In June 2006, a phase Iclinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib, another tyrosine kinase inhibitor currently used as a first-line treatment. In that study 92% of patients (already resistant or unresponsive to imatinib) achieved normal white blood cell counts after five months of treatment.
Nilotinib has a number of adverse effects typical of anti-cancer drugs. These include headache, fatigue, gastrointestinal problems such as nausea, vomiting, diarrhea and constipation, muscle and joint pain, rash and other skin conditions, flu-like symptoms, and reduced blood cell count. Less typical side effects are those of the cardiovascular system, such as hypertension (high blood pressure), various types of arrhythmia, and prolonged QT interval. Nilotinib can also affect the body's electrolyte and glucose balance. Though pulmonary-related adverse effects are rare when compared with imatinib and dasatinib, there is a case report of acute respiratory failure from diffuse alveolar hemorrhage in a patient taking nilotinib.
Nilotinib has been reported as a substrate for OATP1B1 and OATP1B3. Interaction of nilotinib with OATP1B1 and OATP1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions. Nilotinib is an inhibitor of OATP-1B1 transporter but not for OATP-1B3.
It is a substrate for CYP3A4 and hence grapefruit juice and other CYP3A4 inhibitors will increase its action and inducers like St. John's wort will decrease it. Patients report that pomegranates and starfruit may also interfere.
Food should not be eaten two hours before or one hour afterwards because it unpredictably increases its bioavailability, approximately doubling it.
There is weak evidence that nilotinib may be beneficial with Parkinson's disease (PD), with a small clinical trial suggesting it might halt progression and improve symptoms. However, there were significant side effects including infection, liver function tests abnormalities, hallucinations and heart attack, and the benefit in PD disappeared at follow up after drug discontinuation, raising question as to whether it was truly a disease modifying therapy. Nilotinib is currently undergoing phase II studies for treatment of Parkinson's. Scientists and medical professionals have advised caution with over-optimistic interpretation of its effects in Parkinson's due to the significant media hype surrounding the small and early clinical trial.
Novartis announced on April 11, 2011 that it was discontinuing a phase III trial of Tasigna (nilotinib) for investigational use in the first-line treatment of gastrointestinal stromal tumor (GIST) based on the recommendation of an independent data monitoring committee. Interim results showed Tasigna is unlikely to demonstrate superiority compared to Novartis's Gleevec (imatinib)*, the current standard of care in this setting.
^ abManley, P.; Cowan-Jacob, S.; Mestan, J. (2005). "Advances in the structural biology, design and clinical development of Bcr-Abl kinase inhibitors for the treatment of chronic myeloid leukaemia". Biochimica et Biophysica Acta. 1754 (1–2): 3–13. doi:10.1016/j.bbapap.2005.07.040. PMID16172030.
^ abManley, P.; Stiefl, N.; Cowan-Jacob, S.; Kaufman, S.; Mestan, J.; Wartmann, M.; Wiesmann, M.; Woodman, R.; Gallagher, N. (2010). "Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib". Bioorganic & Medicinal Chemistry. 18 (19): 6977–6986. doi:10.1016/j.bmc.2010.08.026. PMID20817538.
^Komoroski, Bernard J.; Zhang, Shimin; Cai, Hongbo; Hutzler, J. Matthew; Frye, Reginald; Tracy, Timothy S.; Strom, Stephen C.; Lehmann, Thomas; Ang, Catharina Y. W. (2004-05-01). "Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures". Drug Metabolism and Disposition. 32 (5): 512–518. doi:10.1124/dmd.32.5.512. ISSN0090-9556. PMID15100173.