REZLIDHIA olutasidenib 150 mg Capsule, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Isocitrate dehydrogenase (IDH) inhibitors class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Olutasidenib is used to treat a certain type of acute myeloid leukemia (AML; a type of cancer that begins in the white blood cells) that has returned or that has not improved after previous treatment(s). Olutasidenib is in a class of medications called IDH1 inhibitors. It works by slowing or stopping the growth of cancer cells.
Read the full MedlinePlus article ↗- Rezlidhia is prescribed for a specific type of blood cancer called acute myeloid leukemia (AML) that has either come back after treatment or stopped responding to it. But it only w...
- What exactly is this medication for — why did my doctor prescribe it?
- Yes, it really does matter. Studies showed that taking olutasidenib with a high-fat meal increased the amount of drug absorbed into your blood by a very large amount — which could...
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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 M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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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 OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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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.
8 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 | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $599.94 | $17,998.15 / 30 capsules |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Rezlidhia 150 mgthis 71332-0005-01 | Rigel | 30 capsules | — | — | 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 11497743 ↗ | Method of use | U-3495 | May 16, 2039 |
| US 11376246 ↗ | Method of use | U-3495 | May 16, 2039 |
| US 11013734 ↗ | Method of use | U-3495 | May 16, 2039 |
| US 11013733 ↗ | Method of use | U-3496 | May 16, 2039 |
| US 9834539 ↗ | Drug substance | U-3497 | Sep 18, 2035 |
| US 11738018 ↗ | Method of use | U-3684 | Jul 17, 2039 |
| US 12275715 ↗ | Drug substance | U-3684 | Sep 18, 2035 |
| US 10532047 ↗ | Drug substance | — | May 16, 2039 |
| US 12053463 ↗ | Drug substance | — | May 16, 2039 |
| US 10959994 ↗ | Drug product | — | May 16, 2039 |
| US 10414752 ↗ | Drug product | — | Sep 18, 2035 |
| US 10550098 ↗ | Drug product | — | Sep 18, 2035 |
| US 11723905 ↗ | Drug product | — | Nov 12, 2039 |
| US 11498913 ↗ | Drug product | — | Sep 18, 2035 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Dec 1, 2027 |
| ODE-413 | Orphan Drug Exclusivity (7-year) | Dec 1, 2029 |
Is there a generic version of REZLIDHIA 150 MG CAPSULE?
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 71332-0005-01 You're viewing this | 30 CAPSULE in 1 BOTTLE (71332-005-01) | 2022-12-01 | Active |
🧭 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 | — Not published for this NDC No photo available yet for this listing. |
| 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) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: DIFFERENTIATION SYNDROME Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution [see Warnings and Precautions ( 5.1 )] .
WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate corticosteroids and hemodynamic monitoring until symptom resolution.
( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Relapsed or Refractory Acute Myeloid Leukemia REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14.1 )] . REZLIDHIA is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Select patients based on presence of IDH1 mutation(s). ( 2.1 ) Recommended dosage: 150 mg orally twice daily, until disease progression or unacceptable toxicity. ( 2.2 ) Take on an empty stomach at least 1 hour before or 2 hours after a meal. ( 2.2 )
2.1Patient Selection Select patients for the treatment of relapsed or refractory AML with REZLIDHIA based on the presence of IDH1 mutations in blood or bone marrow [see Clinical Trials ( 14.1 )] . Information on FDA- approved tests for the detection of IDH1 mutations in AML is available at http://www.fda.gov/CompanionDiagnostics.
2.2Recommended Dosage The recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or unacceptable toxicity. Administer REZLIDHIA capsules orally about the same time each day. Do not administer 2 doses within 8 hours.
Take on an empty stomach at least 1 hour before or 2 hours after a meal [see Clinical Pharmacology ( 12.3 )] . For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response. Swallow REZLIDHIA capsules whole.
Do not break, open, or chew the capsules. If a dose of REZLIDHIA is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of REZLIDHIA is missed or not taken at the usual time, administer the dose as soon as possible and at least 8 hours prior to the next scheduled dose.
Return to the normal schedule the following day.
