Skip to Content

Nilotinib Dosage

Medically reviewed on August 27, 2018.

Applies to the following strengths: 200 mg; 150 mg; 50 mg

Usual Adult Dose for Chronic Myelogenous Leukemia

Philadelphia Chromosome Positive Chronic Myeloid Leukemia (Ph+ CML):
-Newly Diagnosed in Chronic Phase (Ph+ CML-CP): 300 mg orally twice a day, approximately 12 hours apart
-Resistant or Intolerant in Chronic Phase and Accelerated Phase (Ph+ CML-CP and Ph+ CML-AP): 400 mg orally twice a day, approximately 12 hours apart

Comments:
-This drug should be taken on an empty stomach; no food should be consumed for at least 2 hours before the dose and for at least 1 hour after the dose is taken.
-This drug may be given in combination with hematopoietic growth factors (e.g., erythropoietin or G-CSF), hydroxyurea, or anagrelide if clinically indicated.

Uses:
-For newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
-For chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) resistant or intolerant to prior therapy that included imatinib

Usual Pediatric Dose for Chronic Myelogenous Leukemia

1 year and older:
Philadelphia Chromosome Positive Chronic Myeloid Leukemia (Ph+ CML):
-Newly Diagnosed in Chronic Phase (Ph+ CML-CP) or Resistant or Intolerant in Chronic Phase and Accelerated Phase (Ph+ CML-CP and Ph+ CML-AP): 230 mg/m2 (rounded to the nearest 50 mg dose [to a maximum single dose of 400 mg]) orally twice a day, approximately 12 hours apart; continue if clinical benefit is observed or until unacceptable toxicity occurs

Comments:
-This drug should be taken on an empty stomach; no food should be consumed for at least 2 hours before the dose and for at least 1 hour after the dose is taken.
-This drug may be given in combination with hematopoietic growth factors (e.g., erythropoietin or G-CSF), hydroxyurea, or anagrelide if clinically indicated.

Uses:
-For pediatric patients 1 year or older with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
-For pediatric patients 1 year or older with chronic phase Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior tyrosine-kinase inhibitor (TKI) therapy

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

DOSE ADJUSTMENTS FOR ADULT PATIENTS WITH HEPATIC IMPAIRMENT:
Newly diagnosed Ph+ CML in chronic phase:
-Mild, moderate or severe hepatic impairment (Child-Pugh A, B, or C): Reduce dose to 200 mg twice a day; may increase to 300 mg twice a day based on tolerability
Resistant or intolerant Ph+ CML in chronic phase or accelerated phase:
-Mild or moderate hepatic impairment (Child-Pugh A or B): Reduce dose to 300 mg twice a day; may increase to 400 mg twice a day based on tolerability
-Severe hepatic impairment (Child-Pugh C): Reduce dose to 200 mg twice a day followed by a sequential dose escalation to 300 mg twice a day and then to 400 mg twice a day based on tolerability

Dose Adjustments

DISCONTINUATION OF THERAPY AFTER A SUSTAINED MOLECULAR RESPONSE (MR4.5) ON THIS DRUG:
-Eligibility for Discontinuation of Therapy:
---Ph+ CML-CP patients with typical BCR-ABL transcripts who have been taking this drug for a minimum of 3 years and have achieved a sustained molecular response (MR4.5, corresponding to = BCR-ABL/ABL less than or equal to 0.0032% IS) may be eligible for therapy discontinuation.
-Patients with typical BCR-ABL transcripts (i.e., 13a2/b2a2 or e14a2/b3a2) who achieve the sustained MR4.5 criteria are eligible for discontinuation of therapy. Patients should continue to be monitored for possible loss of molecular remission after therapy discontinuation.
-Consider discontinuation of therapy in patients with newly diagnosed Ph+ CML-CP who have: Been treated with this drug for at least 3 years; OR maintained a molecular response of at least MR4.0 (corresponding to = BCR-ABL/ABL less than or equal to 0.01% IS) for one year prior to discontinuation of therapy; OR achieved an MR4.5 for the last assessment taken immediately prior to discontinuation of therapy; OR have been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2); OR have no history of accelerated phase or blast crisis; OR have no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.
-Consider discontinuation of treatment in patients with Ph+ CML-CP that are resistant or intolerant to treatment with imatinib who have achieved a sustained molecular response (MR4.5) on this drug who have: Been treated with this drug for a minimum of 3 years; OR have been treated with imatinib only prior to treatment with this drug; OR have achieved a molecular response of MR4.5 (corresponding to = BCR-ABL/ABL less than or equal to 0.0032% IS); OR have sustained an MR4.5 for a minimum of one year immediately prior to discontinuation of therapy; OR have been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2); OR have no history of accelerated phase or blast crisis; OR have no history of prior attempts of therapy-free remission discontinuation that resulted in relapse.
-Monitor BCR-ABL transcript levels and complete blood count with differential in patients who have discontinued therapy monthly for one year, then every 6 weeks for the second year, and every 12 weeks thereafter.
-Upon the loss of MR4.0 (corresponding to = BCR-ABL/ABL less than or equal to 0.01%IS) during the therapy-free phase, monitor BCR-ABL transcript levels every 2 weeks until BCR-ABL levels remain lower than major molecular response (MMR, corresponding to MR3.0 or = BCR-ABL/ABL less than or equal to 0.1%IS) for 4 consecutive measurements. The patient can then proceed to the original monitoring schedule.

