Danziten™: Bioequivalence at Lower Doses and No Fasting Requirements²

Danziten™ is supplied in a blister pack that assists patients in monitoring their medication doses effectively.

Danziten™ is available as 71 mg and 95 mg tablets.

Danziten™ is taken 2x daily at approximately 12-hour intervals.

Danziten™ may not be substitutable with other nilotinib products on a milligram per milligram basis; to avoid medication errors, including overdosage or underdosage, when using Danziten™ ensure that the recommended dosage of Danziten™ (not other nilotinib products) is prescribed.

NCCN Guidelines for CML state that nilotinib products available in different formulations, dosage form, and strengths are not interchangeable.¹

This chart is offered as a side-by-side comparison based on the product labels. Azurity does not confirm other products’ labels. Reporting of any adverse effects, product quality complaints, or medical information request regarding CML-CP and CML-AP treatment options should be directed to their respective manufacturer.

NCCN Guidelines contain other treatment regimens. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Recommendations for Switching From Tasigna® to Danziten™

Additional Dosing Information

Danziten™ may be given in combination with hematopoietic growth factors, such as erythropoietin or replaced with Granulocyte colony-stimulating factor (G-CSF) if clinically indicated. Danziten™ may be given with hydroxyurea or anagrelide if clinically indicated
Reduce starting dose of Danziten™ in patients with hepatic impairment
Withhold or reduce Danziten™ dosage for hematological toxicities (neutropenia, thrombocytopenia) that are not related to underlying leukemia
For non-hematolgic laboratory abnormalities (Grade ≥3) such as elevated serum lipase, amylase, bilirubin, or hepatic transaminases, withhold Danziten™ and monitor levels, resume treatment at 190 mg once daily when serum levels return to Grade ≤1
Advise patients to swallow the tablets whole with water and not to cut, crush, or chew the tablets
Advise patients to take Danziten™ with or without food. Patients should not consume grapefruit products and other foods that are known to inhibit CYP3A4 at any time during Danziten™ treatment
If the patient missed a dose of Danziten™, the patient should take the next scheduled dose at its regular time. The patient should not take 2 doses at the same time

IMPORTANT SAFETY INFORMATION

DANZITEN^TM (nilotinib) tablets, for oral use

DANZITEN is a kinase inhibitor indicated for the treatment of:

Adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib.

WARNING: QT PROLONGATION and SUDDEN DEATHS

See Full Prescribing Information for complete Boxed Warning.

Nilotinib prolongs the QT interval. Prior to DANZITEN administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. (5.3) Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and following any dose adjustments. (5.3, 5.4, 5.8, 5.12)
Sudden deaths have been reported in patients receiving nilotinib. (5.4) Do not administer DANZITEN to patients with hypokalemia, hypomagnesemia, or long QT syndrome. (4, 5.3)
Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors. (7.1, 7.2)

ADDITIONAL IMPORTANT SAFETY INFORMATION

Contraindications

DANZITEN is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome.

Warnings and Precautions

Substitution With Other Nilotinib Products and Risk of Medication Errors: DANZITEN tablets may not be substitutable with other nilotinib products, including other nilotinib tablets, on a milligram per milligram basis. Confirm that the intended nilotinib product is being prescribed and dispensed.

Myelosuppression: Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction.

Cardiac and Arterial Vascular Occlusive Events: Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during DANZITEN therapy.

Pancreatitis and Elevated Serum Lipase: Monitor serum lipase; if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis.

Hepatotoxicity: Monitor hepatic function tests monthly or as clinically indicated.

Electrolyte Abnormalities: DANZITEN can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating DANZITEN and monitor periodically during therapy.

Tumor Lysis Syndrome: Maintain adequate hydration and correct uric acid levels prior to initiating therapy with DANZITEN.

Hemorrhage: Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed.

Fluid Retention: Monitor patients for unexpected rapid weight gain, swelling, and shortness of breath. Manage medically.

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.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.

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.

Adverse Reactions

The most commonly reported non-hematologic adverse reactions (≥20%) in adult patients are 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.

These are not all the possible side effects of DANZITEN. Please see Full Prescribing Information for a full list.

Drug Interactions

Strong CYP3A Inhibitors: Avoid concomitant use, including grapefruit juice with DANZITEN or reduce DANZITEN dose if concomitant use cannot be avoided.

Strong CYP3A Inducers: Avoid concomitant use with DANZITEN.

Proton Pump Inhibitors: Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors.

See Full Prescribing Information for Specific Drugs and Interactions.

Use in Specific Populations

Lactation: Advise women not to breastfeed.

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

The Important Safety Information does not include all the information needed to use DANZITEN safely and effectively. Please see Full Prescribing Information for DANZITEN.

