Danziten Dosage

Generic name: NILOTINIB 71mg
Dosage form: tablet
Drug class: BCR-ABL tyrosine kinase inhibitors

Medically reviewed by Drugs.com. Last updated on Nov 1, 2024.

Important Use and Administration Instructions

• Nilotinib is available in different formulations, dosage forms, and strengths that are approved with different indications and recommended dosages.
• 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 the recommended dosage of other nilotinib products) is prescribed.
• When switching between DANZITEN (nilotinib) tablets and Tasigna (nilotinib) capsules, use the dosage conversion table.

Recommended Dosage and Administration

Dosage in Adult Patients with Newly Diagnosed Ph+ CML-CP
The recommended dosage of DANZITEN is 142 mg orally twice daily at approximately 12-hour intervals with or without food.
Dosage in Adult Patients with Resistant or Intolerant Ph+ CML-CP and CML-AP
The recommended dosage of DANZITEN is 190 mg orally twice daily at approximately 12-hour intervals with or without food.
Additional Administration Instructions
Advise patients to swallow the tablets whole with water and not to cut, crush, or chew the tablets. If a dose of DANZITEN is missed, the patient should take the next scheduled dose at its regular time. The patient should not take two doses at the same time.
Switching Instructions
Use Table 1 when switching between DANZITEN and Tasigna based on dosage equivalence.

Table 1 Recommendations for Switching between DANZITEN and Tasigna

Approved Indications	DANZITEN dosage	Tasigna dosage
Newly diagnosed Ph+ CML-CP	142 mg orally twice daily	300 mg orally twice daily
Resistant or intolerant Ph+ CML-CP and CML-AP	190 mg orally twice daily	400 mg orally twice daily

Optional Concomitant Therapy

DANZITEN may be given in combination with hematopoietic growth factors, such as erythropoietin or G-CSF if clinically indicated. DANZITEN may be given with hydroxyurea or anagrelide if clinically indicated.

Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Discontinuation of Treatment After a Sustained Molecular Response (MR4.5) on DANZITEN

Patient Selection
Eligibility for Discontinuation of Treatment
Ph+ CML-CP patients with typical BCR-ABL transcripts, who have been taking DANZITEN 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. 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 DANZITEN. Patients must continue to be monitored for possible loss of molecular remission after treatment discontinuation. Use the same FDA-authorized test to consistently monitor molecular response levels while on and off treatment.
Consider discontinuation in patients with newly diagnosed Ph+ CML-CP who have:
• been treated with DANZITEN for at least 3 years
• maintained a molecular response of at least MR4.0 (corresponding to = BCR-ABL/ABL ≤ 0.01% IS) for one year prior to discontinuation of therapy
• achieved an MR4.5 for the last assessment taken immediately prior to discontinuation of therapy
• been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2)
• no history of accelerated phase or blast crisis
• no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.
Consider discontinuation in patients with Ph+ CML-CP that are resistant or intolerant to imatinib who have achieved a sustained molecular response (MR4.5) on DANZITEN who have:
• been treated with DANZITEN for a minimum of 3 years
• been treated with imatinib only prior to treatment with DANZITEN
• achieved a molecular response of MR4.5 (corresponding to = BCR-ABL/ABL ≤ 0.0032% IS)
• sustained an MR4.5 for a minimum of one year immediately prior to discontinuation of therapy
• been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2)
• no history of accelerated phase or blast crisis
• no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.
Monitor BCR-ABL transcript levels and complete blood count (CBC) with differential in patients who have discontinued DANZITEN therapy monthly for one year, then every 6 weeks for the second year, and every 12 weeks thereafter.
Upon the loss of MR4.0 (corresponding to = BCR-ABL/ABL ≤ 0.01% IS) during the treatment-free phase, monitor BCR-ABL transcript levels every 2 weeks until BCR-ABL levels remain lower than major molecular response [(MMR), corresponding to MR3.0 or = BCR-ABL/ABL ≤ 0.1% IS] for 4 consecutive measurements. The patient can then proceed to the original monitoring schedule.

Reinitiation of Treatment in Patients Who Lose Molecular Response After Discontinuation of Therapy with DANZITEN

• Newly diagnosed patients who lose MMR must reinitiate treatment within 4 weeks at the dose level prior to discontinuation of therapy. Patients who reinitiate DANZITEN therapy should have their BCR-ABL transcript levels monitored monthly until major molecular response is re-established and every 12 weeks thereafter.
• Patients resistant or intolerant to prior treatment that included imatinib with confirmed loss of MR4.0 (2 consecutive measures separated by at least 4 weeks showing loss of MR4.0) or loss of MMR must reinitiate treatment within 4 weeks at the dose level prior to discontinuation of therapy. Patients who reinitiate DANZITEN therapy should have their BCR-ABL transcript levels monitored monthly until previous major molecular response or MR4.0 is re-established and every 12 weeks thereafter.

Dosage Modification for QT Interval Prolongation

See Table 2 for dose adjustments for QT interval prolongation.

Table 2. Dosage Adjustments for Adult Patients with QT Prolongation

Degree of QTc Prolongation	Dosage Adjustment
ECGs with a QTc greater than 480 msec	1. Withhold DANZITEN, and perform an analysis of serum potassium and magnesium, and if below lower limit of normal, correct with supplements to within normal limits. Concomitant medication usage must be reviewed. 2. Resume within 2 weeks at prior dose if QTcF returns to less than 450 msec and to within 20 msec of baseline. 3. If QTcF is between 450 msec and 480 msec after 2 weeks, reduce the dose to 190 mg once daily in adults. 4. Discontinue DANZITEN if, following dose-reduction to 190 mg once daily in adults, QTcF returns to greater than 480 msec. 5. An ECG should be repeated approximately 7 days after any dose adjustment.
Abbreviation: ECG, electrocardiogram.

Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation’s Tasigna® (nilotinib) capsules. However, due to Novartis Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Dosage Modifications for Myelosuppression

Withhold or reduce DANZITEN dosage for hematological toxicities (neutropenia, thrombocytopenia) that are not related to underlying leukemia (Table 3).

Table 3. Dosage Adjustments for Neutropenia and Thrombocytopenia

Diagnosis	Degree of Myelosuppression	Dosage Adjustment
Adult patients with: • Newly diagnosed Ph+ CML in chronic phase at 142 mg twice daily • Resistant or intolerant Ph+ CML in chronic phase or accelerated phase at 190 mg twice daily	ANC less than 1 x 109/L and/or platelet counts less than 50 x 109/L	1. Stop DANZITEN and monitor blood counts. 2. Resume within 2 weeks at prior dose if ANC greater than 1 x 109/L and platelets greater than 50 x 109/L. 3. If blood counts remain low for greater than 2 weeks, reduce the dose to 190 mg once daily.
Abbreviations: ANC, absolute neutrophil count; Ph+ CML, Philadelphia chromosome positive chronic myeloid leukemia.

Dosage Modifications for Selected Non-Hematologic Laboratory Abnormalities and Other Toxicities

See Table 4 for dosage adjustments for elevations of lipase, amylase, bilirubin, and/or hepatic transaminases..

Table 4. Dosage Adjustments for Selected Non-Hematologic Laboratory Abnormalities

Degree of Non- Hematologic Laboratory Abnormality	Dosage Adjustment
Elevated serum lipase or amylase greater than or equal to Grade 3	Adult patients: 1. Withhold DANZITEN and monitor serum lipase or amylase. 2. Resume treatment at 190 mg once daily if serum lipase or amylase returns to less than or equal to Grade 1.
Elevated bilirubin greater than or equal to Grade 3 in adult patients	Adult patients: 1. Withhold DANZITEN and monitor bilirubin. 2. Resume treatment at 190 mg once daily if bilirubin returns to less than or equal to Grade 1.
Elevated hepatic transaminases greater than or equal to Grade 3	Adult patients: 1. Withhold DANZITEN and monitor hepatic transaminases. 2. Resume treatment at 190 mg once daily if hepatic transaminases return to less than or equal to Grade 1.

If clinically significant moderate or severe non-hematologic toxicity develops (including medically severe fluid retention), see Table 5 for dosage adjustments.

Table 5. Dosage Adjustments for Other Non-Hematologic Toxicities

Degree of “Other Non-Hematologic Toxicity”	Dosage Adjustment
Other clinically moderate or severe non- hematologic toxicity	Adult patients: 1. Withhold DANZITEN until toxicity has resolved. 2. Resume treatment at 190 mg once daily if previous dose was 142 mg twice daily in adult patients newly diagnosed with CML-CP or 190 mg twice daily in adult patients with resistant or intolerant CML-CP and CML-AP. 3. Discontinue treatment if the prior dose was 190 mg once daily in adult patients 4. If clinically appropriate, consider re-escalation of the dose to 142 mg (newly diagnosed Ph+ CML-CP) or 190 mg (resistant or intolerant Ph+ CML-CP and CML- AP) twice daily.
Abbreviations: CML-AP, chronic myeloid leukemia-accelerated phase; CML-CP, chronic myeloid leukemia-chronic phase; Ph+, Philadelphia chromosome positive.

Recommended DANZITEN Dosage in Patients with Hepatic Impairment

If possible, consider alternative therapies. If DANZITEN must be administered to patients with hepatic impairment, the recommended DANZITEN dosage is provided in Table 6.

Table 6. Recommended DANZITEN Dosage in Patients with Hepatic Impairment

Diagnosis	Degree of Hepatic Impairment	DANZITEN Dosage
Newly diagnosed Ph+ CML in chronic phase	Mild (Child-Pugh A), Moderate (Child-Pugh B), or Severe (Child- Pugh C)	Reduce DANZITEN dosage to 95 mg twice daily. Increase DANZITEN dosage to 142 mg twice daily based on tolerability.
Resistant or intolerant Ph+ CML in chronic phase or accelerated phase	Mild or Moderate	Reduce DANZITEN dosage to 142 mg twice daily. Increase DANZITEN dosage to 190 mg twice daily based on tolerability.
	Severe	Reduce DANZITEN dosage to 95 mg twice daily. Increase DANZITEN dosage to 142 mg twice daily and then to 190 mg twice daily based on tolerability.

Dosage Modification for Strong CYP3A4 Inhibitors

Avoid the concomitant use of strong CYP3A4 inhibitors. Should treatment with any of these agents be required, interrupt therapy with DANZITEN.
If concomitant use is required, reduce DANZITEN dosage to 142 mg once daily in patients with resistant or intolerant Ph+ CML or to 95 mg once daily in patients with newly diagnosed Ph+ CML-CP. If the strong inhibitor is discontinued, allow a washout period of 5 half-lives before adjusting DANZITEN dose upward to the indicated dose. For patients who cannot avoid use of strong CYP3A4 inhibitors, monitor closely for prolongation of the QT interval.