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Pregnancy Category: D
Pharmacologic: enzyme inhibitors
Pharmacologic: enzyme inhibitors
genetic implication Newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase.genetic implication Chronic or accelerated phase Ph+ CML that has not responded to other treatment, including imatinib.
Inhibits kinases which may be produced by malignant cell lines.
Inhibits production of malignant cells lines with decreased proliferation of leukemic cells.
Absorption: Well absorbed following oral administration. Blood levels are significantly ↑ by food.
Metabolism and Excretion: Mostly metabolized by the liver; metabolites are not active.
Half-life: 17 hr.
Time/action profile (blood levels)
|PO||unknown||3 hr||12 hr|
Contraindicated in: Hypokalemia or hypomagnesemia;Long QT syndrome;Concurrent use of medications known to prolong QT interval;Concurrent use of strong inhibitors of the CYP3A4 enzyme system (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice);Concurrent use of strong inducers of the CYP3A4 enzyme system (e.g. dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John's wort);Galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption (capsules contain lactose); Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Concurrent use of other drugs that prolong QT interval;Concurrent use of proton pump inhibitors (may ↓ bioavailability of nilotinib);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; Obstetric: Women with child-bearing potential (effective contraception required); Pediatric: Safety not established.
Adverse Reactions/Side Effects
Central nervous system
- fatigue (most frequent)
- headache (most frequent)
Ear, Eye, Nose, Throat
- torsades de pointes (life-threatening)
- QT interval prolongation
- hepatotoxicity (life-threatening)
- ↑ lipase (most frequent)
- constipation (most frequent)
- diarrhea (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
- abdominal discomfort
- pruritus (most frequent)
- rash (most frequent)
Fluid and Electrolyte
- musculoskeletal pain
- fever (most frequent)
- night sweats
- tumor lysis syndrome
Drug-Drug interactionStrong CYP3A4 inhibitors including ketoconazole, itraconaole, voriconazole, clarithromycin, telithromycin, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, and nefazodone may result in ↑ blood levels and toxicity and should be avoided if possible; if concurrent use is necessary, ↓ nilotinib dose.Strong CYP3A4 inducers including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentin may ↓ blood levels and effectiveness and should be avoided.Nilotinib inhibits the following enzyme systems: CYP3A4, CYP2C8, CYP2C9, and CYP2D6 ; concurrent use of drugs metabolized by these systems may result in toxicity of these agents.Nilotinib induces the following enzyme systems: CYP2D6, CYP2C8, CYP2C9 ; concurrent use of drugs metabolized by these systems may result ↓ therapeutic effectiveness of these agents.Concurrent use of other drugs that prolong QT interval ; may ↑ risk of serious arrhythmias; avoid concomitant 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.May ↑ midazolam levels.St. John's wort may ↓ levels and effectiveness; avoid concurrent use.Grapefruit juice may ↑ blood levels and toxicity and should be avoided.
Newly Diagnosed Ph+ CML Chronic Phase
Oral (Adults) 300 mg twice daily; adjustment may be required for toxicity; Concurrent use of strong CYP3A4 inhibitor (ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)—200 mg once daily.
Hepatic ImpairmentOral (Adults) Mild, moderate or severe hepatic impairment—200 mg twice daily; may ↑ to 300 mg twice daily if tolerates
Resistant or Intolerant Ph+ CML Chronic or Accelerated Phase
Oral (Adults) 400 mg twice daily; adjustment may be required for toxicity; Concurrent use of strong CYP3A4 inhibitor (ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)—300 mg once daily.
Hepatic ImpairmentOral (Adults) Mild or moderate hepatic impairment—300 mg twice daily; may ↑ to 400 mg twice daily if tolerates; Severe hepatic impairment—200 mg twice daily; may ↑ to 300 mg twice daily, and eventually to 400 mg twice daily if tolerates
Capsules: 150 mg, 200 mg
- Monitor ECG to assess the QTc interval at baseline, 7 days after initiation of therapy, and periodically thereafter. For ECGs with QTc >480 msec, withhold nilotinib and check serum potassium and magnesium. If below lower limit of normal, correct to normal with supplements. Review concomitant medications for effects on electrolytes. If QTc returns to <450 msec and within 20 msec of baseline within 2 wk, return ot prior dose. If QTc is <480 msec and >450 msec after 2 wk, reduce nilotinib dose to 400 mg once daily. Following dose reduction to 400 mg once daily, if QTc return to >480 msec, discontinue nilotinib. Repeat ECG approximately 7 days after any dose adjustment.