REINITIATION OF THERAPY IN PATIENTS WHO LOSE MOLECULAR RESPONSE AFTER DISCONTINUATION OF THERAPY WITH THIS DRUG:
-Newly diagnosed patients who lose MMR should reinitiate therapy within 4 weeks at the dose level prior to discontinuation of therapy. Patients who reinitiate therapy should have their BCR-ABL transcript levels monitored monthly until major molecular response is reestablished and every 12 weeks thereafter.

QT INTERVAL PROLONGATION:
ECGs with QTc greater than 480 msec:
-Stop this drug; analyze serum potassium and magnesium; if below lower limit of normal, correct with supplements to within normal limits. Review concomitant medication usage.
-Resume within 2 weeks at prior dose if QTcF returns to less than 450 msec and to within 20 msec of baseline.
-If QTcF is between 450 msec and 480 msec after 2 weeks, reduce the dose to 400 mg once a day.
-If, following dose-reduction to 400 mg once a day, QTcF returns to greater than 480 msec, discontinue this drug.
-Repeat ECG approximately 7 days after any dose adjustment.

MYELOSUPPRESSION:
-Withhold or dose reduce for hematological toxicities (e.g., neutropenia, thrombocytopenia) that are not related to underlying leukemia.

NEUTROPENIA AND THROMBOCYTOPENIA:
-Adult patients with newly diagnosed P+ CML in chronic phase at 300 mg twice daily OR resistant or intolerant Ph+ CML in chronic phase or accelerated phase at 400 mg twice daily with Absolute Neutrophil Count (ANC) less than 1 x 10(9)/L and/or platelet counts less than 50 x 10(9)/L:
-Stop this drug and monitor blood counts.
-Resume within 2 weeks at prior dose if ANC is greater than 1 x 10(9)/L and platelets greater than 50 x 10(9)/L.
-If blood counts remain low for more than 2 weeks, reduce dose to 400 mg once a day.
-Pediatric patients with newly diagnosed P+ CML in chronic phase at 230 mg/m2 twice daily OR resistant or intolerant Ph+ CML in chronic phase or accelerated phase at 230 mg/m2 twice daily with ANC less than 1 x 10(9)/L and/or platelet counts less than 50 x 10(9)/L:
-Stop this drug and monitor blood counts.
-Resume within 2 weeks at prior dose if ANC is greater than 1.5 x 10(9)/L and platelets greater than 75 x 10(9)/L.
-If blood counts remain low for more than 2 weeks, reduce dose to 230 mg/m2 once a day.
-If the event occurs after dose reduction, consider discontinuing therapy.

NON-HEMATOLOGICAL LABORATORY ABNORMALITIES:
-PATIENTS WITH GRADE 3 OR GREATER ELEVATIONS OF SERUM LIPASE OR AMYLASE:
Adults:
-Withhold this drug and monitor serum lipase or amylase.
-Resume therapy at 400 mg once a day if serum lipase or amylase when elevations return to Grade 1 or less.
Pediatric Patients:
-Withhold this drug until the event returns Grade 1 or less.
-Resume therapy at 230 mg/m2 once daily if prior dose was 230 mg/m2 twice daily; discontinue therapy if prior dose was 230 mg/m2 once daily.
-ELEVATED BILIRUBIN GREATER THAN OR EQUAL TO GRADE 3 IN ADULT PATIENTS AND GREATER THAN OR EQUAL TO GRADE 2 IN PEDIATRIC PATIENTS:
Adults:
-Withhold this drug and monitor bilirubin.
-Resume therapy at 400 mg once daily if bilirubin returns to less than or equal to Grade 1.
Pediatric Patients:
-Withhold this drug until the event returns to less than or equal to Grade 1.
-Resume therapy at 230 mg/m2 once daily if prior dose was 230 mg/m2 twice daily; discontinue therapy if prior dose was 230 mg/m2 once daily, and recovery to Grade 1 or less takes longer than 28 days.
-ELEVATED HEPATIC TRANSAMINASES GREATER THAN OR EQUAL TO GRADE 3:
Adults:
-Withhold this drug and monitor hepatic transaminases.
-Resume therapy at 400 mg once daily if hepatic transaminases returns to Grade 1 or less.
Pediatric Patients:
-Withhold this drug until the event returns to Grade 1 or less.
-Resume therapy at 230 mg/m2 once daily if prior dose was 230 mg/m2 twice daily; discontinue therapy if prior dose was 230 mg/m2 once daily, and recovery to Grade 1 or less takes longer than 28 days.

