Nilotinib

Chronic Myeloid Leukemia (CML), Philadelphia chromosome-positive (Ph+), newly diagnosed

Chronic Myeloid Leukemia (CML), Philadelphia chromosome-positive (Ph+), newly diagnosed

Chronic Myeloid Leukemia (CML), Philadelphia chromosome-positive (Ph+), chronic phase (CP), resistant or intolerant to prior therapy including imatinib

Chronic Myeloid Leukemia (CML), Philadelphia chromosome-positive (Ph+), chronic phase (CP), resistant or intolerant to prior therapy including imatinib

Chronic Myeloid Leukemia (CML), Philadelphia chromosome-positive (Ph+), accelerated phase (AP), resistant or intolerant to prior therapy including imatinib

Chronic Myeloid Leukemia (CML), Philadelphia chromosome-positive (Ph+), accelerated phase (AP), resistant or intolerant to prior therapy including imatinib

Myelosuppression

Incidence: Reported in the clinician-authored database; frequency not established

QT prolongation

Incidence: Reported in the clinician-authored database; frequency not established

Pancreatitis

Incidence: Reported in the clinician-authored database; frequency not established

Hepatotoxicity

Incidence: Reported in the clinician-authored database; frequency not established

Fluid retention

Incidence: Reported in the clinician-authored database; frequency not established

Cardiovascular events

Incidence: Reported in the clinician-authored database; frequency not established

Rash

Incidence: Reported in the clinician-authored database; frequency not established

Diarrhea

Incidence: Reported in the clinician-authored database; frequency not established

FDA BOXED WARNING — QT PROLONGATION AND SUDDEN DEATH — serious

Symptoms: FDA BOXED WARNING — QT PROLONGATION AND SUDDEN DEATH: Nilotinib (Tasigna) prolongs the QT interval, and sudden deaths have been reported in patients taking it. Before starting nilotinib and periodically during treatment, the prescriber will monitor for and correct low potassium or low magnesium levels. Nilotinib must not be given to patients with hypokalemia, hypomagnesemia, or long QT syndrome. Avoid other medicines known to prolong the QT interval and strong CYP3A4 inhibitors, and avoid taking nilotinib with food (take at least 2 hours after and 1 hour before eating) — taking it with food or these interacting drugs can significantly worsen QT prolongation. ECG monitoring is required at baseline, about 7 days after starting, and periodically thereafter, and after any dose change.

Action: Follow the urgency stated and seek prompt or emergency care when indicated.

May increase risk of liver and pancreatic toxicity — serious

Symptoms: May increase risk of liver and pancreatic toxicity. Can cause severe myelosuppression (low blood counts). May cause birth defects (embryo-fetal toxicity); avoid use in pregnancy and use effective contraception during treatment.

Action: Follow the urgency stated and seek prompt or emergency care when indicated.

Contraindications recorded in the clinician database — serious

Symptoms: Contraindications recorded in the clinician database: Contraindicated in patients with hypersensitivity to nilotinib or excipients, and those with long QT syndrome. Use caution in patients with cardiac disease, electrolyte imbalances, hepatic impairment, or pancreatitis. Monitor for myelosuppression, liver dysfunction, and metabolic disturbances.

Action: Follow the urgency stated and seek prompt or emergency care when indicated.

Pregnancy

The FDA-approved Tasigna (nilotinib) prescribing information states nilotinib can cause fetal harm when given to a pregnant woman: animal studies showed embryo-fetal lethality and skeletal variations at maternal exposures roughly 0.5-2 times the human recommended dose. Women should be advised of the potential fetal risk and use effective contraception during treatment and for 14 days after the final dose.

Breastfeeding

The FDA-approved Tasigna (nilotinib) prescribing information advises women not to breastfeed during treatment and for 14 days after the last dose. Human milk data are not available, but nilotinib was detected in the milk of lactating rats at levels roughly twice plasma levels; because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended.

Children

Frequency: Not applicable. Weight Based: Not recommended for pediatric use. Max Daily Dose: Not applicable. Max Single Dose: Not applicable. Age Restrictions: Safety not established in children

Renal_impairment

Renal impairment: the FDA-approved label states the effect of renal impairment on nilotinib pharmacokinetics is unknown, and no specific renal dose adjustment is recommended. Hepatic impairment: the label recommends specific dose reductions decided by the prescriber. For newly diagnosed chronic-phase CML, the starting dose is reduced to 200 mg twice daily in mild, moderate, or severe hepatic impairment, with the prescriber able to increase to 300 mg twice daily based on tolerability. For resistant/intolerant chronic- or accelerated-phase CML, the dose is reduced to 300 mg twice daily in mild-to-moderate hepatic impairment, or 200 mg twice daily in severe hepatic impairment, with possible increases at the prescriber's discretion based on tolerability.

Hepatic_impairment

Renal impairment: the FDA-approved label states the effect of renal impairment on nilotinib pharmacokinetics is unknown, and no specific renal dose adjustment is recommended. Hepatic impairment: the label recommends specific dose reductions decided by the prescriber. For newly diagnosed chronic-phase CML, the starting dose is reduced to 200 mg twice daily in mild, moderate, or severe hepatic impairment, with the prescriber able to increase to 300 mg twice daily based on tolerability. For resistant/intolerant chronic- or accelerated-phase CML, the dose is reduced to 300 mg twice daily in mild-to-moderate hepatic impairment, or 200 mg twice daily in severe hepatic impairment, with possible increases at the prescriber's discretion based on tolerability.

United States

• Tasigna50 mg, 150 mg, 200 mg · novartis pharmaceuticals corporation
• DANZITEN71 mg, 95 mg · azurity pharmaceuticals, inc.
• CAVHANZA60 mg, 80 mg · cycle pharmaceuticals ltd

Canada

• TASIGNA