2.3Monitoring and Dosage Modifications for Adverse Reactions Assess blood counts, and blood chemistries including liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months; once every other week for the third month; once in the fourth month, and once every other month for the duration of therapy. Manage any abnormalities promptly [see Warnings and Precautions ( 5.1 and 5.2 ) and Adverse Reactions ( 6.1 )] . Interrupt dosing or reduce dose for toxicities.
See Table 1 for dosage modification guidelines. Table 1: Recommended Dosage Modifications for REZLIDHIA Adverse Reactions Recommended Action Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] If differentiation syndrome is suspected, withhold REZLIDHIA until signs and symptoms improve. Administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days.
Resume REZLIDHIA at 150 mg twice daily after resolution of differentiation syndrome. If a recurrence of differentiation syndrome is suspected, withhold REZLIDHIA and institute treatment per above guidance. After resolution of symptoms, REZLIDHIA may be resumed at a reduced dose of 150 mg once daily for a minimum of 7 days, after which it can be increased to 150 mg twice daily.
Noninfectious leukocytosis [see Adverse Reactions ( 6.1 )] Initiate treatment with hydroxyurea, as per standard practices. Taper hydroxyurea only after leukocytosis improves or resolves. Grade 3 Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.
Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03). hepatotoxicity [see Warnings and Precautions ( 5.2 )] Withhold REZLIDHIA and monitor liver function tests, twice per week, until laboratory values have returned to baseline or Grade 1 toxicity. Resume REZLIDHIA at a reduced dose of 150 mg once daily and continue monitoring; may increase to 150 mg twice daily if hepatotoxicity resolves to baseline for at least 28 days. If hepatotoxicity (Grade 3) recurs at 150 mg once daily, discontinue REZLIDHIA.
Grade 4 hepatotoxicity or AST or ALT >3x ULN and total bilirubin >2x ULN and alkaline phosphatase <2x ULN in the absence of a clear alternative explanation [see Warnings and Precautions ( 5.2 )] Permanently discontinue REZLIDHIA Other Grade 3 or higher toxicity considered related to treatment [see Adverse Reactions ( 6.1…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules: 150 mg opaque white capsules imprinted with "OLU 150". Capsules: 150 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hepatotoxicity : Monitor liver function tests during treatment with REZLIDHIA. If hepatotoxicity occurs, interrupt and reduce or discontinue REZLIDHIA. ( 2.3 , 5.2 )
5.1Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% (25/153) of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients [see Adverse Reactions (6.1)]. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal.
Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dosage interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.
If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms.
Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence [see Dosage and Administration ( 2.3 )] .
5.2Hepatotoxicity REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity [see Adverse Reactions ( 6.1 )] . One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury.
The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.
Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity [see Dosage and Administration ( 2.3 )] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] Hepatotoxicity [see Warnings and Precautions ( 5.2 )] 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 most common (≥20%) adverse reactions, including laboratory abnormalities, are aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rigel Pharmaceuticals, Inc. at 1-800-983-1329 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Relapsed or Refractory AML The safety of REZLIDHIA 150 mg administered twice daily was evaluated in 153 adults with relapsed or refractory AML with an IDH1 mutation [see Clinical Studies ( 14.1 )] . Among the 153 patients who received REZLIDHIA, 35% were exposed for at least 6 months and 21% were exposed for at least 1 year. The median duration of exposure to REZLIDHIA was 4.7 months (range: 0.1 to 34 months).
Serious adverse reactions occurred in 25% of patients who received REZLIDHIA. Serious adverse reactions in ≥5% included differentiation syndrome (9%) and transaminitis (6%). Fatal adverse reactions occurred in 1% of patients who received REZLIDHIA, due to differentiation syndrome.
Permanent discontinuation of REZLIDHIA due to an adverse reaction occurred in 8% of patients. Adverse reactions leading to permanent discontinuation in ≥1% of patients included transaminitis, differentiation syndrome, and gallbladder disorders. Dosage interruptions of REZLIDHIA due to an adverse reaction occurred in 32% of patients.
Adverse reactions which required dosage interruption in >5% of patients included transaminitis and differentiation syndrome. Dose reductions of REZLIDHIA due to an adverse reaction occurred in 11% of patients. Adverse reactions which required dose reductions in ≥2% of patients included transaminitis.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. Table 2 summarizes the adverse reactions in the clinical trial for relapsed or refractory AML.
