Xospata gilteritinib 40 mg Tablet, 90-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other protein kinase inhibitors class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Gilteritinib is used to treat a certain type of acute myeloid leukemia (AML) that has worsened or returned after treatment with other chemotherapy medications. Gilteritinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
Read the full MedlinePlus article ↗- Xospata targets a protein called FLT3 that is mutated in your leukemia cells — think of it as a stuck accelerator driving the cancer cells to multiply out of control. Gilteritinib...
- What exactly is Xospata treating in my body?
- You can take Xospata with or without food — that's one less thing to worry about. A high-fat meal does slightly delay how quickly the drug peaks in your bloodstream, but it doesn't...
- Can I take Xospata with food, or does it matter?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Gilteritinib Fumarate — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII 9XZ8H6N6OH
A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 2165RE0K14
A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $323.80 | $29,142.11 / 90 tablets |
| Medicare drug plans payPart D · Q2 2026 | $323.91 | $29,151.53 / 90 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Xospata 40 mgthis 00469-1425-90 | Astellas | 90 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 9487491 ↗ | Method of use | U-2456 | Jul 28, 2030 |
| US 11938133 ↗ | Drug product | — | Jul 1, 2036 |
| US 11944620 ↗ | Drug product | — | Jul 1, 2036 |
| US 11938130 ↗ | Drug product | — | Jul 1, 2036 |
| US 10786500 ↗ | Drug product | — | Jul 1, 2036 |
| US 8969336 ↗ | Drug substance | — | Nov 28, 2032 |
| US 11938131 ↗ | Drug product | — | Jul 1, 2036 |
| US 11938132 ↗ | Drug product | — | Jul 1, 2036 |
Is there a generic version of XOSPATA 40 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00469-1425-21 | 1 BOTTLE in 1 CARTON (0469-1425-21) / 21 TABLET in 1 BOTTLE | 2022-04-30 | Active |
| 00469-1425-90 You're viewing this | 1 BOTTLE in 1 CARTON (0469-1425-90) / 90 TABLET in 1 BOTTLE | 2018-11-29 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 00469-1425-90?
What is the difference between NDC 00469-1425-90 and NDC 00469-1425-21?
What NDC number is used to bill for this package of Xospata gilteritinib 40 mg Tablet?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: DIFFERENTIATION SYNDROME Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] .
WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
( 5.1 , 6.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE XOSPATA is a kinase inhibitor indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. ( 1.1 )
1.1Relapsed or Refractory Acute Myeloid Leukemia XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION 120 mg orally once daily. ( 2.2 )
2.1Patient Selection Select patients for the treatment of AML with XOSPATA based on the presence of FLT3 mutations in the blood or bone marrow [see Clinical Studies ( 14 )]. Information on FDA-approved tests for the detection of a FLT3 mutation in AML is available at http://www.fda.gov/CompanionDiagnostics .
2.2Recommended Dosage The recommended starting dose of XOSPATA is 120 mg orally once daily with or without food. Response may be delayed. In the absence of disease progression or unacceptable toxicity, treatment for a minimum of 6 months is recommended to allow time for a clinical response.
Do not break or crush XOSPATA tablets. Administer XOSPATA tablets orally about the same time each day. If a dose of XOSPATA is missed or not taken at the usual time, administer the dose as soon as possible on the same day, and at least 12 hours prior to the next scheduled dose.
Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.
2.3Dosage Modifications Assess blood counts and blood chemistries, including creatine phosphokinase, prior to the initiation of XOSPATA, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy. Perform electrocardiogram (ECG) prior to initiation of treatment with gilteritinib, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt dosing or reduce dose for toxicities as per Table 1 .
Table 1: Dosage Modifications for XOSPATA-Related Toxicities Grade 1 is mild, Grade 2 is moderate, Grade 3 is serious, Grade 4 is life-threatening. Adverse Reaction Recommended Action Differentiation Syndrome • If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days [see Warnings and Precautions ( 5.1 )] . • Interrupt XOSPATA if severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids [see Warnings and Precautions ( 5.1 )] . • Resume XOSPATA when signs and symptoms improve to Grade 2 or lower.
