Names and pronunciation
(eye-del′a-lis′ib) Zydelig
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Drug reference
(eye-del′a-lis′ib) Zydelig
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Func. class.: Antineoplastic, biologic response modifier
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Chem. class.: Signal transduction inhibitor (STI)
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ACTION: Selective, small-molecule inhibitor of one kinase (expressed in both normal and malignant B-cells). Induces apoptosis and inhibited prolif- eration, inhibits several cell signaling I pathways
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USES: Treatment of relapsed chronic lymphocytic leukemia (CLL), in combi- nation with riTUXimab, in those for whom riTUXimab alone should not be used; non-Hodgkin’s lymphoma (NHL), relapsed follicular B-cell non-Hodgkin’s lymphoma in those who have received at least 2 prior systemic therapies and are refractory to both riTUXimab/alkylating agent
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CONTRAINDICATIONS: Infu- sion-related reaction, serious rash, pregnancy Precautions: Serious allergic reactions, grade 3 or 4 neutropenia, breastfeeding, hyperglycemia/hypoglycemia
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Black Box Warning: Serious hepatotoxicity, grade 3 or higher diarrhea or colitis, fatal/se- rious pneumonitis, GI perforation, infection Black Box Warning: Hepatic failure: in- creased LFTs within the first 12 wk and were reversible with dose interruption. Monitor LFTs q2wk × 3 mo, then q4wk for 3 mo, and q1-3mo thereafter; monitor weekly if AST or ALT are >3 times the up- per limit of normal (ULN) or bilirubin >1.5 × ULN. Hepatotoxicity may require treatment interruption, dose reduction, or discontinu- ation of therapy Black Box Warning: Severe diarrhea/GI perforation: The occurrence of ≥7 stools/ day over baseline or hospitalization due to diarrhea may require interruption, dose reduction, or permanent discontinuation. Assess for abdominal pain, chills, fever, or nausea/vomiting. If intestinal perforation occurs, permanently discontinue Black Box Warning: Infections/pneu- monitis: monitor for cough, dyspnea, hy- poxia, and bilateral interstitial infiltrates, or a decline in O2 saturation by >5%. If pneumonitis is suspected, hold therapy. Permanently discontinue for pneumonitis and consider corticosteroids • Pregnancy/breastfeeding: do not use in pregnancy/breastfeeding
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SIDE EFFECTS CNS: Insomnia, fatigue, fever, headache, chills, pain RESP: Pneumonitis, dyspnea, cough, severe infection ENDO: Hypoglycemia, hyperglycemia, hyponatremia INTEG: Rash EENT: Sinusitis GI: Nausea, vomiting, hepatic failure, GI perforation, stomatitis, colitis, diarrhea, anorexia, abdominal pain, GERD HEMA: Thrombocytopenia, neutropenia, anemia SYST: Serious/fatal rashes, infection, sepsis
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INTERACTIONS Avoid use with CYP3A4 inhibitors, induc- ers, substrates • Decrease: Action with strong CYP3A inducers (phenytoin, carBAMazepine, ri- fAMPin) may need dosage increase • Increase toxicity—CYP3A inhibitors (ketoconazole, verapamil, dilTIAZem) • Increase: CYP3A substrates (cycloSPO- RINE, fentanyl, tacrolimus, ergots, warfa- rin), avoid concurrent use Drug/Lab Test Increase: LFTs
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DOSAGE AND ROUTES Follicular lymphoma • Adult: PO 150 mg bid until disease progression or unacceptable toxicity Chronic lymphocytic leukemia • Adult: PO 150 mg bid with rituximab 375 mg/m2 IV, then 500 mg/m2 IV q2wk for 4 doses, then q4wk for 3 doses, for a total of 8 infusions Hepatic dose • AST/ALT >3-5 × ULN: No change; monitor AST/ALT at least every week until ≤1 × ULN • AST/ALT >5-20 × ULN: Hold doses, monitor AST/ALT at least every week, when AST/ALT are ≤1 × ULN, resume at 100 mg bid • AST/ALT >20 × ULN: Permanently dis continue • Bilirubin >1.5-3 × ULN: No change; monitor bilirubin at least every week until ≤1 × ULN • Bilirubin >3-10 × ULN: Hold treat ment; monitor bilirubin at least every week; when bilirubin is ≤1 × ULN, resume treatment at 100 mg bid • Bilirubin >10 × ULN: Permanently dis continue
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Available forms: Tabs 100, 150 mg
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Administer: • Take without regard to food; do not crush or dissolve tabs • Do not take 2 doses at the same time; if a dose is missed by <6 hr, take the dose, take next dose at usual time Therapeutic drug monitoring: dosage adjustments due to treatment-related toxicity • Moderate diarrhea (4-6 stools/day over baseline): Continue current dosing; monitor at least every week until diarrhea is resolved • Severe diarrhea (≥7 stools/day over baseline) or diarrhea requiring hospitalization: Hold treatment, and monitor at least every week for resolu tion. When diarrhea has resolved, resume with 100 mg bid • Life-threatening diarrhea: Perma nently discontinue treatment • Neutropenia: ANC 1000-1499 cells/ mm3: no change; ANC 500-999 cells/ mm3: continue current dosing; monitor ANC at least every week; ANC <500 cells/ mm3: hold treatment and monitor ANC at least every week, when ANC ≥500 cells/ mm3, resume treatment at 100 mg bid • Thrombocytopenia: Platelet count 50,000-75,000 cells/mm3: no change; platelet count 25,000-49,000 cells/ mm3: continue dose; monitor platelet count at least every week; platelet count <25,000 cells/mm3: hold treatment, monitor platelet count at least every week, when platelet count ≥25,000 cells/ mm3, resume treatment at 100 mg bid • Symptomatic pneumonitis (any se- verity): Discontinue treatment • Other severe or life-threatening tox- icities: Hold until toxicity is resolved; if resuming treatment, reduce the dose to 100 mg bid; permanently discontinue treatment for any recurrence of severe or life-threatening toxicity after rechallenge
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Assess:
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Evaluate: • Therapeutic response: Decreased dis- ease progression
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • Pregnancy/breastfeeding: to report planned or suspected pregnancy; to use effective contraception during treatment and for at least 1 mo after the last dose; to avoid breastfeeding • To report new or worsening side effects • To take tabs whole, not to crush or chew; to take with food for GI upset HIGH ALERT
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PHARMACOKINETICS 84% protein binding, half-life 8.2 hr, peak 1.5 hr
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• Adult: PO 150 mg bid until disease progression or unacceptable toxicity Chronic lymphocytic leukemia
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• Adult: PO 150 mg bid with rituximab 375 mg/m2 IV, then 500 mg/m2 IV q2wk for 4 doses, then q4wk for 3 doses, for a total of 8 infusions Hepatic dose
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• AST/ALT >3-5 × ULN: No change; monitor AST/ALT at least every week until ≤1 × ULN
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• AST/ALT >5-20 × ULN: Hold doses, monitor AST/ALT at least every week, when AST/ALT are ≤1 × ULN, resume at 100 mg bid
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• AST/ALT >20 × ULN: Permanently dis continue
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• Bilirubin >1.5-3 × ULN: No change; monitor bilirubin at least every week until ≤1 × ULN
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• Bilirubin >3-10 × ULN: Hold treat ment; monitor bilirubin at least every week; when bilirubin is ≤1 × ULN, resume treatment at 100 mg bid
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• Bilirubin >10 × ULN: Permanently dis continue
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