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Zydelig: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on July 13, 2023.

1. How it works

  • Zydelig is a brand (trade) name for idelalisib which may be used to treat relapsed chronic lymphocytic leukemia in combination with rituximab.
  • Zydelig works by inhibiting phosphoinositide 3-kinase (PI3K) PI3Kδ, which is expressed in normal and cancerous B-cells. This enzyme is one of many that form part of the PI3K/AKT/mTOR pathway, which is a pathway involved in cell growth and survival, as well as several other processes that are frequently activated in many cancers. Zydelig causes cell death and inhibits the proliferation of cells derived from cancerous B-cells and primary tumor cells. It also inhibits several cell signaling pathways (the way cells communicate with each other), 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.
  • Zydelig belongs to the class of medicine known as phosphoinositide 3-kinase (PI3K) inhibitors.

2. Upsides

  • May be used to treat relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Used in combination with rituximab. Not indicated for first-line treatment of any patient. Do not use it in combination with bendamustine and rituximab.
  • PI3K inhibitors are usually given to treat certain cancers that have relapsed or are unresponsive to other cancer treatments. Typically, at least two other cancer treatments need to have been tried and been unsuccessful or not tolerated before PI3K inhibitors are given.
  • Less likely than copanlisib to cause high blood pressure (hypertension).
  • Usually taken orally twice daily. Tablets should be swallowed whole.
  • Available as a 100mg and 150mg dose.
  • May be taken with or without food.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Fever, diarrhea, nausea. abdominal pain, vomiting, reflux, pneumonia, rash, decreased appetite, sepsis, and insomnia are the most common side effects reported. Other common side effects include oral herpes, joint pain, tiredness, pain, mouth ulcers, dehydration, sinusitis, urinary tract infections, and bronchitis.
  • Severe and potentially life-threatening reactions have been reported with PI3K inhibitors such as Zydelig including several grade 3 (severe, covering more than 30% body surface area or with evidence of infection) skin reactions, including exfoliative dermatitis and toxic epidermal necrolysis. A dermatologist should be consulted and Zydelig withheld if any skin reaction occurs.
  • Severe or fatal liver damage has been reported in 16-18% of patients receiving Zydelig, including elevations in liver enzymes (AST or ALT) greater than 5 times the upper limit of normal. These were usually reported within the first 12 weeks of treatment and were reversible with dose interruption. Liver function should be monitored before and during therapy.
  • An increase in the number of infections, and infections associated with unusual organisms, such as Pneumocystis jirovecii and cytomegalovirus (CMV) have been reported rarely associated with PI3K inhibitor use, including Zydelig. Fatal and serious infections occurred in 48% of people treated with Zydelig. CMV status should be assessed monthly and antiviral treatment initiated and Zydelig withheld if CMV levels are increasing, or discontinued if there is evidence of end-organ damage such as colitis, hepatitis, or retinitis.
  • Severe, potentially life-threatening diarrhea or colitis (grade 3 or higher) has occurred in 20% of patients treated with Zydelig and rituximab, and this diarrhea responds poorly to antimotility agents. Diarrhea can occur at any time and avoid use with other drugs that can also cause diarrhea. Resolution time ranged from 1 week to 1 month. Fatal and serious intestinal perforation has also occurred. Corticosteroids may be needed.
  • Pneumonitis has also been associated with PI3K inhibitors. Time to onset ranged from less than 1 to 15 months. Monitor for any unusual respiratory symptoms such as cough, or shortness of breath.
  • Serious hypersensitivity reactions, including anaphylaxis, have also been reported.
  • Bone marrow suppression, including grade 3 or 4 events, occurred in 58% of people treated with Zydelig. Blood counts should be monitored weekly or two weekly during the first 6 months of treatment, and treatment may need to be withheld, the dosage reduced or discontinued depending on the severity and persistence of the neutropenia.
  • Dosage adjustment, or Zydelig withheld or discontinued may be necessary for some side effects.
  • Zydelig is not recommended during pregnancy because of the risk of congenital malformations and reduced fetal weight. Effective contraception should be used during treatment with Zydelig and for 1 month after the last dose. Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Zydelig and for 3 months after the last dose. Do not breastfeed during your treatment with Zydelig and for 1 month after the last dose.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Zydelig is an oral PI3K inhibitor that may be used in combination with rituximab for the treatment of relapsed chronic lymphocytic leukemia. Severe and potentially life-threatening reactions have been reported with Zydelig including severe diarrhea, liver toxicity, and skin reactions, but one randomized RCT reported 19.4 months of progression-free survival (PFS) with Zydelig compared to 6.5 months with placebo.

