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Nilotinib 150 mg Capsule — NDC 60505-3801-02 package photo

Nilotinib 150 mg Capsule

by Apotex Corp. · 4 CARTON in 1 CARTON (60505-3801-2) / 2 BLISTER PACK in 1 CARTON (60505-3801-3) / 14 CAPSULE in 1 BLISTER PACK (60505-3801-0)
NDC 60505-3801-02
🏷️ FDA NDC (as labeled) 60505-3801-2 billing pads the package segment with a zero
Rx only Generic On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →
⚠️
Other active recalls for Nilotinib (different manufacturers) — 2 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class III · Feb 18, 2026 — Failed Tablet/Capsule Specifications: Observed OOS results at 6-months long-term stability condition for Description test and Appearance by Visual Inspection test. (Cipla USA, Inc.) · FDA recall D-0381-2026
Class III · Feb 18, 2026 — Failed Tablet/Capsule Specifications: Observed OOS results at 6-months long-term stability condition for Description test and Appearance by Visual Inspection test. (Cipla USA, Inc.) · FDA recall D-0382-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 60505-3801-2
Product NDC 60505-3801
11-digit billing NDC 60505380102
NCPDP billing unit EA — each (per item)
UNII F41401512X
UPC 0360505380152, 0360505380251, 0360505380374
Application # ANDA203640
SPL Set ID 8283672c-619f-fe60-3d25-040f95ac1440
Established class (EPC) Kinase Inhibitor
Mechanism of action Bcr-Abl Tyrosine Kinase Inhibitors; Cytochrome P450 2C8 Inhibitors; Cytochrome P450 2D6 Inhibitors; Cytochrome P450 2B6 Inducers; Cytochrome P450 2C8 Inducers; UGT1A1 Inhibitors; P-Glycoprotein Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-05-23
Route ORAL
Dosage form CAPSULE
Substance NILOTINIB
GPI-14 21531860200115
GCN Seq No 066453
GCN 28737
HICL code 035149
Ingredient (HICL) Nilotinib Hcl
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 NILOTINIB HCL 150 MG CAPSULE
FDB brand name Nilotinib Hcl
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 60505-3801-2 — a 5-4-1 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 package segment → 60505-3801-02. 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) BCR-ABL tyrosine kinase inhibitors
How it works Bcr-Abl Tyrosine Kinase Inhibitors, Cytochrome P450 2D6 Inhibitors, P-Glycoprotein Inhibitors, Cytochrome P450 2C8 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

LabelerApotex Corp.
Application holderAPOTEX INC
FDA applicationANDA203640 (ANDA)
Labeler code60505
First marketedMay 2025
Product typeHuman Prescription Drug
Portfolio306 products on file
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 NILOTINIB HCL 150 MG CAPSULE Ingredient Nilotinib Hcl
📖 What it is MedlinePlus · NLM

Nilotinib is used to treat certain types of chronic myeloid leukemia (CML; a type of cancer of the white blood cells). Nilotinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein in cancer cells. This helps to stop or slow the spread of cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
📖 Read our full Nilotinib guide →
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 Red / Yellow / Orange
ShapeCapsule
ImprintAPO;N50
Size14 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 5138Q19F1X
    Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
  • UNII 68401960MK
    Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
  • 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 XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • 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 EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • 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.
  • UNII LQA7B6G8JG
    A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
  • 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 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • 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.

13 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 DailyMedingredient 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 systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $151.07 $16,919.91 / 112 capsules
Medicare drug plans payPart D · Q2 2026 $116.98 $13,102.31 / 112 capsules
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

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Tasigna 150 mg 00078-0592-51 Novartis 28 capsules AB FDA listed
nilotinib 150 mg 13668-0710-57 Torrent 112 capsules AB FDA listed
Nilotinib 150 mg 31722-0779-33 Camber 112 capsules AB FDA listed
Nilotinib 150 mg 43598-0455-46 Dr. 112 capsules AB FDA listed
Nilotinib 150 mgthis 60505-3801-02 Apotex 1792 capsules AB FDA listed
nilotinib 150 mg 72205-0238-63 Novadoz 28 capsules AB FDA listed
nilotinib 150 mg 73190-0033-11 AvKARE 28 capsules AB FDA listed
Nilotinib 150 mg 76282-0789-58 EXELAN 1792 capsules FDA listed
Nilotinib 150 mg 69097-0031-74 Cipla 1792 capsules FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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

🏛️
2025
On the market since
May 2025
📍
2026
Currently FDA-listed
1 year listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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 60505-3801-02, 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.
📅 Q2 2025 – Q4 2025 · 3 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
435
Units reimbursed last 4 qtrs
42.8K
Gross reimbursed last 4 qtrs
$6.47M
Avg / prescription
$14,873.68
Avg / unit
$151.07
Latest quarter Q4 2025
197Rx
Fee-for-service vs managed care
21% FFS 79% MCO
Fee-for-service · 91 Rx Managed care · 344 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: 2,272 units · 29.1 per 100k residents WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 2,800 units · 27.9 per 100k residents MI New York: 2,856 units · 14.6 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 3,612 units · 85.3 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: 1,372 units · 10.9 per 100k residents IL Indiana: 2,072 units · 30.2 per 100k residents IN Ohio: 4,368 units · 37.1 per 100k residents OH Pennsylvania: 1,232 units · 9.5 per 100k residents PA New Jersey: 1,344 units · 14.5 per 100k residents NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: 3,024 units · 51.4 per 100k residents CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 5,656 units · 64.9 per 100k residents VA Maryland: 2,560 units · 41.4 per 100k residents MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: 1,288 units · 17.3 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 2,800 units · 25.8 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: 2,408 units · 10.7 per 100k residents FL
Units reimbursed · per 100k residents
9.585.3
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 Oregon 85.3 /100k
2 Virginia 64.9 /100k
3 Colorado 51.4 /100k
4 Maryland 41.4 /100k
5 Ohio 37.1 /100k
6 Indiana 30.2 /100k
7 Washington 29.1 /100k
8 Michigan 27.9 /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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
60505-3801-02 You're viewing this 4 CARTON in 1 CARTON (60505-3801-2) / 2 BLISTER PACK in 1 CARTON (60505-3801-3) / 14 CAPSULE in 1 BLISTER PACK (60505-3801-0) 2025-05-23 Active

