Komzifti ziftomenib 200 mg Capsule, 90-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Menin Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Ziftomenib is used to treat a certain type of acute myeloid leukemia (AML; a type of that begins in the white blood cells). Ziftomenib is in a class of medications called menin inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
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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 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 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 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 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
5 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 · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Komzifti 200 mgthis 84696-0200-90 | Kura | 90 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 12410184 ↗ | Drug substance | U-4347 | Jul 16, 2044 |
| US 12410184 ↗ | Drug substance | U-4348 | Jul 16, 2044 |
| US 11944627 ↗ | Method of use | U-4347 | Sep 6, 2038 |
| US 11944627 ↗ | Method of use | U-4349 | Sep 6, 2038 |
| US 11673898 ↗ | Method of use | U-4350 | Mar 15, 2037 |
| US 11673898 ↗ | Method of use | U-4351 | Mar 15, 2037 |
| US 10869868 ↗ | Method of use | U-4352 | Jan 26, 2037 |
| US 10869868 ↗ | Method of use | U-4353 | Jan 26, 2037 |
| US 10174041 ↗ | Method of use | U-4350 | Mar 16, 2036 |
| US 10174041 ↗ | Method of use | U-4354 | Mar 16, 2036 |
| US 10781218 ↗ | Drug substance | — | Mar 15, 2037 |
| US 12521396 ↗ | Drug product | — | Jul 16, 2044 |
| US 10077271 ↗ | Drug substance | — | Mar 16, 2036 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Nov 13, 2030 |
Is there a generic version of KOMZIFTI 200 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 |
|---|---|---|---|
| 84696-0200-90 You're viewing this | 90 CAPSULE in 1 BOTTLE (84696-200-90) | 2025-11-13 | Active |
🧭 About this NDC listing & data coverage
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| 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) | — 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, has occurred with KOMZIFTI. Signs and symptoms may include fever, joint pain, hypotension, hypoxia, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, pulmonary infiltrates, acute kidney injury, and rashes. If differentiation syndrome is suspected, interrupt KOMZIFTI and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement [see Dosage and Administration ( 2.5 ), Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.1 )] .
WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. If differentiation syndrome is suspected, interrupt KOMZIFTI and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement.
( 2.5 , 5.1 , 6.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE KOMZIFTI is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14 )] . KOMZIFTI is a menin inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Select patients for treatment with KOMZIFTI based on the presence of an NPM1 mutation. ( 2.1 ) Recommended dosage: 600 mg orally once daily until disease progression or unacceptable toxicity. For patients without confirmed disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for a clinical response.
( 2.2 ) See Full Prescribing Information for administration instructions and dosage modifications. ( 2.3 , 2.4 , 2.5 )
2.1Patient Selection Select patients for the treatment of relapsed or refractory AML with KOMZIFTI based on the presence of an NPM1 mutation [see Clinical Studies ( 14 )] . An FDA-approved test for the detection of NPM1 mutations is not currently available.
2.2Recommended Dosage The recommended dosage of KOMZIFTI is 600 mg taken orally once daily until disease progression or unacceptable toxicity. Do not start KOMZIFTI until the white blood cell (WBC) count is reduced to less than 25 x 10⁹/L. For patients without confirmed disease progression or unacceptable toxicity, treatment for a minimum of 6 months is recommended to allow time for a clinical response.
2.3Administration Instructions Administer KOMZIFTI once daily on an empty stomach (at least 1 hour before or 2 hours after a meal) [see Clinical Pharmacology ( 12.3 )]. Administer KOMZIFTI orally at about the same time each day. Swallow capsules whole.
Do not open, break, or chew the capsules. If a dose of KOMZIFTI 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.
2.4Dosage Modifications for Concomitant Use of Acid-Reducing Agents Avoid concomitant use of proton pump inhibitors (PPIs) with KOMZIFTI. Avoid concomitant use of a histamine-2 (H2) receptor antagonist or a locally acting antacid with KOMZIFTI [see Drug Interactions ( 7.1 )] . If concomitant use cannot be avoided: Take KOMZIFTI 2 hours before or 10 hours after administration of an H2 receptor antagonist.
Take KOMZIFTI 2 hours before or 2 hours after administration of a locally acting antacid.
