Leukemias, lymphomas, and other hematologic cancers:
Indications for: XALKORI
Relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive in pediatric patients aged ≥1yr and young adults. Unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive in adult and pediatric patients aged ≥1yr.
Limitations of Use:
Safety and efficacy have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.
Adult Dosage:
Swallow whole. IMT: 250mg twice daily. ALCL (young adults): usually 280mg/m2 twice daily. Dosage based on BSA (may combine different strengths, if needed): 0.60–0.80m2: 200mg twice daily; 0.81–1.16m2: 250mg twice daily; 1.17–1.51m2: 400mg twice daily; 1.52–1.69m2: 450mg twice daily; ≥1.70m2: 500mg twice daily. Both: continue until disease progression or unacceptable toxicity. Provide antiemetic and antidiarrheal agents for GI toxicities. Consider replacing electrolytes, IV or oral hydration for patients at risk of dehydration. Dose modifications for concomitant strong CYP3A inhibitors, moderate/severe hepatic impairment, severe renal impairment, hematologic and non-hematologic toxicities: see full labeling.
Children Dosage:
ALCL or IMT: <1yr or (BSA <0.60m2): not established. Swallow whole. Assess ability to swallow intact capsules before prescribing. ≥1yr: usually 280mg/m2 twice daily. Dosage based on BSA (may combine different strengths, if needed): 0.60–0.80m2: 200mg twice daily; 0.81–1.16m2: 250mg twice daily; 1.17–1.51m2: 400mg twice daily; 1.52–1.69m2: 450mg twice daily; ≥1.70m2: 500mg twice daily. Continue until disease progression or unacceptable toxicity. Provide antiemetic and antidiarrheal agents for GI toxicities. Consider replacing electrolytes, IV or oral hydration for patients at risk of dehydration. Dose modifications for concomitant strong CYP3A inhibitors, moderate/severe hepatic impairment, severe renal impairment, hematologic and non-hematologic toxicities: see full labeling.
XALKORI Warnings/Precautions:
Monitor ALT, AST and total bilirubin every 2 weeks during first 2 months, then monthly, and more frequently for elevated transaminases; temporarily suspend, reduce dose, or permanently discontinue as clinically indicated. Monitor CBCs with differential monthly and more frequently if Grade 3 or 4 abnormalities, fever or infection occurs. Risk of severe interstitial lung disease (ILD)/pneumonitis: monitor for pulmonary symptoms; permanently discontinue if occurs. Congenital long QT syndrome; avoid. History of or predisposition for QTc prolongation (eg, CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QT interval): consider monitoring ECG, electrolytes periodically. Torsade de pointes, ventricular tachycardia, serious arrhythmia: permanently discontinue if QTc >500ms or ≥60ms change from baseline. Monitor HR and BP regularly; discontinue if life-threatening bradycardia occurs. Perform eye assessment monthly in all patients. In ALCL or IMT (peds & young adults): obtain eye exam prior to and within 1 month of initiation (include retinal exam), then every 3 months thereafter; permanently discontinue if Grade 3 or 4 ocular disorders or severe visual loss occurs. Hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. Use effective contraception during and for at least 45 days (females) or 90 days (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 45 days after the last dose).
XALKORI Classification:
Tyrosine kinase inhibitor.
XALKORI Interactions:
Avoid concomitant strong CYP3A inhibitors (eg, itraconazole, ketoconazole, grapefruit, or grapefruit juice). Avoid concomitant strong CYP3A inducers (eg, rifampin). Avoid concomitant CYP3A substrates with narrow therapeutic indices (eg, oral midazolam); if needed, reduce doses. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin); adjust dose or discontinue. Avoid drugs known to prolong QT interval. Caution with moderate CYP3A inhibitors.
Adverse Reactions:
Vision disorders, nausea, diarrhea, vomiting, decreased appetite, fatigue; NSCLC: also edema, constipation, elevated transaminases, upper RTI, dizziness, neuropathy; ALCL: also headache, musculoskeletal pain, stomatitis, pyrexia, abdominal pain, cough, pruritus, Grade 3 or 4 lab abnormalities (neutropenia, lymphopenia, thrombocytopenia); IMT: also edema, abdominal pain, rash, upper RTI, cough, pyrexia, musculoskeletal pain, constipation, headache. All: hepatotoxicity (may be fatal), bradycardia.
Generic Drug Availability:
NO
How Supplied:
Caps—60
Respiratory and thoracic cancers:
Indications for: XALKORI
Metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test.
Adult Dosage:
Confirm ALK or ROS1-positive NSCLC with an FDA-approved test before treating. Swallow whole. 250mg twice daily until disease progression or intolerance. Concomitant strong CYP3A inhibitors (if unavoidable): reduce to 250mg once daily. Moderate hepatic impairment (AST and total bilirubin >1.5–≤3×ULN): 200mg twice daily; severe (AST and total bilirubin >3×ULN): 250mg once daily. Severe renal impairment (CrCl <30mL/min) not requiring dialysis: 250mg once daily. Dose modifications for hematologic and non-hematologic toxicities: see full labeling.
Children Dosage:
Not established.
XALKORI Warnings/Precautions:
Monitor ALT, AST and total bilirubin every 2 weeks during first 2 months, then monthly, and more frequently for elevated transaminases; temporarily suspend, reduce dose, or permanently discontinue as clinically indicated. Monitor CBCs with differential monthly and more frequently if Grade 3 or 4 abnormalities, fever or infection occurs. Risk of severe interstitial lung disease (ILD)/pneumonitis: monitor for pulmonary symptoms; permanently discontinue if occurs. Congenital long QT syndrome; avoid. History of or predisposition for QTc prolongation (eg, CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QT interval): consider monitoring ECG, electrolytes periodically. Torsade de pointes, ventricular tachycardia, serious arrhythmia: permanently discontinue if QTc >500ms or ≥60ms change from baseline. Monitor HR and BP regularly; discontinue if life-threatening bradycardia occurs. Perform eye assessment monthly in all patients. In ALCL or IMT (peds & young adults): obtain eye exam prior to and within 1 month of initiation (include retinal exam), then every 3 months thereafter; permanently discontinue if Grade 3 or 4 ocular disorders or severe visual loss occurs. Hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. Use effective contraception during and for at least 45 days (females) or 90 days (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 45 days after the last dose).
XALKORI Classification:
Tyrosine kinase inhibitor.
XALKORI Interactions:
Avoid concomitant strong CYP3A inhibitors (eg, itraconazole, ketoconazole, grapefruit, or grapefruit juice). Avoid concomitant strong CYP3A inducers (eg, rifampin). Avoid concomitant CYP3A substrates with narrow therapeutic indices (eg, oral midazolam); if needed, reduce doses. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin); adjust dose or discontinue. Avoid drugs known to prolong QT interval. Caution with moderate CYP3A inhibitors.
Adverse Reactions:
Vision disorders, nausea, diarrhea, vomiting, decreased appetite, fatigue; NSCLC: also edema, constipation, elevated transaminases, upper RTI, dizziness, neuropathy; ALCL: also headache, musculoskeletal pain, stomatitis, pyrexia, abdominal pain, cough, pruritus, Grade 3 or 4 lab abnormalities (neutropenia, lymphopenia, thrombocytopenia); IMT: also edema, abdominal pain, rash, upper RTI, cough, pyrexia, musculoskeletal pain, constipation, headache. All: hepatotoxicity (may be fatal), bradycardia.
Generic Drug Availability:
NO
How Supplied:
Caps—60
