Luhan Pharmachem Co., Ltd.

Luhan pharmachem Co., Ltd. supplies Nilotinib bulk active pharmaceutical ingredient (API) to the pharmaceutical industry. Our Nilotinib is manufactured by cGMP compliant facility. Welcome to contact us for further details including current DMF status for the product and up to date regulatory status of the manufacturing facility. We look forward to assisting you with your research and development projects.

What is Nilotinib HCl?

Nilotinib (AMN107, trade name Tasigna), in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia.

Clinical Uses

Nilotinib was approved as Tasigna in the USA and the EU for drug-resistant chronic myelogenous leukemia(CML). In June 2006, a Phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib (trade name: Gleevec [USA]/ Glivec[Europe/Australia/Latin America]), another tyrosine kinase inhibitor currently used as a first-line treatment. In that study 92% of patients (already resistant or unresponsive to imatinib) achieved a normal white blood cell counts after five months of treatment. The drug carries a black box warning for possible heart complications.

What is the mechanism of action?

Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN107 to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP1-like-1-PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN107 for myeloproliferative diseases characterised by these kinase fusions (Stover et al, 2005; Weisberg et al, 2005). AMN107 also inhibits the c-Kit receptor kinase, including the D816V-mutated variant of KIT, at pharmacologically achievable concentrations, supporting potential utility in the treatment of mastocytosis, and gastrointestinal stromal tumours (Weisberg et al, 2005; von Bubnoff et al, 2005; Gleixner et al, 2006).

Pharmacology

Nilotinib inhibits the kinases BCR-ABL,[7] KIT, LCK, EPHA3, EPHA8, DDR1, DDR2, PDGFRB, MAPK11 and ZAK.

Nilotinib possesses an in vitro Bcr-Abl binding potency 30 times greater than imatinib in imatinib-resistant cells, and 5-7 times greater than imatinib in imatinib-susceptible leukemic cells. The clinical importance of nilotinib¡¯s greater binding affinity is not established in patients with imatinib-susceptible disease. Nilotinib absorption greatly decreases with increasing dose above 400 mg. Absorption increases significantly in the presence of food. The clinical course of CML begins with an indolent chronic phase, but can quickly progress to the more aggressive accelerated, then blast phases if left untreated.

What are the side effects of Nilotinib HCl?

Adverse events associated with the use of Nilotinib HCl in CML-CP patients may include, but are not limited to, the following:

• Rash
• Pruritis
• Nausea
• Fatigue
• Headache
• Constipation
• Diarrhea
• Vomiting
• Thrombocytopenia
• Neutropenia

Adverse events associated with the use of Nilotinib HCl in CML-AP patients may include, but are not limited to, the following:

• Rash
• Pruritus
• Constipation
• Thrombocytopenia
• Neutropenia
• Pneumonia
• Febrile neutropenia
• Leukopenia
• Intracranial hemorrhage
• Elevated lipase
• Pyrexia

Recommended Dosing

FDA (USA): 400 mg orally twice daily, approximately 12 hours apart and should not be taken with food. The capsules should be swallowed whole with water. No food should be consumed for at least 2 hours before the dose is taken and no food should be consumed for at least one hour after. Dose adjustment may be required for hematologic and non-hematologic toxicities, and drug interactions.

EMA (Europe): The recommended dose of nilotinib is 400 mg twice daily. Treatment should be continued as long as the patient continues to benefit. Nilotinib should be taken twice daily approximately 12 hours apart and must not be taken with food. The capsules should be swallowed whole with water. No food should be consumed for 2 hours before the dose is taken and no food should be consumed for at least one hour after the dose is taken. Nilotinib may be given in combination with haematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated. Nilotinib may be given with hydroxyurea or anagrelide if clinically indicated.

Storage

Store Nilotinib HCl at or below -20 degrees C.

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.