Females and males of reproductive potential: Verify pregnancy status in females of reproductive potential prior to the initiation of TURALIO. 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 male patients with female partners of reproductive potential to use effective contraception during treatment with TURALIO and for 1 week after the final dose.
 
Renal impairment: Reduce the dose when administering TURALIO to patients with mild to severe renal impairment (CLcr 15 to 89 mL/min, estimated by Cockcroft-Gault [C-G] using actual body weight).
 
Hepatic impairment: Reduce the dosage of TURALIO for patients with moderate hepatic impairment (total bilirubin greater than 1.5 and up to 3 times ULN, not due to Gilbert’s syndrome, with any AST). TURALIO has not been studied in patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times ULN and any AST).
 
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.
 
Reference: TURALIO® New Dosing Regimen Approved in the U.S. for Certain Patients with Tenosynovial Giant Cell Tumor. News release. https://daiichisankyo.us/press-releases/-/article/turalio-new-dosing-regimen-approved-in-the-u-s-for-certain-patients-with-tenosynovial-giant-cell-tumor. Accessed October 20, 2022.
 
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©2022 Daiichi Sankyo, Inc. PP-US-TU-0941 10/22
 
 
 
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