Table 2: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory AML in the Clinical Trial Olutasidenib 150 mg BID N=153 Body System Adverse Reaction All Grades (%) Grade 3 or 4 (%) Gastrointestinal Disorders Nausea 38 0 Constipation 26 0 Mucositis Mucositis includes gingival hypertrophy, gingivitis, gingivitis ulcerative, oral disorder, colitis, mouth ulceration, stomatitis, tongue ulceration, oral pain, oropharyngeal pain, pharyngitis, proctalgia, and colitis ischemic. 23 3 Diarrhea 20 1 Abdominal pain Includes multiple similar adverse reaction terms.
18 1 Vomiting 17 1 General Disorders and Administration Site Conditions Fatigue/malaise 36 3 Pyrexia 24 1 Edema 18 3 Musculoskeletal and Connective Tissue Disorders Arthralgia Arthralgia grouped term includes arthralgia, bone pain, back pain, neck pain, pain in extremity, arthritis, joint effusion, joint range of motion decreased, and joint swelling. 28 3 Blood System and Lymphatic Disorders Leukoc…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong or moderate CYP3A Inducers: Avoid concomitant use. ( 7.1 ) Sensitive CYP3A Substrates: Avoid concomitant use. Monitor if unavoidable. ( 7.1 )
7.1Effect of Other Drugs on Olutasidenib Strong or Moderate CYP3A4 Inducers Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Olutasidenib is a CYP3A substrate. Concomitant use of REZLIDHIA with a strong CYP3A inducer decreases olutasidenib Cmax and AUC, which may reduce REZLIDHIA efficacy [see Clinical Pharmacology ( 12.3 )] .
Concomitant use of REZLIDHIA with a moderate CYP3A inducer may also decrease olutasidenib Cmax and AUC, which may also reduce REZLIDHIA efficacy, based on observations from concomitant use with a strong CYP3A inducer.
7.2Effect of Olutasidenib on Other Drugs Sensitive CYP3A Substrates Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs. Olutasidenib induces CYP3A.
Concomitant use of REZLIDHIA may decrease plasma concentrations of sensitive CYP3A substrates, which may reduce the substrate’s efficacy [see Clinical Pharmacology ( 12.3 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on animal embryo-fetal toxicity studies, REZLIDHIA may cause fetal harm when administered to a pregnant woman. There are no available data on REZLIDHIA use in pregnant women to evaluate for a drug-associated risk. In embryo-fetal development studies, oral olutasidenib resulted in embryo-fetal death and altered fetal growth when administered to pregnant rats and rabbits during the period of organogenesis at exposures up to 10 times and 0.7 times, respectively, the human exposure at the recommended daily 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%-4% and 15%-20%, respectively. Data Animal Data Olutasidenib was administered twice daily via oral gavage at dose levels of 25, 125, or 250 mg/kg/dose (50, 250, or 500 mg/kg/day) to pregnant rats during organogenesis (gestation days 6-17).
An increase in fetal supernumerary rib was observed at the high dose (10 times the AUC at the clinical dose of 150 mg BID). In a pilot study, administration of olutasidenib orally to pregnant rats during organogenesis resulted in an increase in post-implantation loss at doses of 250 and 450 mg/kg/day (9 and 10 times the AUC at the clinical dose of 150 mg BID). Olutasidenib was administered twice daily via oral gavage at dose levels of 10, 20, or 40 mg/kg/dose (20, 40, or 80 mg/kg/day) to pregnant rabbits during the period of organogenesis (gestation days 7- 20).
Maternal toxicity noted as reduced body weight gain occurred at 80 mg/kg/day. An increase in fetal supernumerary rib and increased post-implantation loss occurred at the high dose of 80 mg/kg/day (0.7 times the AUC at the clinical dose of 150 mg BID).
8.2Lactation Risk Summary There are no data on the presence of olutasidenib or its metabolites in human milk, the effects on the breastfed child, or milk production. Because many drugs are excreted in human milk, and due to the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.
