NDC 00078-0698-99 — RYDAPT 25 mg Capsule, Liquid Filled

🆔 Identity & classification

FDA NDC (as labeled) 0078-0698-99

Product NDC 0078-0698

11-digit billing NDC 00078069899

NCPDP billing unit EA — each (per item)

RxCUI 1919088

UNII ID912S5VON

Application # NDA207997

SPL Set ID 11fa3fc9-6776-49a6-b1c1-653f627c3e58

Established class (EPC) Kinase Inhibitor

Mechanism of action Receptor Tyrosine Kinase Inhibitors

DEA schedule Non-controlled

Marketing category NDA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2017-04-28

Route ORAL

Dosage form CAPSULE, LIQUID FILLED

Substance MIDOSTAURIN

GPI-14 21533030000130

GPI class Rydapt

GCN Seq No 077344

GCN 43327

HICL code 044227

Ingredient (HICL) Midostaurin

HIC1 code V

Therapeutic class — broad (HIC1) Neoplasms

HIC2 code V1

Therapeutic class — intermediate (HIC2) Antineoplastic Drugs

HIC3 code V1Q

Therapeutic class — specific (HIC3) Antineoplastic Systemic Enzyme Inhibitors

AHFS code 10:00.00.00

AHFS class Antineoplastic Agents

FDB label name RYDAPT 25 MG CAPSULE

FDB brand name Rydapt

Legend status F — Federal legend — prescription drug or device

TE code (Orange Book) AB · RLD · RS

Why two NDCs? The FDA registers this code as 0078-0698-99 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00078-0698-99. Same drug, same package — only the format differs.

Where does this data come from?

Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Kinase Inhibitor class.

Pharmacologic class Kinase Inhibitor

Drug family (ATC) Other protein kinase inhibitors

How it works Receptor Tyrosine Kinase Inhibitors

Where does this data come from?

Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerNovartis Pharmaceuticals Corporation

Application holderNOVARTIS PHARMACEUTICALS CORP

FDA applicationNDA207997 (NDA)

Labeler code00078

First marketedApr 2017

Product typeHuman Prescription Drug

Portfolio209 products on file

🔎 All NDCs from Novartis Pharmaceuticals Corporation

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).

Where does this data come from?

Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name RYDAPT 25 MG CAPSULE Ingredient Midostaurin

📖 What it is MedlinePlus · NLM

Midostaurin is used with other chemotherapy drugs to treat certain types of acute myeloid leukemia (AML; a type of cancer of the white blood cells). Midostaurin is also used to certain types of mastocytosis (a blood disorder in which there are too many mast cells [a certain kind of white blood cell]). Midostaurin is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of mast and cancer cells.

Read the full MedlinePlus article ↗

📗 Our plain-language guide HelloPharmacist

📖 Read our full Midostaurin guide →

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →

Where does this data come from?

Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color Orange

ShapeCapsule

ImprintPKC;NVR

Size25 mm

ScoringNot scored

One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.

Where does this data come from?

Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

UNII H4N855PNZ1
Alpha-tocopherol is a form of vitamin E, a fat-soluble antioxidant derived from natural or synthetic sources. In medicines, it prevents oils and fats from breaking down and becoming rancid, protecting the product's stability and shelf life.
UNII 3K9958V90M
A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
UNII CID8Z8N95N
Carminic acid is a red-to-purple dye extracted from cochineal insects. It's used in medicines as a colorant to give tablets, capsules, or liquids their red or pink appearance.
UNII 8470G57WFM
Corn oil is a vegetable oil extracted from corn kernels. It's used in medicines as a solvent to dissolve active ingredients and help the body absorb them, and sometimes as a lubricant in capsules.
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.
UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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.
UNII PDC6A3C0OX
Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
UNII 0HO1H52958
Hypromellose 2910 is a plant-derived cellulose that forms a protective coating around tablets or capsules. It slows how fast the medicine releases, helps protect the active ingredient, and improves how the product looks.
UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
UNII 7YC686GQ8F
A synthetic oily substance made from castor oil. It works as a solubilizer and emulsifier to help mix oily and water-based ingredients together in the medicine.
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.
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.
UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

14 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?

Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?

No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.

Why might an inactive ingredient be missing?

Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.

Can inactive ingredients matter?

Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 mL	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	$217.99	—
Medicare drug plans payPart D · Q2 2026	$234.70	—

Where does this data come from?

NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Rydapt 25 mgthis 00078-0698-99	Novartis	2 capsules	—	AB	FDA listed	—

About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.

Where does this data come from?

Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️

2017

First FDA approval

Apr 2017

📍

2026

Currently FDA-listed

9 years listed

🛡️

2030

Latest patent/protection listed

not a guaranteed launch date

🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Dec 2030. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.

📅 FDA approved Apr 28, 2017 AB TE-rated RLD RS ⏳ ~4.2 yr to latest listed protection

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.

Patents & exclusivity — FDA Orange Book

US 8575146 — method of use (U-2008)

US 7973031 — method of use (U-2007)

2017 2019 2021 2023 2025 2027 2029 2031

Today

LOE

Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo

🏛️FDA exclusivity

FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.

