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nilotinib (Tasigna)

Indications: - FDA-approved for Philadelphia chromosome-positive CML - FDA-approved for imatinib resistant CML - may have disease-modifying benefits in Alzheimer's disease [4] - Parkinson's disease? [5,6]; Lewy body disease? [6,7] Dosage: - 300 mg PO BID - patients in remission may be eligible for discontinuation after 3 years of therapy [2] Capsules 150 mg Pharmacokinetics: - crosses blood-brain barrier - metabolized by CYP3A4 Monitor: - liver function tests periodically Adverse effects: - boxed warning for QT prolongation & sudden death Drug interactions: - induces & inhibits CYP2C8 & CYP2C9 - inhibits CYP2D6 - inhibits CYP3A4 Mechanism of action: - tyrosine kinase inhibitor - targets discoidin domain receptors, including Abelson tyrosine kinase - increases CSF dopamine turnover - reduces CSF tau (indcependent of Abelson tyrosine kinase inhibition)) Notes: - nilotinib is now generic in the U.S. [7]

Interactions

drug adverse effects of tyrosine kinase inhibitor(s)

General

small inhibitory antineoplastic agent (ib drug) antineoplastic tyrosine kinase inhibitor

References

  1. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  2. Nelson R FDA Updates Labeling for Nilotinib: Treatment Can Be Stopped. Medscape - Dec 22, 2017. https://www.medscape.com/viewarticle/890566
  3. Ingram I. FDA OKs Tasigna for Rare Leukemia in Children. Approved in first- and second-line settings. MedPage Today. March 22, 2018 https://www.medpagetoday.com/hematologyoncology/leukemia/71936
  4. George J Alzheimer's Markers Altered With Cancer Drug -Early nilotinib study suggests it has potential to be a disease-modifying drug. MedPage Today May 29, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/86770 - Nackerdien Z Cancer Drug Nilotinib Changes Alzheimer's Disease Biomarkers - his may be a first step towards a disease-modifying treatment, phase II study suggests. MedPage Today 2020-06-18 https://www.medpagetoday.org/neurology/alzheimersdisease/87151 - Turner RS, Hebron ML, Lawler A et al Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease. Ann Neurol 2020. May 28 PMID: 32468646 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25775
  5. Pagan FL, Hebron ML, Wilmarth B et al Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2019 Dec 16;77(3):309-17 PMID: 31841599 Free PMC article
  6. Pagan F, Hebron M, Valadez EH et al Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies. J Parkinsons Dis. 2016 Jul 11;6(3):503-17. PMID: 27434297 Free PMC article.
  7. Brooks M Leukemia Drug Shows Promise in Lewy Body Dementia. Medscape. Nov 5, 2024 https://www.medscape.com/viewarticle/leukemia-drug-shows-promise-lewy-body-dementia-2024a1000k73