Pexidartinib, an inhibitor of multiple receptor tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), c-Kit proto-oncogene proteins (c-Kit), and fms-like tyrosine kinase-3 (Flt-3), is an antineoplastic agent.1
Pexidartinib hydrochloride is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (also referred to as giant cell tumor of the tendon sheath [GCT-TS] or pigmented villonodular synovitis [PVNS]) associated with severe morbidity or functional limitations that is not amenable to improvement with surgery.1 Pexidartinib has been designated an orphan drug by FDA for the treatment of this condition.6
Safety and efficacy of pexidartinib are based on results from a double-blind, randomized, placebo-controlled study (ENLIVEN) in 120 adult patients with symptomatic tenosynovial giant cell tumor for whom surgical removal of the tumor would be associated with worsening functional limitation or severe morbidity.1 In the initial phase of the study, patients enrolled in the study were randomized to receive pexidartinib hydrochloride 400 mg in the morning and 600 mg in the evening for 2 weeks followed by 400 mg twice daily or placebo therapy for 24 weeks.1, 2 In the second phase of the study, patients randomized to placebo crossed over to open-label pexidartinib hydrochloride until disease progression or toxicity occurred.1, 2 Patients previously treated with a tyrosine kinase inhibitor, except for pexidartinib or another biologic CSF-1 or CSF-1R inhibitor, were eligible for the study.2 Patients with metastatic tenosynovial giant cell tumor or active cancer requiring treatment were excluded from the study.2 The median age of patients enrolled in the study was 44 years (range: 18-79); 59% were females, 88% were white, 53% had previously undergone surgery, 88% were diagnosed with diffuse tenosynovial giant cell tumor, and 9% previously received systemic therapy.1 Disease locations were knee (61%), ankle (18%), hip (11%), wrist (3%), foot (3%) and other (5%).1 The primary efficacy outcome measure was overall response rate as assessed by blinded independent central review (BICR) at week 25 according to RECIST v1.1.1 Additional efficacy outcome measures were mean change from baseline in range of motion of the affected joint at week 25 and overall response rate as assessed by BICR at week 25 using tumor volume score (TVS; defined as the estimated volume of the maximally distended synovial cavity or tendon sheath involved measured in 10% increments).1
At week 25, overall response rate (according to RECIST) was 38 or 0% in patients receiving pexidartinib or placebo, respectively.1, 2 Overall response rate (according to TVS) also was improved in patients receiving pexidartinib (56%) compared with placebo (0%).1, 2 Analysis of mean change from baseline in range of motion at week 25 demonstrated a statistically significant improvement in patients randomized to pexidartinib compared with placebo.1, 2 At a median follow-up duration of 22 months, overall response rate according to RECIST or TVS was 53 or 67%, respectively, in 30 patients initially randomized to placebo who crossed over to open-label pexidartinib.2
Of note, the efficacy of pexidartinib 250 mg orally twice daily given with a low-fat meal was established based on studies of pexidartinib 400 mg orally twice daily given on an empty stomach and additional pharmacokinetic data indicating that there was no clinically significant difference in the relative exposure between the 2 dosages.1
Tenosynovial giant cell tumor is a rare tumor which arises from the synovium, bursae, and tendon sheaths of young adults between 20-40 years of age.4 The spectrum of the therapeutic approaches to managing this disease ranges from observation and symptom management, to surgical interventions.5 Tumor growth appears to be driven by a mutation involving chromosome 1p13, which induces overexpression of colony stimulating factor-1 (CSF-1) on tumor cells resulting in subsequent migration of non-neoplastic monocytes and macrophages expressing the CSF-1 receptor (CSF-1R) to the tumor site; therefore, systemic therapies targeting CSF-1R have been used in patients with inoperable tenosynovial giant cell tumor and when surgery would cause excess morbidity.4, 5
Pexidartinib is administered orally with a low-fat meal (approximately 11-14 grams of total fat).1 Administration of pexidartinib with a high-fat meal (approximately 55-65 grams of total fat) increases pexidartinib concentrations and may increase the risk of adverse reactions.1
Swallow pexidartinib capsules whole; do not open, break, or chew the capsules.1
