Duvelisib

COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines of systemic therapy. Limitations of Use: COPIKTRA is not indicated or recommended for the treatment of any patients with CLL or SLL as initial or second line treatment due to an increased risk of treatment-related mortality. COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines lines of systemic therapy.

Duvelisib is an inhibitor of PI3K with inhibitory activity predominantly against PI3K-δ and PI3K-γ isoforms expressed in normal and malignant B-cells. Duvelisib induced growth inhibition and reduced viability in cell lines derived from malignant B-cells and in primary CLL tumor cells. Duvelisib inhibits several key cell-signaling pathways, including B-cell receptor signaling and CXCR12-mediated chemotaxis of malignant B-cells. Additionally, duvelisib inhibits CXCL12-induced T cell migration and M-CSF and IL-4 driven M2 polarization of macrophages.

25 mg orally, twice daily. Modify dosage for toxicity. Recommended Dosage The recommended dose of COPIKTRA is 25 mg administered as oral capsules twice daily (BID) with or without food. A cycle consists of 28 days. The capsules should be swallowed whole. Advise patients not to open, break, or chew the capsules. Advise patients that if a dose is missed by fewer than 6 hours, to take the missed dose right away and take the next dose as usual. If a dose is missed by more than 6 hours, advise patients to wait and take the next dose at the usual time.

None. None.

Boxed warning: Treatment-related mortality occurred in 15% of COPIKTRA-treated patients. Fatal and/or serious infections occurred in 31% of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected. Fatal and/or serious diarrhea or colitis occurred in 18% of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA. Hepatotoxicity: Monitor hepatic function. Neutropenia: Monitor blood counts. Embryo-Fetal toxicity: COPIKTRA can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception.

The following adverse reactions have been associated with COPIKTRA in clinical trials and are discussed in greater detail in other sections of the prescribing information: Treatment-related Mortality Infections Diarrhea or Colitis Cutaneous Reactions Pneumonitis Hepatotoxicity Neutropenia The most common adverse reactions ( > 20%) are diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

CYP3A4 inhibitors: Reduce COPIKTRA dose to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors. Strong CYP3A4 inducers: Avoid coadministration. Moderate CYP3A4 inducers: Avoid coadministration. If coadministration cannot be avoided, increase the dose of COPIKTRA. CYP3A4 substrates: Monitor for signs of toxicities when co-administering COPIKTRA with sensitive CYP3A substrates.

Store at 20° to 25°C (68° to 77°F), with excursions permitted at 15° to 30°C (59° to 86°F).