🧭 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 60505-3801-2, 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: 60505-3801-02, written without dashes as 60505380102. 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 60505-3801-02, the first segment (60505) is the labeler code FDA assigned to Apotex Corp.; the middle segment (3801) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (02) 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 Apotex Corp.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Apotex Corp. 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.
🚨 Boxed Warning ~1 min read

WARNING: QT PROLONGATION and SUDDEN DEATHS Nilotinib prolongs the QT interval. Prior to nilotinib administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies [see Warnings and Precautions ( 5.2 )]. Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments [see Warnings and Precautions ( 5.2 , 5.3 , 5.7 , 5.12 )].

Sudden deaths have been reported in patients receiving nilotinib [see Warnings and Precautions ( 5.3 )]. Do not administer nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Contraindications ( 4 ) , Warnings and Precautions ( 5.2 )]. Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 , 7.2 )].

Avoid food 2 hours before and 1 hour after taking the dose [see Dosage and Administration ( 2.1 )]. WARNING: QT PROLONGATION and SUDDEN DEATHS See full prescribing information for complete boxed warning. Nilotinib prolongs the QT interval.

Prior to nilotinib administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. ( 5.2 ) Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments. ( 5.2 , 5.3 , 5.7 , 5.12 ) Sudden deaths have been reported in patients receiving nilotinib.

( 5.3 ) Do not administer nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome. ( 4 , 5.2 ) Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors. ( 7.1 , 7.2 ) Avoid food 2 hours before and 1 hour after taking the dose.

( 2.1 )

🎯 Indications and Usage ~1 min read

1 INDICATIONS AND USAGE Nilotinib is a kinase inhibitor indicated for the treatment of: Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. ( 1.1 ) Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. ( 1.2 ) Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP and CML-AP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy.

( 1.3 )

1.1Adult and Pediatric Patients With Newly Diagnosed Ph+ CML-CP Nilotinib capsules are indicated for the treatment of adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.

1.2Adult Patients With Resistant or Intolerant Ph+ CML-CP and CML-AP Nilotinib capsules are indicated for the treatment of adult patients with chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) resistant or intolerant to prior therapy that included imatinib.

1.3Pediatric Patients With Resistant or Intolerant Ph+ CML-CP and CML-AP Nilotinib capsules are indicated for the treatment of pediatric patients greater than or equal to 1 year of age with chronic phase and accelerated phase Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior tyrosine-kinase inhibitor (TKI) therapy.

⏱️ Dosage and Administration ~3 min read

2 D OSAGE AND ADMINISTRATION Recommended Adult Dose: Newly diagnosed Ph+ CML-CP: 300 mg orally twice daily. Resistant or intolerant Ph+ CML-CP and CML-AP: 400 mg orally twice daily. ( 2.1 ) Recommended Pediatric Dose: Newly Diagnosed Ph+ CML-CP or Ph+ CML-CP resistant or intolerant to prior TKI therapy: 230 mg/m 2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg).

( 2.1 ) See Dosage and Administration for full dosing instructions and dose- reduction instructions for toxicity. ( 2.1 ) Reduce starting dose in patients with baseline hepatic impairment. ( 2.7 ) Eligible newly diagnosed adult patients with Ph+ CML-CP who have received nilotinib capsules for a minimum of 3 years and have achieved a sustained molecular response (MR4.5) and patients with Ph+ CML-CP resistant or intolerant to imatinib who have received nilotinib capsules for at least 3 years and have achieved a sustained molecular response (MR4.5) may be considered for treatment discontinuation.

( 2.2 , 2.3 , 5.16 )

2.1Recommended Dosage Dose nilotinib capsules twice daily at approximately 12-hour intervals on an empty stomach. No food should be consumed for at least 2 hours before the dose is taken and for at least 1 hour after the dose is taken. Advise patients to swallow the capsules whole with water [see Boxed Warning , Clinical Pharmacology ( 12.3 )].

For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in 1 teaspoon of applesauce (puréed apple). The mixture should be taken immediately (within 15 minutes) and should not be stored for future use [see Clinical Pharmacology ( 12.3 )]. Nilotinib capsules may be given in combination with hematopoietic growth factors, such as erythropoietin or G-CSF if clinically indicated.

Nilotinib capsules may be given with hydroxyurea or anagrelide if clinically indicated. Dosage in Adult Patients with Newly Diagnosed Ph+ CML-CP The recommended dosage of nilotinib capsules is 300 mg orally twice daily. Dosage in Adult Patients with Resistant or Intolerant Ph+ CML-CP and CML-AP The recommended dosage of nilotinib capsules is 400 mg orally twice daily.

Dosage in Pediatric Patients with Newly Diagnosed Ph+ CML-CP or Resistant or Intolerant Ph+ CML-CP and CML-AP The recommended dosage of nilotinib capsules for pediatric patients is 230 mg/m 2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg) (see Table 1). If needed, attain the desired dose by combining different strengths of nilotinib capsules. Continue treatment as long as clinical benefit is observed or until unacceptable toxicity occurs.

Table 1: Pediatric Dosing of Nilotinib Capsules (230 mg/m 2 Twice Daily, Maximum Single Dose of 400 mg) Body Surface Area Single Dose Total Daily Dose Up to 0.32 m 2 50 mg 100 mg 0.33 – 0.54 m 2 100 mg 200 mg 0.55 – 0.76 m 2 150 mg 300 mg 0.77 – 0.97 m 2 200 mg 400 mg 0.98 – 1.19 m 2 250 mg 500 mg 1.20 – 1.41 m 2 300 mg 600 mg 1.42 – 1.63 m 2 350 mg 700 mg ≥ 1.64 m 2 400 mg 800 mg

2.2Discontinuation of Treatment After a Sustained Molecular Response (MR4.5) on Nilotinib Capsules Patient Selection Eligibility for Discontinuation of Treatment Ph+ CML-CP patients with typical BCR-ABL transcripts, who have been taking nilotinib capsules for a minimum of 3 years and have achieved a sustained molecular response (MR4.5, corresponding to = BCR-ABL/ABL ≤ 0.0032% IS), may be eligible for treatment discontinuation [see Clinical Studies ( 14.3 , 14.4 )] . Information on FDA authorized tests for the detection and quantitation of BCR-ABL transcripts to determine eligibility for treatment discontinuation is available at http://www.fda.gov/CompanionDiagnostics.

Patients with typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), who achieve the sustained MR4.5 criteria, are eligible for discontinuation of nilotinib capsules treatment. Patients must continue to be monitored for possible loss of molecular remission after treatment discontinuat…

💊 Dosage Forms and Strengths 75 words

3 DOSAGE FORMS AND STRENGTHS Capsules: 50 mg hard gelatin capsule with yellow opaque body and light orange opaque cap imprinted “APO N50” in black ink. 150 mg hard gelatin capsule with red opaque body and red opaque cap imprinted “APO N150” in black ink. 200 mg hard gelatin capsule with yellow opaque body and yellow opaque cap imprinted “APO N200” in maroon ink. Capsules: 50 mg, 150 mg and 200 mg ( 3 )

Contraindications 35 words

4 CONTRAINDICATIONS Nilotinib capsules are contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome [see Boxed Warning ]. Nilotinib capsules are contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome. ( 4 )

⚠️ Warnings and Cautions ~3 min read

5 WARNINGS AND PRECAUTIONS Myelosuppression : Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose-reduction. ( 5.1 ) Cardiac and Arterial Vascular Occlusive Events : Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during nilotinib therapy. ( 5.4 ) Pancreatitis and Elevated Serum Lipase: Monitor serum lipase; if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis.

( 5.5 ) Hepatotoxicity : Monitor hepatic function tests monthly or as clinically indicated. ( 5.6 ) Electrolyte Abnormalities : Nilotinib can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating nilotinib and monitor periodically during therapy.

( 5.7 ) Tumor Lysis Syndrome : Maintain adequate hydration and correct uric acid levels prior to initiating therapy with nilotinib. ( 5.8 ) Hemorrhage : Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed.

( 5.9 ) Fluid Retention : Monitor patients for unexpected rapid weight gain, swelling, and shortness of breath. Manage medically. ( 5.13 ) Effects on Growth and Development in Pediatric Patients : Growth retardation has been reported in pediatric patients treated with nilotinib.

Monitor growth and development in pediatric patients. ( 5.14 ) Embryo-Fetal toxicity : Advise patients of potential risk to a fetus and to use effective contraception. ( 5.15 , 8.1 , 8.3 ) Treatment Discontinuation : Patients must have typical BCR-ABL transcripts.

An FDA-authorized test with a detection limit below MR4.5 must be used to determine eligibility for discontinuation. Patients must be frequently monitored by the FDA authorized test to detect possible loss of remission. ( 5.16 )

5.1Myelosuppression Treatment with nilotinib can cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. Perform CBCs every 2 weeks for the first 2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding nilotinib temporarily or dose reduction [see Dosage and Administration ( 2.5 )].

5.2QT Prolongation Nilotinib has been shown to prolong cardiac ventricular repolarization as measured by the QT interval on the surface electrocardiogram (ECG) in a concentration-dependent manner [see Adverse Reactions ( 6.1 ) , Clinical Pharmacology ( 12.2 )] . Prolongation of the QT interval can result in a type of ventricular tachycardia called torsade de pointes, which may result in syncope, seizure, and/or death. Electrocardiograms should be performed at baseline, 7 days after initiation of nilotinib, and periodically as clinically indicated and following dose adjustments [see Dosage and Administration ( 2.4 ) Warnings and Precautions ( 5.12 )] .

Nilotinib should not be used in patients who have hypokalemia, hypomagnesemia, or long QT syndrome. Before initiating nilotinib and periodically, test electrolyte, calcium, and magnesium blood levels. Hypokalemia or hypomagnesemia must be corrected prior to initiating nilotinib and these electrolytes should be monitored periodically during therapy [see Warnings and Precautions ( 5.12 )].

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with food and/or strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT. Therefore, coadministration with food must be avoided and concomitant use with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT should be avoided [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1 , 7.2 )] . The presence of hypokalemia and hypomagnesemia may further prolong the QT interval [see Warnings and Precautions ( 5.7 , 5.12 )].

5.3Sudden Deaths Sudden deaths have been reported in 0.3% of patients with CML treated…

🤒 Adverse Reactions ~3 min read

6 ADVERSE REACTIONS The following clinically significant adverse reactions can occur with nilotinib and are discussed in greater detail in other sections of labeling: Myelosuppression [see Warnings and Precautions ( 5.1 )] QT Prolongation [see Boxed Warning, Warnings and Precautions ( 5.2 )] Sudden Deaths [ see Boxed Warning, Warnings and Precautions ( 5.3 )] Cardiac and Arterial Vascular Occlusive Events [see Warnings and Precautions ( 5.4 )] Pancreatitis and Elevated Serum Lipase [see Warnings and Precautions ( 5.5 )] Hepatotoxicity [see Warnings and Precautions ( 5.6 )] Electrolyte Abnormalities [see Boxed Warning, Warnings and Precautions ( 5.7 )] Hemorrhage [see Warnings and Precautions ( 5.9 )] Fluid Retention [see Warnings and Precautions ( 5.13 )] The most commonly reported non-hematologic adverse reactions (≥ 20%) in adult and pediatric patients were nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, and night sweats.

Hematologic adverse drug reactions include myelosuppression: thrombocytopenia, neutropenia, and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 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. In Adult Patients With Newly Diagnosed Ph+ CML-CP The data below reflect exposure to nilotinib from a randomized trial in patients with newly diagnosed Ph+ CML in chronic phase treated at the recommended dose of 300 mg twice daily (n = 279).

The median time on treatment in the nilotinib 300 mg twice daily group was 61 months (range, 0.1 to 71 months). The median actual dose intensity was 593 mg/day in the nilotinib 300 mg twice daily group. The most common (greater than 10%) non-hematologic adverse drug reactions were rash, pruritus, headache, nausea, fatigue, alopecia, myalgia, and upper abdominal pain.

Constipation, diarrhea, dry skin, muscle spasms, arthralgia, abdominal pain, peripheral edema, vomiting, and asthenia were observed less commonly (less than or equal to 10% and greater than 5%) and have been of mild-to-moderate severity, manageable and generally did not require dose reduction. Increase in QTcF greater than 60 msec from baseline was observed in 1 patient (0.4%) in the 300 mg twice daily treatment group. No patient had an absolute QTcF of greater than 500 msec while on study drug.

The most common hematologic adverse drug reactions (all Grades) were myelosuppression, including: thrombocytopenia (18%), neutropenia (15%), and anemia (8%). See Table 9 for Grade 3/4 laboratory abnormalities. Discontinuation due to adverse reactions, regardless of relationship to study drug, was observed in 10% of patients.

In Adult Patients With Resistant or Intolerant Ph+ CML-CP and CML-AP In the single-arm, open-label multicenter clinical trial, a total of 458 patients with Ph+ CML-CP and CML-AP resistant to or intolerant to at least one prior therapy, including imatinib were treated (CML-CP=321; CML-AP = 137) at the recommended dose of 400 mg twice daily. The median duration of exposure in days for CML-CP and CML-AP patients is 561 (range, 1 to 1096) and 264 (range, 2 to 1160), respectively. The median dose intensity for patients with CML-CP and CML-AP is 789 mg/day (range, 151 to 1110) and 780 mg/day (range, 150 to 1149), respectively, and corresponded to the planned 400 mg twice daily dosing.

The median cumulative duration in days of dose interruptions for the CML-CP patients was 20 (range, 1 to 345), and the median duration in days of dose interruptions for the CML-AP patients was 23 (range, 1 to 234). In patients with CML-CP, the most commonly reported non-hematologic adverse drug reactions (greater than or e…

🔄 Drug Interactions ~2 min read

5.8Tumor Lysis Syndrome Tumor lysis syndrome (TLS) cases have been reported in nilotinib treated patients with resistant or intolerant CML. Malignant disease progression, high white blood cell (WBC) counts and/or dehydration were present in the majority of these cases. Due to potential for TLS, maintain adequate hydration and correct uric acid levels prior to initiating therapy with nilotinib.

7 DRUG INTERACTIONS Strong CYP3A Inhibitors : Avoid concomitant use with nilotinib, or reduce nilotinib dose if coadministration cannot be avoided. ( 7.1 ) Strong CYP3A Inducers : Avoid concomitant use with nilotinib. ( 7.1 ) Proton Pump Inhibitors : Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors. ( 7.1 )

7.1Effect of Other Drugs on Nilotinib Strong CYP3A Inhibitors Concomitant use with a strong CYP3A inhibitor increased nilotinib concentrations compared to nilotinib alone [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of nilotinib toxicities. Avoid concomitant use of strong CYP3A inhibitors with nilotinib. If patients must be coadministered a strong CYP3A4 inhibitor, reduce nilotinib dose [see Dosage and Administration ( 2.8 )].

Strong CYP3A Inducers Concomitant use with a strong CYP3A inducer decreased nilotinib concentrations compared to nilotinib alone [see Clinical Pharmacology ( 12.3 )] , which may reduce nilotinib efficacy. Avoid concomitant use of strong CYP3A inducers with nilotinib. Proton Pump Inhibitors Concomitant use with a proton pump inhibitor (PPI) decreased nilotinib concentrations compared to nilotinib alone [see Clinical Pharmacology ( 12.3 )] , which may reduce nilotinib efficacy.

Avoid concomitant use of PPI with nilotinib. As an alternative to PPIs, use H2 blockers approximately 10 hours before or approximately 2 hours after the dose of nilotinib, or use antacids approximately 2 hours before or approximately 2 hours after the dose of nilotinib.