2.5Dosage Modifications for Adverse Reactions Manage any abnormalities promptly [see Warnings and Precautions ( 5.1 , 5.2 ) and Adverse Reactions ( 6.1 )] . Interrupt or reduce dose for adverse reactions as per Table 1 and Table 2 . Table 1 Recommended Management and Dosage Modifications for KOMZIFTI for Adverse Reactions Adverse Reaction a Recommended Action a Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. b Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. c See Table 2 for the reduced dose levels.
Differentiation syndrome [see Warnings and Precautions ( 5.1 )] If differentiation syndrome is suspected, interrupt KOMZIFTI. Administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days and provide supportive care. Resume KOMZIFTI at the same dose level when signs and symptoms improve and are Grade ≤ 2 b .
Noninfectious leukocytosis (e.g., sudden or significant white blood cell (WBC) increase, including WBC doubling within the first 2 weeks of administration or an absolute increase of 10 x 10 9 /L) Evaluate for differentiation syndrome. Initiate treatment with hydroxyurea, as per standard institutional practices, and leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves.
Interrupt KOMZIFTI if leukocytosis is not controlled with hydroxyurea within 48 hours. If interrupted, resume KOMZIFTI at the same dose level once WBC counts are controlled. Nonhematological adverse reactions Grade ≥ 3 b [see Adverse Reactions ( 6.1 )] Interrupt KOMZIFTI until recovery to Grade ≤ 2 b .
Resume KOMZIFTI at the same dose level. If the same Grade ≥ 3 toxicity recurs, interrupt KOMZIFTI unt…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules of ziftomenib are available in 200 mg strength. The capsules are white and are imprinted with “ZIF 200” in black ink. Capsules: 200 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS QTc Interval Prolongation: Monitor electrocardiograms and electrolytes. Correct hypokalemia and hypomagnesemia prior to treatment. Interrupt KOMZIFTI if the QTc interval is > 500 ms. ( 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 )
5.1Differentiation Syndrome KOMZIFTI can cause fatal or life-threatening differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells. Symptoms of differentiation syndrome, including those seen in patients treated with KOMZIFTI, may include fever, hypoxia, joint pain, hypotension, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, acute kidney injury, and rashes.
In the clinical trial, differentiation syndrome occurred in 29 (26%) of 112 patients with relapsed or refractory AML with an NPM1 mutation who were treated with KOMZIFTI at the recommended dosage. Differentiation syndrome was Grade 3 in 13% and fatal in two patients. In broader evaluation of all patients with any genetic form of AML treated with KOMZIFTI monotherapy in clinical trials, differentiation syndrome occurred in 25% of patients.
Four fatal cases of differentiation syndrome occurred out of 39 patients with KMT2A -rearranged AML treated with KOMZIFTI. KOMZIFTI is not approved for use in patients with KMT2A -rearranged AML. In the 112 patients with an NPM1 mutation, differentiation syndrome was observed with and without concomitant hyperleukocytosis, in as early as 3 days and up to 46 days after KOMZIFTI initiation.
The median time to onset was 15 days. Two patients experienced more than one differentiation syndrome event. Treatment was interrupted and resumed in 15 (13%) patients, while it was permanently discontinued in 2 (2%) patients [see Adverse Reactions ( 6.1 )] .
Prior to starting treatment with KOMZIFTI, reduce the WBC counts to less than 25 x 10⁹/L. If differentiation syndrome is suspected, interrupt KOMZIFTI, initiate oral or intravenous corticosteroids (e.g., dexamethasone 10 mg every 12 hours) for a minimum of 3 days with hemodynamic and laboratory monitoring. Resume treatment with KOMZIFTI at the same dose level when signs and symptoms improve and are Grade 2 or lower.
Taper corticosteroids over a minimum of 3 days after adequate control or resolution of symptoms [see Dosage and Administration ( 2.5 )] . Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment.
5.2QTc Interval Prolongation KOMZIFTI can cause QT (QTc) interval prolongation [see Clinical Pharmacology ( 12.2 ) ] . In the clinical trial, QTc interval prolongation was reported as an adverse reaction in 12% of 112 patients treated with KOMZIFTI at the recommended dosage for relapsed or refractory AML with an NPM1 mutation. QTc interval prolongation was Grade 3 in 8% of patients.
