Introduction
Chronic Myeloid Leukaemia is a type of cancer that occurs when bone marrow produces too many leucocytes (white blood cells) . This over production of leucocytes occurs when they grow uncontrollably by overcoming the cell regulation cycle. Cells not undergoing the regulation cycle continue to divide without dying ,causing an overcrowding of cells, hence, forming a tumour in bone marrow. The tumour can become an even more serious issue when the cancer cells from a tumour spreads to other tissues in the body(metastasis) (1). Novartis Oncology (a Novartis International AG company) is the producer and developer of nilotinib, which is a treatment option for Chronic Myeloid Leukaemia (CML). Nilotinib is available by prescription under the brand name Tasigna® (2). Nilotinib is a Tyrosine Kinase inhibitor, which inhibits the BCR-ABL protein tyrosine kinase by changing its conformation, preventing signal transduction, hence, stopping cancer cell multiplication (3). Nilotinib is administered when the patient shows positivity for the genetic mutation that forms the Philadelphia Chromosome (Ph+), which is associated with this branch of leukaemia(4) . It is commonly used if traditional leukaemia medication, such as Imatinib, does not work (5) or the patient develops resistance to imantinib (6). The purpose of nilotinib is to slow down or stop cancer cell proliferation that results in the ‘chronic’ and ‘accelerated’ phases of Chronic Myeloid Leukaemia (7) by obstructing the signal pathway in which the cancer cells use to grow. With most anti-cancer medication, there are many side effects when taking nilotinib. The most common side effects are low blood cell count, rash and headaches.Tasigna® is available as capsules that are taken orally, twice a day (9). In New Zealand Tasigna® is fully subsidised for patients who meet the requirements from the PHARMAC Restriction Spacial Authority for Subsidy, Form SA1489 (10). In recent years, Nilotinib has been considered for treatment of other cancers (11) as well as Parkinson’s disease (12). Composition and Structure Tasigna® is available as a prescription in tablet form. The tablets have an opaque red, hard gelatin outer coat with white-yellow powder inside. Thse tablets are taken orally. Nilotinib is the active ingredient in the tablet, wth 150-200mg of nilotinib per capsule. Newly diagnosed Ph+ CML patients take 300mg of nilotinib daily whereas resistant and intolerant Ph+ CML patients take 400mg daily. For both categories of patients, that equates to taking one tablet of Tasigna, twice a day (13). Nilotinib was orignially invented as a second generation protein kinase inhibtor drug because there were some patients who were developing resistence to or could not take imantinib (14) .Imantinib is the traditional drug prescribed to Ph+ CML patients (15) Nilotinib is similar to imantinib in its chemical structure but nilotinib replaces the N-methylpiperazine ring in imantinib with a trifluorinated imidazole. This is more energetically favourable for nilotinib because in imantinib, there are two hydrogen bonds between the N-methylpiperazine and lie360 and His361 of ABL. These parts consume a lot of energy which lessens the drugs effects. Nilotinib is also the better drug because its imidazole ring has a better topological fit in a hydrophobic pocket of the kinase. It is also a molecule that inihibits ABL with a higher potency. (16) Fig 1: Chemical structures of Imantinib and Nilotinib Absorption, Distribution, Metabolism and Excretion …show more content…
Nilotinib could be a risk in patients who already have heart complications as it is known to cause heart problems such as angina and palpitation (39). The causes of side effects in nilotinib are not yet fully understood but it is believed that because nilotinib acts on bone cells to suppress tumour growth, bone pain and fatigue arise from the lack of bone cells (40). The drug could be ineffective in patients who already have heart, liver and kidney problems (41). Nilotinib should not be taken by women who are pregnant and lactacting as it is known that nilotinib cases human fetal malformations or even irreversible damage. Children under the age of 18 years of age are also at risk if they take nilotinib (42). Nilotinib is known to interact with many drugs, such as CoA reductase inhibitors and even certain types of food, such as liquorice and grapefruit so patients have to take nilotinib on an empty stomach. So patients would have to fast 1 hour before and 2 hours after taking the medicine