Posterior Reversible Encephalopathy Syndrome • Discontinue XOSPATA. QTc interval greater than 500 msec • Interrupt XOSPATA. • Resume XOSPATA at 80 mg when QTc interval returns to within 30 msec of baseline or less than or equal to 480 msec. QTc interval increased by >30 msec on ECG on day 8 of cycle 1 • Confirm with ECG on day 9. • If confirmed, consider dose reduction to 80 mg.
Pancreatitis • Interrupt XOSPATA until pancreatitis is resolved. • Resume XOSPATA at 80 mg. Other Grade 3 or higher toxicity considered related to treatment. • Interrupt XOSPATA until toxicity resolves or improves to Grade 1 . • Resume XOSPATA at 80 mg.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 40 mg as light yellow, round-shaped, film-coated tablets debossed with the Astellas logo and ‘235’ on the same side. Tablets: 40 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials [see Adverse Reactions ( 6 ) and Description ( 11 )] . Hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials. ( 4 , 6.1 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Posterior reversible encephalopathy syndrome (PRES): Discontinue XOSPATA in patients who develop PRES. ( 2.3 , 5.2 , 6.1 ) • Prolonged QT Interval: Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.
( 2.3 , 5.3 , 12.2 , 6.1 ) • Pancreatitis: Interrupt and reduce the dose in patients who develop pancreatitis. ( 2.3 , 5.4 ) • Embryo-Fetal Toxicity: XOSPATA can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to a fetus and to use effective contraception.
( 5.5 , 8.1 , 8.3 )
5.1Differentiation Syndrome Of 319 patients treated with XOSPATA in the clinical trials, 3% experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms and other clinical findings of differentiation syndrome in patients treated with XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction.
Some cases had concomitant acute febrile neutrophilic dermatosis. Differentiation syndrome occurred as early as 1 day and up to 82 days after XOSPATA initiation and has been observed with or without concomitant leukocytosis. Of the 11 patients who experienced differentiation syndrome, 9 (82%) recovered after treatment or after dose interruption of XOSPATA.
If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. Taper corticosteroids after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment.
If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt XOSPATA until signs and symptoms are no longer severe [see Dosage and Administration ( 2.3 )] .
5.2Posterior Reversible Encephalopathy Syndrome Of 319 patients treated with XOSPATA in the clinical trials, 1% experienced posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI).
Discontinue XOSPATA in patients who develop PRES [see Dosage and Administration ( 2.3 ) and Adverse Reactions ( 6.1 )] .
5.3Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 317 patients with a post-baseline QTc measurement on treatment with XOSPATA in the clinical trial, 1% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with gilteritinib, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles.
Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec [see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.2 )] . Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.
5.4Pancreatitis Of 319 patients treated with XOSPATA in the clinical trials, 4% experienced pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis [see Dosage and Administration ( 2.3 )] .
5.5Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant wom…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Differentiation syndrome [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Posterior reversible encephalopathy syndrome [see Warnings and Precautions ( 5.2 )] • Prolonged QT interval [see Warnings and Precautions ( 5.3 )] • Pancreatitis [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥20%) are transaminase increased, myalgia/arthralgia, fatigue/malaise, fever, mucositis, edema, rash, noninfectious diarrhea, dyspnea, nausea, cough, constipation, eye disorders, headache, dizziness, hypotension, vomiting, and renal impairment.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety profile of XOSPATA is based on 319 patients with relapsed or refractory AML treated with gilteritinib 120 mg daily in three clinical trials. The median duration of exposure to XOSPATA was 3.6 months (range 0.1 to 43.4 months).
Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These included cardiac arrest (1%) and one case each of differentiation syndrome and pancreatitis. The most frequent (≥5%) nonhematological serious adverse reactions reported in patients were fever (13%), dyspnea (9%), renal impairment (8%), transaminase increased (6%) and noninfectious diarrhea (5%).
Of the 319 patients, 91 (29%) required a dose interruption due to an adverse reaction; the most common adverse reactions leading to dose interruption were aspartate aminotransferase increased (6%), alanine aminotransferase increased (6%) and fever (4%). Twenty patients (6%) required a dose reduction due to an adverse reaction. Twenty-two (7%) discontinued XOSPATA treatment permanently due to an adverse reaction.
The most common (>1%) adverse reactions leading to discontinuation were aspartate aminotransferase increased (2%) and alanine aminotransferase increased (2%). Overall, for the 319 patients, the most frequent (≥10%) all-grade nonhematological adverse reactions reported in patients were transaminase increased (51%), myalgia/arthralgia (50%), fatigue/malaise (44%), fever (41%), mucositis (41%), edema (40%), rash (36%), noninfectious diarrhea (35%), dyspnea (35%), nausea (30%), cough (28%), constipation (28%), eye disorders (25%), headache (24%), dizziness (22%), hypotension (22%), vomiting (21%), renal impairment (21%), abdominal pain (18%), neuropathy (18%), insomnia (15%) and dysgeusia (11%).
The most frequent (≥5%) grade ≥3 nonhematological adverse reactions reported in patients were transaminase increased (21%), dyspnea (12%), hypotension (7%), mucositis (7%), myalgia/arthralgia (7%), and fatigue/malaise (6%). Shifts to grades 3-4 nonhematologic laboratory abnormalities included phosphate decreased 42/309 (14%), alanine aminotransferase increased 41/317 (13%), sodium decreased 37/314 (12%), aspartate aminotransferase increased 33/317 (10%), calcium decreased 19/312 (6%), creatine kinase increased 20/317 (6%), triglycerides increased 18/310 (6%), creatinine increased 10/316 (3%), and alkaline phosphatase increased 5/317 (2%).
Adverse reactions reported in the first 30 days of therapy on the ADMIRAL Study [see Clinical Studies ( 14 )] are shown in Tables 2 and 3 , according to whether patients were preselected for high intensity or low intensity chemotherapy. Table 2: Adverse Reactions Reported in ≥10% (Any Grade) or ≥5% (Grade 3-5) Grade 3-5 includes serious, life-threatening and fatal adverse reactions of Patients with Relapsed or Refractory AML in the Pre-selected High Intensity Chemotherapy Subgroup in the First…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Combined P-gp and Strong CYP3A Inducers: Avoid concomitant use. ( 7.1 ) • Strong CYP3A Inhibitors: Consider alternative therapies. If the concomitant use of strong CYP3A inhibitors cannot be avoided, monitor patients more frequently for XOSPATA adverse reactions. ( 2.3 , 7.1 ) • P-gp, BCRP, OCT1 Substrates: Decrease the dose of the substrates when coadministered with gilteritinib and as clinically indicated. ( 7.2 )
7.1Effect of Other Drugs on XOSPATA Combined P-gp and Strong CYP3A Inducers Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure which may decrease XOSPATA efficacy [see Clinical Pharmacology ( 12.3 )] . Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers. Strong CYP3A Inhibitors Concomitant use of XOSPATA with a strong CYP3A inhibitor increases gilteritinib exposure [see Clinical Pharmacology ( 12.3 )] .
Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity [see Dosage and Administration ( 2.3 )] .
7.2Effect of XOSPATA on Other Drugs Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor Concomitant use of gilteritinib may reduce the effects of drugs that target the 5HT 2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient [see Clinical Pharmacology ( 12.3 )] . P-gp, BCRP, and OCT1 Substrates Based on in vitro data, gilteritinib is a P-gp, breast cancer resistant protein (BCRP), and organic cation transporter 1 (OCT1) inhibitor.