The heart-rate corrected QT interval (using Fridericia's method) (QTcF) was greater than 500 msec in 9% of patients, and the increase from baseline QTcF was greater than 60 msec in 12% of patients. KOMZIFTI dose reduction was required for 1% of patients due to QTc interval prolongation [see Adverse Reactions ( 6.1 )] . QTc prolongation occurred in 14% of the 42 patients less than 65 years of age and in 10% of the 70 patients 65 years of age or older.
Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with KOMZIFTI. Perform an ECG prior to initiation of treatment with KOMZIFTI, and do not initiate KOMZIFTI in patients with QTcF > 480 msec. Perform an ECG at least once weekly for the first four weeks on treatment, and at least monthly thereafter.
Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms (Grade 3) [see Dosage and Administration ( 2.5 )] . In patients with congenital long QTc syndrome, conges…
🤒 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 )] QTc Interval Prolongation [see Warnings and Precautions ( 5.2 )] The most common adverse reactions (≥20%) are infection without an identified pathogen, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increased. ( 6.1 ) The most common laboratory abnormalities (≥10%) are aspartate aminotransferase increased, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, bilirubin increased, potassium increased.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kura Oncology, Inc., at 1-844-KURAONC, 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. Relapsed or Refractory AML with an NPM1 Mutation The safety of KOMZIFTI for the treatment of patients with relapsed or refractory AML with an NPM1 mutation was evaluated in KO-MEN-001 [see Clinical Studies ( 14 )] . Patients received KOMZIFTI 600 mg once daily (n=112).
The median duration of exposure to KOMZIFTI was 2.2 months (range 0.1 to 21.5 months). Fatal adverse reactions occurred in 4 (4%) patients who received KOMZIFTI, including 2 with differentiation syndrome, 1 with infection, and 1 with sudden death. Serious adverse reactions were reported in 79% of patients who received KOMZIFTI.
Serious adverse reactions occurring in ≥ 5% of patients included infection without an identified pathogen (29%), febrile neutropenia (18%), bacterial infection (16%), differentiation syndrome (16%), and dyspnea (6%). Dosage interruption of KOMZIFTI due to an adverse reaction occurred in 54% of patients. Adverse reactions that required dose interruption in ≥ 2% of patients included infection without an identified pathogen (15%), differentiation syndrome (13%), febrile neutropenia (5%), pyrexia (4%), electrocardiogram QT prolonged (4%), leukocytosis (4%), bacterial infection (3%), cardiac failure (2%), cholecystitis (2%), diarrhea (2%), pruritus (2%), and thrombosis (2%).
Dose reduction of KOMZIFTI due to an adverse reaction occurred in 4% of patients. Permanent discontinuation of KOMZIFTI due to an adverse reaction occurred in 21% of patients. Adverse reactions that required permanent discontinuation of KOMZIFTI in ≥ 2% of patients were infection without an identified pathogen (8%), bacterial infection (4%), cardiac arrest (2%), and differentiation syndrome (2%).
The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, infection without an identified pathogen, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, bilirubin increased, potassium increased, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increased.
Table 3 summarizes the adverse reactions in KO-MEN-001. Table 3 Adverse Reactions Reported in ≥20% (Any Grade) or ≥5% (Grade 3 or 4) of Patients with Relapsed or Refractory AML †Includes the following fatal adverse reactions: infection (n=1) and differentiation syndrome (n=2). *No Grade 4 events were reported for this adverse reaction. a Includes abdominal abscess, abscess limb, anal abscess, anorectal infection, bronchitis, conjunctivitis, device related infection, device related sepsis, diverticulitis, emphysematous cystitis, enterocolitis infectious…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong or Moderate CYP3A4 Inhibitors: Monitor more frequently for adverse reactions. ( 7.1 ) Strong or Moderate CYP3A4 Inducers: Avoid concomitant use. ( 7.1 ) Proton Pump Inhibitors: Avoid concomitant use.
( 2.4 , 7.1 ) H2 Receptor Antagonists and Antacids: Avoid concomitant use. If concomitant use cannot be avoided, modify KOMZIFTI administration time. ( 2.4 , 7.1 ) Drugs that Prolong the QTc Interval: Avoid concomitant use.
