Nilotinib Dosage

This dosage information may not include all the information needed to use Nilotinib safely and effectively. See additional information for Nilotinib.

The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Chronic Myelogenous Leukemia

For use in patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase:
Initial dose: 300 mg orally twice daily, approximately 12 hours apart

For use in patients with chronic phase or accelerated phase Ph+ CML resistant to or intolerant to prior therapy that included imatinib:
Initial dose: 400 mg orally twice daily, approximately 12 hours apart

Treatment should continue as long as the patient does not show evidence of progression or unacceptable toxicity.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

If possible, alternative therapies should be considered. If nilotinib must be administered to this patient with liver dysfunction, a lower starting dose is recommended and QT interval should be monitored closely.

The initial dosage for patients with chronic phase or accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) resistant to or intolerant to prior therapy with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) liver dysfunction is 300 mg twice daily followed by dose escalation to 400 mg twice daily based on tolerability. The initial dose for patients with severe liver dysfunction (Child-Pugh Class C) is 200 mg twice daily followed by a sequential dose escalation to 300 mg twice daily and then to 400 mg twice daily based on tolerability.

The initial dosage for patients with newly diagnosed Philadelphia chromosome positive myelogenous leukemia (CML) chronic phase with mild, moderate, or severe liver dysfunction is 200 mg twice daily followed by dose escalation to 300 mg twice daily based on tolerability.

Elevated hepatic transaminases greater than or = Grade 3:
1) Withhold nilotinib, and monitor hepatic transaminases
2) Resume treatment at 400 mg once daily if hepatic transaminases return to less than or = Grade 1

Dose Adjustments

Dose adjustment may be required for hematologic and nonhematologic toxicities, and drug interactions.

Dose Adjustments for QT prolongation
ECGs with a QTc greater than 480 msec:
1) Withhold nilotinib, and perform an analysis of serum potassium and magnesium, and if below the lower limit of normal, correct with supplements to within normal limits. Concomitant medication usage must be reviewed.
2) Resume within 2 weeks at prior dose if QTcF returns to less than 450 msec and to within 20 msec of baseline.
3) If QTcF is between 450 msec and 480 msec after 2 weeks reduce the dose to 400 mg once daily.
4) If, following dose reduction to 400 mg once daily, QTcF returns to greater than 480 msec, nilotinib should be discontinued.
5) An ECG should be repeated approximately 7 days after any dose adjustment.

Myelosuppression: Nilotinib may need to be withheld and/or the dose of nilotinib may need to be reduced for hematological toxicities (neutropenia, thrombocytopenia) that are not related to underlying leukemia.
Dose Adjustments for Neutropenia and Thrombocytopenia

Newly diagnosed Ph+ CML in chronic phase at 300 mg twice daily and resistant or intolerant Ph+ CML in chronic phase or accelerated phase at 400 mg twice daily:
Absolute Neutrophil Count (ANC) less than 1.0 x 10(9)/L and/or platelet counts less than 50 x 10(9)/L:
1) Stop Nilotinib, and monitor blood counts
2) Resume within 2 weeks at prior dose if the ANC is greater than 1.0 x 10(9)/L and platelets are greater than 50 x 10(9)/L
3) If blood counts remain low for more than 2 weeks, reduce twice daily the dose to 400 mg once daily

Adjustments for selected nonhematologic laboratory abnormalities:

Elevated serum lipase or amylase greater than or = Grade 3:
1) Withhold nilotinib, and monitor serum lipase or amylase
2) Resume treatment at 400 mg once daily if serum lipase or amylase return to less than or = Grade 1.

Elevated bilirubin greater than or = Grade 3:
1) Withhold nilotinib, and monitor bilirubin
2) Resume treatment at 400 mg once daily if bilirubin return to less than or = Grade 1

Elevated hepatic transaminases greater than or = Grade 3:
1) Withhold nilotinib, and monitor hepatic transaminases
2) Resume treatment at 400 mg once daily if hepatic transaminases return to less than or = Grade 1

If other clinically significant moderate or severe nonhematologic toxicity develops, dosing should be withheld, and may be resumed at 400 mg once daily when the toxicity has resolved. If clinically appropriate, escalation of the dose back to 300 mg (newly diagnosed Ph+ CML-CP) or 400 mg (resistant or intolerant Ph+ CML-CP and CML-AP) twice daily should be considered.