🧪Product / substance patents

Patents covering the active ingredient, product, formulation, or related drug features.

🎯Method-of-use patents

Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.

🛈 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.

Listed patents (2)

Patent	Type	Use code	Expires
US 8575146 ↗	Method of use	U-2008	Dec 2, 2030
US 7973031 ↗	Method of use	U-2007	Oct 9, 2028

Common questions

Is there a generic version of RYDAPT 25 MG CAPSULE?

Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for RYDAPT 25 MG CAPSULE. See the alternatives section for substitutable, lower-cost products.

The FDA approved a generic — why can’t I get it at my pharmacy yet?

FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.

Why do different websites show different generic release dates?

Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.

What does “FDA listed” mean?

It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.

What does a patent or protection date mean here?

It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).

What does “current Orange Book estimate” mean?

It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.

Can a generic come out before the last patent expires?

Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.

Can a generic come out after the listed dates?

Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.

What is the difference between patents and exclusivity?

Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.

Why are there multiple patent dates?

One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.

Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.

Where does this data come from?

Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 00078-0698-99, not the drug overall. Other pack sizes report separately.

💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.

📅 Q1 2025 – Q4 2025 · 4 quarters of data

ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.

Prescriptions last 4 qtrs

12

Units reimbursed last 4 qtrs

840

Gross reimbursed last 4 qtrs

$183.1K

Avg / prescription

$15,259.26

Avg / unit

$217.99

Latest quarter Q4 2025

12Rx

Fee-for-service vs managed care ⓘ

100% FFS

Fee-for-service · 12 Rx Managed care · 0 Rx

State Medicaid map

Units reimbursed · per 100k residents

8.48.4

gray = no data reported ⓘ

Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.

Tap or hover a state

…for its Medicaid breakdown

🏆 Top states by units · per 100k residents

1 Michigan 8.4 /100k

National units — by quarter

💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.

2 capsules00078-0698-19 35 Rx · $951,987

2 capsules this page00078-0698-99 12 Rx · $183,111

Drug total (last 4 qtrs): 47 Rx · 5,320 units · $1,135,098 gross reimbursed

Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Rydapt — the program that covers self-administered drugs. 1 manufacturer.

⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Rydapt. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.

Period

Total Part D spend

$7.89M

Claims incl. refills

323

Beneficiaries

140

Spend / beneficiary

$56,339.21

Spend / claim

$24,419.47

Trend by period

💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

📦 Packaging — all sizes for this product

Package NDC	Description	Marketing start	Status
00078-0698-19	4 CARTON in 1 CARTON (0078-0698-19) / 14 BLISTER PACK in 1 CARTON (0078-0698-51) / 2 CAPSULE, LIQUID FILLED in 1 BLISTER PACK (0078-0698-02)	2017-04-28	Active
00078-0698-99 You're viewing this	2 CARTON in 1 CARTON (0078-0698-99) / 14 BLISTER PACK in 1 CARTON (0078-0698-51) / 2 CAPSULE, LIQUID FILLED in 1 BLISTER PACK (0078-0698-02)	2017-04-28	Active

Pack size FAQ

What quantity is in NDC 00078-0698-99?

NDC 00078-0698-99 is listed by the FDA — 2 carton in 1 carton / 14 blister pack in 1 carton / 2 capsule, liquid filled in 1 blister pack.

What NDC number is used to bill for this package of RYDAPT 25 mg Capsule, Liquid Filled?

Bill NDC 00078-0698-99 — the 11-digit billing format is 00078069899. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product

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

“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?

The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.

Is the NDC printed on the package the same as the 11-digit billing NDC?

Yes, they identify this exact package in different formats. The FDA registers it as 0078-0698-99, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00078-0698-99, written without dashes as 00078069899. The Identity section at the top of this page lists every form of this code.

What do the three segments of this NDC mean?

In 00078-0698-99, the first segment (00078) is the labeler code FDA assigned to Novartis Pharmaceuticals Corporation; the middle segment (0698) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (99) identifies this exact package size and type. Together they name one specific package of one specific product.

Is this package still being marketed?

Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Novartis Pharmaceuticals Corporation. Listing status can change — the directory data on this page refreshes weekly.

Does this product come in other package sizes?

Yes — the FDA directory lists 1 other package presentation of this same product, including 2 capsules (00078-0698-19). Each has its own NDC and its own page — see the package list near the top of this page.

Who lists this product with the FDA?

Novartis Pharmaceuticals Corporation is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.

Do I need a prescription for this product?

This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.

This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.

Where does this data come from?

Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.

🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients

🎯 Indications and Usage 184 words ▾

1 INDICATIONS AND USAGE RYDAPT is a kinase inhibitor indicated for the treatment of adult patients with: Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. ( 1.1 ) Limitations of Use: RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML. Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

( 1.2 )

1.1Acute Myeloid Leukemia RYDAPT is indicated in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA approved test [see Dosage and Administration (2.1), Clinical Studies (14.1)]. Limitations of Use RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

1.2Systemic Mastocytosis RYDAPT is indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION AML : 50 mg orally twice daily with food. ( 2.1 , 2.2 , 2.4 ) ASM, SM-AHN, and MCL : 100 mg orally twice daily with food. ( 2.3 , 2.4 )

2.1Patient Selection Select patients for the treatment of AML with RYDAPT based on the presence of FLT3 mutation positivity [see Clinical Studies (14)] . Information on FDA-approved tests for the detection of FLT3 mutation in AML is available at: http://www.fda.gov/CompanionDiagnostics.