If a dose of pexidartinib is missed or vomited, the prescribed dose should be taken at the next scheduled time; an additional dose should not be administered to replace the missed dose.1
Store pexidartinib at 20-25°C (excursions permitted to 15-30°C).1
Dosage of pexidartinib hydrochloride is expressed in terms of pexidartinib.1
For the treatment of symptomatic tenosynovial giant cell tumor, the recommended adult dosage of pexidartinib is 250 mg orally twice daily with a low-fat meal (approximately 11-14 grams of total fat).1 Continue therapy until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
If adverse reactions occur during pexidartinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage reduction is required, the dosage of pexidartinib should be reduced as described in Table 1.1
Dose Reduction Level | Dosage Reduction after Recovery from Toxicity (Initial Dosage = 250 mg twice daily with low-fat meal) |
|---|---|
First | Resume at 125 mg in the morning and 250 mg in the evening (for a total daily dosage of 375 mg) |
Second | Resume at 125 mg twice daily (for a total daily dosage of 250 mg) |
Third | Permanently discontinue drug |
The following table indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for certain adverse effects according to severity.1
Adverse Reaction and Severity | Modification |
|---|---|
Hepatotoxicity | |
ALT and/or AST concentrations >3-5 times the ULN | Withhold therapy and monitor liver function tests weekly |
If AST and ALT improve to ≤3 times the ULN within 4 weeks, resume at reduced dosage (see Table 1); permanently discontinue drug if elevated AST and/or ALT concentrations persist for ≥4 weeks | |
ALT and/or AST concentrations >5-10 times the ULN | Withhold therapy and monitor liver function tests twice weekly |
If AST and ALT improve to ≤3 times the ULN within 4 weeks, resume at reduced dosage (see Table 1); permanently discontinue drug if elevated AST and/or ALT concentrations persist for ≥4 weeks | |
ALT and/or AST concentrations >10 times the ULN | Permanently discontinue drug and monitor liver function tests twice weekly until AST or ALT improves to ≤5 times the ULN, then monitor weekly until AST or ALT improves to ≤3 times the ULN |
Alkaline phosphatasea concentrations >2 times the ULN with gamma-glutamyl transferase (GGT) concentrations >2 times the ULN | Permanently discontinue drug and monitor liver function tests twice weekly until alkaline phosphatase concentrations improve to ≤5 times the ULN, and then monitor weekly until alkaline phosphatase concentrations improve to ≤2 times the ULN |
Total bilirubin concentrations exceeding the ULN to <2 times the ULN | Withhold therapy and monitor liver function tests twice weekly |
If alternate etiology is confirmed and total bilirubin concentration improves to less than the ULN within 4 weeks, resume at reduced dosage (see Table 1) | |
If total bilirubin concentration does not improve to less than the ULN within 4 weeks, permanently discontinue drug | |
Direct bilirubin concentrations exceeding the ULN to <1.5 times the ULN | Withhold therapy and monitor liver function tests twice weekly |
If alternate etiology is confirmed and direct bilirubin concentration improves to less than the ULN within 4 weeks, resume at reduced dosage (see Table 1) | |
If direct bilirubin concentration does not improve to less than the ULN within 4 weeks, permanently discontinue drug | |
Total bilirubin concentrations ≥2 times the ULN | Permanently discontinue drug and monitor liver function tests twice weekly until total bilirubin concentration improves to the ULN or less |
Direct bilirubin concentrations ≥1.5 times the ULN | Permanently discontinue drug and monitor liver function tests twice weekly until direct bilirubin concentration improves to the ULN or less |
Other Toxicity | |
Severe or intolerable | Withhold therapy until toxicity improves or resolves; resume at reduced dosage (see Table 1) |
aConfirm alkaline phosphatase elevations as liver isoenzyme fraction.1
Concomitant Use with Moderate or Strong CYP3A Inhibitors or UGT Inhibitors
Avoid concomitant use of pexidartinib and moderate or strong CYP3A inhibitors or UGT inhibitors.1 If concomitant use cannot be avoided, reduce the dosage of pexidartinib as described in Table 3.1 If the moderate or strong CYP3A inhibitor or UGT inhibitor is discontinued, return the pexidartinib dosage (after 3 elimination half-lives of the CYP3A or UGT inhibitor) to the dosage used prior to initiation of the CYP3A or UGT inhibitor.1