DOSE MODIFICATIONS FOR OTHER NON-HEMATOLOGIC TOXICITIES:
-OTHER CLINICALLY MODERATE OR SEVERE NON-HEMATOLOGIC TOXICITY:
Adults:
-Withhold this drug until toxicities resolve.
-Resume therapy at 400 mg once daily if previous dose was 300 mg twice daily in adult patients newly diagnosed with CML-CP or 400 mg twice daily in adult patients with resistant or intolerant CML-CP and CML-AP.
-Discontinue therapy if the prior dose was 400 mg once daily in adults.
-If clinically appropriate, consider re-escalation of the dose to 300 mg (newly diagnosed Ph+ CML-CP) or 400 mg (resistant or intolerant Ph+ CML-CP and Ph + CML-AP) twice a day.
Pediatric Patients:
-Withhold this drug until toxicities resolve.
-Resume therapy at 230 mg/m2 once daily if previous dose was 230 mg/m2 twice daily; discontinue therapy if prior dose was 230 mg/m2 once daily.
-If clinically appropriate, consider re-escalation of the dose to 230 mg/m2 twice daily.

STRONG CYP450 3A4 INHIBITORS (INCLUDING GRAPEFRUIT PRODUCTS):
-Avoid concomitant use; if treatment with a strong CYP450 3A4 inhibitor is required, interrupt this drug.
-If concomitant use is required, consider reducing dose to 300 mg once a day in resistant or intolerant Ph+ CML-CP and Ph+ CML-AP or to 200 mg once a day in newly diagnosed Ph+ CML-CP; monitor closely for QT interval prolongation.
-If the strong CYP450 3A4 inhibitor is discontinued, allow a washout period before adjusting dose upward.
-For patients who cannot avoid use of strong CYP450 3A inhibitors, monitor closely for prolongation of the QT interval.

Precautions

US BOXED WARNING: QT PROLONGATION AND SUDDEN DEATHS:
-This drug prolongs the QT interval. Prior to drug administration and periodically during therapy, monitor for hypokalemia or hypomagnesemia and correct deficiencies.
-Obtain ECGs to monitor the QTc at baseline, 7 days after initiation, periodically thereafter, and following any dose adjustments.
-Sudden deaths have been reported in patients receiving this drug. Do not administer to patients with hypokalemia, hypomagnesemia, or long QT syndrome.
-Avoid concomitant use of drugs known to prolong the QT interval and strong CYP450 3A4 inhibitors.
-Avoid food 2 hours before and 1 hour after taking the dose.

CONTRAINDICATIONS:
-Hypokalemia
-Hypomagnesemia
-Long QT syndrome

Safety and efficacy have not been established in patients younger than 1 year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
-Take without food; do not consume food for at least 2 hours before the dose and for at least 1 hour after the dose is taken.
-Swallow capsules whole with water.
-If unable to swallow capsules, disperse the contents of each capsule in 1 teaspoon of applesauce and swallow the mixture immediately (within 15 minutes); do not store for future use.
-Missed dose: If a dose is missed, take the next scheduled dose at its regular time; two doses should not be taken at the same time.

Storage requirements:
-Keep in original package to protect from moisture.
-Do not store above 30 degrees Celsius.

General:
-The effectiveness of this drug is based on major molecular response and cytogenetic response rates for newly diagnosed Ph+CML-CP, and on hematologic and cytogenetic response rates for resistant or intolerant Ph+CML-CP and Ph+CML-AP patients.

Monitoring:
-Cardiovascular: ECG at baseline, 7 days after initiating therapy, following dose adjustments, and periodically during therapy.
-Hematologic: CBC every 2 weeks for the first 2 months and then monthly thereafter, or as clinically indicated.
-Hepatic: Hepatic function tests monthly or as clinically indicated.
-Metabolic: Chemistry panels, including electrolytes, calcium, and magnesium prior to initiating and periodically during therapy; glucose prior to initiating and periodically during first year of therapy and at least yearly during chronic therapy; serum lipase levels monthly or as clinically indicated; lipid profile prior to initiation, at 3 and 6 months after beginning therapy, and at least yearly.

Patient advice:
-Instruct patients to seek medical attention for signs and symptoms of pancreatitis, hepatotoxicity, abnormal bleeding, or unexplained weight gain or edema.
-Instruct the patient on the importance of taking this medication on an empty stomach and to not consume any food for 2 hours before the dose and 1 hour after the dose is taken.
-Inform patients that there are a number of potential drug interactions with this drug and they should speak with a healthcare professional before starting any new medications including over the counter medications and herbal supplements.
-Instruct patients to talk to their health care provider if they are pregnant, planning to become pregnant, or breastfeeding.
-Advise patients that this drug may cause side effects such as dizziness and visual problems that may affect their ability to drive and perform potentially hazardous activities such as operating machinery.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide