Nilotinib

Nilotinib capsules are a kinase inhibitor indicated for the treatment of: Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. ( 1.1 ) Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib. ( 1.2 ) Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy. …

• Recommended Adult Dose: Newly diagnosed Ph+ CML-CP: 300 mg orally twice daily
• Resistant or intolerant Ph+ CML-CP and CML-AP: 400 mg orally twice daily
• Recommended Pediatric Dose: Newly Diagnosed Ph+ CML-CP or Ph+ CML-CP resistant or intolerant to prior TKI therapy: 230 mg/m 2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg)
• See Dosage and Administration for full dosing instructions and dose-reduction instructions for toxicity
• Reduce starting dose in patients with baseline hepatic impairment
• Eligible newly diagnosed adult patients with Ph+ CML-CP who have received nilotinib capsules for a minimum of 3 years and have achieved a sustained molecular response (MR4.5) and patients with Ph+ CML-CP resistant or intolerant to imatinib who have received nilotinib capsules for at least 3 years and have achieved a sustained molecular response (MR4.5) may be considered for treatment discontinuation
• Recommended Dosage Dose nilotinib capsules twice daily at approximately 12-hour intervals on an empty stomach
• No food should be consumed for at least 2 hours before the dose is taken and for at least 1 hour after the dose is taken
• Advise patients to swallow the capsules whole with water [ see Boxed Warning , Clinical Pharmacology ]
• For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in 1 teaspoon of applesauce (puréed apple). …

Capsules: 50 mg light yellow opaque colour body and red opaque colour cap imprinted with “MN5” with black ink. 150 mg red opaque colour body and red opaque colour cap imprinted with“MN4” with black ink. 200 mg light yellow opaque colour body and light yellow opaque colour cap imprinted with “MN3” with black ink. Capsules: 50 mg, 150 mg, and 200 mg ( 3 )

• The safety and effectiveness of nilotinib have been established
• In pediatric patients greater than or equal to 1 year of age with newly diagnosed and resistant or intolerant Ph+ CML in chronic phase [see Clinical Studies ]
• There are no data for pediatric patients under 2 years of age
• Use of nilotinib
• In pediatric patients 1 year to less than 2 years of age with newly diagnosed or resistant or intolerant Ph+ CML in chronic phase is supported by efficacy
• In pediatric patients 2 to 6 years of age for these indications. …

In the clinical trials of nilotinib (patients with newly diagnosed Ph+ CML-CP and resistant or intolerant Ph+ CML-CP and CML-AP), approximately 12% and 30% of patients were 65 years or over, respectively. Patients with newly diagnosed Ph+ CML-CP: There was no difference in major molecular response between patients aged less than 65 years and those greater than or equal to 65 years. …

• Advise the patient to read the FDA-approved patient labeling (Medication Guide)
• A Medication Guide is required for distribution with nilotinib
• The complete text of the Medication Guide is reprinted at the end of this document
• Myelosuppression Advise patients that treatment with nilotinib can cause serious thrombocytopenia, neutropenia, and anemia
• Advise patients to seek immediate medical attention if symptoms suggestive of low blood counts occur, such as fever, chills or other signs of infection, unexplained bleeding or bruising, or unexplained weakness or shortness of breath [ see Warnings and Precautions ]. …

• Nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome [ see Boxed Warning ]
• Nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome

Strong CYP3A Inhibitors : Avoid concomitant use with nilotinib, or reduce nilotinib dose if coadministration cannot be avoided. ( 7.1 ) Strong CYP3A Inducers : Avoid concomitant use with nilotinib. ( 7.1 ) Proton Pump Inhibitors : Use short-acting antacids or H2 blockers as an alternative to proton pump inhibitors. ( 7.1 ) 7.1 Effect of Other Drugs on Nilotinib Strong CYP3A Inhibitors Concomitant use with a strong CYP3A inhibitor increased nilotinib concentrations compared to nilotinib alone [ see Clinical Pharmacology (12.3) ] , which may increase the risk of nilotinib toxicities. Avoid concomitant use of strong CYP3A inhibitors with nilotinib. …

Myelosuppression : Monitor complete blood count (CBC) during therapy and manage by treatment interruption or dose reduction. ( 5.1 ) Cardiac and Arterial Vascular Occlusive Events : Evaluate cardiovascular status, monitor and manage cardiovascular risk factors during nilotinib therapy. ( 5.4 ) Pancreatitis and Elevated Serum Lipase : Monitor serum lipase; if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis. ( 5.5 ) Hepatotoxicity : Monitor hepatic function tests monthly or as clinically indicated. …

The following clinically significant adverse reactions can occur with nilotinib and are discussed in greater detail in other sections of labeling: Myelosuppression [ see Warnings and Precautions (5.1) ] QT Prolongation [ see Boxed Warning , Warnings and Precautions (5.2) ] Sudden Deaths [ see Boxed Warning , Warnings and Precautions (5.3) ] Cardiac and Arterial Vascular Occlusive Events [ see Warnings and Precautions (5.4) ] Pancreatitis and Elevated Serum Lipase [ see Warnings and Precautions (5.5) ] Hepatotoxicity [ see Warnings and Precautions (5.6) ] Electrolyte Abnormalities [ see Boxed Warning , Warnings and Precautions (5.7) ] Hemorrhage [ see Warnings and Precautions (5.9) ] Fluid Re …

8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, nilotinib can cause fetal harm when administered to a pregnant woman [ see Clinical Pharmacology (12.1) ] . There are no available data in pregnant women to inform the drug-associated risk. …

Overdose with nilotinib has been reported, where an unspecified number of nilotinib capsules were ingested in combination with alcohol and other drugs. Events included neutropenia, vomiting, and drowsiness. In the event of overdose, observe the patient and provide appropriate supportive treatment.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.