Coadministration of gilteritinib may increase the exposure of P-gp, BCRP, and OCT1 substrates, which may increase the incidence and severity of adverse reactions of these substrates [see Clinical Pharmacology ( 12.3 )]. For P-gp, BCRP, or OCT1 substrates where small concentration changes may lead to serious adverse reactions, decrease the dose or modify the dosing frequency of such substrate and monitor for adverse reactions as recommended in the respective prescribing information.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on findings from animal studies (see Data) and its mechanism of action, XOSPATA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on XOSPATA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, administration of gilteritinib to pregnant rats during organogenesis caused adverse developmental outcomes including embryo-fetal lethality, suppressed fetal growth, and teratogenicity at maternal exposures (AUC 24 ) approximately 0.4 times the AUC 24 in patients receiving the recommended dose ( see Data ).
Advise pregnant women of the potential risk to a fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In an embryo-fetal development study in rats, pregnant animals received oral doses of gilteritinib of 0, 0.3, 3, 10, and 30 mg/kg/day during the period of organogenesis. Maternal findings at 30 mg/kg/day (resulting in exposures approximately 0.4 times the AUC 24 in patients receiving the recommended dose) included decreased body weight and food consumption.
Administration of gilteritinib at the dose of 30 mg/kg/day also resulted in embryo-fetal death (postimplantation loss), decreased fetal body and placental weight, and decreased numbers of ossified sternebrae and sacral and caudal vertebrae, and increased incidence of fetal gross external (anasarca, local edema, exencephaly, cleft lip, cleft palate, short tail, and umbilical hernia), visceral (microphthalmia; atrial and/or ventricular defects; and malformed/absent kidney, and malpositioned adrenal, and ovary), and skeletal (sternoschisis, absent rib, fused rib, fused cervical arch, misaligned cervical vertebra, and absent thoracic vertebra) abnormalities.
Single oral administration of [ 14 C] gilteritinib to pregnant rats resulted in transfer of radioactivity to the fetus similar to that observed in maternal plasma on day 14 of gestation. In addition, distribution profiles of radioactivity in most maternal tissues and the fetus on day 18 of gestation were similar to that on day 14 of gestation.
8.2Lactation Risk Summary There are no data on the presence of gilteritinib and/or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Following administration of radiolabeled gilteritinib to lactating rats, milk concentrations of radioactivity were higher than radioactivity in maternal plasma at 4 and 24 hours post-dose. In animal studies, gilteritinib and/or its metabolite(s) were distributed to the tissues in infant rats via the milk.
Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.
8.3Females and Males of Reproductive Potential XOSPATA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy testing Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating XOSPATA treatment [see Use in Specific Populations ( 8.1 )] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of XOSPATA.
Males Advise males of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of XOSPATA.
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been establishe…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal studies (see Data) and its mechanism of action, XOSPATA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on XOSPATA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, administration of gilteritinib to pregnant rats during organogenesis caused adverse developmental outcomes including embryo-fetal lethality, suppressed fetal growth, and teratogenicity at maternal exposures (AUC 24 ) approximately 0.4 times the AUC 24 in patients receiving the recommended dose ( see Data ).
Advise pregnant women of the potential risk to a fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In an embryo-fetal development study in rats, pregnant animals received oral doses of gilteritinib of 0, 0.3, 3, 10, and 30 mg/kg/day during the period of organogenesis. Maternal findings at 30 mg/kg/day (resulting in exposures approximately 0.4 times the AUC 24 in patients receiving the recommended dose) included decreased body weight and food consumption.
Administration of gilteritinib at the dose of 30 mg/kg/day also resulted in embryo-fetal death (postimplantation loss), decreased fetal body and placental weight, and decreased numbers of ossified sternebrae and sacral and caudal vertebrae, and increased incidence of fetal gross external (anasarca, local edema, exencephaly, cleft lip, cleft palate, short tail, and umbilical hernia), visceral (microphthalmia; atrial and/or ventricular defects; and malformed/absent kidney, and malpositioned adrenal, and ovary), and skeletal (sternoschisis, absent rib, fused rib, fused cervical arch, misaligned cervical vertebra, and absent thoracic vertebra) abnormalities.