2.2Recommended Dosage in Acute Myeloid Leukemia The recommended dose of RYDAPT for patients with AML is 50 mg orally twice daily with food on Days 8 to 21 of each cycle of induction with cytarabine and daunorubicin and on Days 8 to 21 of each cycle of consolidation with high-dose cytarabine. For a description of the experience with single-agent treatment with RYDAPT beyond induction and consolidation [see Clinical Studies (14.1)] .

2.3Recommended Dosage in ASM, SM-AHN, and MCL The recommended dose of RYDAPT for patients with ASM, SM-AHN, and MCL is 100 mg orally twice daily with food. Continue treatment until disease progression or unacceptable toxicity occurs. Table 1 provides recommendations for dose modifications of RYDAPT in patients with ASM, SM-AHN, and MCL.

Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment. Table 1: RYDAPT Dose Modifications for Patients with Systemic Mastocytosis Criteria RYDAPT Dosing ANC less than 1 x 10 9 /L attributed to RYDAPT in patients without MCL, or ANC less than 0.5 x 10 9 /L attributed to RYDAPT in patients with baseline ANC value of 0.5-1.5 x 10 9 /L Interrupt RYDAPT until ANC greater than or equal to 1 x 10 9 /L, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily.

Discontinue RYDAPT if low ANC persists for greater than 21 days and is suspected to be related to RYDAPT. Platelet count less than 50 x 10 9 /L attributed to RYDAPT in patients without MCL, or platelet count less than 25 x 10 9 /L attributed to RYDAPT in patients with baseline platelet count of 25-75 x 10 9 /L Interrupt RYDAPT until platelet count greater than or equal to 50 x 10 9 /L, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. Discontinue if low platelet count persists for greater than 21 days and is suspected to be related to RYDAPT.

Hemoglobin less than 8 g/dL attributed to RYDAPT in patients without MCL, or life-threatening anemia attributed to RYDAPT in patients with baseline hemoglobin value of 8 to 10 g/dL Interrupt RYDAPT until hemoglobin greater than or equal to 8 g/dL, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. Discontinue if low hemoglobin persists for greater than 21 days and is suspected to be related to RYDAPT. Grade 3/4 nausea and/or vomiting despite optimal anti-emetic therapy Interrupt RYDAPT for 3 days (6 doses), then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily.

Other Grade 3/4 non-hematological toxicities Interrupt RYDAPT until event has resolved to less than or equal to Grade 2, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily. Abbreviations: ANC, absolute neutrophil count; MCL, mast cell leukemia. National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) severity: Grade 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = life-threatening symptoms.

2.4Recommended Administration Administer prophylactic anti-emetics before treatment with RYDAPT to reduce the risk of nausea and vomiting. Administer RYDAPT orally with food, twice daily at approximately 12-hour intervals [see Clinical Pharmacology (12.3)]. Do not open or crush RYDAPT capsules.

If a dose of RYDAPT is missed or vomited, do not make up the dose; take the next dose at the usual scheduled time. Consider interval assessments of QT by electrocardiogram (ECG) if RY…

💊 Dosage Forms and Strengths 25 words ▾

3 DOSAGE FORMS AND STRENGTHS 25 mg capsules: pale orange oblong soft capsule with red ink imprint ‘PKC NVR’. Capsules: 25 mg ( 3 )

⛔ Contraindications 59 words ▾

4 CONTRAINDICATIONS RYDAPT is contraindicated in patients with hypersensitivity to midostaurin or to any of the excipients [see Description (11)]. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment) [see Adverse Reactions (6.1)]. Hypersensitivity to midostaurin or any of the excipients. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity : RYDAPT may cause fetal harm when administered to a pregnant woman. Advise of the potential risk to a fetus. ( 5.1 , 8.1 ) Pulmonary Toxicity : Monitor for symptoms of interstitial lung disease or pneumonitis. Discontinue RYDAPT in patients with signs or symptoms of pulmonary toxicity. Fatal cases have occurred. ( 5.2 )

5.1Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal reproduction studies, RYDAPT may cause fetal harm when administered to pregnant women. In animal studies, midostaurin caused embryo-fetal toxicities, including late embryo-fetal death and reduced fetal birth weight, with delays in fetal growth at doses lower than the recommended human dose. Advise pregnant women of the potential risk to the fetus.

Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT therapy. Advise females of reproductive potential to use effective contraception during treatment with RYDAPT and for 4 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with RYDAPT and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3), Clinical Pharmacology (12.1)] .

5.2Pulmonary Toxicity Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy. Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology.