8.4Pediatric Use The safety and effectiveness of REZLIDHIA have not been established in pediatric patients.
8.5Geriatric Use Among the 153 patients with relapsed or refractory AML with an IDH1 mutation treated with REZLIDHIA, 116 (76%) were 65 years of age or older and 48 (31%) were 75 years or older. No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.
8.6Renal Impairment No dosage modification is recommended for patients with mild to moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min, as estimated by Cockcroft-Gault). The recommended dosage of REZLIDHIA has not been established in patients with severe renal impairment (CLcr 15 to 29 mL/min as estimated by Cockcroft-Gault), kidney failure (CLcr <15 mL/min, as estimated by Cockcroft-Gault), and patients on dialysis [see Clinical Pharmacology ( 12.3 )] .
8.7Hepatic Impairment No dosage modification is recommended for patients with mild (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment [see Clinical Pharmacology ( 12.3 )] . In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.1 )] . The recommended dosage of REZLIDHIA has not been established in patients with severe hepatic impairment (total bilirubin >3 times ULN with any AST) [see Clinical Pharmacolo…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on animal embryo-fetal toxicity studies, REZLIDHIA may cause fetal harm when administered to a pregnant woman. There are no available data on REZLIDHIA use in pregnant women to evaluate for a drug-associated risk. In embryo-fetal development studies, oral olutasidenib resulted in embryo-fetal death and altered fetal growth when administered to pregnant rats and rabbits during the period of organogenesis at exposures up to 10 times and 0.7 times, respectively, the human exposure at the recommended daily 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%-4% and 15%-20%, respectively. Data Animal Data Olutasidenib was administered twice daily via oral gavage at dose levels of 25, 125, or 250 mg/kg/dose (50, 250, or 500 mg/kg/day) to pregnant rats during organogenesis (gestation days 6-17).
An increase in fetal supernumerary rib was observed at the high dose (10 times the AUC at the clinical dose of 150 mg BID). In a pilot study, administration of olutasidenib orally to pregnant rats during organogenesis resulted in an increase in post-implantation loss at doses of 250 and 450 mg/kg/day (9 and 10 times the AUC at the clinical dose of 150 mg BID). Olutasidenib was administered twice daily via oral gavage at dose levels of 10, 20, or 40 mg/kg/dose (20, 40, or 80 mg/kg/day) to pregnant rabbits during the period of organogenesis (gestation days 7- 20).
Maternal toxicity noted as reduced body weight gain occurred at 80 mg/kg/day. An increase in fetal supernumerary rib and increased post-implantation loss occurred at the high dose of 80 mg/kg/day (0.7 times the AUC at the clinical dose of 150 mg BID).
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of REZLIDHIA have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Among the 153 patients with relapsed or refractory AML with an IDH1 mutation treated with REZLIDHIA, 116 (76%) were 65 years of age or older and 48 (31%) were 75 years or older. No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods.
The most common of such mutations in patients with AML are R132H and R132C substitutions. In vitro, olutasidenib inhibited mutated IDH1 R132H, R132L, R132S, R132G, and R132C proteins; wild-type IDH1 or mutated IDH2 proteins were not inhibited. Olutasidenib inhibition of mutant IDH1 led to decreased 2-HG levels in vitro and in in vivo xenograft models.
12.2Pharmacodynamics The mean [% coefficient of variation (%CV)] reduction in 2-HG plasma concentration was 59.1% (122%) by pre-dose Cycle 2 and was sustained throughout the treatment period in patients with AML and IDH1 mutations following the approved recommended olutasidenib dosage. Increased olutasidenib exposure was correlated with the increased probability of differentiation syndrome and Grade ≥3 hepatotoxicity in patients with AML following the approved recommended olutasidenib dosage. Cardiac Electrophysiology The largest mean increase in QTc interval was 6.2 msec (upper 90% confidence interval = 9.7 msec) in 33 patients with advanced hematologic malignancies with an IDH1 mutation following a single dose and multiple doses of the approved recommended olutasidenib dosage under fasted conditions.
This increase in the QTc interval was concentration dependent. Increased QT prolongation is expected with increased exposures of olutasidenib under a fed condition compared to that under fasting conditions [see Clinical Pharmacology ( 12.3 )] . The clinical impact of this increase could not be determined because QTc intervals were not evaluated at higher olutasidenib exposures.