If concomitant use is unavoidable, monitor patients more frequently for QTc interval prolongations. ( 5.2 , 7.1 )
7.1Effect of Other Drugs on KOMZIFTI Strong or Moderate CYP3A4 Inhibitors Monitor patients more frequently for KOMZIFTI-associated adverse reactions. Ziftomenib is primarily metabolized by CYP3A. Concomitant use of KOMZIFTI with strong or moderate CYP3A4 inhibitors increases ziftomenib exposure [see Clinical Pharmacology ( 12.3 )], which may increase the risk of adverse reactions such as QT prolongation.
Strong or Moderate CYP3A4 Inducers Avoid concomitant use of KOMZIFTI with strong or moderate CYP3A4 inducers. Ziftomenib is primarily metabolized by CYP3A. Concomitant use of KOMZIFTI with strong or moderate CYP3A4 inducers may decrease ziftomenib exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce the efficacy of KOMZIFTI.
Gastric Acid Reducing Agents Concomitant administration of ziftomenib with proton pump inhibitors (PPIs) decreases ziftomenib exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce the efficacy of KOMZIFTI. Avoid concomitant use of KOMZIFTI with PPIs. Avoid concomitant use of KOMZIFTI with H2 receptor antagonists (H2RAs) or locally acting antacids.
If concomitant use cannot be avoided, modify KOMZIFTI administration time [see Dosage and Administration ( 2.4 )] . Drugs that Prolong the QT Interval Avoid concomitant use of KOMZIFTI with other product(s) with a known potential to prolong the QTc interval. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated [see Warnings and Precautions ( 5.2 )] .
Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms [see Dosage and Administration ( 2.5 )] . Ziftomenib causes QTc interval prolongation [see Clinical Pharmacology ( 12.2 )] . Concomitant use of KOMZIFTI with other products that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsades de pointes, other serious arrhythmias, and sudden death [see Warnings and Precautions ( 5.2 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on KOMZIFTI use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of ziftomenib to pregnant mice during the period of organogenesis resulted in adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and altered fetal growth at maternal exposures approximately 0.3 times the human exposure (AUC) at the recommended dose (see Data ) .
Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Ziftomenib was administered orally twice daily to pregnant mice at doses of 6, 20, and 60 mg/kg/day during organogenesis (gestation days 6-15).
Decreased fetal body weight, embryo-fetal lethality, fetal external and skeletal malformations and variations (cleft palate, fused cervical arches, absent lumbar vertebrae fused and/or misaligned costal cartilage, absent or short rib, supernumerary site in the suture bone or split palatine of the skull, and/or fused, unossified, and/or incompletely ossified sternebrae) were noted at all doses. At the dose of 6 mg/kg/day in mice, the maternal exposure was approximately 0.3 times the human exposure at the recommended dose of 600 mg once daily.
8.2Lactation Risk Summary There are no data on the presence of ziftomenib or its metabolites in human milk or the effects of ziftomenib or its metabolites on the breastfed child or milk production. Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with KOMZIFTI and for 2 weeks after the last dose.
8.3Females and Males of Reproductive Potential Based on findings in animals and its mechanism of action, KOMZIFTI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating KOMZIFTI. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 6 months after the last dose.
Males Advise males with female partners of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 3 months after the last dose. Infertility Based on findings in animals, KOMZIFTI may impair fertility in females and males of reproductive potential. Findings in animals were not reversible after a 4-week recovery period [see Nonclinical Toxicology ( 13.1 )].
8.4Pediatric Use Safety and effectiveness of KOMZIFTI in pediatric patients have not been established.
8.5Geriatric Use Of the 112 patients with relapsed or refractory AML with an NPM1 mutation treated with KOMZIFTI, 70 (63%) patients were 65 years of age or older and 31 (28%) were 75 years or older. No overall differences in effectiveness, safety, or pharmacokinetics of KOMZIFTI were observed between patients aged 65 years or older and younger patients [see Clinical Studies ( 14 ) and Clinical Pharmacology ( 12.3 )].
8.6Renal Impairment No dose adjustment is required for patients with mild or moderate (CL Cr 30 to 89 mL/min) renal impairment. The effects of severe (CL Cr less than 30 mL/min) renal impairment have not been studied [see Clinical Pharmacology ( 12.3 )].