5.3Risk of Prolonged Severe Neutropenia and Thrombocytopenia in Pediatric Patients Treated With Combination Chemotherapy Prolonged Grade 4 neutropenia and thrombocytopenia occurred in two pediatric patients with AML who received an unapproved formulation of midostaurin in combination with chemotherapy, including anthracyclines, fludarabine, and cytarabine; these two patients were coadministered an azole antifungal (a strong CYP3A4 inhibitor), which may increase midostaurin concentrations and subsequently, the risk of toxicity [see Drug Interactions (7.1), Use in Specific Populations (8.4)] .

The safety and effectiveness of RYDAPT in pediatric patients have not been established.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Pulmonary Toxicity [see Warnings and Precautions (5.2)] AML : The most common adverse reactions (≥ 20%) were febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, electrocardiogram (ECG) QT prolonged, and upper respiratory tract infection. ( 6.1 ) ASM, SM-AHN, or MCL : The most common adverse reactions (≥ 20%) were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache, and dyspnea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com/ 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. Acute Myeloid Leukemia The safety evaluation of RYDAPT (50 mg twice daily with food) in patients with newly diagnosed FLT3 mutated AML is based on a randomized, double-blind, trial of RYDAPT (n = 345) or placebo (n = 335) with chemotherapy [see Clinical Studies (14.1)] .

The overall median duration of exposure was 42 days (range, 2 to 576 days) for patients in the RYDAPT plus chemotherapy arm versus 34 days (range, 1 to 465 days) for patients in the placebo plus chemotherapy arm. On the RYDAPT plus chemotherapy arm, 35% of patients completed induction and consolidation therapy, compared to 25% of patients on the placebo plus chemotherapy arm. The most frequent (incidence greater than or equal to 20%) adverse drug reactions (ADRs) in the RYDAPT plus chemotherapy arm were febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, ECG QT prolonged, and upper respiratory tract infections.

The most frequent Grade 3/4 adverse reactions (incidence ≥ 10%) were febrile neutropenia, device-related infection, and mucositis. The most frequent serious adverse reaction (≥ 10%) in patients in the RYDAPT plus chemotherapy arm was febrile neutropenia (16%), which occurred at a similar rate in the placebo arm (16%). Discontinuation due to any adverse reaction occurred in 9% of patients in the RYDAPT arm versus 6% in the placebo arm.

The most frequent (> 1%) Grade 3/4 adverse reactions leading to discontinuation in the RYDAPT arm was renal insufficiency (1%). Excluding deaths due to disease progression, no fatal adverse reactions occurred in the study. Overall, the most frequent non-treatment related cause of death in the RYDAPT plus chemotherapy arm was sepsis (2%) and occurred at a similar rate in the placebo arm (2%).

Table 2 presents the frequency category of adverse reactions reported in the randomized trial in patients with newly diagnosed FLT3 mutated AML. Adverse reactions are listed according to body system. Within each body system, the adverse reactions are ranked by frequency, with the most frequent reactions first.

Table 3 presents the key laboratory abnormalities from the same randomized trial in patients with newly diagnosed FLT3 mutated AML. Table 2: Common Adverse Reactions (≥ 10% Incidence and ≥ 2% More Frequent on the Midostaurin Arm) of Patients with Acute Myeloid Leukemia in Study 1 All Grades Grades ≥ 3 Adverse Reaction RYDAPT + chemo n = 229 1 % Placebo + chemo n = 226 1 % RYDAPT + chemo n = 345 1 % Placebo + chemo n = 335 1 % Gastrointestinal disorders Nausea 83 70 6 10 Mucositis a 66 62 11 13 Vomiting 61 53 3 5 Hemorrhoids 15 11 1 0 Blood and lymphatic system disorders Febrile neutropenia 83 81 84 83 Petechiae 36 27 1 1 Nervous system disorders Headache a 46 38 3 3 Musculoskeletal and connecti…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors : Strong CYP3A4 inhibitors may increase exposure to midostaurin and its active metabolites. Consider alternative therapies that do not strongly inhibit CYP3A4 or monitor for increased risk of adverse reactions. ( 7.1 ) Strong CYP3A4 Inducers : Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and its active metabolites.

( 7.1 ) CYP2B6, BCRP, OATP1B1 Substrates : Dose adjustments for coadministered CYP2B6, BCRP, and OATP1B1 substrates may be necessary with RYDAPT. ( 7.2 )

7.1Effect of Other Drugs on RYDAPT Table 6 lists the potential effects of the coadministration of strong CYP3A modulators on RYDAPT. Table 6: Drug Interactions with RYDAPT That Affect Midostaurin Strong CYP3A Inhibitors a The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation-dependent. Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (e.g., low dose, single strength). b The induction potency of St.

John’s wort may vary widely based on preparation. Clinical Impact Coadministration of RYDAPT with strong CYP3A inhibitors may increase midostaurin concentrations. The increase in midostaurin concentrations may be pronounced if strong CYP3A inhibitors are administered during the first week of RYDAPT administration [see Clinical Pharmacology (12.3)].

Increased midostaurin concentrations may increase the risk of toxicity. Prevention or Management Consider alternative therapies that do not strongly inhibit CYP3A activity. Alternatively, with coadministration of RYDAPT and strong CYP3A inhibitors, monitor patients for increased risk of adverse reactions, especially during the first week of consecutive RYDAPT administration in advanced SM population, and during first week of RYDAPT administration in each cycle of chemotherapy in AML population.

Examples Boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, grapefruit juice a , idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, troleandomycin, voriconazole Strong CYP3A Inducers Clinical Impact Coadministration of RYDAPT with strong CYP3A inducers may decrease midostaurin concentrations [see Clinical Pharmacology (12.3)].

Decreased midostaurin concentrations may reduce efficacy. Prevention or Management Avoid coadministration of RYDAPT with strong CYP3A4 inducers. Examples Carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St.

John’s wort b

7.2Effect of RYDAPT on Other Drugs CYP2B6 Substrates RYDAPT decreased the systemic exposure of a sensitive CYP2B6 substrate [see Clinical Pharmacology (12.3)] . Dose adjustments for the coadministered CYP2B6 substrate may be necessary with RYDAPT. Substrates of Transporters Coadministration of RYDAPT increased the exposure of a breast cancer resistance protein (BCRP) and organic anion transporter polypeptide (OATP)1B1 substrate [see Clinical Pharmacology (12.3)] .

Dose adjustments for the coadministered BCRP or OATP1B1 substrates may be necessary with RYDAPT.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation : Advise females not to breastfeed. ( 8.2 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RYDAPT during pregnancy. Females who may have been exposed to RYDAPT during pregnancy directly or through a male partner receiving RYDAPT therapy should contact the Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com/ . Risk Summary Based on mechanism of action and findings in animal reproduction studies, RYDAPT may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] .

There are no available data on RYDAPT use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, oral administration of midostaurin to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicities, including late embryo-fetal death and reduced fetal birth weight, with delays in fetal growth at doses lower than the recommended human dose (see Data) . Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population are unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. 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 When midostaurin was administered to female rats prior to mating and through the first week of pregnancy at a dose of 60 mg/kg/day [approximately 0.1 times the human exposure at the recommended dose based on area under the curve (AUC)], there were increases in pre- and post-implantation loss, including total litter loss, resulting in a reduction in the number of live embryos. During organogenesis, midostaurin administered at oral doses greater than or equal to 3 mg/kg/day (approximately 0.004 times the human exposure at the recommended dose by AUC) to pregnant female rats caused late embryo-fetal death.

Dilated lateral brain ventricles were observed in offspring of rats given doses greater than or equal to 3 mg/kg/day. Extra rib and reduced fetal birth weight with effects on fetal growth (severe renal pelvic cavitation and widened anterior fontanelle) were observed in the absence of maternal toxicity at the highest dose of 30 mg/kg/day (approximately 0.05 times the human exposure at the recommended dose by AUC). Midostaurin administered orally to pregnant rabbits during organogenesis led to maternal toxicity with spontaneous abortions and some delay in fetal growth (reduced fetal birth weight) at doses greater than or equal to 10 mg/kg/day (approximately 0.01 times the human exposure at the recommended dose by AUC).

In an oral pre- and postnatal development study in the rat, adverse effects upon maternal performance included dams with signs of dystocia and a lower live litter size at 30 mg/kg/day (approximately 0.05 times the human exposure at the recommended dose by AUC). For the F1 offspring, lower body weights, accelerated complete eye opening and delayed auricular startle ontogeny were noted at 30 mg/kg/day.

8.2Lactation Risk Summary There are no data on the presence of midostaurin or its active metabolites in human milk, the effect on the breastfed infant, or the effect on milk production. Orally administered midostaurin and its active metabolites pass into the milk of lactating rats within 1 hour of a 30 mg/kg/day dose, with approximately 5 times more in the milk of lactating rats compared to plasma. Because of the potential for serious adverse reactions in breastfed infants from RYDAPT, advise women not to breastfeed during treatment with RYDAPT and for 4 months after the last dose.

8.3Females and Males of Reproductive Potential RYDAPT may cause fetal harm when administered to a pregnant…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RYDAPT during pregnancy. Females who may have been exposed to RYDAPT during pregnancy directly or through a male partner receiving RYDAPT therapy should contact the Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com/ . Risk Summary Based on mechanism of action and findings in animal reproduction studies, RYDAPT may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] .

There are no available data on RYDAPT use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, oral administration of midostaurin to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicities, including late embryo-fetal death and reduced fetal birth weight, with delays in fetal growth at doses lower than the recommended human dose (see Data) . Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population are unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. 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 When midostaurin was administered to female rats prior to mating and through the first week of pregnancy at a dose of 60 mg/kg/day [approximately 0.1 times the human exposure at the recommended dose based on area under the curve (AUC)], there were increases in pre- and post-implantation loss, including total litter loss, resulting in a reduction in the number of live embryos. During organogenesis, midostaurin administered at oral doses greater than or equal to 3 mg/kg/day (approximately 0.004 times the human exposure at the recommended dose by AUC) to pregnant female rats caused late embryo-fetal death.

