Tasigna nilotinib

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Tasigna - nilotinib

• Manufacturer Novartis
• FDA Approval Date October 2007

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Tasigna - nilotinib Clinical Application

• Indications
• Philadelphia chromosome-positive chronic
  myelogenous leukemia in adult patients resistant
  or intolerant to prior therapy
• Ph acute lymphoblastic leukemia
• Systemic mastocytosis
• Hypereosinophilic syndrome

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Tasigna - nilotinib Clinical Application

• Contraindications
• Hypokalemia
• Hypomagnesemia
• Long QT syndrome
• Black Box Warning
• QT prolongation
• Sudden deaths

• Warnings/Precautions
• Thrombocytopenia
• Neutropenia
• Anemia
• Hepatotoxicity
• Pregnancy Category D

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Tasigna - nilotinib Drug Facts Pharmacology
http//www.hai-bin.net/images/CML03.jpg
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Tasigna - nilotinib Drug Facts

• Pharmacokinetics
• A AUC ? 82 when given after high fat meals
• D 98 protein bound
• M hepatic oxidation and hydroxylation
• E 90 eliminated in feces t1/2 17 hrs

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Tasigna - nilotinib Drug Interactions

• Drug Interactions Object Drugs

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Tasigna - nilotinib Drug Interactions

• Drug Interactions Precipitant Drugs

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Tasigna - nilotinib Adverse Effects
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Tasigna - nilotinib Monitoring Parameters

• Efficacy Monitoring
• Hematologic at 3 month
• Cytologic at 6 month
• Toxicity Monitoring
• CBC weekly x 8 weeks, then Q 2 weeks thereafter
• EKG baseline, 7 days after initiation,
  periodically thereafter
• Electrolytes periodically
• Hepatic function periodically
• Serum lipase periodically

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Tasigna - nilotinib Prescription Information
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Tasigna - nilotinib Pivotal Trial

• Inclusion
• Ph CML-CP
• 18 y.o.
• Imatinib resistance or intolerance
• Normal hepatic, renal, and cardiac function
• K and Mg2 levels WNL
• Adequate performance status

• Exclusion
• Accelerated or blastic phases
• Received imatinib for 7 days prior to study
• Received hydroxyurea 2 days prior to study
• Receiving other medications prolonging QTc
  interval
• Receiving other CYP 3A4 inhibitors

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Tasigna - nilotinib Pivotal Trial

• Method
• N 280
• Dose 400mg PO BID ? may ? 600mg BID
• Statistics
• One-sided p 0.025
• 90 power
• Response rate of 21 or more out of 132 would be
  sufficient to reject null hypothesis

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Tasigna - nilotinib Pivotal Trial

• 1 Endpoint
• Overall major cytogenetic response
• 2 Endpoints
• Time to major cytogenetic response
• Duration of major cytogenetic response
• CHR
• Time to and duration of CHR
• Overall survival

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Tasigna - nilotinibPivotal Trial Results
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Tasigna - nilotinibPivotal Trial

• Limitation
• Phase II, open-label trial ? Not RCT
• Conclusion
• Nilotinib is a highly active, safe, and effective
  alternative for patients who become resistant or
  intolerant to imatinib

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Tasigna - nilotinib Summary

• Nilotinib is a second generation Bcr-Abl tyrosine
  kinase inhibitor with more selectivity and
  potency against CML cells compared to imatinib
• Black Box Warnings include QTc prolongation and
  sudden deaths
• Contraindicated in patients with hypomagnesemia,
  hypokalemia, and long QT syndrome
• Monitor for thrombocytopenia, neutropenia,
  hepatic impairment, and electrolyte imbalances
• Place in therapy reserved for patients with Ph
  CML who are resistant or intolerant to imatinib
  it is being studied as first line

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Tasigna - nilotinib References

• Tasigna package insert. Novartis Pharmaceuticals
  Corporation. Feb. 2008. (http//www.pharma.us.nov
  artis.com/product/pi/pdf/tasigna.pdf)
• http//www.tasigna.com Accessed 12 Feb. 2008.
• Kantarjian H, et al. Nilotinib (formerly AMN107),
  a highly selective BCR-ABL tyrosine kinase
  inhibitor, is effective in patients with
  Philadelphia chromosome-positive chronic
  myelogenous leukemia in chronic phase following
  imatinib resistance or intolerance. Blood
  2007110(10)3540-6.
• http//www.hai-bin.net/images/CML03.jpg