Pharmacological Class:
Phosphatidylinositol 3-kinase inhibitor.
Active Ingredient(s):
Idelalisib 100mg, 150mg; tablets.
Company
Gilead Sciences, Inc.
Indication(s):
Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate due to other co-morbidities. Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least 2 prior systemic therapies. Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies.
Pharmacology:
Idelalisib inhibits PI3K delta kinase, which is expressed in normal and malignant B-cells. Idelalisib induces apoptosis, inhibits proliferation in cell lines derived from malignant B-cells and in primary tumor cells, and inhibits several cell signaling pathways (including B-cell receptor, CXCR4, CXCR5), which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib resulted in inhibition of chemotaxis and adhesion, and reduced cell viability.
Clinical Trials:
Zydelig was eva luated in a placebo-controlled study that involved 220 subjects with relapsed CLL who required treatment and were unable to tolerate standard chemoimmunotherapy. Subjects were randomized 1:1 to receive 8 doses of rituximab in combination with either an oral placebo twice daily or Zydelig 150mg twice daily until disease progression or unacceptable toxicity.
The primary endpoint was progression free survival (PFS), as assessed by an independent review committee. The trial was stopped for efficacy following the first pre-specified interim analysis. A second interim analysis continued to show a statistically significant improvement for Zydelig + rituximab vs. placebo + rituximab for the primary endpoint of PFS (HR 0.18, [95% CI: 0.10, 0.32]; P<0.0001).
The safety and efficacy of Zydelig in patients with FL and SLL were also eva luated in multicenter clinical trials.
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Swallow whole. ≥18 years: initially 150mg twice daily; continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.
Children:
<18 years: not established.
Contraindication(s):
History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis.
Warnings/Precautions:
Risk of fatal/serious hepatotoxicity: monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every 1–3 months thereafter; if ALT/AST >3XULN, monitor weekly until resolved; if ALT/AST >5XULN, withhold and continue monitoring weekly until resolved. Monitor for diarrhea or colitis; withhold if severe and discontinue if life-threatening. Risk of fatal/serious pneumonitis; monitor for pulmonary symptoms, interstitial infiltrates, or a decline by >5% in oxygen saturation; if suspected, interrupt or discontinue as indicated. Risk of fatal/serious intestinal perforation; discontinue permanently if occurs. Monitor for severe cutaneous or serious allergic reactions; discontinue if occur. Monitor CBCs at least every 2 weeks for the first 3 months, and at least weekly if neutrophils <1.0Gi/L. Pregnancy (Category D); avoid. Use effective contraception during treatment and for at least 1 month after last dose. Nursing mothers: not recommended.
Interaction(s)
Avoid concomitant drugs that may cause hepatotoxicity or diarrhea. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenytoin, St. John’s wort, carbamazepine) or CYP3A substrates (eg, oral midazolam). Concomitant strong CYP3A inhibitors (eg, ketoconazole); monitor for idelalisib toxicity.
Adverse Reaction(s)
Diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, rash, neutropenia, hypertriglyceridemia, hyperglycemia, ALT/AST elevations.
How Supplied:
Tabs—60
LAST UPDATED:
11/10/2014