Concomitant use with strong inhibitors of CYP450 3A4:
Grapefruit products and concomitant use of strong inhibitors of CYP450 3A4 should be avoided. Interruption of nilotinib therapy is recommended if treatment with any of these agents is necessary. If concomitant therapy with a strong CYP450 3A4 inhibitor is required, close monitoring for QT interval prolongation is suggested and a dose reduction to 300 mg once daily in patients with resistant or intolerant Ph+ CML or to 200 mg once daily in patients with newly diagnosed Ph+ CML-CP should be considered. However, there are no clinical data supporting this dose adjustment in patients receiving strong CYP450 3A4 inhibitors. When a strong inhibitor of CYP450 3A4 is discontinued, a washout period should be allowed to transpire prior to escalating the dose of nilotinib to the recommended dose.

Concomitant use with strong inducers of CYP450 3A4:
Concomitant use of nilotinib with St. John's Wort or strong inducers of CYP450 3A4 should be avoided. An increase in the dose of nilotinib when used concomitantly with these agents is unlikely to compensate for the loss of exposure.

Precautions

Nilotinib prolongs the QT interval. Sudden deaths have been reported in patients receiving nilotinib. The relative early occurrence of some of these deaths relative to the initiation of nilotinib suggests the possibility that ventricular repolarization abnormalities may have contributed to their occurrence. Nilotinib should not be used in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Hypokalemia and or hypomagnesemia must be corrected prior to nilotinib administration and should be periodically monitored. Drugs known to prolong the QT interval and strong CYP450 3A4 inhibitors should be avoided.

Nilotinib has been shown to prolong cardiac ventricular repolarization as measured by the QT interval on the surface ECG in a concentration-dependent manner. Prolongation of the QT interval can result in a type of ventricular tachycardia called Torsade de pointes, which may result in syncope, seizure, and/or death. An ECG should be obtained at baseline, seven days after initiation of therapy, after dose adjustments, and periodically thereafter.

Nilotinib may cause electrolyte abnormalities, including hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Electrolyte abnormalities should be corrected prior to initiating nilotinib therapy. Serum electrolytes should be monitored periodically throughout therapy.

Treatment with nilotinib can cause grade 3/4 thrombocytopenia, neutropenia and anemia. Complete blood counts should be performed every two weeks for the first 2 months and then monthly thereafter, or as clinically indicated. Myelosuppression has generally been reversible and usually managed by withholding nilotinib temporarily or dose reduction. Chemistry panels should be checked periodically.

Avoid concomitant use of grapefruit products and inhibitors or inducers of CYP450 3A4. If patients must be coadministered a strong CYP450 3A4 inhibitor, dose reduction should be considered and the QT interval should be monitored closely.

Food increases blood levels of nilotinib with a resultant increased potential for QT prolongation. Avoid food 2 hours before and 1 hour after a dose.

Use of nilotinib may cause an increase in serum bilirubin, AST/ALT, and alkaline phosphatase. Liver function tests are recommended monthly or as clinically indicated. Nilotinib should be used with caution in patients with liver dysfunction; a dose reduction and close monitoring of the QT interval are recommended in these patients.

The use of nilotinib can cause increases in serum lipase. Caution is recommended in patients with a previous history of pancreatitis. Serum lipase and lipid profile should be checked periodically. In case lipase elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis.

Tumor lysis syndrome has been reported. Malignant disease progression, elevated WBC counts and/or dehydration were present in the majority of these cases. Maintain adequate hydration and correct uric acid levels prior to initiating dasatinib therapy.

Patients with a total gastrectomy should have more frequent follow-up and if necessary a dosage increase may be considered.

Since the capsules contain lactose, nilotinib is not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

Nilotinib should not be used during pregnancy. Women should be advised not to become pregnant when taking nilotinib. Sexually active female patients should use effective contraception during treatment.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for nilotinib. It includes a Medication Guide and communication plan. Additional information is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.

The bioavailability of nilotinib is increased with food. No food should be consumed at least 2 hours before and at least one hour after the dose is taken.

The capsules should be swallowed whole with water. In patients unable to swallow capsules, the contents of each capsule may be dispersed in one teaspoon of applesauce (pureed apple) and immediately administered (within 15 minutes). The mixture should not be stored for future use.

If a dose is missed, the patient should not take a makeup dose, but should resume taking the next prescribed daily dose.

Complete blood counts should be performed every two weeks for the first two months and then monthly thereafter. Chemistry panels should be checked periodically. ECGs should be obtained at baseline, seven days after initiation, and periodically thereafter, as well as following dose adjustments.

Nilotinib may be given in combination with hematopoietic growth factors such as erythropoietin or GCSF if clinically indicated. Nilotinib may be given with hydroxyurea or anagrelide if clinically indicated.

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