Dilated lateral brain ventricles were observed in offspring of rats given doses greater than or equal to 3 mg/kg/day. Extra rib and reduced fetal birth weight with effects on fetal growth (severe renal pelvic cavitation and widened anterior fontanelle) were observed in the absence of maternal toxicity at the highest dose of 30 mg/kg/day (approximately 0.05 times the human exposure at the recommended dose by AUC). Midostaurin administered orally to pregnant rabbits during organogenesis led to maternal toxicity with spontaneous abortions and some delay in fetal growth (reduced fetal birth weight) at doses greater than or equal to 10 mg/kg/day (approximately 0.01 times the human exposure at the recommended dose by AUC).

In an oral pre- and postnatal development study in the rat, adverse effects upon maternal performance included dams with signs of dystocia and a lower live litter size at 30 mg/kg/day (approximately 0.05 times the human exposure at the recommended dose by AUC). For the F1 offspring, lower body weights, accelerated complete eye opening and delayed auricular startle ontogeny were noted at 30 mg/kg/day.

🧒 Pediatric Use 174 words ▾

8.4Pediatric Use Safety and effectiveness of RYDAPT have not been established in pediatric patients. The safety and effectiveness of an unapproved midostaurin formulation was investigated, but not established in two open-label studies: a study in 22 pediatric patients aged 6 months to 17 years who received midostaurin as a single agent for relapsed or refractory leukemia [NCT00866281] and a study in 4 patients aged 8 to 14 years who received midostaurin in combination with chemotherapy for newly diagnosed FLT3-mutated AML [NCT03591510].

Prolonged Grade 4 neutropenia and thrombocytopenia occurred in 2 of the 4 pediatric patients with AML who received midostaurin in combination with chemotherapy, including anthracyclines, fludarabine, and cytarabine [see Warnings and Precautions (5.3)] . Grade 4 thrombocytopenia lasted for 44 days in one patient and Grade 4 thrombocytopenia and Grade 4 neutropenia lasted for 51 days and 46 days, respectively, in the other patient. These two patients were coadministered an azole antifungal (a strong CYP3A4 inhibitor), which may increase midostaurin concentrations and subsequently, the risk of toxicity [see Drug Interactions (7.1)] .

🧓 Geriatric Use 115 words ▾

8.5Geriatric Use Of the 142 patients with advanced SM in clinical studies of RYDAPT, 64 (45%) were aged 65 and over, and 16 (11%) were aged 75 years and over. No overall differences in safety or response rate were observed between the subjects aged 65 and over compared with younger subjects. Greater sensitivity of older individuals cannot be ruled out.

Clinical studies in AML with RYDAPT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, administration for elderly patients should be cautious, based on patient’s eligibility for concomitant chemotherapy and reflecting the greater frequency of concomitant disease or other drug therapy.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Midostaurin is a small molecule that inhibits multiple receptor tyrosine kinases. In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, as well as members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors.

Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells.

12.2Pharmacodynamics Cardiac Electrophysiology The effect of RYDAPT (75 mg twice daily for 3 days) on the QTc interval was evaluated in a randomized, placebo and moxifloxacin controlled, multiple-dose, blinded, parallel study. There was no clinically significant prolongation of QTc interval or relationship between changes in QTc and concentrations for midostaurin and its active metabolites (CGP62221 and CGP52421). The study duration was not long enough to estimate the effects of the metabolite CGP52421 on the QT/QTc interval.

In pooled clinical studies in patients with advanced SM, 4.7% patients had a post-baseline QTcF > 480 ms, no patients had a QTcF > 500 ms, and 6.3% patients had a QTcF > 60 ms compared to baseline. In a randomized placebo-controlled study in patients with AML, the proportion of patients with QTc prolongation was higher in patients randomized to midostaurin as compared to placebo (QTcF > 480 ms: 10.1% vs 5.7%; QTcF > 500 ms: 6.2% vs 2.6%; QTcF > 60 ms change from baseline: 18.4% vs 10.7%).

12.3Pharmacokinetics Midostaurin exhibits time-dependent pharmacokinetics with an initial increase in minimum concentrations (C min ) that reach the highest C min concentrations during the first week followed by a decline to a steady-state after approximately 28 days. The pharmacokinetics of the CGP62221 showed a similar trend. The plasma concentrations of CGP52421 continued to increase after one month of treatment.

The highest C min and steady-state of midostaurin, CGP62221, and CGP52421 were similar when RYDAPT was administered with food at a dose of 50 mg twice daily or 100 mg twice daily. Absorption The time to maximal concentrations (T max ) occurred between 1 to 3 hours post dose in the fasted state. Effect of Food Midostaurin exposure, represented by AUC over time to infinity (AUC inf ), increased 1.2-fold when RYDAPT was coadministered with a standard meal (457 calories, 50 g fat, 21 g proteins, and 18 g carbohydrates) and 1.6-fold when coadministered with a high-fat meal (1007 calories, 66 g fat, 32 g proteins, and 64 g carbohydrates) compared to when RYDAPT was administered in a fasted state.