To Report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.

References

1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Chronic Myeloid Leukemia V.3.2025. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 3, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. DANZITEN [prescribing information]. Woburn, MA: Azurity Pharmaceuticals, Inc; 2024. 3. Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31(7):1525-1531. 4. Boons CCLM, Timmers L, Janssen JJWM, et al. Response and Adherence to Nilotinib in Daily practice (RAND study): an in-depth observational study of chronic myeloid leukemia patients treated with nilotinib. Eur J Clin Pharmacol. 2020;76(9):1213-1226. 5. Tan BK, Tan SB, Chen L. Medication-related issues associated with adherence to long-term tyrosine kinase inhibitors for controlling chronic myeloid leukemia: a qualitative study. Patient Prefer Adherence. 2017;11:1027-1034. 6. Tasigna [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2024. 7. Radich J, Mauro M, Jain P, et al. Population pharmacokinetic (PopPK) modeling for a novel nilotinib formulation. Presented at: SOHO 2024 Annual World; September 4-7, 2024; Houston, TX. 8. Data on file. Azurity Pharmaceuticals. 2024. 9. Hughes TP, Saglio G, Kantarjian HM, et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014;123(9):1353-1360.

Danziten CONNECT^SM Co-Pay Program Terms and Conditions:

The patient must have a valid prescription for Danziten^TM (nilotinib).
The patient must be 18 years of age or older to be eligible for this program.
The program is not valid for prescriptions that are eligible for reimbursement, in whole or in part by Medicaid, Medicare, or other federal or state healthcare programs (including any state prescription drug assistance programs and the Government Health Insurance Plan available in Puerto Rico [formerly known as “La Reforma De Salud”]).
This program is not valid for prescriptions that are eligible for reimbursement by private insurance plans or other health or pharmacy benefit programs that reimburse you for the entire cost of your prescription drugs.
Each patient is limited to one active Co-pay offer at a time during this offer period and the Co-pay assistance offer is not transferable.
The program cannot be combined with any other rebate, coupon, free trial, or similar offer for the specified prescription.
The Co-pay Program is not health insurance.
This offer is good only in the United States and Puerto Rico as allowed by law.
Offer valid until the end of the current calendar year.
Azurity reserves the right to rescind, revoke, or amend co-pay assistance without notice.
For questions regarding the Co-pay assistance, please call the Help Desk at 1-888-215-8350.

First Free Month Offer Terms and Conditions

The patient must have a valid prescription for Danziten^TM (nilotinib).
The patient must be 18 years of age or older to be eligible for this program.
This offer is good for all eligible patients who are residents of the United States or Puerto Rico. Void where prohibited by law.
Offer is limited to one per patient per lifetime and is not transferable. Not valid if reproduced.
This first free month offer is not health insurance.
No claim for reimbursement for product dispensed pursuant to this offer may be submitted to any third-party payer, whether a commercial, private or a government payer.
This offer cannot be combined with any other rebate/offer, free trial or similar for the specified prescription.
Valid only for patients new to Danziten^TM (nilotinib) and for their first month of medication. Existing and restart patients to Danziten^TM (nilotinib) are not eligible.

Patient Instructions: This first free month offer is valid for up to a 30 days’ supply of Danziten^TM (nilotinib). Offer must be presented to your pharmacist along with a valid prescription. Offer is valid for your first prescription of Danziten^TM (nilotinib) and one per patient per lifetime. Please call 1-800-657-7613 with any questions. Azurity and its service providers reserve the right to rescind, recall, revoke or amend this without notice at any time.

Pharmacist Instructions: The first free month offer must accompany a valid prescription. Patient must be naïve to Danziten^TM (nilotinib). One offer per patient per lifetime and for patient’s first month of medication. No substitution allowed. Please dispense at no cost to the patient. For reimbursement, please submit this electronically as a primary claim to BIN# 610524, RxPCN 1016, and RxGroup# 40028208. Do not submit to any other payer. For questions, please call the Help Desk at 1-800-657-7613. Azurity and its service providers reserve the right to rescind, recall, revoke or amend this without notice at any time.

Study Design⁷

A validated PopPK model was used to predict and simulate steady-state PK and food effects on systemic exposure for Danziten™ vs Tasigna® using data from healthy subject studies.

Data from 14 bioavailability/bioequivalence clinical studies in healthy subjects (28,779 observations, 502 healthy subjects) was pooled. Fifty subjects were randomly selected to extract key PK parameters (AUC_ss, C_maxss, C_minss). One hundred study replicates were simulated to assess bioequivalence probability between formulations under fasted conditions.

Danziten™: Bioequivalence at Lower Doses and No Fasting Requirements2