8.7Hepatic Impairment No dose adjustment is required for patients with mild (bilirubin less than or equal to ULN and AST greater than ULN or bilirubin less than or equal to 1.5 x ULN) or moderate (bilirubin 1.5 to 3 x ULN) hepatic impairment. The effects of severe hepatic impairment (…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on KOMZIFTI use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of ziftomenib to pregnant mice during the period of organogenesis resulted in adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and altered fetal growth at maternal exposures approximately 0.3 times the human exposure (AUC) at the recommended dose (see Data ) .
Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Ziftomenib was administered orally twice daily to pregnant mice at doses of 6, 20, and 60 mg/kg/day during organogenesis (gestation days 6-15).
Decreased fetal body weight, embryo-fetal lethality, fetal external and skeletal malformations and variations (cleft palate, fused cervical arches, absent lumbar vertebrae fused and/or misaligned costal cartilage, absent or short rib, supernumerary site in the suture bone or split palatine of the skull, and/or fused, unossified, and/or incompletely ossified sternebrae) were noted at all doses. At the dose of 6 mg/kg/day in mice, the maternal exposure was approximately 0.3 times the human exposure at the recommended dose of 600 mg once daily.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of KOMZIFTI in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 112 patients with relapsed or refractory AML with an NPM1 mutation treated with KOMZIFTI, 70 (63%) patients were 65 years of age or older and 31 (28%) were 75 years or older. No overall differences in effectiveness, safety, or pharmacokinetics of KOMZIFTI were observed between patients aged 65 years or older and younger patients [see Clinical Studies ( 14 ) and Clinical Pharmacology ( 12.3 )].
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Ziftomenib is a menin inhibitor that blocks the interaction of menin and lysine [K]-specific methyltransferase 2A (KMT2A). Acute leukemias can be driven by mutations in NPM1 that recruit the wild-type menin-KMT2A complex to promoters of leukemogenic genes. Susceptible NPM1 mutations are defined as those that result in loss of the nucleolar localization signal and the insertion of a new nuclear export signal leading to cytoplasmic accumulation of mutant NPM1 protein that disrupts normal cell function and drives leukemogenesis through altered gene expression.
Pharmacologic disruption of the menin-KMT2A protein-protein interaction by ziftomenib blocks oncogenic activity of mutant NPM1, which induces differentiation of leukemic cells as evidenced by increased expression of differentiation markers. In nonclinical studies, ziftomenib demonstrated in vitro and in vivo antitumor activity in models of NPM1 -mutant leukemia.
12.2Pharmacodynamics Ziftomenib exposure-response relationships have not been fully characterized and the time course of pharmacodynamic response is unknown. Cardiac Electrophysiology The effect of KOMZIFTI on the QTc interval was evaluated at 600 mg (the approved recommended dosage) in patients with relapsed or refractory acute myeloid leukemia in KO-MEN-001 (n=133). The increase in the QTc interval was concentration-dependent with the largest mean increase in QTc interval predicted to be 7.7 ms (upper confidence interval = 12.6 ms) after administration of ziftomenib 600 mg once daily.
There were 9 subjects (7%) with QTcF > 500 ms and an increase in QTc > 60 ms over baseline [see Warnings and Precautions ( 5.2 )] .
12.3Pharmacokinetics Ziftomenib pharmacokinetics were characterized in patients with relapsed or refractory AML. Pharmacokinetic parameters are presented as mean (% CV), unless otherwise specified. Table 5 Ziftomenib Pharmacokinetics in Patients with R/R AML Abbreviations: C max = maximum plasma concentration; AUC = area under the time concentration curve; T max = time to peak concentration a Steady-state (Cycle 2 Day 1). b Approximately 1,000 calories, 60% fat, 25% carbohydrates, 15% protein.