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 |
In patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN, not due to Gilbert syndrome, with any AST concentration), the recommended dosage of pexidartinib is 125 mg twice daily with a low-fat meal.1
The pharmacokinetics of pexidartinib have not been studied in severe hepatic impairment (total bilirubin 3-10 times the ULN with any AST concentration).1
In patients with mild to severe renal impairment (creatinine clearance 15-89 mL/minute), the recommended dosage of pexidartinib is 125 mg in the morning and 250 mg in the evening with a low-fat meal.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
A boxed warning regarding the risk of serious and potentially fatal liver injury is included in the prescribing information for pexidartinib.1 Because of this risk, pexidartinib is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).1 Requirements of the REMS program may be accessed at [Web] or calling 833-887-2546.1
Hepatotoxicity including liver failure and life-threatening vanishing bile duct syndrome, ductopenia, and symptomatic cholestasis (including severe pruritus) has been reported in patients receiving pexidartinib; these effects can occur despite monitoring and prompt drug discontinuation.1 In clinical trials, 2 of 768 pexidartinib-treated patients developed irreversible cholestatic liver injury; one patient with a confirmed case of vanishing bile duct syndrome required a liver transplant and one patient died with advanced cancer and ongoing hepatotoxicity.1 The mechanism by which cholestatic hepatotoxicity occurs has not been elucidated, and the occurrence of the toxicity cannot be predicted.1 It is unknown if liver injury occurs in the absence of elevated transaminases.1
Of the initial 609 patients administered pexidartinib under the REMS program, 32 (5.3%) developed a liver injury event of concern, defined as any serious liver-related outcome or any liver abnormality that triggers drug discontinuation per the prescribing information.1 The development of liver toxicity occurred within 71 days of the first dose of pexidartinib in these patients.1 Ten patients required hospitalization and two developed vanishing bile duct syndrome.1 At the time of data analysis, half of the 32 patients had not fully recovered, including 6 patients followed for at least 6 months after treatment discontinuation.1
In the ENLIVEN study, 3 (5%) of 61 patients who received pexidartinib developed signs of serious liver injury (defined as serum ALT or AST concentrations ≥3 times the ULN with total bilirubin ≥2 times the ULN); peak serum ALT concentrations ranged from 6-9 times the ULN, peak total bilirubin concentrations ranged from 2.5-15 times the ULN, and alkaline phosphatase concentrations were ≥2 times the ULN.1 Serum ALT, AST, and total bilirubin concentrations improved to <2 times the ULN 1-7 months after discontinuing pexidartinib.1
Avoid pexidartinib in patients with preexisting elevated AST or ALT concentrations; total bilirubin or direct bilirubin greater than ULN; or active liver or biliary tract disease, including increased alkaline phosphatase.1
Administration of pexidartinib with a high-fat meal increases exposure to the drug by 100% and may increase the risk of hepatotoxicity; therefore, pexidartinib must be administered on an empty stomach, either 1 hour before or 2 hours after a meal or snack.1
Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase (GGT) prior to the initiation of pexidartinib, weekly for the first 8 weeks, every 2 weeks for the next month, and then every 3 months thereafter.1 Based on the severity of hepatotoxicity, temporary interruption of therapy, dosage reduction, or permanent discontinuance of the drug may be necessary.1 Clinicians should refer patients to a hepatologist if liver tests do not return to normal.1 Recurrence of elevated serum aminotransferases, bilirubin, or alkaline phosphatase may occur following resumption of pexidartinib therapy at a reduced dosage.1 When pexidartinib is resumed following resolution of hepatotoxicity, liver function tests should be monitored weekly for the initial month after rechallenge.1
Other Warnings and Precautions
Based on animal data and its mechanism of action, pexidartinib may cause fetal harm when administered during pregnancy.1 Available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of pexidartinib; however, malformations, increased postimplantation loss, and abortion have been observed in animal studies at exposures approximately equal to the human exposure at the recommended dosage of 800 mg based on AUC.1
