Drug information of Nilotinib

Mechanism of effect

Binds to and stabilizes th.e inactive conformation of the kinase domain of Abl protein

Pharmacodynamic

Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML)

Pharmacokinetics

C max is reached 3 h after oral administration. Steady state is reached in approximately 8 days. Bioavailability is increased when given with a meal. Compared with fasting, the AUC is increased by 82% when given 30 min after a high-fat meal. Serum protein binding is approximately 98%. The main metabolic pathways are oxidation and hydroxylation. The metabolites are inactive Elimination half-life is approximately 17 h. Approximately 93% of the administered dose is eliminated in feces within 7 days

Drug indications

Ph+ CML

Dosage

Adults PO 400 mg twice daily for resistant or intolerant CML; 300 mg twice daily for newly diagnosed CML

Drug contraindications

Hypokalemia , hypomagnesemia , long QT syndrome

Side effects

Migraine , nausea , Headache , insomnia , chest pain , Dermatit , dry mouth , constipation , abdominal pain , decreased appetite , dizziness , vomiting , fatigue , Blurred vision , Hepatic dysfunction , rash , flushing , Bradycardia , Depression , Diarrhea , Dyspnea , asthenia , Night sweats , urticaria , pruritus , Hypertension , Throat irritation , thrombocytopenia , neutropenia , lymphopenia , anemia , Erythema , cardiac arrhythmias , palpitations , paresthesia , acne , dyspepsia , Urinary tract infection , edema , Peripheral edema , Cough , Hyperthyroidism , hypothyroidism , weight decrease , myalgia , Hypomagnesemia , Bone pain , blood in stool , Alopecia , anorexia , malaise , conjunctivitis , Gynecomastia , gastritis , hyperlipidemia , Arthralgia , pain in the extremities , back pain , Upper respiratory tract infection , Tremor , Hyper-cholesteremia , Hyperkalemia , Hypokalemia , Hyperglycemia , Hypocalcemia , hemorrhage , stomatitis , dry eyes , Nasopharyngitis , eye irritation , hypercalcemia , hyponatremia , pneumonia , upper stomach pain , acute pancreatitis , ECG prolonged QT , coronary artery disease, , cyanosis , hematoma , hypertensive crisis , pericardial effusion , disturbance in attention , jaundice , diabetes mellitus

Interactions

Ergotamine-C , Esomeprazole , Ipratropium bromide , Ifosfamide , Budesonide , Promethazine , Primidone , Pantoprazole , Tamsulosin , Trastuzumab , Topotecan , Daunorubicin , Domperidone , Rabeprazole , Salbutamol , Fluticasone propinate , Glibenclamide , Lansoprazole , Aluminium gel , Amiodarone , Itraconazole , Imatinib , Doxepin , Cimetidine , Quinidine , Midazolam , Hydroxychloroquine , Voriconazole , Ketoconazole , Clarithromycin , Clozapine , Sotalol , Phenobarbital , Phenytoin , Lithium carbonate , Maprotiline , Moxifloxacin , Carbamazepine , Disulfiram , Bisoprolol , Rifabutin , Ranolazine , Toremifene , Prochlorperazine , Histrelin , ISOPROTERENOL , ritonavir , mitotane , Dolasetron , Palonosetron , vandetanib , Droperidol , sparfloxacin , Procainamide , Mefloquine , Indapamide , Dofetilide , Inotuzumab‎ , Promazine , Vasopressin , Arsenic trioxide , Halofantrine , Grepafloxacin , Mibefradil , cobicistat , Delavirdine , Terfenadine , Abarelix , Asenapine , Alfuzosin , Pazopanib , Perflutren , Pimavanserin , Dexlansoprazole , lenvatinib , Apalutamide , Edoxaban , Pitolisant , Entrectinib , Lorlatinib , gilteritinib , glasdegib , riociguat , oleandomycin , Bepridil , bedaquiline , Gefitinib , Dasatinib , Gemtuzumab , Remdesivir , lasmiditan , vemurafenib , Meningococcal conjugate vaccine , Fidaxomicin , Halaven

Alerts

1-QT interval prolongation and sudden deaths have been reported. 2- Do not use nilotinib in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Correct hypokalemia and hypomagnesemia prior to starting therapy and monitor serum levels periodically. 3-Avoid drugs known to prolong the QT interval and strong CYP3A4 inhibitors. Patients should avoid food 2 h before and 1 h after taking a dose. 4- A dose reduction is recommended in patients with hepatic impairment. Obtain ECGs at baseline, 7 days after initiation, and periodically thereafter, as well as following any dose adjustments

Points of recommendation

• For oral use only. Capsules should be swallowed whole with water only. • Do not administer with food. Food should not be consumed for at least 2 h before or at least 1 h after a dose is taken. • Administer twice daily at approximately 12-h intervals. • May be given in combination with hematopoietic growth factors, such as erythropoietin or granulocyte colony-stimulating factor, or with hydroxyurea or anagrelide if clinically indicated. • For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in 1 tsp of applesauce (pureed apple). The mixture should be taken immediately (within 15 min) and should not be stored for future use.

Pregnancy level

D

Related drugs

bosutinib , zanubrutinib , tucatinib