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Idelalisib structure
Trade namesZydelig
Other namesGS-1101, CAL-101
  • 5-Fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]-4(3H)-quinazolinone
Clinical data
Drug classPhosphoinositide 3-kinase inhibitor[1]
Main usesChronic lymphocytic leukemia (CLL), follicular lymphoma, small lymphocytic lymphoma (SLL)[2][3]
Side effectsInfection, low white blood cells, diarrhea, liver problems, rash, fever[3]
  • AU: D
  • US: N (Not classified yet)
Routes of
By mouth (tablets)
Onset of actionTmax = 1.5 hours
Typical dose150 mg BID[2]
External links
License data
Legal status
  • US: ℞-only
  • EU: Rx-only [3]
  • In general: ℞ (Prescription only)
Protein binding>84%[2]
MetabolismAldehyde oxidase (~70%), CYP3A4 (~30%);[4] UGT1A4 (minor)
MetabolitesGS-563117 (inactive in vitro)
Elimination half-life8.2 hours
ExcretionFeces (78%), urine (14%)
Chemical and physical data
Molar mass415.432 g·mol−1
3D model (JSmol)
  • CC[C@H](Nc1ncnc2nc[nH]c12)c4nc3cccc(F)c3c(=O)n4c5ccccc5
  • InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1

Idelalisib, sold under the brand name Zydelig, is a medication used to treat chronic lymphocytic leukemia (CLL), follicular lymphoma, and small lymphocytic lymphoma (SLL).[2][3] It is used when other treatments have failed or are not appropriate.[2][5] It is taken by mouth.[2]

Common side effects include infection, low white blood cells, diarrhea, liver problems, rash, and fever.[3] Other side effects may include allergic reactions.[2] Use in pregnancy may harm the baby.[2] It is a phosphoinositide 3-kinase inhibitor which blocks PI3Kδ.[1][3]

Idelalisib was approved for medical use in the United States and Europe in 2014.[1][3] In the United Kingdom a month of treatment costs the NHS about £3,100 as of 2021.[5] This amount in the United States costs about 12,300 USD.[6]

Medical uses

Idelalisib is a second-line drug used for when chronic lymphocytic leukemia (CLL) has relapsed. Used in combination with rituximab,[7] idelalisib is to be used in patients for whom rituximab alone would be considered appropriate therapy due to other existing medical conditions.[7] It appears to be effective and leads to improvement of lymphadenopathy and splenomegaly. However, the lymphocyte counts take longer to decrease to normal levels with idelalisib. It is not recommended as a first-line treatment.[2]

It is also approved for the treatment of follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), both in patients who have received at least two prior systemic therapies.[2]


It is generally used at a dose of 150 mg twice per day.[2] In those with significant side effects 100 mg twice per day may be used.[3]

Side effects

Grade 2 psoriasis-like rash (erythematosquamous papules and plaques), several months after idelalisib use

Side effects include diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash. Laboratory abnormalities may include: neutropenia, hypertriglyceridemia, hyperglycemia and elevated levels of liver enzymes. Idelalisib's safety and effectiveness to treat relapsed FL and relapsed SLL were established in a clinical trial with 123 participants with slow-growing (indolent) non-Hodgkin lymphomas. All participants were treated with idelalisib and were evaluated for complete or partial disappearance of their cancer after treatment (objective response rate, or ORR). Results showed 54% of participants with relapsed FL and 58% of participants with SLL experienced ORR.[8]

The U.S. label for idelalisib has a boxed warning describing toxicities that can be serious and fatal, including liver toxicity, severe diarrhea, colon inflammation, lung tissue inflammation (pneumonitis) and intestinal perforation, and the manufacturer was required to put in place a Risk Evaluation and Mitigation Strategy (REMS) under which the risk of toxicities would be managed.[9]

In March 2016, as reports were made from three ongoing clinical trials of serious adverse events and deaths, mostly due to infections, the European Medicines Agency opened a review of the drug and its risks.[10] On March 21, 2016 Gilead Sciences (the manufacturer of idelalisib) alerted healthcare providers about decreased overall survival and increased risk of serious infections in patients with CLL and indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib.[11] The company also disclosed that it stopped six clinical trials in patients with CLL, SLL and iNHL due to an increased rate of adverse events, including deaths.[12] In 2016, the EMA recommended that people on idelalisib should be given medication against the lung infection Pneumocystis jirovecii pneumonia and this should be continued for up to 6 months after idelalisib has stopped. In addition, people should be monitored for signs of infection.[13]


Mechanism of action of Idelalisib is the inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase[14]

Mechanism of action

PI3Kδ is expressed in normal and malignant B-cells. By inhibiting it, idelalisib induces apoptosis and prevents proliferation in cell lines derived from malignant B-cells and in primary tumor cells. It also inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in the trafficking and homing of B-cells to the lymph nodes and bone marrow.[2] Idelisib reduces the levels of CD20 on the surface of malignant B lymphocytes by interfering with the IL4-STAT6,[15] which might explain some of its repressive effects on the biology of B cells, but also impair its efficacy in combination with anti-CD20 antibodies (rituximab, ofatumumab etc).

