nilotinib

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3 hr	12 hr

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 arrhythmias0
;
Hepatic impairment (↓ dose if 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);
Rep: Women of reproductive potential;
Pedi: May affect growth and development of children; safety and effectiveness not established in children <1 yr.

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, voriconazole, clarithromycin, atazanavir, nelfinavir, ritonavir, and nefazodone, may ↑ levels and risk of toxicity; avoid concurrent use. 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 risk of toxicity of CYP3A4 substrates, including atorvastatin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, lovastatin, midazolam, simvastatin, sirolimus, and tacrolimus.
QT interval prolonging drugs may ↑ risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
Proton pump inhibitors, H2 receptor antagonists, and antacids may ↓ absorption 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 risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

Capsules should NOT be substituted with tablets on a milligram per milligram basis.

Newly Diagnosed Chronic Phase Ph+ Chronic Myelogenous Leukemia

PO (Adults ): Capsules: 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. Tablets: 142 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): Capsules: 200 mg once daily; Tablets: 95 mg once daily.
PO (Children ≥1 yr): Capsules: 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.

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment: Capsules: 200 mg twice daily; may ↑ to 300 mg twice daily if tolerated; Tablets: 95 mg twice daily; may ↑ to 142 mg twice daily if tolerated.

Hepatic Impairment

PO (Children ≥1 yr): Mild, moderate, or severe hepatic impairment: Capsules: 200 mg twice daily; may ↑ to 300 mg twice daily if tolerated.

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

PO (Adults ): Capsules: 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. Tablets: 190 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): Capsules: 300 mg once daily; Tablets: 142 mg once daily.
PO (Children ≥1 yr): Capsules: 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.

Hepatic Impairment

(Adults ): Mild or moderate hepatic impairment: Capsules: 300 mg twice daily; may ↑ to 400 mg twice daily if tolerated; Tablets: 142 mg twice daily; may ↑ to 190 mg twice daily if tolerated. Severe hepatic impairment: Capsules: 200 mg twice daily; may ↑ to 300 mg twice daily and eventually to 400 mg twice daily if tolerated; Tablets: 95 mg twice daily; may ↑ to 142 mg twice daily and eventually 190 mg twice daily if tolerated.

Hepatic Impairment

(Children ≥1 yr): Mild or moderate hepatic impairment: Capsules: 300 mg twice daily; may ↑ to 400 mg twice daily if tolerated. Severe hepatic impairment: Capsules: 200 mg twice daily; may ↑ to 300 mg twice daily and eventually to 400 mg twice daily if tolerated.

Hepatic Impairment

PO (Adults and Children ≥1 yr): Mild or moderate hepatic impairment: 300 mg twice daily; may ↑ to 400 mg twice daily if tolerated. Severe hepatic impairment: 200 mg twice daily; may ↑ to 300 mg twice daily and eventually to 400 mg twice daily if tolerated.

Availability ⬆ ⬇

(Generic available)