Midostaurin maximum concentrations (C max ) were reduced by 20% with a standard meal and by 27% with a high-fat meal compared to a fasted state. T max was delayed when RYDAPT was administered with a standard meal or a high-fat meal (median T max = 2.5 hrs to 3 hrs) [see Dosage and Administration (2.5)]. Distribution Midostaurin has an estimated geometric mean volume of distribution (% coefficient of variation) of

95.2L (31%). Midostaurin and its metabolites are distributed mainly in plasma in vitro . Midostaurin, CGP62221, and CGP52421 are greater than 99.8% bound to plasma protein in vitro .

Midostaurin is mainly bound to α1-acid glycoprotein in vitro . Elimination The geometric mean terminal half-life (% coefficient of variation) is 19 hours (39%) for midostaurin, 32 hours (31%) for CGP62221 and 482 hours (25%) for CGP52421. Metabolism Midostaurin is primarily metabolized by CYP3A4.

CGP62221 and CGP52421 (mean ± standard deviation) account for 28 ± 2.7% and 38 ± 6.6% respectively of the total…

🧬 Mechanism of Action 121 words ▾

12.1Mechanism of Action Midostaurin is a small molecule that inhibits multiple receptor tyrosine kinases. In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, as well as members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors.

Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells.

📦 How Supplied / Storage and Handling 97 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING RYDAPT 25 mg capsules Pale orange oblong soft capsule with red ink imprint ‘PKC NVR’; available in: 56 soft capsules………………………………………………………………………………………NDC 0078-0698-99 Contents: Each carton contains two inner packs, each with 28 capsules (7 blister cards with 4 capsules each) 112 soft capsules……………………………………………………………………………………..NDC 0078-0698-19 Contents: Each carton contains four inner packs, each with 28 capsules (7 blister cards with 4 capsules each) 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].

Store in the original container to protect from moisture.

📋 Description 121 words ▾

11 DESCRIPTION Midostaurin is a kinase inhibitor for oral use. The molecular formula for midostaurin is C 35 H 30 N 4 O 4 . The molecular weight is 570.65 g/mol.

The chemical name of midostaurin is Benzamide, N -[(9 S ,10 R ,11 R ,13 R )-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1 H ,9 H -diindolo[1,2,3- gh :3′,2′,1′- lm ]pyrrolo[3,4- j ][1,7]benzodiazonin-11- yl ]- N -methyl-. The chemical structure of midostaurin is shown below: RYDAPT is supplied as a soft capsule containing 25 mg of midostaurin. The capsule contains carmine, corn oil mono-di-triglycerides, dehydrated alcohol, ferric oxide red, ferric oxide yellow, gelatin, glycerin 85%, hypromellose 2910, polyethylene glycol 400, polyoxyl 40 hydrogenated castor oil, propylene glycol, purified water, titanium dioxide, and vitamin E.

Structural Formula

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Pulmonary Adverse Reactions Inform patients to seek medical attention for new cough, chest discomfort, or shortness of breath [see Warnings and Precautions (5.2)]. Gastrointestinal Adverse Reactions Inform patients that RYDAPT can cause nausea, vomiting, and diarrhea.

Advise patients to contact their healthcare provider if these symptoms occur or are persisting despite supportive medications [see Adverse Reactions (6.1)]. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYDAPT and for 4 months after the last dose.

Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)]. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with RYDAPT and for 4 months after the last dose [see Use in Specific Populations (8.3)]. Advise females who may have been exposed to RYDAPT during pregnancy directly or through male partner receiving RYDAPT therapy to contact the Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com/ [see Use in Specific Populations (8.1)] .

Lactation Advise women not to breastfeed during treatment with RYDAPT and for 4 months after the last dose [see Use in Specific Populations (8.2)]. Infertility Advise females and males of reproductive potential that RYDAPT may impair fertility [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)]. Distributed by: Novartis Pharmaceuticals Corporation One Health Plaza East Hanover, New Jersey 07936 T2023-25

Glossary — plain-language definitions of medical terms used in this label:

contraindicated: Should not be used in that situation, because the risk is considered too high.

in vitro: In a laboratory dish or test tube rather than in a living person or animal; results may not carry over to people.

abdominal pain: Pain, cramping, or discomfort felt anywhere in the belly area.

absolute neutrophil count: A blood test number showing how many infection-fighting neutrophil white blood cells you have.

Absorption: How a medicine moves from where it is taken, such as the stomach or gut, into the bloodstream.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

ANC: A blood test number showing how many infection-fighting neutrophil white blood cells you have.

anemia: A low level of red blood cells or the oxygen-carrying protein inside them, which can cause tiredness, weakness, and paleness.

angioedema: Rapid swelling deep under the skin, often around the eyes, lips, tongue, or throat.

animal reproduction studies: Tests in pregnant animals used to check whether a medicine might harm a developing baby.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

baseline: A person's starting condition, measured before treatment begins, used to see how much they change later on.