12.3Pharmacokinetics The pharmacokinetics of olutasidenib have been characterized in patients with AML following the approved recommended dosage, unless otherwise specified. The mean (%CV) olutasidenib steady-state daily area under the plasma drug concentration over time curve (AUC 0-12-h,ss ) is 43050 (34.0%) ng·h/mL and steady-state maximum plasma concentration (Cmax,ss) is 3573 (45.6%) ng/mL following the approved recommended dosage. Olutasidenib C max and AUC increase less-than proportionally over a dosage range from 100 mg to 300 mg (0.33 to 1 time the recommended total daily dose); however, this finding should not affect the recommended dosage of REZLIDHIA.
Olutasidenib accumulation ratios ranging from 7.7 and 9.5 were observed following the approved recommended dosage. Steady-state plasma levels are reached within 14 days. Absorption The median (min, max) time to maximum concentration (t max ) of olutasidenib is approximately 4 (1, 8) hours following a single oral dose of 150 mg.
Effect of Food The mean (CV%) of olutasidenib C max increased by 191% (20.6%) and AUC inf increased by 83% (18.3%) following administration of a single 150 mg dose of olutasidenib with a high-fat meal (approximately 800 to 1,000 calories, with approximately 50% of total caloric content of the meal from fat) in healthy subjects. Distribution The mean (CV%) apparent volume of distribution of olutasidenib is 319 (28.1%) L. The plasma protein binding of olutasidenib is approximately 93%.
Elimination The mean (CV%) half-life (t1⁄2) of olutasidenib is approximately 67 (51.2%) hours and the mean (CV%) apparent oral clearance (CL/F) of olutasidenib is 4 (60.5%) L/h. Metabolism Olutasidenib metabolism involves N-dealkylation, demethylation, oxidative deamination followed by oxidation, mono-oxidation with subsequent glucuronidation. Olutasidenib is primarily (90%) metabolized by cytoc…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods.
The most common of such mutations in patients with AML are R132H and R132C substitutions. In vitro, olutasidenib inhibited mutated IDH1 R132H, R132L, R132S, R132G, and R132C proteins; wild-type IDH1 or mutated IDH2 proteins were not inhibited. Olutasidenib inhibition of mutant IDH1 led to decreased 2-HG levels in vitro and in in vivo xenograft models.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Capsule Strength Description Package Configuration NDC Number 150 mg White hard gelatin capsules with black ink print "OLU 150" White high-density polyethylene (HDPE) bottle with child-resistant closure 71332-005-01 Each bottle contains 30 capsules Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Olutasidenib is an isocitrate dehydrogenase-1 (IDH1) inhibitor. The chemical name is (S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile. The chemical structure is: The molecular formula is C 18 H 15 ClN 4 O 2 and the molecular weight is 354.79 g/mol.
Olutasidenib is a white to off-white to brown powder that is practically insoluble in aqueous solutions between pH 1.2 and 7.4. REZLIDHIA (olutasidenib) is available as hard gelatin capsules for oral administration. Each capsule contains 150 mg olutasidenib and the following ingredients: croscarmellose sodium, magnesium stearate and microcrystalline cellulose.
The capsule shell contains gelatin and titanium dioxide. Each capsule is printed with black ink containing ferrosoferric oxide, propylene glycol, and shellac. chemical structure
💬 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 start of therapy and up to 18 months on treatment. Ask patients to immediately report any symptoms suggestive of differentiation syndrome, such as fever, cough or difficulty breathing, decreased urinary output, low blood pressure, weight gain, or swelling of their arms or legs, to their healthcare provider for further evaluation [see Warnings and Precautions ( 5.1 )] .
Hepatotoxicity Advise patients of the potential for hepatic effects and to immediately report any associated signs and symptoms such as right upper abdominal discomfort, dark urine, jaundice, anorexia, or fatigue to their healthcare provider for further evaluation [see Warnings and Precautions ( 5.2 )] . Gastrointestinal Adverse Reactions Advise patients on the risks of experiencing gastrointestinal reactions such as nausea, constipation, diarrhea, vomiting, abdominal pain, and mucositis. Ask patients to report these events to their healthcare provider and advise patients how to manage them [see Adverse Reactions ( 6.1 )] .