Capsules (Tasigna): 50 mg; 150 mg; 200 mg
Tablets (Danziten): 71 mg; 95 mg

Assessment ⬆ ⬇

Monitor ECG to assess the QTc interval at baseline, 7 days after initiation of therapy, after any dose adjustment, and periodically thereafter. If QTc interval >480 msec, hold nilotinib and check serum potassium and magnesium. If serum potassium and magnesium below lower limit of normal, correct to normal with supplements. Review concurrent medications for effects on electrolytes. If QTc interval returns to <450 msec and within 20 msec of baseline within 2 wk, return to prior dose. If QTc interval <480 msec and >450 msec after 2 wk,↓ dose to 400 mg once daily. Following dose ↓ to 400 mg once daily, if QTc interval returns to >480 msec, discontinue nilotinib.
Monitor for myelosuppression. Assess for bleeding (bleeding gums; bruising; petechiae; blood in stools, urine, or emesis); avoid IM injections and taking rectal temperatures if platelet count is low. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for fatigue, dyspnea, and orthostatic hypotension.
Monitor for tumor lysis syndrome (high WBC counts, hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, dehydration). Prevent by maintaining adequate hydration and correcting uric acid levels prior to starting nilotinib.
Monitor for signs/symptoms of severe fluid retention (unexpected rapid weight gain or swelling) and for signs/symptoms of respiratory or cardiac compromise (shortness of breath) periodically during therapy; evaluate cause and treat patients as needed.
Pedi: Monitor growth and development in pediatric patients receiving nilotinib.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor serum electrolytes prior to and periodically during therapy. May cause hypokalemia, hypomagnesemia, hypophosphatemia, hyperkalemia, hypocalcemia, hyperglycemia, and hyponatremia.
- Monitor CBC every 2 wk for 1st 2 mo and monthly thereafter or as indicated. If ANC <1.0 × 10⁹ cells/L and/or platelets <50 × 10⁹cells/L, hold nilotinib and monitor blood counts. Resume within 2 wk at prior dose if ANC recover to >1.0 × 10⁹cells/L and platelets >50 × 10⁹cells/L. If blood counts remain low for >2 wk, ↓ dose to 400 mg once daily. Myelosuppression is generally reversible.
- May ↑ serum lipase or amylase. If serum lipase or amylase ↑ to Grade ≥3, hold nilotinib and continue to monitor serum lipase and amylase levels. If serum lipase or amylase return to Grade ≤1, resume nilotinib at 400 mg once daily (230 mg/m² once daily if prior dose was 230 mg/m² twice daily). For pediatric patients, hold nilotinib until serum lipase or amylase return to Grade ≤1. Resume nilotinib at 230 mg/m² once daily if prior dose was 230 mg/m² twice daily; discontinue nilotinib if prior dose was 230 mg/m² once daily.
- Monitor liver function tests monthly. May ↑ serum ALT, AST, and bilirubin. If AST, ALT, or bilirubin ↑ to Grade ≥3, hold nilotinib and monitor bilirubin. If AST, ALT, or bilirubin return to Grade ≤1, resume nilotinib at 400 mg once daily. For pediatric patients, hold nilotinib until serum bilirubin returns to Grade ≤1; then resume nilotinib at 230 mg/m² once daily if prior dose was 230 mg/m² twice daily; discontinue nilotinib if prior dose was 230 mg/m² once daily and recovery to Grade ≤1 takes >28 days.
- Monitor lipid panel and glucose before starting and periodically during first year of therapy and then yearly during chronic therapy.
- Upon discontinuation, monitor BCR-ABL transcript levels and CBC with differential monthly for 1 yr, then every 6 wk for 2nd yr, and every 12 wk thereafter.

Implementation ⬆ ⬇

Do not confuse nilotinib with neratinib or niraparib.
Correct hypokalemia and hypomagnesemia prior to beginning therapy.
Indications for use and dosing differ between capsule and tablet formulations; do not substitute capsules and tablets (or vice versa) on a mg-per-mg basis.
PO:
Administer capsules twice daily at 12-hr intervals on an empty stomach, ≥1 hr before and 2 hr after food. Administer tablets with or without food.
DNC: Swallow capsules and tablets whole with water; do not cut, crush, or chew tablets.
- Patients unable to swallow capsule may open capsule and sprinkle contents of each capsule in one teaspoon of applesauce. Swallow mixture within 15 min. Do not use more than one teaspoon of applesauce and use only applesauce.
- Avoid antacids <2 hr before or after administration; avoid H₂ antagonists < 10 hr before or <2 hr after administration.

Patient/Family Teaching ⬆ ⬇

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 provider. 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort, during therapy.
Instruct patient to notify health care provider 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; ↑ 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 provider.
Discuss the possibility of hair loss with patient. Explore methods of coping. Regrowth usually occurs 2–3 mo after discontinuation of therapy.
Rep: May cause fetal harm. Advise women of reproductive potential to use highly effective contraception during therapy and for ≥14 days following last dose and to avoid breastfeeding for ≥14 days following last dose. Advise patient to notify health care provider immediately if pregnancy is suspected.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