Chronic Myeloid Leukaemia is a type of cancer that occurs when bone marrow produces too many leucocytes (white blood cells) . This over production of leucocytes occurs when they grow uncontrollably by overcoming the cell regulation cycle. Cells not undergoing the regulation cycle continue to divide without dying ,causing an overcrowding of cells, hence, forming a tumour in bone marrow. The tumour can become an even more serious issue when the cancer cells from a tumour spreads to other tissues in the body(metastasis) (1). Novartis Oncology (a Novartis International AG company) is the producer and developer of nilotinib, which is a treatment option for Chronic Myeloid Leukaemia (CML). Nilotinib is available by prescription under the brand name Tasigna® (2). Nilotinib is a Tyrosine Kinase inhibitor, which inhibits the BCR-ABL protein tyrosine kinase by changing its conformation, preventing signal transduction, hence, stopping cancer cell multiplication (3). Nilotinib is administered when the patient shows positivity for the genetic mutation that forms the Philadelphia Chromosome (Ph+), which is associated with this branch of leukaemia(4) . It is commonly used if traditional leukaemia medication, such as Imatinib, does not work (5) or the patient develops resistance to imantinib (6). The purpose of nilotinib is to slow down or stop cancer cell proliferation that results in the ‘chronic’ and ‘accelerated’ phases of Chronic Myeloid Leukaemia (7) by obstructing the signal pathway in which the cancer cells use to grow. With most anti-cancer medication, there are many side effects when taking nilotinib. The most common side effects are low blood cell count, rash and headaches.Tasigna® is available as capsules that are taken orally, twice a day (9). In New Zealand Tasigna® is fully subsidised for patients who meet the requirements from the PHARMAC Restriction Spacial Authority for Subsidy, Form SA1489 (10). In recent years, Nilotinib has been considered for treatment of other cancers (11) as well as Parkinson’s disease (12). Composition and Structure Tasigna® is available as a prescription in tablet form. The tablets have an opaque red, hard gelatin outer coat with white-yellow powder inside. Thse tablets are taken orally. Nilotinib is the active ingredient in the tablet, wth 150-200mg of nilotinib per capsule. Newly diagnosed Ph+ CML patients take 300mg of nilotinib daily whereas resistant and intolerant Ph+ CML patients take 400mg daily. For both categories of patients, that equates to taking one tablet of Tasigna, twice a day (13). Nilotinib was orignially invented as a second generation protein kinase inhibtor drug because there were some patients who were developing resistence to or could not take imantinib (14) .Imantinib is the traditional drug prescribed to Ph+ CML patients (15) Nilotinib is similar to imantinib in its chemical structure but nilotinib replaces the N-methylpiperazine ring in imantinib with a trifluorinated imidazole. This is more energetically favourable for nilotinib because in imantinib, there are two hydrogen bonds between the N-methylpiperazine and lie360 and His361 of ABL. These parts consume a lot of energy which lessens the drugs effects. Nilotinib is also the better drug because its imidazole ring has a better topological fit in a hydrophobic pocket of the kinase. It is also a molecule that inihibits ABL with a higher potency. (16) Fig 1: Chemical structures of Imantinib and Nilotinib Absorption, Distribution, Metabolism and Excretion …show more content…
Nilotinib could be a risk in patients who already have heart complications as it is known to cause heart problems such as angina and palpitation (39). The causes of side effects in nilotinib are not yet fully understood but it is believed that because nilotinib acts on bone cells to suppress tumour growth, bone pain and fatigue arise from the lack of bone cells (40). The drug could be ineffective in patients who already have heart, liver and kidney problems (41). Nilotinib should not be taken by women who are pregnant and lactacting as it is known that nilotinib cases human fetal malformations or even irreversible damage. Children under the age of 18 years of age are also at risk if they take nilotinib (42). Nilotinib is known to interact with many drugs, such as CoA reductase inhibitors and even certain types of food, such as liquorice and grapefruit so patients have to take nilotinib on an empty stomach. So patients would have to fast 1 hour before and 2 hours after taking the medicine