Nilotinib (Tasigna)

General information

Class/mechanism: Tyrosine kinase inhibitor of Bcr-Abl, the constitutively active tyrosine kinase resulting from the Philadelphia chromosome abnormality in CML. Nilotinib binds to the inactive conformation of the Abl kinase domain and stabilizes it.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established

• Chronic myeloid leukemia

Diseases for which it is used

• Hypereosinophilic syndrome
• Ph+ B-cell ALL
• Systemic mastocytosis

Patient drug information

• Nilotinib (Tasigna) package insert
• Nilotinib (Tasigna) patient drug information (Chemocare)
• Nilotinib (Tasigna) patient drug information (UpToDate)

History of changes in FDA indication

• 2007-10-29: Granted accelerated approval for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included Imatinib (Gleevec). (Based on A2101)
  • 2011-01-14: Converted to regular approval for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included Imatinib (Gleevec).
• 2010-06-17: Granted accelerated approval for the treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. (Approval extended to first-line setting; based on ENESTnd)
  • 2015-01-27: Converted to regular approval.
• 2017-12-22: FDA label updated: Patients with newly diagnosed Ph+ CML in the chronic phase (CP) and resistant or intolerant Ph+ CML-CP patients who have achieved a sustained molecular response (MR4.5) may be considered for discontinuation after at least three years of nilotinib. To be considered for discontinuation, patients must have typical BCR-ABL transcripts. An FDA-authorized test with a detection limit below at least MR4.5 must be used to determine discontinuation eligibility. Patients must be frequently monitored by this test to detect possible loss of remission. (Based on ENESTfreedom and ENESTop)
• 2018-03-22: FDA approved for pediatric patients 1 year of age or older with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). (Approval extended to pediatric setting; based on DIALOG)
• 2018-03-22: FDA approved for pediatric patients 1 year of age or older with Ph+ CML-CP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy. (Approval extended to pediatric setting; based on CAMN107A2120)

History of changes in EMA indication

• 2007-11-19: Initial authorization

History of changes in Health Canada indication

• 2008-09-09: Initial notice of compliance with conditions
• 2011-11-30: Conditions were met

History of changes in PMDA indication

• 2009-01-21: Initial approval for the treatment of imatinib-resistant, chronic phase and accelerated phase chronic myelogenous leukemia.
• 2010-12-21: New additional indications and a new dosage for the treatment of chronic- or accelerated-phase chronic myelocytic leukaemia.

Also known as

• Code name: AMN-107
• Brand name: Tasigna