7.2Drugs That Prolong the QT Interval Avoid coadministration of nilotinib with agents that may prolong the QT interval, such as anti-arrhythmic drugs [see Boxed Warning, Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.2 )].

👥 Use in Specific Populations ~3 min read

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

8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, nilotinib can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal lethality, fetal effects, and fetal variations in rats and rabbits at maternal exposures (AUC) approximately 2 and 0.5 times, respectively, the exposures in patients at the recommended 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 is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of nilotinib up to 100 mg/kg/day and 300 mg/kg/day, respectively, during the period of organogenesis. In rats, oral administration of nilotinib produced embryo-lethality/fetal effects at doses ≥ 30 mg/kg/day.

At ≥ 30 mg/kg/day, skeletal variations of incomplete ossification of the frontals and misshapen sternebra were noted, and there was an increased incidence of small renal papilla and fetal edema. At 100 mg/kg/day, nilotinib was associated with maternal toxicity (decreased gestation weight, gravid uterine weight, net weight gain, and food consumption) and resulted in a single incidence of cleft palate and two incidences of pale skin were noted in the fetuses. A single incidence of dilated ureters was noted in a fetus also displaying small renal papilla at 100 mg/kg/day.

Additional variations of forepaw and hindpaw phalanx unossified, fused sternebra, bipartite sternebra ossification, and incomplete ossification of the cervical vertebra were noted at 100 mg/kg/day. In rabbits, oral administration of nilotinib resulted in the early sacrifice of two females, maternal toxicity and increased resorption of fetuses at 300 mg/kg/day. Fetal skeletal variations (incomplete ossification of the hyoid, bent hyoid, supernumerary short detached ribs and the presence of additional ossification sites near the nasals, frontals and in the sternebral column) were also increased at this dose in the presence of maternal toxicity.

Slight maternal toxicity was evident at 100 mg/kg/day but there were no reproductive or embryo-fetal effects at this dose. At 30 mg/kg/day in rats and 300 mg/kg/day in rabbits, the maternal systemic exposure (AUC) were 72700 ng*hr/mL and 17100 ng*hr/mL respectively, representing approximately 2 and 0.5 times the exposure in humans at the highest recommended dose 400 mg twice daily. When pregnant rats were dosed with nilotinib during organogenesis and through lactation, the adverse effects included a longer gestational period, lower pup body weights until weaning and decreased fertility indices in the pups when they reached maturity, all at a maternal dose of 60 mg/kg (i.e., 360 mg/m 2 , approximately 0.7 times the clinical dose of 400 mg twice daily based on body surface area).

At doses up to 20 mg/kg (i.e., 120 mg/m 2 , approximately 0.25 times the clinical dose of 400 mg twice daily based on body surface area) no adverse effects were seen in the maternal animals or the pups.

8.2Lactation Risk Summary There are no data on the presence of nilotinib or its metabolites in human milk or its effects on a breastfed child or on milk production. However, nilotinib is present in the milk of lactating rats. Because of the potential for serious adverse reactions in a breastfed…

🤰 Pregnancy ~3 min read

8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, nilotinib can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of nilotinib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal lethality, fetal effects, and fetal variations in rats and rabbits at maternal exposures (AUC) approximately 2 and 0.5 times, respectively, the exposures in patients at the recommended 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 is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of nilotinib up to 100 mg/kg/day and 300 mg/kg/day, respectively, during the period of organogenesis. In rats, oral administration of nilotinib produced embryo-lethality/fetal effects at doses ≥ 30 mg/kg/day.

At ≥ 30 mg/kg/day, skeletal variations of incomplete ossification of the frontals and misshapen sternebra were noted, and there was an increased incidence of small renal papilla and fetal edema. At 100 mg/kg/day, nilotinib was associated with maternal toxicity (decreased gestation weight, gravid uterine weight, net weight gain, and food consumption) and resulted in a single incidence of cleft palate and two incidences of pale skin were noted in the fetuses. A single incidence of dilated ureters was noted in a fetus also displaying small renal papilla at 100 mg/kg/day.

Additional variations of forepaw and hindpaw phalanx unossified, fused sternebra, bipartite sternebra ossification, and incomplete ossification of the cervical vertebra were noted at 100 mg/kg/day. In rabbits, oral administration of nilotinib resulted in the early sacrifice of two females, maternal toxicity and increased resorption of fetuses at 300 mg/kg/day. Fetal skeletal variations (incomplete ossification of the hyoid, bent hyoid, supernumerary short detached ribs and the presence of additional ossification sites near the nasals, frontals and in the sternebral column) were also increased at this dose in the presence of maternal toxicity.

Slight maternal toxicity was evident at 100 mg/kg/day but there were no reproductive or embryo-fetal effects at this dose. At 30 mg/kg/day in rats and 300 mg/kg/day in rabbits, the maternal systemic exposure (AUC) were 72700 ng*hr/mL and 17100 ng*hr/mL respectively, representing approximately 2 and 0.5 times the exposure in humans at the highest recommended dose 400 mg twice daily. When pregnant rats were dosed with nilotinib during organogenesis and through lactation, the adverse effects included a longer gestational period, lower pup body weights until weaning and decreased fertility indices in the pups when they reached maturity, all at a maternal dose of 60 mg/kg (i.e., 360 mg/m 2 , approximately 0.7 times the clinical dose of 400 mg twice daily based on body surface area).

At doses up to 20 mg/kg (i.e., 120 mg/m 2 , approximately 0.25 times the clinical dose of 400 mg twice daily based on body surface area) no adverse effects were seen in the maternal animals or the pups.

