Nilotinibum
Nilotinibum Uses, Dosage, Side Effects, Food Interaction and all others data.
Nilotinibum is a potent inhibitor of BCR-ABL tyrosine kinase. It binds to and stabilises the inactive conformation of the kinase domain of Abl protein.
Nilotinibum is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML).
Trade Name | Nilotinibum |
Availability | Prescription only |
Generic | Nilotinib |
Nilotinib Other Names | Nilotinib, Nilotinibum |
Related Drugs | hydroxyurea, cyclophosphamide, Gleevec, Sprycel, Tasigna, Bosulif |
Type | |
Formula | C28H22F3N7O |
Weight | Average: 529.5158 Monoisotopic: 529.183792976 |
Groups | Approved, Investigational |
Therapeutic Class | Targeted Cancer Therapy |
Manufacturer | |
Available Country | |
Last Updated: | September 19, 2023 at 7:00 am |
Uses
Treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The study is ongoing and further data will be required to determine long-term outcome.
Treatment of chronic phase (CP) and accelerated phase (AP) Ph+ CML in adult patients resistant to or intolerant to prior therapy that included imatinib. Clinical benefit, such as improvement in disease-related symptoms or increased survival, has not been demonstrated.
Nilotinibum is also used to associated treatment for these conditions: Chronic Phase Chronic Myeloid Leukemia, Refractory Gastrointestinal stromal tumor, Refractory, accelerated phase Chronic myeloid leukemia
How Nilotinibum works
Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinibum inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinibum 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).
Dosage
Nilotinibum dosage
Adult: 400 mg bid. May continue until patient shows unacceptable toxicity or evidence of progression.
Patient on strong CYP3A4 inhibitor: Reduce dose to 300 mg once daily, or to 200 mg once daily in newly-diagnosed chronic phase Philadelphia chronic myelogenous leukaemia. Dose may be adjusted to usual dose after a washout period.
Patient on drugs that prolong QT interval (e.g. antiarrhythmics): Reduce dose and closely monitor for QT interval prolongation.
Hepatic Impairment: Use a lower starting dose.
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.
Side Effects
Rash, pruritus, hepatotoxicity, headache, fever, fatigue, GI disturbances (nausea, constipation, diarrhoea), alopecia, asthenia, muscle spasms, arthralgia, myalgia, pain (e.g. musculoskeletal or chest pain), oedema, folliculitis, papilloma, insomnia, dizziness, vertigo, anxiety, paraesthesia, hyperhidrosis, dry skin, urticaria, acne, conjunctivitis, dry eye, flushing, dyspnoea, cough, myelosuppression (e.g. thrombocytopenia, neutropenia, and anaemia), thrombotic disorders or haemorrhage, arrhythmias, heart failure, pericarditis, palpitations, HTN, angina, MI; elevated AST/ALT, serum lipase; electrolyte imbalances.
Precaution
Patient with history of pancreatitis, with total gastrectomy. Hepatic impairment. Maintain adequate hydration and correct uric acid levels, hypomagnesaemia, hypokalaemia and other electrolyte imbalances prior to therapy. Pregnancy and lactation.
Interaction
Drugs that inhibit gastric acid secretion (e.g. PPIs) may reduce solubility and bioavailability of nilotinib.
Food Interaction
- Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of nilotinib, causing increased serum levels of nilotinib.
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of nilotinib.
- Take on an empty stomach. Food increases the AUC of nilotinib. Separate nilotinib administration from meals by at least one hour before and two hours after eating.
[Major] GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of nilotinib.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.
Because nilotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.
ADJUST DOSING INTERVAL: Food increases the oral bioavailability of nilotinib.
The mechanism of interaction is unknown.
Compared to the fast state, nilotinib systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high-fat meal.
Because nilotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.
MANAGEMENT: Patients treated with nilotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract.
In addition, no food should be consumed for at least 2 hours before and 1 hour after a nilotinib dose.
Nilotinibum Drug Interaction
Major: escitalopram, hydroxychloroquine, fluoxetineModerate: metoprolol, metoprolol, pantoprazoleUnknown: rosuvastatin, ferrous fumarate, methenamine, furosemide, levothyroxine, pregabalin, acetaminophen, acetaminophen, vitamin a topical, levothyroxine, thiamine, cyanocobalamin, pyridoxine, cholecalciferol
Nilotinibum Disease Interaction
Major: pancreatitis, QT prolongationModerate: cardiovascular disease, fluid retention, bone marrow suppression, electrolyte abnormalities, hepatic impairment, lactose intolerance
Elimination Route
Orally available
Half Life
15 hours
Pregnancy & Breastfeeding use
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Contraindication
Patient with hypokalaemia, hypomagnesaemia or long QT syndrome. Concomitant use with potent CYP3A4 inhibitors or antiarrhythmics and other QT prolonging drugs. Concomitant use with potent CYP3A4 inducers.
Acute Overdose
Symptoms: Neutropenia, vomiting and drowsiness.
Management: Monitor patient and give supportive treatment.
Storage Condition
Store below 30° C.
Innovators Monograph
You find simplified version here Nilotinibum
Nilotinibum contains Nilotinib see full prescribing information from innovator Nilotinibum Monograph, Nilotinibum MSDS, Nilotinibum FDA label