Verify pregnancy status in females of reproductive potential prior to initiation of therapy.1
Pregnant females should be apprised of the potential risk to a fetus.1 Advise females of reproductive potential to use effective nonhormonal contraception during treatment with pexidartinib and for 1 month after discontinuing treatment; nonhormonal contraceptives should be used because concomitant use of pexidartinib and hormonal contraceptives may result in decreased systemic exposure to the hormonal contraceptive and reduced efficacy.1
Males with female partners of reproductive potential should also use effective contraception during treatment with pexidartinib and for 1 week after discontinuing treatment.1
Potential Risks Associated with a High-fat Meal
Pexidartinib administration with a high-fat meal increases serum concentrations of the drug, which may increase the incidence and severity of adverse reactions, including hepatotoxicity.1 Patients should take pexidartinib with a low-fat meal (approximately 11-14 grams of total fat) and avoid taking the drug with a high-fat meal (approximately 55 to 65 grams of total fat).1 Refer patients to a dietitian as necessary.1
Based on animal data and its mechanism of action, pexidartinib may cause fetal harm when administered during pregnancy.1
Available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of pexidartinib.1
It is not known whether pexidartinib or its metabolites are distributed into human milk.1 The effects of the drug on breast-fed infants or on the production of milk are also unknown.1
Because of the potential for serious adverse reactions to pexidartinib in breast-fed infants, females should be advised not to breast-feed while receiving the drug and for at least one week after the last dose.1
Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to the initiation of pexidartinib.1
Advise females of reproductive potential to use effective nonhormonal contraception during treatment with pexidartinib and for 1 month after the final dose; nonhormonal contraceptives should be used because concomitant use of pexidartinib and hormonal contraceptives may result in decreased systemic exposure to the hormonal contraceptive and reduced efficacy.1
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with pexidartinib and for at least 1 week after the final dose.1
Results of animal studies suggest that pexidartinib may impair male and female fertility.1
Safety and efficacy of pexidartinib have not been established in pediatric patients.1
Experience with pexidartinib in patients ≥65 years of age is insufficient to determine whether geriatric patients respond differently than younger individuals.1
No clinically significant differences in the pharmacokinetics of pexidartinib in patients with mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] with AST greater than ULN or total bilirubin greater than 1 up to 1.5 times ULN with any AST concentration); no dosage adjustment is necessary.1
In patients with moderate hepatic impairment (total bilirubin greater than 1.5 to 3 times ULN, not due to Gilbert syndrome, with any AST concentration), the AUC of pexidartinib was increased by 43% compared to patients with normal hepatic function; the manufacturer recommends reducing the dosage of pexidartinib to 125 mg twice daily with a low-fat meal in patients with moderate hepatic impairment.1
Pexidartinib has not been studied in severe (total bilirubin greater than 3-10 times ULN and any AST concentration) hepatic impairment.1
Mild to severe renal impairment (creatinine clearance 15-89 mL/minute) increases the AUC of pexidartinib by approximately 30% compared to patients with normal renal function; the manufacturer recommends reducing the dosage of pexidartinib to 125 mg in the morning and 250 mg in the evening with a low-fat meal in patients with renal impairment.1
No clinically significant differences in the pharmacokinetics of pexidartinib observed based on race or gender.1
Adverse effects occurring in >20% of patients: Increased lactate dehydrogenase concentrations, increased AST/ALT concentrations, hair color changes, fatigue, decreased neutrophils, increased cholesterol, increased alkaline phosphatase concentrations, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate.1
Pexidartinib is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A4 and glucuronidation by uridine diphosphate-glucuronosyltransferase to the major inactive N -glucuronide metabolite.1