🧒 Pediatric Use ~2 min read

8.4Pediatric Use The safety and effectiveness of nilotinib capsules have been established in pediatric patients greater than or equal to 1 year of age with newly diagnosed and resistant or intolerant Ph+ CML in chronic phase [see Clinical Studies ( 14.5 )] . There are no data for pediatric patients under 2 years of age. Use of nilotinib capsules in pediatric patients 1 year to less than 2 years of age with newly diagnosed or resistant or intolerant Ph+ CML in chronic phase is supported by efficacy in pediatric patients 2 to 6 years of age for these indications.

The safety and effectiveness of nilotinib capsules have been established in pediatric patients greater than or equal to 1 year of age with resistant or intolerant Ph+ CML in accelerated phase based on evidence of effectiveness from an adequate and well-controlled single-arm study in adults [see Clinical Studies ( 14.2 )] with safety data from two pediatric studies as described in the next paragraph. Use of nilotinib capsules in pediatric patients 1 to less than 18 years of age is supported by evidence from two clinical trials [see Clinical Studies ( 14.5 )] .

The 25 patients with newly diagnosed Ph+ CML-CP were in the following age groups: 6 children (age 2 to less than 12 years) and 19 adolescents (age 12 to less than 18 years). The 44 patients with resistant or intolerant Ph+ CML-CP included 18 children (age 2 to less than 12 years) and 26 adolescents (age 12 to less than 18 years). All pediatric patients received nilotinib treatment at a dose of 230 mg/m 2 twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg).

No differences in efficacy or safety were observed between the different age subgroups in the two trials. The frequency, type, and severity of adverse reactions observed were generally consistent with those observed in adults, with the exception of the laboratory abnormalities of hyperbilirubinemia (Grade 3/4: 16%) and transaminase elevation (AST Grade 3/4: 2.9%, ALT Grade 3/4: 10%), which were reported at a higher frequency in pediatric patients than in adults [see Adverse Reactions ( 6.1 )]. For pediatric growth and development, growth retardation has been reported in pediatric patients with Ph+ CML-CP treated with nilotinib capsules [see Warnings and Precautions ( 5.14 ) Adverse Reactions (6.1)].

The safety and effectiveness of nilotinib capsules in pediatric patients below the age of 1 year with newly diagnosed, or resistant or intolerant Ph+ CML in chronic phase and accelerated phase, have not been established.

🧓 Geriatric Use 153 words

8.5Geriatric Use In the clinical trials of nilotinib (patients with newly diagnosed Ph+ CML-CP and resistant or intolerant Ph+ CML-CP and CML-AP), approximately 12% and 30% of patients were 65 years or over, respectively. Patients with newly diagnosed Ph+ CML-CP: There was no difference in major molecular response between patients aged less than 65 years and those greater than or equal to 65 years. Patients with resistant or intolerant CML-CP: There was no difference in major cytogenetic response rate between patients aged less than 65 years and those greater than or equal to 65 years.

Patients with resistant or intolerant CML-AP: The hematologic response rate was 44% in patients less than 65 years of age and 29% in patients greater than or equal to 65 years. No major differences for safety were observed in patients greater than or equal to 65 years of age as compared to patients less than 65 years.

🆘 Overdosage 43 words

10 OVERDOSAGE Overdose with nilotinib has been reported, where an unspecified number of nilotinib capsules were ingested in combination with alcohol and other drugs. Events included neutropenia, vomiting, and drowsiness. In the event of overdose, observe the patient and provide appropriate supportive treatment.

🧬 Clinical Pharmacology ~3 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro , nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML.

Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20 to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1 (3.7 nM).

12.2Pharmacodynamics Based on exposure-response analyses for efficacy, a relationship between drug exposure and a greater likelihood of response was observed in clinical studies. Based on exposure-response analyses for safety, a relationship between exposure and a greater likelihood of safety events, including a higher occurrence of total bilirubin elevations, was observed in clinical studies. Cardiac Electrophysiology Nilotinib is associated with concentration-dependent QT prolongation.

At a dose of nilotinib 400 mg twice daily given without food in healthy subjects, the maximum mean placebo-adjusted QTcF changes were 10.4 msec (90% CI: 2.85, 18.0). After a single dose of nilotinib 800 mg (two times the maximum approved recommended dosage) given with a high fat meal to healthy subjects, the maximum mean placebo-adjusted QTcF changes were) 18.0 msec (90% CI: 9.65, 25.8). Peak plasma concentrations in the QT study were 26% lower than or comparable with those observed in patients enrolled in the single-arm study [see Boxed Warning , Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 )].

12.3Pharmacokinetics Steady-state nilotinib exposure was dose-dependent with less than dose-proportional increases in systemic exposure at dose levels higher than 400 mg given as once or twice daily dosing. In adult patients with resistant or intolerant Ph+ CML given nilotinib 400 mg twice daily, the steady-state mean (%CV) C max and AUC 0-12h were 2260 ng/mL (35%) and 18000 ng·h/mL (33%), respectively. In adult patients with newly diagnosed Ph+ CML given nilotinib 300 mg twice daily, the steady-state mean (%CV) C max and AUC 0-12h were 1540 ng/mL (48%) and 13337 ng·h/mL (46%), respectively.

Steady state conditions were achieved by Day 8. An increase in serum exposure to nilotinib between the first dose and steady state was approximately 2-fold for daily dosing and 3.8-fold for twice daily dosing. The average steady state nilotinib trough and peak concentrations did not change over 12 months.

