• Newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase.
• Chronic or accelerated phase Ph+ CML in adult patients who are resistant or intolerant to prior treatment, including imatinib.
• Chronic or accelerated phase Ph+ CML in pediatric patients 1 yr who are resistant or intolerant to prior tyrosine-kinase inhibitor treatment.

Contraindicated in:

• Hypokalemia or hypomagnesemia
• Long QT syndrome
• Galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption (capsules contain lactose)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Electrolyte abnormalities; correct prior to administration to ↓ risk of arrhythmias
• Hepatic impairment (↓ dose required for Grade 3 elevated bilirubin, transaminases or lipase)
• Total gastrectomy (may need to ↑ dose or use alterative therapy)
• History of pancreatitis
• Patients with genetically reduced UGT1A1 activity (presence of UGT1A1*28 allele) (↑ risk of hyperbilirubinemia)
• Women of reproductive potential
• Pedi: May affect growth and development of children; safety and effectiveness not established in children <1 yr.

CV: hypertension, MI, palpitations, pericardial effusion, peripheral arterial disease, QT interval prolongation, TORSADES DE POINTES.

Derm: pruritus, rash, alopecia, flushing.

EENT: vertigo.

F and E: hyperkalemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia.

GI: ↑lipase, constipation, diarrhea, nausea, vomiting, abdominal discomfort, anorexia, ascites, dyspepsia, flatulence, hepatitis B virus reactivation, HEPATOTOXICITY.

Hemat: bleeding, myelosupression.

Metab: hyperglycemia.

MS: ↓growth, musculoskeletal pain.

Neuro: fatigue, headache, dizziness, paresthesia, STROKE.

Resp: pleural effusion, pulmonary edema.
Misc: fever, night sweats, tumor lysis syndrome.

Drug-Drug:

• StrongCYP3A4 inhibitors, including ketoconazole, itraconazole, voriconazole, clarithromycin, atazanavir, nelfinavir, ritonavir, and nefazodone, may ↑ levels and the risk of toxicity; avoid concurrent use, if possible; if concurrent use is necessary, ↓ nilotinib dose.
• StrongCYP3A4 inducers, including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine, may ↓ levels and effectiveness; avoid concurrent use.
• May ↑ levels and the risk of toxicity of CYP3A4 substrates, including atorvastatin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, lovastatin, midazolam, simvastatin, sirolimus, and tacrolimus.
• Concurrent use of other drugs that prolong QT interval; may ↑ risk of serious arrhythmias; avoid concurrent use.
• Proton pump inhibitors, H₂ receptor antagonists, and antacids may ↓ the bioavailability of nilotinib; avoid concurrent use of proton pump inhibitors; doses of H₂ receptor antagonists may be administered 10 hr before or 2 hr after nilotinib; doses of antacids may be administered 2 hr before or after nilotinib.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

• Grapefruit juice may ↑ levels and the risk of toxicity; avoid concurrent use.

• Capsules: 50 mg; 150 mg; 200 mg;

Newly Diagnosed Chronic Phase Ph+ Chronic Myelogenous Leukemia

• PO (Adults): 300 mg twice daily; treatment discontinuation may be considered in patients who have received nilotinib for 3 yr and achieved a sustained molecular response; if patients lose molecular response after discontinuing therapy, restart nilotinib within 4 wk at the dose level prior to discontinuation; Concurrent use of strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, or voriconazole): 200 mg once daily.
• PO (Children 1 yr): 230 mg/m² twice daily (max single dose = 400 mg) until disease progression or unacceptable toxicity; treatment discontinuation may be considered in patients who have received nilotinib for 3 yr and achieved a sustained molecular response; if patients lose molecular response after discontinuing therapy, restart nilotinib within 4 wk at the dose level prior to discontinuation; Concurrent use of strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, or voriconazole): 200 mg once daily.

Resistant or Intolerant Chronic or Accelerated Phase Ph+ Chronic Myelogenous Leukemia

• PO (Adults): 400 mg twice daily; treatment discontinuation may be considered in patients who have received nilotinib for 3 yr and achieved a sustained molecular response; if patients lose molecular response after discontinuing therapy, restart nilotinib within 4 wk at the dose level prior to discontinuation; Concurrent use of strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, or voriconazole): 300 mg once daily.
• PO (Children 1 yr): 230 mg/m² twice daily (max single dose = 400 mg) until disease progression or unacceptable toxicity; treatment discontinuation may be considered in patients who have received nilotinib for 3 yr and achieved a sustained molecular response; if patients lose molecular response after discontinuing therapy, restart nilotinib within 4 wk at the dose level prior to discontinuation; Concurrent use of strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, or voriconazole): 200 mg once daily.

Tasigna

• Inhibits kinases, which may be produced by malignant cell lines.

• Inhibits production of malignant cells lines with decreased proliferation of leukemic cells.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors, kinase inhibitors

Absorption: Well absorbed following oral administration. Levels are significantly ↑ by food.

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP3A4 isoenzyme to inactive metabolites. Primarily excreted in the feces (93%), with 69% being excreted unchanged.

Half-life: 17 hr.

(plasma concentrations)

• Instruct patient to take nilotinib as directed, approximately 12 hr apart. If a dose is missed, skip dose and resume taking next prescribed dose. Nilotinib is a long-term treatment; do not stop medication or change dose without consulting health care professional. Advise patient to read the Medication Guide before starting and with each Rx refill, in case of changes.
• Advise patient to avoid grapefruit, grapefruit juice, or products with grapefruit extract during therapy; may cause toxicity.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort, during therapy.
• Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; signs of fluid retention; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use a soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate bleeding.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Discuss the possibility of hair loss with patient. Explore methods of coping. Regrowth usually occurs 2–3 mo after discontinuation of therapy.
• May cause fetal harm. Advise women of reproductive potential to use highly effective contraception during therapy and for at least 14 days following last dose and to avoid breastfeeding for at least 14 days following last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.

ni-LO-ti-nib