Binding profile

Idelalisib is a competitive inhibitor of the ATP binding site of the PI3Kδ catalytic domain. Its in vitro potency and selectivity relative to the other Class I PI3K isoforms is the following:[16]

PI3K isoform IC50, nM IC50-based PI3Kδ-fold selectivity
PI3Kα 8,600 453
PI3Kβ 4,000 211
PI3Kγ 2,100 110
PI3Kδ 19 1



In July 2014, the FDA and EMA granted idelalisib approval to treat different types of leukemia.[8][17] The FDA is also granted approval for idelalisib to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma. Idelalisib is intended to be used in patients who have received at least two prior systemic therapies.

Society and culture


Idelalisib was developed by Gilead Sciences. Idelalisib had annual sales of $168 million (USD) during the year of 2016, up from $132 million (USD) in 2015.[18]


  1. 1.0 1.1 1.2 "Idelalisib Monograph for Professionals". Archived from the original on 24 October 2020. Retrieved 25 November 2021.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 "Zydelig- idelalisib tablet, film coated". DailyMed. 22 October 2018. Archived from the original on 23 October 2020. Retrieved 21 October 2020.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Zydelig EPAR". European Medicines Agency (EMA). Archived from the original on 23 October 2020. Retrieved 21 October 2020.
  4. "Clinical Pharmacology and Biopharmaceutics Review: Zydelig (idelalisib)" (PDF). U.S. Food and Drug Administration. p. 6. Archived (PDF) from the original on 28 April 2016. Retrieved 15 April 2016.
  5. 5.0 5.1 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1029. ISBN 978-0857114105.
  6. "Zydelig Prices, Coupons & Patient Assistance Programs". Archived from the original on 17 April 2021. Retrieved 25 November 2021.
  7. 7.0 7.1 Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. (March 2014). "Idelalisib and rituximab in relapsed chronic lymphocytic leukemia". The New England Journal of Medicine. 370 (11): 997–1007. doi:10.1056/NEJMoa1315226. PMC 4161365. PMID 24450857.
  8. 8.0 8.1 "FDA approves Zydelig for three types of blood cancers" (Press release). Food and Drug Administration. July 23, 2014. Archived from the original on January 3, 2016. Retrieved October 21, 2021.
  9. "Press Announcements — FDA approves Zydelig for three types of blood cancers". Archived from the original on 2016-01-03. Retrieved 2016-03-14.
  10. "European Medicines Agency — News and Events — EMA reviews cancer medicine Zydelig". Archived from the original on 2016-03-15. Retrieved 2016-03-14.
  11. "Important Drug Warning: Decreased Overall Survival and Increased Risk of Serious Infections in Patients Receiving ZYDELIG (idelalisib)" (PDF). Gilead Sciences, Inc. March 21, 2016. Archived from the original (PDF) on 8 May 2016. Retrieved 19 April 2016.
  12. "Drug Safety and Availability — FDA Alerts Healthcare Professionals About Clinical Trials with Zydelig (idelalisib) in Combination with Other Cancer Medicines". FDA Center for Drug Evaluation and Research. Archived from the original on 20 April 2016. Retrieved 19 April 2016.
  13. "CHMP confirms recommendations for use of Zydelig". European Medicines Agency (EMA). 15 September 2016. Archived from the original on 29 October 2020. Retrieved 21 October 2021.
  14. Almasri, Mohammad; Amer, Marah; Ghanej, Joseph; Mahmoud, Abdurraouf Mokhtar; Gaidano, Gianluca; Moia, Riccardo (February 2022). "Druggable Molecular Pathways in Chronic Lymphocytic Leukemia". Life. 12 (2): 283. doi:10.3390/life12020283. ISSN 2075-1729.
  15. Sandova V, Pavlasova GM, Seda V, Cerna KA, Sharma S, Palusova V, Brychtova Y, Pospisilova S, Fernandes SM, Panovska A, Doubek M, Davids MS, Brown JR, Mayer J, Mraz M (July 2021). "IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3Kdelta inhibitor idelalisib". Haematologica. doi:10.3324/haematol.2021.278644. PMID 34196167.
  16. "Committee for Medicinal Products for Human Use Assessment Report: Zydelig (idelalisib)" (PDF). European Medicines Agency. p. 17. Archived (PDF) from the original on 2 April 2016. Retrieved 19 April 2016.
  17. "European Medicines Agency recommends approval of two new treatment options for rare cancers" (Press release). European Medicines Agency. July 25, 2014. Archived from the original on November 12, 2020. Retrieved October 21, 2021.
  18. "Annual Sales of Idelalisib reported using PharmaCompass' compilation of Annual Reports of Global Pharmaceutical Companies". Pharmacompass. Archived from the original on January 21, 2019. Retrieved January 21, 2019.

External links

External sites: