Idelalisib

Zydelig is indicated, in combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Zydelig is a kinase inhibitor indicated for the treatment of patients with: Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Limitations of use: Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent non-Hodgkin lymphomas.

Idelalisib is an inhibitor of phosphatidylinositol 3-kinase, PI3Kδ, which is expressed in normal and malignant B-cells. Idelalisib induced apoptosis and inhibited proliferation in cell lines derived from malignant B-cells and in primary tumor cells. Idelalisib inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, 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.

Recommended dosage: 150 mg orally twice daily. Recommended Dosage The recommended dosage of Zydelig is 150 mg administered orally twice daily with or without food until disease progression or unacceptable toxicity. The optimal and safe dosing regimen for patients who receive treatment longer than several months is unknown. Swallow tablets whole. If a planned dose of Zydelig is missed by less than 6 hours, take the missed dose as soon as possible and take the next dose as usual. If a dose of Zydelig is missed by more than 6 hours, skip the missed dose and take the next dose at the usual time.

Zydelig is contraindicated in patients with a history of serious hypersensitivity reactions to idelalisib, including anaphylaxis, or patients with a history of toxic epidermal necrolysis with any drug. History of serious hypersensitivity reactions to idelalisib, including anaphylaxis, or history of toxic epidermal necrolysis with any drug.

Boxed warning: Fatal and/or serious hepatotoxicity occurred in 16% of Zydelig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig as recommended. Fatal and/or serious and severe diarrhea or colitis occurred in 20% of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Fatal and/or serious pneumonitis occurred in 4% of Zydelig-treated patients. Severe Cutaneous Reactions: Monitor patients for the development of severe cutaneous reactions. Permanently discontinue Zydelig if confirmed. Hypersensitivity Reactions: Permanently discontinue Zydelig and institute appropriate supportive measures. Neutropenia: Monitor blood counts. Interrupt Zydelig until resolution and resume at reduced dose. Embryo-fetal Toxicity: May cause fetal harm.

The following clinically significant adverse reactions are described elsewhere in the labeling. Hepatotoxicity Severe Diarrhea or Colitis Pneumonitis Infections Intestinal Perforation Severe Cutaneous Reactions Hypersensitivity Reactions Neutropenia The most common adverse reactions (incidence ≥30%) in patients treated with Zydelig in combination trials are diarrhea, pneumonia, pyrexia, fatigue, rash, cough, and nausea. Common laboratory abnormalities are neutropenia, ALT elevations and AST elevations.

Strong CYP3A Inhibitors: Additional monitoring required if alternative therapy is not available. Strong CYP3A Inducers: Avoid coadministration of strong CYP3A inducers. CYP3A Substrates: Avoid coadministration of sensitive CYP3A substrates.

Store between 20–30 °C (68–86 °F) with excursions permitted 15–30 °C (59–86 °F).