In vitro studies indicate that pexidartinib is likely to inhibit CYP2B6 and induce CYP2B6 at clinically relevant concentrations.1 Pexidartinib is likely to inhibit UGT1A1 at clinically relevant concentrations.1 Pexidartinib is an inhibitor of multidrug and toxin extrusion (MATE) 1, MATE2-K, organic anion transporter protein (OATP) 1B1, OATP1B3 and OATP2B1.1 In vitro, pexidartinib is not a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), OAT1, OAT3, organic cation transporter (OCT) 1, OCT2, OATP1B1, OATP1B3, OATP2B1, or bile salt export pump (BSEP).1
Drugs and Foods Affecting Hepatic Microsomal Enzymes
Moderate or Strong CYP3A Inhibitors
Concomitant use of pexidartinib and moderate or strong CYP3A inhibitors may increase concentrations of pexidartinib and increase the risk and severity of adverse reactions.1 When pexidartinib was used concomitantly with itraconazole (strong CYP3A inhibitor) peak plasma concentration and AUC of pexidartinib increased by 48 and 70%, respectively.1 Concomitant use of pexidartinib and fluconazole (moderate CYP3A4 inhibitor), is predicted to increase peak plasma concentration and AUC of pexidartinib by 41 and 67%, respectively, at steady state.1
Avoid concomitant use of pexidartinib and moderate or strong CYP3A inhibitors, including grapefruit and grapefruit products.1 If concomitant use cannot be avoided, reduce the dosage of pexidartinib as described in Table 3.1 If the moderate or strong CYP3A inhibitor is discontinued, return the pexidartinib dosage (after 3 elimination half-lives of the CYP3A inhibitor) to the dosage used prior to initiation of the CYP3A inhibitor.1
Concomitant use of pexidartinib and moderate or strong CYP3A inducers may decrease concentrations of pexidartinib and reduce efficacy of the drug.1 When pexidartinib was used concomitantly with rifampin (strong CYP3A inducer) peak plasma concentration and AUC of pexidartinib decreased by 33 and 65%, respectively.1 Concomitant use of pexidartinib and efavirenz (moderate CYP3A inducer), is predicted to decrease peak plasma concentration and AUC of pexidartinib by 27 and 38%, respectively, at steady state.1
Avoid concomitant use of pexidartinib and strong CYP3A inducers, including St. John's wort ( Hypericum perforatum ).1
Drugs Metabolized by Hepatic Microsomal Enzymes
Concomitant use of pexidartinib and substrates of CYP3A (e.g., midazolam, hormonal contraceptives) may decrease systemic exposure to the CYP3A substrate and reduce efficacy of the substrate drug.1 When the CYP3A substrate midazolam was administered concomitantly with pexidartinib (400 mg twice daily), peak plasma concentration and AUC of midazolam decreased by 28 and 59%, respectively.1
Avoid concomitant use of pexidartinib with hormonal contraceptives and other CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures.1 If concomitant use cannot be avoided, consult the manufacturer's labeling of the CYP3A substrate drug for dosage modification recommendations.1
Substrates of Other CYP Isoenzymes
When the CYP2C19 substrate omeprazole was administered concomitantly with pexidartinib (single 800-mg dose), peak plasma concentration and AUC of omeprazole decreased by 37 and 17%, respectively.1
The effect of pexidartinib on CYP2C8 substrates is not expected to be clinically relevant.1
Drugs Affecting or Affected by P-glycoprotein Transport
When a single 1.8-g dose of pexidartinib was used concomitantly with the P-gp substrate digoxin, peak plasma concentration and AUC of digoxin increased by 30 and 9%, respectively.1
Drugs Affected by Uridine Diphosphate-glucuronosyltransferase
Concomitant use of uridine diphosphate-glucuronosyltransferase (UGT) inhibitors may increase concentrations of pexidartinib and increase the risk and severity of adverse reactions.1 When pexidartinib was used concomitantly with probenecid (UGT inhibitor) peak plasma concentration and AUC of pexidartinib increased by 5 and 60%, respectively.1
Avoid concomitant use of pexidartinib and UGT inhibitors.1 If concomitant use cannot be avoided, reduce the dosage of pexidartinib as described in Table 3.1 If the UGT inhibitor is discontinued, return the pexidartinib dosage (after 3 elimination half-lives of the UGT inhibitor) to the dosage used prior to initiation of the UGT inhibitor.1
Drugs Affecting Gastric Acidity
Concomitant use of pexidartinib with proton-pump inhibitors decreases pexidartinib concentrations and reduces efficacy of the drug.1 When pexidartinib was used concomitantly with esomeprazole (proton-pump inhibitor) peak plasma concentration and AUC of pexidartinib decreased by 55 and 50%, respectively.1 The effect of H2-receptor antagonists and locally-acting antacids on pexidartinib pharmacokinetics has not been studied.1