BCRP: A protein pump that moves certain drugs out of cells, affecting how much of the drug is absorbed.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

contraception: Methods used to prevent pregnancy, such as birth control pills, condoms, or an intrauterine device.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

CYP3A4: One of the most important liver and gut enzymes, responsible for breaking down a large share of all medicines.

diarrhea: Loose, watery bowel movements that happen more often than normal.

Distribution: How a medicine spreads from the blood into the body's tissues and organs after it is absorbed.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

double-blind: A study in which neither the patients nor their doctors know who is getting the real medicine and who is getting the dummy.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

edema: Swelling caused by extra fluid trapped in the body's tissues.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

electrocardiogram: A quick, painless test that records the heart's electrical activity to check its rhythm and rate.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

embryo-fetal toxicity: Harm to a developing baby in the womb, such as birth defects, slowed growth, or loss of the pregnancy.

epistaxis: A nosebleed.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

febrile: Having a fever, or relating to a fever.

febrile neutropenia: A fever that happens when infection-fighting white blood cells are very low, which can be a sign of serious infection.

fertility: The natural ability to become pregnant or to father a child.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

flushing: Temporary redness and warmth of the skin, often on the face and neck, from widening of small blood vessels.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

hemoglobin: The iron-containing protein inside red blood cells that carries oxygen throughout the body.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hyperglycemia: High blood sugar, meaning there is more glucose (sugar) in the blood than normal.

hypersensitivity: An overreaction of the body's defense system to a substance, causing symptoms such as rash, swelling, or trouble breathing.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

interstitial lung disease: A group of conditions in which the tissue around the lungs' air sacs becomes scarred or inflamed, making breathing harder.

lactation: The making and release of milk from a mother's breasts after giving birth.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Metabolism: How the body chemically changes a medicine, usually in the liver, into other substances.

metabolite: A new substance formed when the body breaks a medicine down.

monotherapy: Treatment using a single medicine by itself.

mucositis: Painful swelling and sores in the moist lining of the mouth, throat, or digestive tract.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

neutropenia: A low level of neutrophils, a type of white blood cell that fights infection, which can make it easier to catch infections.

neutrophil: A type of white blood cell that is one of the body's main defenders against infection.

Nonclinical Toxicology: The label section summarizing safety findings from laboratory and animal studies, rather than from studies in people.

OATP: A group of transporter proteins that carry certain drugs into cells, especially in the liver.

open-label: A study in which both the patients and their doctors know which treatment each person is receiving.

organogenesis: The early stage of pregnancy when the developing baby's organs are first forming.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

petechiae: Tiny flat red or purple spots on the skin caused by small amounts of bleeding underneath.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

placebo: An inactive treatment with no real medicine in it, such as a sugar pill, used for comparison in a study.

placebo-controlled: Describes a study that compares people taking the real medicine against people taking a dummy pill with no active ingredient.

pneumonitis: Inflammation of the lung tissue that is not caused by an infection and can lead to cough and breathlessness.

potency: How much of a medicine is needed to produce a given effect; a more potent medicine works at a smaller dose.

Pregnancy Exposure Registry: A study that collects health information from women who took a medicine while pregnant to learn how safe it is.

pyrexia: A raised body temperature; a fever.

QTc: A number from a heart tracing (ECG) that measures the heart's electrical recovery time, adjusted for the heart rate.

randomized: Assigned to a treatment group purely by chance, like a coin flip, so the groups being compared start out fair and similar.

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

refractory: Describing a disease that does not respond to, or improve with, treatment.

reproductive potential: The ability to have children, meaning a person who could become pregnant or could father a child.

sepsis: A serious, body-wide reaction to an infection in which the body's own response can start to injure its tissues and organs.

substrate: A drug or other substance that a particular enzyme or transporter acts on.

terminal half-life: The time it takes blood levels to fall by half during the final, slowest stage of removal.

thrombocytopenia: A low level of platelets, the blood cells that help form clots, which can lead to easier bruising or bleeding.

transporter: A protein that moves drugs across cell membranes, carrying them either into or out of cells.

upper respiratory tract infection: An infection of the nose, sinuses, or throat, such as the common cold.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

volume of distribution: A calculated value showing how widely a medicine spreads into body tissues versus staying in the blood.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

🔗 Related NDC lookups

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💊 Related drugs in this class

Other drugs that share this product’s specific therapeutic class — Antineoplastic Systemic Enzyme Inhibitors.

Abemaciclib 00002-4483-54 Dasatinib 00003-0524-11 Imatinib Mesylate 00054-0248-22 Bosutinib 00069-0135-01 Axitinib 00069-0145-01 Palbociclib 00069-0187-21 Dacomitinib 00069-0197-30 Crizotinib 00069-0251-60 Talazoparib Tosylate 00069-0252-30 Sunitinib Malate 00069-0550-38 Nilotinib Hcl 00078-0526-51 Pazopanib Hcl 00078-0670-66 Lapatinib Ditosylate 00078-0671-19 Ceritinib 00078-0694-48 Ribociclib Succinate 00078-0860-01

Where does this data come from?

Other drugs sharing this product’s First Databank therapeutic class (HIC3). Each links to that NDC’s page in our directory.