Absorption Relative bioavailability of nilotinib capsule is approximately 50%, as compared to an oral drink solution (pH of 1.2 to 1.3). Peak concentrations of nilotinib are reached 3 hours after oral administration. Nilotinib is a substrate of P-gp in vitro.

Median steady-state trough concentration of nilotinib was decreased by 53% in patients with total gastrectomy compared to patients who had not undergone surgeries [ see Warnings and Precautions ( 5.10 )]. Effect of Food Compared to the fasted state, the systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high fat meal (meal of 800 to 1000 calories with fat being 50% of total caloric content; approximately: 150 calories from protein, 250 calories from carbohydrates, and 500-600 calories from fat).

Single dose administration of two 200 mg nilotinib capsules each dispersed in 1 teaspoon of applesauce and administered within 15 minutes was shown to be bioequivalent to a single dose administration of two 200 mg intact capsules. Distribution The blood-to-serum ratio of nilotinib is 0.68. Serum protein binding is approximately 98%.

Elimination The mean (CV%) apparent elimination half-life is estimated to be approximately 17 hours (69%) and the mean (CV%) apparent clearance approxim…

🧬 Mechanism of Action 108 words

12.1Mechanism of Action Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro , nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML.

Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20 to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1 (3.7 nM).

📦 How Supplied / Storage and Handling 208 words

16 HOW SUPPLIED/STORAGE AND HANDLING Nilotinib capsules, 50 mg are available for oral administration as hard gelatin capsules with yellow opaque body and light orange opaque cap imprinted “APO N50” in black ink. They are supplied as follows: Bottles of 120 NDC 60505-3803-7 Nilotinib capsules, 150 mg are available for oral administration as hard gelatin capsules with red opaque body and red opaque cap imprinted “APO N150” in black ink. They are supplied as follows: Outer Carton containing 4 inner cartons (4x28) NDC 60505-3801-2 Inner Carton of 28 capsules (2x14) NDC 60505-3801-3 Blisters of 28 capsules (2x14) NDC 60505-3801-0 Nilotinib capsules, 200 mg are available for oral administration as hard gelatin capsules with yellow opaque body and yellow opaque cap imprinted “APO N200” in maroon ink.

They are supplied as follows: Outer Carton containing 4 inner cartons (4x28) NDC 60505-3802-2 Inner Carton of 28 capsules (2x14) NDC 60505-3802-3 Blisters of 28 capsules (2x14) NDC 60505-3802-0 Each inner carton contains two blister cards of 14 capsules each, for dosing two in the morning and two in the evening at 12 hour intervals over a 7 day period. Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

📋 Description ~1 min read

11 DESCRIPTION Nilotinib capsules contain nilotinib, which belongs to a pharmacologic class of drugs known as kinase inhibitors. Nilotinib drug substance, in the form of monohydrochloride monohydrate, is a white to off-white powder with the molecular formula and weight, respectively, of C 28 H 22 F 3 N 7 O•HCl • H 2 O and 584 g/mole (corresponding molecular formula and weight of nilotinib base, anhydrous are C 28 H 22 F 3 N 7 O and 529 g/mole respectively). The solubility of nilotinib in aqueous solutions decreases with increasing pH.

Nilotinib is not optically active. The pK a 1 was determined to be 2.1; pK a 2 was estimated to be 5.4. The chemical name of nilotinib monohydrochloride monohydrate is 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide, monohydrochloride, monohydrate.

Its structure is shown below: Nilotinib capsules, for oral use, contain 50 mg, 150 mg, or 200 mg nilotinib base, anhydrous (equivalent to 55 mg, 165 mg, and 221 mg nilotinib hydrochloride monohydrate respectively) with the following inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate and poloxamer. The capsule shells contain gelatin, iron oxide red (50 mg and 150 mg), iron oxide yellow and titanium dioxide. The capsules are imprinted with edible black ink or maroon ink.

The black ink is comprised of ammonium hydroxide, iron oxide black, propylene glycol and shellac. The maroon ink is comprised of ammonia solution, D&C Red #7 calcium lake, FD&C Blue #2 aluminum lake, FD&C Red # 40 aluminum lake, propylene glycol and shellac. chemical structure of nilotinib

💬 Information for Patients ~3 min read

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). A Medication Guide is required for distribution with nilotinib capsules. The complete text of the Medication Guide is reprinted at the end of this document.

Myelosuppression Advise patients that treatment with nilotinib can cause serious thrombocytopenia, neutropenia, and anemia. Advise patients to seek immediate medical attention if symptoms suggestive of low blood counts occur, such as fever, chills or other signs of infection, unexplained bleeding or bruising, or unexplained weakness or shortness of breath [see Warnings and Precautions ( 5.1 )]. QT Prolongation Advise patients that nilotinib can cause possibly life-threatening, abnormal heart beat.

Advise patients to seek immediate medical attention if symptoms of abnormal heart beat occur, such as feeling light-headed, faint or experiencing an irregular heartbeat [see Warnings and Precautions ( 5.2 )]. Cardiac and Arterial Vascular Occlusive Events Advise patients that cardiovascular events (including ischemic heart disease, peripheral arterial occlusive disease, and ischemic cerebrovascular events) have been reported. Advise patients to seek immediate medical attention if any symptoms suggestive of a cardiovascular event occur, such as chest or leg pain, numbness or weakness, or problems walking or speaking occur suddenly [see Warnings and Precautions ( 5.4 )].

Pancreatitis and Elevated Serum Lipase Advise patients that nilotinib can increase the risk of pancreatitis and that patients with a previous history of pancreatitis may be at greater risk. Advise patients to seek immediate medical attention if symptoms suggestive of pancreatitis occur, such as sudden stomach area pain with accompanying nausea and vomiting [see Warnings and Precautions ( 5.5 )]. Hepatotoxicity Advise patients that nilotinib can increase the risk of hepatotoxicity and that patients with previous history of liver diseases may be at risk.

Advise patients to seek immediate medical attention if any symptoms suggestive of hepatotoxicity occur, such as stomach pain, yellow skin and eyes, and dark-colored urine [see Warnings and Precautions ( 5.6 )]. Tumor Lysis Syndrome Advise patients that nilotinib capsules can cause TLS and to seek immediate medical attention if any symptoms suggestive of TLS occur, such as an abnormal heartbeat or less urine production [see Warnings and Precautions ( 5.8 )]. Hemorrhage Advise patients that serious hemorrhagic events, including fatal events, have occurred in patients with CML treated with nilotinib capsules.

Advise patients to seek immediate medical attention if symptoms suggestive of hemorrhage occur, such as uncontrolled bleeding, changes in eyesight, unconsciousness, or sudden headache or sudden confusion in surroundings [ see Warnings and Precautions ( 5.9 )]. Fluid Retention Advise patients that nilotinib capsules can cause fluid retention and to seek immediate medical attention if any symptoms suggestive of fluid retention, such as shortness of breath, rapid weight gain, or swelling occur [see Warnings and Precautions ( 5.13 )].

Effects on Growth and Development in Pediatric Patients Inform pediatric patients and their caregivers of the possibility of developing growth abnormalities. Growth retardation has been reported in pediatric patients treated with nilotinib capsules. Therefore, monitor growth and development in pediatric patients [see Warnings and Precautions ( 5.14 )] .

Treatment-Free Remission (TFR) Advise patients that frequent monitoring is required to detect possible loss of remission if TFR is attempted. Advise patients that musculoskeletal symptoms, such as muscle pain, pain in extremity, joint pain, bone pain, or spinal pain, may occur more frequently than before treatment discontinuation [see Warnings and Precautions ( 5.16) ]. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus.

Advise females of reproductive…

💬 Medication Guide ~3 min read

MEDICATION GUIDE NILOTINIB (nye loe’ ti nib) CAPSULES What is the most important information I should know about nilotinib capsules? Nilotinib capsules can cause a possible life-threatening heart problem called QTc prolongation. QTc prolongation causes an irregular heartbeat, which may lead to sudden death.

Your healthcare provider should check the electrical activity of your heart with a test called an electrocardiogram (ECG): • before starting nilotinib capsules • with any dose changes • 7 days after starting nilotinib capsules • regularly during nilotinib treatment You may lower your chances for having QTc prolongation with nilotinib capsules if you: Take nilotinib capsules on an empty stomach: ο Avoid eating food for at least 2 hours before the dose is taken, and ο Avoid eating food for at least 1 hour after the dose is taken.

Avoid grapefruit, grapefruit juice, and any supplement containing grapefruit extract during treatment with nilotinib capsules. Food and grapefruit products increase the amount of nilotinib in your body. Avoid taking other medicines or supplements with nilotinib capsules that can also cause QTc prolongation.

Nilotinib capsules can interact with many medicines and supplements and increase your chance for serious and life- threatening side effects. Do not take any other medicine during treatment with nilotinib capsules unless your healthcare provider tells you it is okay to do so. If you cannot swallow nilotinib capsules whole, you may open the nilotinib capsule and sprinkle the contents of each capsule in 1 teaspoon of applesauce (puréed apple).

Swallow the mixture right away (within 15 minutes). For more information, see “How should I take nilotinib capsules?” Call your healthcare provider right away if you feel lightheaded, faint, or have an irregular heartbeat during treatment with nilotinib capsules. These can be symptoms of QTc prolongation.

What are nilotinib capsules? Nilotinib capsules are a prescription medicine used to treat: adults and children who have been newly diagnosed with a certain type of leukemia called Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. adults with chronic phase Ph+ CML or accelerated phase Ph+ CML who: ο are no longer benefiting from other treatments, including imatinib (Gleevec), or ο have taken other treatments, including imatinib (Gleevec), and cannot tolerate them. Children with chronic phase Ph+ CML or accelerated phase Ph+ CML who: ο are no longer benefiting from treatment with a tyrosine-kinase inhibitor medicine, or ο have taken a tyrosine-kinase inhibitor medicine and cannot tolerate it.

It is not known if nilotinib capsules are safe and effective in children younger than 1 year of age with newly diagnosed, resistant, or intolerant Ph+ CML in chronic phase. The long-term effects of treating children with nilotinib capsules for a long period of time are not known. Who should not take nilotinib capsules?

Do not take if you have: low levels of potassium or magnesium in your blood long QTc syndrome Before taking nilotinib capsules, tell your healthcare provider about all of your medical conditions, including if you: have heart problems have had a stroke or other problems due to decreased blood flow to the brain have problems with decreased blood flow to your legs have irregular heartbeat have QTc prolongation or a family history of it have liver problems have had pancreatitis have low blood levels of potassium or magnesium in your blood have a severe problem with lactose (milk sugar) or other sugars.

Nilotinib capsules contain lactose. Most people who have mild or moderate lactose intolerance can take nilotinib capsules. have bleeding problems had a surgical procedure involving the removal of the entire stomach (total gastrectomy) are pregnant or plan to become pregnant. Nilotinib can harm your unborn baby.

Tell your healthcare provider right away if you are pregnant, or if you become pregnant during treatment with nilotinib…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.