Parameter Dosage 600 mg once daily (with strong CYP3A4 inhibitors) 600 mg once daily (without CYP3A4 inhibitors) General Information Exposure a C max (ng/mL) 617 (33) 288 (41) AUC (ng•h/mL) 13,185 (36) 5,512 (48) Dose Proportionality Dose proportional over 200 mg to 600 mg once daily doses (0.33 to 1.0 times the recommended dose of 600 mg once daily) Accumulation ~ 3-fold Absorption T max [Median (range)] (hours) 4.1 (0.5, 8.15) Absolute Bioavailability 12.9% Effect of Food High-Fat Meal b AUC and C max increased 4-fold Distribution Apparent Volume of Distribution (L) 30100 (98%) Protein Binding 99% (albumin) Elimination Half-Life (hours) 189.8 (23) 93.6 (21) Apparent Clearance (L/h) 41.5 (29) 101.2 (27) Metabolism Primary Pathway CYP3A Excretion Feces 86% (73% as unchanged drug) Urine 0.5% (0.03% as unchanged drug) Specific Populations No clinically significant differences in the pharmacokinetics of ziftomenib were observed based on age (18 to 86 years), sex, race, ethnicity, mild (bilirubin less than or equal to ULN and AST greater than ULN or bilirubin less than or equal to 1.5 x ULN) or moderate (bilirubin 1.5 to 3 x ULN) hepatic impairment, or mild to moderate (CL Cr 30 to 89 mL/min) renal impairment.
The effects of severe hepatic impairment (bilirubin greater than 3 x ULN) or severe renal impairment (CL Cr less than 30 mL/min) on ziftomenib pharmacokinetics have not been studied. Drug Interaction Studies Clinical Studies and Model-Informed Approaches Gastric Acid Reducing Agents: Administration of PPIs reduced ziftomenib AUC 0-inf by 53% and C max by 70%. Strong, Moderate, or Weak CYP3A4 Inhibitors: Itraconazole, voriconazole, and posaconazole (strong CYP3A4 inhibitors) are estimated to increase ziftomenib AUC by up to 3-fold and C max by up to 2-fold.
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🧬 Mechanism of Action ▾
12.1Mechanism of Action Ziftomenib is a menin inhibitor that blocks the interaction of menin and lysine [K]-specific methyltransferase 2A (KMT2A). Acute leukemias can be driven by mutations in NPM1 that recruit the wild-type menin-KMT2A complex to promoters of leukemogenic genes. Susceptible NPM1 mutations are defined as those that result in loss of the nucleolar localization signal and the insertion of a new nuclear export signal leading to cytoplasmic accumulation of mutant NPM1 protein that disrupts normal cell function and drives leukemogenesis through altered gene expression.
Pharmacologic disruption of the menin-KMT2A protein-protein interaction by ziftomenib blocks oncogenic activity of mutant NPM1, which induces differentiation of leukemic cells as evidenced by increased expression of differentiation markers. In nonclinical studies, ziftomenib demonstrated in vitro and in vivo antitumor activity in models of NPM1 -mutant leukemia.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied KOMZIFTI 200 mg capsules are supplied as white capsules printed with “ZIF 200” in black ink. KOMZIFTI capsules are available in white, induction-sealed, square, high-density polyethylene bottles of 90 capsules with child-resistant closure (NDC 84696-200-90). 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].
📦 Storage and Handling ▾
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 KOMZIFTI contains ziftomenib, a menin inhibitor. The chemical name is ( S )-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1-(2-(4-(methylsulfonyl)piperazin-1-yl)propyl)-1 H -indole-2-carbonitrile. The chemical structure is: The molecular formula is C 33 H 42 F 3 N 9 O 2 S 2 and the molecular weight is 717.88 g/mol.
Ziftomenib is a white to off-white powder and is highly soluble in aqueous solution at pH 1.2 and practically insoluble at pH ≥4. KOMZIFTI (ziftomenib) is available as a 200 mg capsule for oral administration. Each KOMZIFTI capsule contains 200 mg ziftomenib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, and sodium lauryl sulfate.
The capsule shells, imprinted with black ink, contain the following inactive ingredients: hypromellose and titanium dioxide. 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 risk of developing differentiation syndrome as early as 3 days after the start of therapy and during treatment. Instruct patients to immediately report any symptoms suggestive of differentiation syndrome, such as fever, joint or bone pain, dizziness, shortness of breath or difficulty breathing, cough, chest pain, rapid weight gain, rash, decreased urinary output, or swelling in the hands, feet, ankles, or legs, to their healthcare provider for further evaluation [see Boxed Warning and Warnings and Precautions ( 5.1 )] .
