Nilotinib hydrochloride

What is nilotinib hydrochloride?

Nilotinib hydrochloride is a targeted cancer drug belonging to the class of medicines known as tyrosine kinase inhibitors (TKIs). It is also known by the trade name Tasigna and is classified as a kinase inhibitor.^[3] The substance is a chemically synthesised small molecule and is authorised as a medicine in the European Union.^[1] Nilotinib was first approved in the United States in 2007.^[3]

How does nilotinib hydrochloride work?

Nilotinib blocks a tyrosine kinase protein called BCR-ABL. This protein is made by leukaemia cells that carry an abnormal chromosome known as the Philadelphia chromosome. By blocking BCR-ABL, nilotinib stops the leukaemia cells with the Philadelphia chromosome from growing.^[2] Most people with CML have the Philadelphia chromosome.^[2]

Which conditions is nilotinib hydrochloride used or studied for?

• Newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase — nilotinib is authorised for adult and paediatric patients aged 1 year and older with this condition.^[3]
• Chronic phase and accelerated phase Ph+ CML resistant to or intolerant to prior therapy — nilotinib is indicated for adult patients whose disease no longer responds to or cannot be continued with other treatments.^[3]
• Chronic myeloid leukaemia (CML) in general — nilotinib may be used as a first treatment for chronic phase CML when imatinib cannot be taken, or when other treatments such as imatinib do not work, stop working, or cause difficult side effects.^[2]

How is nilotinib hydrochloride given?

Nilotinib hydrochloride is given as hard capsules for oral use.^[1] The capsules are swallowed whole with water and are taken on an empty stomach, at least 2 hours before a meal and not eating for 1 hour after the dose.^[2] The medicine is typically taken twice a day, about 12 hours apart.^[2] If a patient cannot swallow the capsules, the powder from the capsule can be mixed with a teaspoon of apple sauce and swallowed immediately.^[2]

What do the clinical trials show?

One registered trial investigated nilotinib hydrochloride. The trial (2022-501325-20-00) was a Phase 1 study comparing the bioavailability of nilotinib 200 mg hard capsules with the reference product Tasigna 200 mg hard capsules in 20 healthy subjects.^[1] The study has been completed.^[1]

What is measured in this trial?

The primary outcome measured pharmacokinetic endpoints, which describe how the drug is absorbed, distributed, and eliminated by the body. These included Cmax (the maximum concentration of the drug in the blood), tmax (the time to reach that maximum concentration), AUC0-t and AUC0-∞ (the total exposure to the drug over time), and t1/2 (the half-life, or how long it takes for half the drug to leave the body).^[1] The aim was to explore whether the test product and the reference product are absorbed to a similar extent in the body.^[1]

Who can take part in this trial?

This bioavailability study enrolled healthy subjects rather than patients with CML.^[1] Bioavailability studies in healthy volunteers are typically used to compare how two formulations of the same medicine behave in the body without the influence of disease.

What side effects are known?

Nilotinib can prolong the QT interval, which is a measure of the electrical activity of the heart. Sudden deaths have been reported in patients receiving nilotinib.^[3] Patients should not receive nilotinib if they have low blood potassium (hypokalemia), low blood magnesium (hypomagnesemia), or long QT syndrome.^[3] In the long-term ENESTnd study, numerically more cardiovascular events occurred in patients receiving nilotinib compared with imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. However, few deaths in any treatment arm were associated with cardiovascular events, infections, or pulmonary diseases.^[4]