Single oral administration of [ 14 C] gilteritinib to pregnant rats resulted in transfer of radioactivity to the fetus similar to that observed in maternal plasma on day 14 of gestation. In addition, distribution profiles of radioactivity in most maternal tissues and the fetus on day 18 of gestation were similar to that on day 14 of gestation.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 319 patients in clinical studies of XOSPATA, 43% were age 65 years or older, and 13% were 75 years or older. No overall differences in effectiveness or safety were observed between patients age 65 years or older and younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.
12.2Pharmacodynamics In patients with relapsed or refractory AML administered gilteritinib 120 mg, substantial (>90%) inhibition of FLT3 phosphorylation was rapid (within 24 hours after first dose) and sustained, as characterized by an ex vivo plasma inhibitory activity (PIA) assay. Cardiac Electrophysiology The effect of XOSPATA 120 mg once a day on the QTc interval has been evaluated in patients, which showed an absence of large mean increases (i.e., 20 msec) in the QTc interval. Of 317 patients with a post-baseline QTc measurement on treatment with gilteritinib at 120 mg in clinical trials, 4 patients (1.3%) experienced a QTcF >500 msec.
Additionally, across all doses 2.3% of patients with relapse/refractory AML had a maximum post-baseline QTcF interval >500 msec [see Warnings and Precautions ( 5.3 )].
12.3Pharmacokinetics The following pharmacokinetic parameters were observed following administration of gilteritinib 120 mg once daily, unless otherwise specified. Gilteritinib exposure (C max and AUC 24 ) increases proportionally with once daily doses ranging from 20 mg to 450 mg (0.17 to 3.75 times the recommended dosage) in patients with relapsed or refractory AML. Gilteritinib mean (±SD) steady-state C max is 374 ng/mL (±190) and AUC 24 is 6943 ng•hr/mL (±3221).
Steady-state plasma levels are reached within 15 days of dosing with an approximate 10-fold accumulation. Absorption The time to maximum gilteritinib concentration (t max ) observed is approximately between 4 and 6 hours post dose in the fasted state. Effect of Food In healthy adults administered a single gilteritinib 40 mg dose (0.3 times the recommended dosage), gilteritinib C max decreased by 26% and AUC decreased by less than 10% when co-administered with a high-fat meal (approximately 800 to 1,000 total calories with 500 to 600 fat calories, 250 carbohydrate calories, 150 protein calories) compared to a fasted state.
Median t max was delayed 2 hours when gilteritinib was administered with a high-fat meal. Distribution The population mean (%CV) estimates of apparent central and peripheral volume of distribution were 1092 L (9.22%) and 1100 L (4.99%), respectively, which may indicate extensive tissue distribution. In vivo , gilteritinib is approximately 94% bound to human plasma proteins.
In vitro , gilteritinib is primarily bound to human serum albumin. Elimination The estimated half-life of gilteritinib is 113 hours, and the estimated apparent clearance is
14.85L/h. Metabolism Gilteritinib is primarily metabolized via CYP3A4 in vitro . At steady state, the primary metabolites in humans include M17 (formed via N-dealkylation and oxidation), M16 and M10 (both formed via N‑dealkylation).
None of these 3 metabolites exceeded 10% of overall parent exposure. Excretion After a single radiolabeled dose, gilteritinib is excreted in feces with 64.5% of the total administered dose recovered in feces. Of the total radiolabeled dose of gilteritinib, 16.4% was recovered in urine as unchanged drug and metabolites.
