Nilotinib


Full Generic Medicine Info
Dosage/Direction for Use

Oral
Chronic phase Philadelphia chromosome positive chronic myelogenous leukaemia
Adult: In patients with newly-diagnosed case: 300 mg bid. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Child: In paediatric patients with newly diagnosed case, resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy: 230 mg/m2 bid rounded to the nearest 50 mg dose. Max: 400 mg as single dose. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Hepatic impairment: In patients with newly-diagnosed case Mild to severe: 200 mg bid, may increase to 300 mg bid based on tolerability.

Oral
Chronic phase Philadelphia chromosome positive chronic myelogenous leukaemia
Adult: With resistance to prior treatment or intolerance to other therapy: 400 mg bid. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Hepatic impairment: With resistance to prior treatment or intolerance to other therapy Mild to moderate (Child-Pugh A or B): 300 mg bid, may increase to 400 mg bid based on tolerability. Severe (Child-Pugh C): 200 mg bid, may increase to 300 mg bid up to 400 mg bid based on tolerability.

Oral
Accelerated phase Philadelphia chromosome positive chronic myelogenous leukaemia
Adult: With resistance to prior treatment or intolerance to other therapy: 400 mg bid. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Hepatic impairment: With resistance to prior treatment or intolerance to other therapy Mild to moderate (Child-Pugh A or B): 300 mg bid, may increase to 400 mg bid based on tolerability. Severe (Child-Pugh C): 200 mg bid, may increase to 300 mg bid up to 400 mg bid based on tolerability.

Special Populations: Pharmacogenomics: Uridine diphosphate glucuronosyl-transferase 1A1 (UGT1A1) Bilirubin is glucuronidated by Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) and polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinaemia during treatment of some drugs including nilotinib. Polymorphisms of UGT1A1*28 allele may be at risk of hyperbilirubinaemia. A pharmacogenetic analysis was conducted to evaluate the polymorphisms of UGT1A1. Studies showed that the largest increases in bilirubin were observed among patients with (TA)7/(TA)7 genotype relative to (TA)6/(TA) 6 and (TA) 6/(TA) 7 genotypes. Caution is recommended in patients with (TA) 7/(TA) 7 genotype (UGT1A1*28).
Administration
Should be taken on an empty stomach. Avoid food at least 2 hr before & at least 1 hr after a dose. Swallow whole, do not chew/crush. Avoid grapefruit products.
Contraindications
Patients with hypokalaemia, hypomagnesaemia or long QT syndrome. Concomitant use with potent CYP3A4 inhibitors or inducers, antiarrhythmics and other QT prolonging drugs.
Special Precautions
Patients with pre-existing risk factors of CV disease, electrolyte imbalance, history of pancreatitis and total gastrectomy. Maintain adequate hydration and correct uric acid levels, hypomagnesaemia, hypokalaemia and other electrolyte imbalances prior to therapy. Hepatic impairment. Pregnancy and lactation. Monitoring Parameters Monitor Philadelphia chromosome status, ECG, QTc, CBC, electrolytes (e.g. K, Ca, Mg), lipid profile, blood glucose, hepatic function (ALT/AST, bilirubin, alkaline phosphatase), serum lipase and amylase, uric acid, and bone marrow assessments at baseline, periodically thereafter or as clinically indicated. Monitor growth and development of paediatric patients.
Adverse Reactions
Significant: Bone marrow suppression (e.g. myelosuppression, thrombocytopenia, neutropenia, anaemia), cardiovascular and arterial vascular-occlusive events, electrolyte imbalance (e.g. hypophosphataemia, hyper/hypokalaemia, hypocalcaemia, hyponatremia), hepatotoxicity, fluid retention (e.g. pleural and pericardial effusions, ascites, pulmonary oedema), tumor lysis syndrome. Ear and labyrinth disorders: Vertigo. Eye disorders: Eye pruritus, conjunctivitis, dry eye, xerophthalmia. I>Gastrointestinal disorders: Nausea, constipation, diarrhoea, vomiting, abdominal pain, dyspepsia. General disorders and administration site conditions: Fatigue, pyrexia, asthenia, peripheral oedema. Hepatobiliary disorders: Abnormal hepatic function. Infections and infestations: Folliculitis, upper respiratory tract infection. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, muscle spasms, bone pain, pain in extremity, back pain. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Insomnia. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea. Skin and subcutaneous tissue disorders: Rash, pruritis, alopecia, dry skin, erythema. Vascular disorders: Hypertension.
Potentially Fatal: Haemorrhage, QT prolongation, sudden death.
Overdosage
Neutropenia, vomiting and drowsiness. Management: Monitor patient and give appropriate supportive treatment.
Drug Interactions
May decrease nilotinib efficacy with PPIs.
Potentially Fatal: Concomitant use with potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, telithromycin) may increase nilotinib serum concentrations. Antiarrhythmics (e.g. amiodarone, disopyramide, procainamide, quinidine, sotalol) and other QT prolonging drugs (e.g. chloroquine, halofantrine, clarithromycin, haloperidol, methadone and moxifloxacin) may increase the risk of prolonged QT interval. Concomitant use with CYP3A4 inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin) may decrease nilotinib serum concentrations.
Food Interaction
Bioavailability is increased with food. Avoid grapefruit juice as it may increase nilotinib serum levels. Avoid St. John's wort as it may decrease nilotinib serum levels.
Action
Nilotinib selectively inhibits tyrosine kinase that targets BCR-ABL kinase, c-KIT and platelet derived growth factor receptor (PDGFR). It binds to the ATP-binding site of BCR-ABL to inhibit BCR-ABL mediated proliferation of leukemic cell lines, thereby inhibiting tyrosine kinase activity. Nilotinib does not have an activity against SRC family but has an activity in imatinib resistance BCR-ABL kinase mutations.
Absorption: Bioavailability: Approx 50%. High-fat meal increases bioavailability. Time to peak plasma concentration: Approx 3 hours.
Distribution: Plasma protein binding: Approx 98%.
Metabolism: Undergoes hepatic oxidation and hydroxylation via CYP3A4 to inactive metabolites.
Excretion: Via faeces (93%, 69% as parent drug). Elimination half-life: Approx 17 hours.
Storage
Oral: Store below 30°C.
ATC Classification
L01EA03 - nilotinib
Disclaimer: This information is independently developed by CIMS based on nilotinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 CIMS. All rights reserved. Powered by CIMSAsia.com
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