Avoid concomitant use of pexidartinib and proton-pump inhibitors.1 The manufacturer recommends use of locally-acting antacids or H2-receptor antagonists as an alternative.1
Concomitant use of pexidartinib and hormonal contraceptives (substrates of CYP3A) may decrease systemic exposure to the hormonal contraceptive and reduce efficacy.1
Avoid concomitant use of pexidartinib with hormonal contraceptives.1 Females of reproductive potential should use effective nonhormonal contraception during pexidartinib therapy and for 1 month after the drug is discontinued.1
Concomitant use of pexidartinib with a high-fat meal (approximately 55-65 grams of fat) increases pexidartinib concentrations, which may result in an increase in the incidence and severity of adverse reactions, including hepatotoxicity.1
Avoid administration of pexidartinib with a high-fat meal.1 Administer the drug with a low-fat meal (approximately 11-14 grams of fat).1
Pexidartinib, an inhibitor of multiple receptor tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), c-Kit proto-oncogene proteins (c-Kit), and fms-like tyrosine kinase-3 (Flt-3), is an antineoplastic agent.1 Overexpression of CSF-1R ligand promotes cell proliferation and accumulation in the synovium.1 In vitro, pexidartinib inhibits proliferation of cell lines dependent on CSF-1R and ligand-induced autophosphorylation of CSF-1R.1 In vivo, pexidartinib also inhibited proliferation of a CSF-1R-dependent cell line.1
Area under the serum concentration-time curve (AUC) and peak plasma concentrations of pexidartinib show linear increases over the single oral dose range of 200-2400 mg administered on an empty stomach.1 Following oral administration, peak plasma concentrations of the drug are achieved in a median of 2.5 hours.1 Steady state concentrations of pexidartinib are achieved in approximately 7 days and accumulation based on AUC is 3.6-fold.1 When administered with a high-fat meal, peak plasma concentrations and AUC of pexidartinib increased by 100% and the time to peak plasma concentrations was delayed by 2.5 hours as compared to on an empty stomach.1 When administered with a low-fat meal, peak plasma concentrations and AUC of pexidartinib increased by 56% and 59% and the time to peak concentrations was delayed by 1.5 hours as compared to on an empty stomach.1 Pexidartinib exhibits high plasma protein binding (99.9% to human serum albumin and 89.9% to α-1 acid glycoprotein).1 Pexidartinib principally undergoes oxidation by CYP3A4 and glucuronidation by UGT1A4, which results in the formation of the N -glucuronide metabolite.1 Following oral administration of a single radiolabeled dose of pexidartinib, approximately 65% of the radioactivity was recovered in feces (44% as unchanged drug) and 27% was recovered in urine as metabolites (≥10% as N -glucuronide).1 The mean elimination half-life of pexidartinib is 26.6 hours.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Pexidartinib hydrochloride is only available through a restricted program called the Turalio® REMS Program.1 Clinicians should consult the Turalio® REMS website at [Web] or call 833-887-2546.1
Pexidartinib hydrochloride can only be obtained through a designated specialty pharmacy.7
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 125 mg (of pexidartinib) | Turalio® | Daiichi Sankyo |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Daiichi Sankyo Inc. Turalio® (pexidartinib) capsules prescribing information. Basking Ridge, NJ; 2025 Jan.
2. Tap WD, Gelderblom H, Palmerini E et al. Pexidartinib for advanced tenosynovial giant cell tumor: results of the randomized phase 3 ENLIVEN study. Lancet . 2019; 394:478-487. [PubMed 33977825]
3. Gouin F, Noailles T. Localized and diffuse forms of tenosynovial giant cell tumor (formerly giant cell tumor of the tendon sheath and pigmented villonodular synovitis). Orthop Traumatol Surg Res . 2017; 103:S91-S97. [PubMed 28057477]
4. Brahmi M, Vinceneux A, Cassier PA. Current Systemic Treatment Options for Tenosynovial Giant Cell Tumor/Pigmented Villonodular Synovitis: Targeting the CSF1/CSF1R Axis. Curr Treat Options Oncol . 2016; 17:10. [PubMed 26820289]
5. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 211810Orig1s000: Multi-discipline review. From FDA website. [Web]
6. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2024 May 20. [Web]
7. Daiichi Sankyo Inc. Daiichi Sankyo access central. From Turalio® for healthcare professionals website. Undated. Accessed 2024 May 20. [Web]