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 ( 5.2 )] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to notify their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )] .
Lactation Advise women not to breastfeed during treatment with KOMZIFTI and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )] . Drug Interactions Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter medications and supplements [see Drug Interactions ( 7.1 )] . Dosing Instructions Advise patients to take KOMZIFTI once daily, at around the same time each day, on an empty stomach, at least 1 hour before or 2 hours after a meal [see Dosage and Administration ( 2.3 )] .
Advise patients to swallow KOMZIFTI capsules whole. Do not open, break, or chew the capsules [see Dosage and Administration ( 2.3 )] . Instruct patients, if they miss a dose of KOMZIFTI, to take the dose 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.
Advise patients not to take 2 doses within 12 hours to make up for the missed dose [see Dosage and Administration ( 2.3 )] . Manufactured for Kura Oncology, Inc., San Diego, CA 92121 KOMZIFTI™ is a trademark of Kura Oncology, Inc. © 2025 Kura Oncology, Inc.
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 11/2025 MEDICATION GUIDE KOMZIFTI (kom-ZIF-tee) (ziftomenib) capsules What is the most important information I should know about KOMZIFTI?
KOMZIFTI can cause serious side effects including: Differentiation Syndrome. Differentiation syndrome is a condition that affects your blood cells that is common during treatment with KOMZIFTI and can be life-threatening or lead to death if not treated. Differentiation syndrome can happen as early as 3 days after you start KOMZIFTI treatment and can also happen later during treatment with KOMZIFTI.
Tell your healthcare provider or go to the nearest hospital emergency room right away if you develop any of the following signs or symptoms of differentiation syndrome during treatment with KOMZIFTI: fever joint or bone pain dizziness shortness of breath or trouble breathing cough chest pain rapid weight gain rash decreased urine output swelling of hands, feet, ankles, or legs If you develop signs and symptoms of differentiation syndrome during treatment with KOMZIFTI, your healthcare provider may temporarily stop KOMZIFTI and give you a corticosteroid medicine.
Your healthcare provider will monitor you until your signs and symptoms improve. See “ What are the possible side effects of KOMZIFTI? ” for more information about side effects. What is KOMZIFTI?
KOMZIFTI is a prescription medicine used to treat adults with acute myeloid leukemia (AML) with a nucleophosmin 1 ( NPM1 ) mutation whose AML has come back or did not improve after previous treatment(s) and who have no other satisfactory treatment options. Your healthcare provider will perform a test to make sure that KOMZIFTI is right for you. It is not known if KOMZIFTI is safe and effective in children.
Before taking KOMZIFTI, 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 levels of salts in your blood (electrolytes), such as potassium and magnesium levels. are pregnant or plan to become pregnant. KOMZIFTI can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider will perform a pregnancy test before you start treatment with KOMZIFTI.
Use effective birth control (contraception) during treatment with KOMZIFTI and for 6 months after the last dose. Males who have female partners who are able to become pregnant: Use effective birth control (contraception) during treatment with KOMZIFTI and for 3 months after the last dose. Talk to your healthcare provider about birth control methods you can use during this time. are breastfeeding or plan to breastfeed.
It is not known if KOMZIFTI passes into your breast milk. Do not breastfeed during your treatment with KOMZIFTI and for 2 weeks after your last dose. Tell your healthcare provider about any other medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
KOMZIFTI and other medicines may affect each other causing side effects. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist.
How should I take KOMZIFTI? Take KOMZIFTI exactly as your healthcare provider tells you to. Do not change your dose or stop taking KOMZIFTI without talking to your healthcare provider.
Take KOMZIFTI 1 time a day around the same time each day. Take KOMZIFTI on empty stomach, at least 1 hour before or 2 hours after a meal. Swallow KOMZIFTI capsules whole.
Do not open, break, or chew the capsules. If you take medicine to reduce stomach acid: Avoid taking a proton pump inhibitor (PPI) medicine with KOMZIFTI. Take KOMZIFTI either 2 hours before or 10 hours after taking an H2 receptor blocker medicine.
Take KOMZIFTI either 2 hours before or 2 hours after taking a locally acting antacid medicine (such as calcium carbonate). If you miss a dose of KOMZIFTI or did not take it at the u…