- Monitor for myelosuppression. Assess for bleeding (bleeding gums, bruising, petechiae, blood in stools, urine, emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for at least 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for fatigue, dyspnea, and othrostatic hypotension.
- Monitor for tumor lysis syndrome (malignant disease progression, high WBC counts, hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcamia, and/or dehydration). Prevent by maintain adequate hydration and correcting uric acid levels prior to starting nilotinib.
- Lab Test Considerations: 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 first 2 mo and monthly thereafter or as indicated. May cause Grade 3/4 thrombocytopenia, neutropenia, and anemia. If ANC is <1.0 × 109/L and/or platelet counts <50 × 109/L, stop nilotinib and monitor blood counts. Resume within 2 wk at prior dose if ANC >1.0 × 109/L and platelets >50 × 109/L. If blood counts remain low for >2 wk, reduce dose to 400 mg once daily. Myelosuppression is generally reversible.
- May cause ↑ serum lipase or amylase. If ↑ to ≥Grade 3, withhold nilotinib and monitor serum levels. Resume treatment at 400 mg once daily if serum lipase or amylase return to ≤Grade 1.
- May cause ↑ serum bilirubin. If ↑ to ≥Grade 3, withhold nilotinib and monitor bilirubin. Resume treatment at 400 mg once daily if serum lipase or amylase return to ≤Grade 1.
- May cause ↑ serum hepatic tranaminases. If ↑ to ≥Grade 3, withhold nilotinib and monitor serum ALT, AST, and alkaline phosphatase. Resume treatment at 400 mg once daily if serum lipase or amylase return to ≤Grade 1.
Potential Nursing DiagnosesDeficient knowledge, related to medication regimen (Patient/Family Teaching)
- Correct hypokalemia and hypomagnesemia prior to beginning therapy.
- Oral: Administer twice daily at 12-hr intervals on an empty stomach, at least 1 hr before and 2 hr after food. Capsule should be swallowed whole with water; do not open capsule.
- Patients unable to swallow capsule may open capsule and sprinkle contents of each capsule in 1 teaspoon of applesauce. Swallow mixture within 15 minutes. Do not use more than 1 teaspoon of applesauce and use only applesauce.
- Avoid antacids less than 2 hr before or after and H2 antagonists less than 10 hr before or less than 2 hr after administration
- 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 difficulty urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patients 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.
- Advise women of childbearing potential to use highly effective contraception during therapy and to avoid breast feeding.
- Decrease in production of leukemic cells.
a miscellaneous antineoplastic.
indications This drug is used to treat chronic- and accelerated-phase Philadelphia chromosome-positive chronic myelogenous leukemia that is resistant to or intolerant of imatinib.
contraindications Known hypersensitivity to this drug, pregnancy, breastfeeding, hypokalemia, hypomagnesemia, and QT prolongation prohibit its use. This drug should not be used simultaneously with grapefruit products.
adverse effects Adverse effects of this drug include headache, dizziness, fatigue, fever, flushing, paresthesia, palpitations, constipation, diarrhea, alopecia, erythemia, hyperamylasemia, hyperbilirubinemia, hyperglycemia, hyperkalemia, hypocalcemia, hyponatremia, hypomagnesemia, diaphoresis, arthralgia, myalgia, back and bone pain, muscle cramps, cough, and dyspnea. Life-threatening side effects include QT prolongation, torsades de pointes, hepatotoxicity, vomiting dyspepsia, pancreatitis, neutropenia, thrombocytopenia, anemia, pancytopenia, and bleeding. Common side effects include nausea, anorexia, abdominal pain, and rash.