|Trade names||Tasigna, others|
|Defined daily dose||not established |
|Metabolism||Liver (mostly CYP3A4-mediated)|
|Elimination half-life||15-17 hours|
|Chemical and physical data|
|Molar mass||529.527 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Nilotinib, sold under the brand name Tasigna, is a medication used to treat chronic myelogenous leukemia (CML) which has the Philadelphia chromosome. It may be used both in initial cases of chronic phase CML as well as in accelerated and chronic phase CML that has not responded to imatinib. It is taken by mouth.
Common side effects may include low platelets, low white blood cells, anemia, rashes, vomiting, diarrhea, and joint pains. Other serious side effects may include QT prolongation, sudden death, pancreatitis, and liver problems. It is not safe for use during pregnancy. Nilotinib is a Bcr-Abl tyrosine kinase inhibitor and works by interfering with signalling within the cancer cell.
Nilotinib was approved for medical use in the United States in 2007. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. In the United Kingdom it costs the NHS £2,433 per month as of 2018. In the United States this amount costs US$14,368 as of 2019.
Nilotinib has a number of adverse effects including 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 high blood pressure, various types of arrhythmia, and prolonged QT interval. Nilotinib can also affect the body's electrolyte and glucose balance. Though lung-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 people taking nilotinib.
Nilotinib carries a black box warning in the United States for possible heart complications. Contraindications include long QT syndrome, hypokalaemia, hypomagnesaemia, pregnancy, planned pregnancy, lactation and galactose/lactose intolerance.
- Tumour lysis syndrome
- Liver impairment
- History of pancreatitis
- Check serum lipase periodically in order to detect pancreatitis
- Total gastrectomy
- Avoid pregnancy or impregnating women
Dose reduction has been recommended in people with liver problems which involves recommendation of lower starting dose and monitoring of any hepatic function abnormalities.
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.
Society and culture
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. Dystonia and cognitive impairment have also been reported as side effects.
Novartis announced on April 11, 2011 that it was discontinuing a phase III trial of nilotinib as 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.
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