Lactation Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )] . Dosing and Storage Instructions Advise patients to swallow capsules whole. Do not break, open, or chew the capsules.
Advise patients to take REZLIDHIA on an empty stomach (at least 1 hour before or 2 hours after a meal). Advise patients that if a dose of REZLIDHIA is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of REZLIDHIA is missed or not taken at the usual time, instruct patients to take the dose as soon as possible unless the next dose is due within 8 hours.
Patients can return to the normal schedule the following day. Store REZLIDHIA at room temperature from 20°C to 25°C (68°F to 77°F). Manufactured by Catalent Greenville, Inc.
1240 Sugg Pkwy, Greenville, NC 27834 Manufactured for Rigel Pharmaceuticals, Inc. South San Francisco, CA 94080 REZLIDHIA ® is a trademark of Rigel Pharmaceuticals, Inc. For more information go to www.REZLIDHIA.com or call 1-800-983-1329.
04/2024
💬 Medication Guide ▾
MEDICATION GUIDE REZLIDHIA ® (REZ-LID-EE-AH) (olutasidenib) capsules What is the most important information I should know about REZLIDHIA? REZLIDHIA 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.
Differentiation syndrome in adults with acute myeloid leukemia (AML) has occurred as early as 1 day and up to 18 months after starting REZLIDHIA. 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 during treatment with REZLIDHIA: fever cough trouble breathing decreased urination dizziness or lightheadedness weight gain swelling of your arms or legs If you develop signs and symptoms of differentiation syndrome, your healthcare provider may treat you with a corticosteroid medicine or a medicine called hydroxyurea and may monitor you in the hospital.
See "What are the possible side effects of REZLIDHIA?" for more information about side effects. What is REZLIDHIA? REZLIDHIA is a prescription medicine used to treat adults with acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) 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 REZLIDHIA is right for you. It is not known if REZLIDHIA is safe and effective in children. Before taking REZLIDHIA, tell your healthcare provider about all of your medical conditions, including if you: have liver problems. are pregnant or plan to become pregnant.
REZLIDHIA may harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if REZLIDHIA passes into your breast milk. Do not breastfeed during your treatment with REZLIDHIA and for 2 weeks after your last dose of REZLIDHIA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should I take REZLIDHIA? Take REZLIDHIA exactly as your healthcare provider tells you to.
Do not change your dose or stop taking REZLIDHIA without talking to your healthcare provider. Take REZLIDHIA 2 times a day (about 12 hours apart) around the same times each day. Take REZLIDHIA on an empty stomach, at least 1 hour before or 2 hours after a meal.
Swallow REZLIDHIA capsules whole. Do not break, open or chew the capsules. If you vomit after taking a dose of REZLIDHIA, do not take another dose.
Take your next dose at your usual time. If you miss a dose of REZLIDHIA or did not take it at the usual time, take your dose as soon as possible and at least 8 hours before your next dose. Return to your normal schedule the following day.
Do not take 2 doses of REZLIDHIA within 8 hours. What are the possible side effects of REZLIDHIA? REZLIDHIA may cause serious side effects, including: See “What is the most important information I should know about REZLIDHIA?” Liver problems.
Changes in liver function tests are common during treatment with REZLIDHIA and can be serious. Your healthcare provider will do blood tests to check your liver function before and during treatment with REZLIDHIA. Tell your healthcare provider right away if you develop any of the following symptoms of liver problems during treatment with REZLIDHIA: yellowing of your skin or the white part of your eyes (jaundice) dark “tea-colored” urine loss of appetite pain on the upper right side of your stomach area feeling very tired or weak The most common side effects of REZLIDHIA in adults with AML include: abnormal liver function tests nausea feeling tired or unwell joint pain constipation shortness of breath fever rash mouth sores diarrhea changes in certain blood tests Tell your healthcare provider if you have any nausea, constipation, diarrhea, vomiting, stomach pain or mouth sores.
Your healthcare provider will do blood tests before you start and d…