Names and pronunciation
(nye-loe′ti-nib) Tasigna
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Drug reference
(nye-loe′ti-nib) Tasigna
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Func. class.: Antineoplastic— miscellaneous
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Chem. class.: Protein-tyrosine kinase inhibitor
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ACTION: Inhibits BCR-ABL tyrosine kinase created in patients with chronic myeloid leukemia (CML)
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USES: Chronic phase/accelerated phase Philadelphia chromosome–positive CML that is resistant or intolerant to ima- tinib
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity
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Black Box Warning: Hypokalemia, hy- pomagnesemia, QT prolongation Precautions: Children, females, geriatric patients, active infections, anemia, cardiac disease, bone marrow suppression, cho- lestasis, diabetes, gelatin hypersensitivity, infertility, galactose-free diet, lactase defi- ciency, neutropenia, pancreatitis, throm- bocytopenia, hepatic disease, alcoholism, angina, ascites, tumor lysis syndrome Black Box Warning: QT prolongation can occur; monitor ECG, left ventricular ejection fraction (LVEF) at baseline, pe- riodically; hypertension, assess for chest pain, palpitations, dyspnea Black Box Warning: Hepatotoxic- ity: monitor LFTs before treatment and monthly; if liver transaminases >5 × IULN, withhold until transaminase levels return to <2.5 × IULN • Myelosuppression: Monitor CBC ×2 mo, then monthly, differential, platelet count; for bleeding: epistaxis, rectal, gin- gival, upper GI, genital and wound bleed- ing; tumor-related hemorrhage may occur rapidly • ANC and platelets: if ANC <1 × 109/L and/or platelets <50 × 109/L, stop until ANC >1.5 × 109/L and platelets >75 ×109/L • Electrolytes: calcium, potassium, magnesium, sodium; lipase, phosphate; hypokalemia, hypomagnesemia should be corrected before use • AST/ALT/bilirubin/lipase/amylase: if increased to grade 3, withhold product; resume at 400 mg daily when levels re- turn to grade 1 or below • Pregnancy/breastfeeding: do not use in pregnancy, breastfeeding
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SIDE EFFECTS CNS: Headache, dizziness, fatigue, fever, flushing, paresthesia CV: QT prolongation, palpitations, tor- sades de pointes, AV block GI: Nausea, hepatotoxicity, vomiting, dyspepsia, anorexia, abdominal pain, constipation, pancreatitis, diarrhea, xerostomia HEMA: Neutropenia, thrombocytopenia, anemia, pancytopenia INTEG: Rash, alopecia, erythema META: Hyperamylasemia, hyperbilirubine- mia, hyperglycemia, hyperkalemia, hypo- calcemia, hyponatremia, hypomagnesemia MISC: Diaphoresis, anxiety MS: Arthralgia, myalgia, back or bone pain, muscle cramps RESP: Cough, dyspnea SYST: Bleeding, tumor lysis syndrome
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INTERACTIONS • Product interactions are numerous • Do not use with phenothiazines, pimo- zide, ziprasidone Increase: QT prolongation—class IA/III antidysrhythmics, some phenothiazines, β agonists, local anesthetics, tricyclics, haloperidol, chloroquine, droperidol, pent- amidine; CYP3A4 inhibitors (amiodarone, clarithromycin, erythromycin, telithromy- cin, troleandomycin), arsenic trioxide, levomethadyl; CYP3A4 substrates (meth- adone, pimozide, QUEtiapine, quiNIDine, risperiDONE, ziprasidone) Increase: hepatotoxicity—acetaminophen Increase: concentrations—ketoconazole, itraconazole, erythromycin, clarithro mycin Increase: plasma concentrations of sim- vastatin, calcium channel blockers Increase: plasma concentration of warfa- rin; avoid use with warfarin, use low- molecular-weight anticoagulants instead Decrease: concentrations—dexamethasone, phenytoin, carBAMazepine, rifampin, PHENobarbital Drug/Herb Decrease: concentration—St. John’s wort Drug/Food Increase: plasma concentrations— grapefruit juice
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DOSAGE AND ROUTES • Adult: PO 300 mg q12hr, continue un- til disease progression (chronic phase, newly diagnosed); 400 mg q12hr, con- tinue until disease progression or unac- ceptable toxicity (accelerated phase). Use with a strong CYP3A4 inducer 200-300 mg daily, depending on the indication • Child/adolescent: PO 230 mg/m2 q12hr until disease progression or un- acceptable toxicity. Round the dose to the nearest 50 mg to a max single dose of 400 mg Adjustment after discontinuation of a strong CYP3A4 inhibitor • Adult: PO reduce to 400 mg bid Use with a strong CYP3A4 inhibitor • Adult: PO reduce dose to 200-300 mg/day depending on indication QT prolongation • QTcF >480 msec: withhold dose Myelosuppression • ANC 1 × 109/L or platelets <50 × 109/L: withhold dose Hepatic dose • Adult: PO (Child-Pugh A/B/C) newly diagnosed CML 200 mg bid, then escala- tion to 300 mg bid initially
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Available forms: Caps 50, 150, 200 mg
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Administer: • Do not break, crush, or chew caps; if whole capsule cannot be swallowed, dis- perse capsule contents in 1 tsp apple- sauce • On empty stomach; separate doses by 12 hr; make-up dose should not be taken if dose is missed • Store at 59°F-86°F (15°C-30°C)
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Assess: • Tumor lysis syndrome: maintain hy- dration, correct uric acid before use with this product
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Evaluate: • Therapeutic response: decrease in progression of disease
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • Infection: to report immediately cough, fever, chills • To report bleeding gums; blood in stools, urine, emesis • About reason for treatment, expected results N • That many adverse reactions may occur • To avoid persons with known upper respiratory tract infections; immunosup- pression is common • To watch for signs, symptoms of low potassium or magnesium • To notify prescriber of all OTC, pre- scription, and herbal products used; not to receive vaccinations without prescrib- er’s approval • Pregnancy/breastfeeding: to use contraception during treatment; not to breastfeed
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PHARMACOKINETICS Protein binding 98%, metabolized by CYP3A4, plasma levels 3 hr, elimination half-life 17 hr
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• Adult: PO 300 mg q12hr, continue un- til disease progression (chronic phase, newly diagnosed); 400 mg q12hr, con- tinue until disease progression or unac- ceptable toxicity (accelerated phase). Use with a strong CYP3A4 inducer 200-300 mg daily, depending on the indication
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• Child/adolescent: PO 230 mg/m2 q12hr until disease progression or un- acceptable toxicity. Round the dose to the nearest 50 mg to a max single dose of 400 mg Adjustment after discontinuation of a strong CYP3A4 inhibitor
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• Adult: PO reduce to 400 mg bid Use with a strong CYP3A4 inhibitor
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• Adult: PO reduce dose to 200-300 mg/day depending on indication QT prolongation
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• QTcF >480 msec: withhold dose Myelosuppression
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• ANC 1 × 109/L or platelets <50 × 109/L: withhold dose Hepatic dose
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• Adult: PO (Child-Pugh A/B/C) newly diagnosed CML 200 mg bid, then escala- tion to 300 mg bid initially
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