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Things to Know About Idelalisib

This content was current as of the date it was released. In science and medicine, information is constantly changing and may become out-of-date as new data emerge.

By Tom Henry – CLL Patient and Pharmacist

Idelalisib (eye-del-a-lis-ib), which is marketed under the tradename of Zydelig® in the United States and Canada, is a selective inhibitor of the lipid kinase PI3Kδ. Upon oral administration, inhibits the PI3Kδ kinase (enzyme) that is expressed by both normal and malignant B-cells. By inhibiting this particular enzyme, idelalisib induces cell death (apoptosis) and prevents proliferation of cell lines derived from malignant B-cells. It also inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which is involved in trafficking and homing of B-cells to the lymph nodes and bone marrow.

Idelalisib is not a first-line therapy, and is used in relapsed CLL or CLL that does not respond to other treatments (refractory). Part of the reason that this is not considered for first-line therapy is that there can be serious and even fatal toxicities associated with this medication:

  • Fatal and/or serious liver toxicity has occurred in 11 to 18% of treated patients.
  • Fatal and/or serious diarrhea or colitis has occurred in 14 to 19% of patients.
  • Fatal and/or serious lung inflammation (pneumonitis) occurred in 4% of patients
  • Fatal and/or serious infections occurred in 21 to 36% of patients

Because of these serious issues, the Food and Drug Administration requires a “Boxed Warning” on all literature and package inserts related to this medication. The decision to use this medication should only be made after careful consideration of the risks versus benefits of this medication, and then only with careful monitoring. This information is not intended to dissuade use of this medication which has been used safely by many patients for periods extending to greater than 3 years. Idelalisib has been shown to induce marked reductions in lymph node size and liver/spleen enlargement in patients with relapsed or refractory CLL, even with bulky refractory disease and extensive prior therapy. Additional clinical benefits include a reduction or an improvement in cytopenias (reduced mature blood cells).

Zydelig® is suppled as tablets in two strengths 150mg and 100mg with the recommended starting dose of 150mg (1 tablet) by mouth twice a day. The 100mg tablets are available to allow tapering the dose down if indicated by adverse effects or predisposing medical factors such as co-morbidities, age and weight.

When taking Zydelig® it is important to take it at approximately the same times each day (approximately 12-hours apart) with a full glass of water and you should maintain good hydration throughout the day. This becomes critical in the event of diarrhea and the volume of water suggested rises to 8 to 10 glasses per day. It is important to swallow the tablet whole and do not break or chew the tablets. This medication can be taken without regard to whether there is food in the stomach.

There are numerous drug to drug interactions to consider, I will only discuss the most significant.

Many HIV and antifungal drugs inhibit the enzyme that metabolizes idelalisib and result in increased blood levels and side effects. The HIV drugs can be recognized because they end in “Vir” and the antifungals end in “Zole”. 

On the opposite side are drugs that induce the enzyme that metabolizes idelalisib and reduces the blood levels and may render the drug sub-therapeutic. These include the anti-seizure medications phenytoin, carbamazepine and phenobarbital, the anti-tubercular drugs rifampin, rifabutin and rifapentine, the steroid dexamethasone and the herbal product St. John’s Wort.

Your provider will evaluate the risks of these interactions and decide to either adjust therapy or potentially switch to similar agents for the same purpose, and do not interact with idelalisib. I must caution that the listing I have provided is only a partial group with more significance. This is why you must discuss all current and contemplated new medications with all your medical team, including your primary care provider.

There are some serious food interactions to consider as well.  Grapefruit, Grapefruit Juice and Seville Oranges inhibit the enzyme that metabolizes idelalisib and the drug levels increase risking worsening of potential side effects. Seville oranges are often used to make orange marmalade and should be avoided. 

The list of POTENTIAL side-effects is long.  Some are merely a nuisance and tend to be transient and others are more severe and require medical intervention.  Seek immediate medical attention:

  • If you get yellowing of the skin or white part of the eye (jaundice), dark or brown (tea-colored urine, pain in the upper right side of your abdomen ore bleeding or bruising more easily than normal which are possible signs of liver problems
  • If the number of bowel movements you have in a day increases to 6 or more
  • If you have new or worsening cough, shortness of breath, difficulty breathing, or wheezing
  • If you have a fever or any signs of an infections
  • If you get new or worsening abdominal pain, chills fever, nausea or vomiting
  • If you get painful sores or ulcers on your skin, lips, in your mouth; a severe rash with blisters or peeling skin or a rash with itching

Idelalisib is a breakthrough in the treatment of CLL. While there are risks, this medication may be one of a limited number of options in relapsed or disease that does not respond to other treatments. Educating yourself and listening to your body will likely bring benefit from this drug.


Thomas Henry is a Registered Pharmacist and CLL Patient. He is President and Senior Consultant for Burlington Consulting Associates, a company that provides consulting services to health systems nationwide. Tom is a CLL Society Medical Advisory Board member and strives to educate other CLL patients through his website which you can find here Home – CLL Pharmacist. He has a forty-two-year career in pharmacy and has served as Chief Pharmacy Officer at two Top-15 Comprehensive Cancer Centers, Moffitt (Tampa, FL) and Roswell Park (Buffalo, NY).

Originally published in The CLL Tribune Q1 2018.