Specific Populations Age (20-87 years), sex, race, mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment and mild (creatinine clearance (CLCr) 50-80 mL/min) or moderate (CLCr 30-50 mL/min) renal impairment do not have clinically meaningful effects on the pharmacokinetics of gilteritinib. The effect of severe hepatic (Child-Pugh Class C) or severe renal impairment (CLCr ≤ 29 mL/min) on gilteritinib pharmacokinetics is unknown. Drug Interaction Studies Clinical Studies Combined P-gp and S…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied XOSPATA (gilteritinib) 40 mg tablets are supplied as light yellow, round-shaped, film-coated tablets debossed with the Astellas logo and ‘235’ on the same side. XOSPATA tablets are available in the following package size: • Bottles of 90 tablets with Child Resistant Closure (NDC 0469-1425-90) Storage Store XOSPATA tablets at 20ºC to 25ºC (68°F to 77°F); excursions permitted between 15ºC to 30ºC (59°F to 86°F) [See USP Controlled Room Temperature]. Keep in original container until dispensed.
Protect from light, moisture and humidity.
📋 Description ▾
11 DESCRIPTION Gilteritinib is a kinase inhibitor. The chemical name is 2-Pyrazinecarboxamide, 6-ethyl-3-[[3-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl] phenyl] amino]-5-[(tetrahydro-2 H -pyran-4-yl) amino]-, (2 E )-2-butenedioate (2:1). The molecular weight is 1221.50 and the molecular formula is (C 29 H 44 N 8 O 3 ) 2 ·C 4 H 4 O 4 .
The structural formula is: Gilteritinib fumarate is a light yellow to yellow powder or crystals that is sparingly soluble in water and very slightly soluble in anhydrous ethanol. XOSPATA (gilteritinib) is provided as a tablet for oral administration. Each tablet contains 40 mg of gilteritinib active ingredient as free base (corresponding to 44.2 mg gilteritinib fumarate).
The inactive ingredients are ferric oxide, hydroxypropyl cellulose, hypromellose, low-substituted hydroxypropyl cellulose, mannitol, magnesium stearate, polyethylene glycol, talc, and titanium dioxide. Structural Formula of Gilteritinib
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Differentiation Syndrome Advise patients of the risks of developing differentiation syndrome as early as 1 day after the start of therapy and during the first 3 months on treatment. Ask patients to immediately report any symptoms suggestive of differentiation syndrome, such as fever, cough or difficulty breathing, rash, low blood pressure, rapid weight gain, swelling of their arms or legs, or decreased urinary output, to their healthcare provider for further evaluation [see Boxed Warning and Warnings and Precautions ( 5.1 )] .
Posterior Reversible Encephalopathy Syndrome Advise patients of the risk of developing posterior reversible encephalopathy syndrome (PRES). Ask patients to immediately report any symptoms suggestive of PRES, such as seizure and altered mental status, to their healthcare provider for further evaluation [see Warnings and Precautions ( 5.2 )]. Prolonged QT Interval Advise patients to consult their healthcare provider immediately if they feel faint, lose consciousness, or have signs or symptoms suggestive of arrhythmia.
Advise patients with a history of hypokalemia or hypomagnesemia of the importance of monitoring their electrolytes [see Warnings and Precautions ( 5.3 )] . Pancreatitis Advise patients of the risk of pancreatitis and to contact their healthcare provider for signs or symptoms of pancreatitis, which include severe and persistent stomach pain, with or without nausea and vomiting [see Warnings and Precautions ( 5.4 )]. Use of Contraceptives • Advise female patients with reproductive potential to use effective contraceptive methods while receiving XOSPATA and for 6 months after completion of treatment. • Advise patients to notify their healthcare provider immediately in the event of a pregnancy or if pregnancy is suspected during XOSPATA treatment. • Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for 4 months after the last dose of XOSPATA [see Use in Specific Populations ( 8.3 )] .
Lactation Advise women not to breastfeed during treatment with XOSPATA for 2 months after the last dose [see Use in Specific Populations ( 8.2 )]. Dosing Instructions • Advise patients not to break, crush or chew the tablets but to swallow them whole with a cup of water. • Instruct patients that, if they miss a dose of XOSPATA, to take it as soon as possible on the same day, and at least 12 hours prior to the next scheduled dose, and return to the normal schedule the following day. Instruct patients to not take 2 doses within 12 hours [see Dosage and Administration ( 2.2 )] .
Distributed by: Astellas Pharma US, Inc. Northbrook, Illinois 60062 XOSPATA is a registered trademark of Astellas Pharma Inc. LeukoStrat is a registered trademark of Invivoscribe, Inc. ©2021 Astellas Pharma US, Inc.
312959-GLT-USA
💬 Medication Guide ▾
MEDICATION GUIDE XOSPATA ® (Zoh spah' tah) (gilteritinib) tablets What is the most important information I should know about XOSPATA? XOSPATA may cause serious side effects, including: • Differentiation Syndrome . Differentiation syndrome is a condition that affects your blood cells and may be life-threatening or lead to death if not treated.
Differentiation syndrome can happen as early as 1 day after starting XOSPATA and during the first 3 months of treatment. Call your healthcare provider or go to the nearest hospital emergency room right away if you develop any of the following symptoms of differentiation syndrome while taking XOSPATA: o fever o cough o trouble breathing o rash o dizziness or lightheadedness o rapid weight gain o swelling of your arms or legs o decreased urination If you develop any of these symptoms of differentiation syndrome, your healthcare provider may treat you with a corticosteroid medicine and may monitor you in the hospital.
See “What are the possible side effects of XOSPATA?” for more information about side effects. What is XOSPATA? XOSPATA is a prescription medicine used to treat adults with acute myeloid leukemia (AML) who have a FMS-like tyrosine kinase 3 (FLT3) mutation: • when the disease has come back, or • has not improved after previous treatment(s).
Your healthcare provider will perform a test to make sure that XOSPATA is right for you. It is not known if XOSPATA is safe and effective in children. Do not take XOSPATA if you are allergic to gilteritinib or any of the ingredients in XOSPATA.
See the end of this Medication Guide for a complete list of ingredients in XOSPATA. Before taking XOSPATA, tell your healthcare provider about all of your medical conditions, including if you: • have any heart problems, including a condition called long QT syndrome. • have problems with abnormal electrolytes such as sodium, potassium, or magnesium levels. • are pregnant or plan to become pregnant. XOSPATA can cause harm to your unborn baby.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with XOSPATA. o If you are able to become pregnant, your healthcare provider may perform a pregnancy test 7 days before you start treatment with XOSPATA. o Females who are able to become pregnant should use effective birth control (contraception) during treatment with XOSPATA and for 6 months after the last dose of XOSPATA. o Males who have female partners that are able to become pregnant should use effective birth control (contraception) during treatment with XOSPATA and for 4 months after the last dose of XOSPATA. • are breastfeeding or plan to breastfeed.
It is not known if XOSPATA passes into your breast milk. Do not breastfeed during treatment with XOSPATA and for 2 months after the last dose of XOSPATA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
XOSPATA may affect the way other medicines work and other medicines may affect how XOSPATA works. How should I take XOSPATA? • Take XOSPATA exactly as your healthcare provider tells you to. Do not change your dose or stop taking XOSPATA without talking to your healthcare provider. • Take XOSPATA 1 time a day at about the same time each day. • Swallow XOSPATA tablets whole.
Do not break, crush, or chew the tablet. • XOSPATA can be taken with or without food. If you miss a dose of XOSPATA, or did not take it at the usual time, take your dose as soon as possible and at least 12 hours before your next dose. Return to your normal schedule the following day.
Do not take 2 doses of XOSPATA within 12 hours. What are the possible side effects of XOSPATA? XOSPATA may cause serious side effects, including: • See “What is the most important information I should know about XOSPATA?” • Posterior Reversible Encephalopathy Syndrome (PRES) .
If you take XOSPATA, you may be at risk of developing a condition involving the…