5. Tips

  • Take Zydelig exactly as your healthcare provider tells you to take it. It is usually taken twice a day, with or without food. Swallow the tablets whole do not crush or chew.
  • If you miss a dose of Zydelig by less than 6 hours, take the missed dose right away. Then take your next dose as usual. If you miss a dose of Zydelig by more than 6 hours, wait and take the next dose of Zydelig at your usual time.
  • Zydelig can cause serious side effects that can lead to death. Tell your doctor about any serious or unusual side effects, such as severe diarrhea, yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea-colored) urine, pain in the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal, shortness of breath, worsening cough, shortness of breath, difficulty breathing, wheezing, fever, nausea, or vomiting. Also tell your healthcare provider right away if you get any of the following skin symptoms such as painful sores or ulcers on your skin, lips, or in your mouth, a severe rash with blisters or peeling skin, or rash with itching.
  • Tell your doctor if you are pregnant or intend to become pregnant. Zydelig may harm your unborn baby and females who are able to become pregnant should have a pregnancy test before starting treatment with Zydelig and use effective birth control (contraception) during treatment with Zydelig and for 1 month after the last dose of Zydelig. Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Zydelig and for 3 months after the last dose. Do not breastfeed during your treatment with Zydelig and for 1 month after the last dose.
  • Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Zydelig interacts with many other medicines.

6. Response and effectiveness

  • One randomized RCT in 220 patients reported a progression-free survival (PFS) of 19.4 months with Zydelig compared to 6.5 months with a placebo. The overall response rate was 83.6% with Zydelig and 15.5% with placebo. A difference in PFS was noted within 2 months of starting Zydelig.

7. Interactions

Medicines that interact with Zydelig may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Zydelig. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Zydelig interacts with over 780 different medications. Common medications that may interact with Zydelig include:

  • alcohol
  • anticoagulants such as dabigatran or warfarin
  • anticonvulsants such as divalproex or phenobarbital
  • antibiotics, such as ciprofloxacin, doxycycline,
  • antidepressants, such as venlafaxine
  • antipsychotics, such as clozapine
  • atomoxetine
  • azathioprine
  • benzodiazepines such as clonazepam,
  • biologics, such as imatinib or nilotinib
  • bowel cleansing agents such as sodium picosulfate
  • cannabis
  • chemotherapy agents such as bendamustine, vinblastine, or vincristine
  • cisapride
  • cortocosteroids such as cortisone, dexamethasone, or fluticasone
  • CYP3A4 inducers, such as erythromycin, diltiazem, itraconazole, ritonavir, or verapamil
  • CYP3A inhibitors, such as erythromycin, ketoconazole, clarithromycin, or verapamil
  • grapefruit juice
  • heart medications such as amlodipine, amiodarone, captopril, or enalapril
  • herbals, such as black cohosh, echinacea, or St. John's wort
  • high cholesterol medications such as atorvastatin
  • HIV medications such as atazanavir, cobicistat, didanosine, efavirenz, etravirine, indinavir, nevirapine, or ritonavir
  • immunosuppressants, such as cyclosporine
  • interferon
  • ketamine
  • loperamide
  • NSAIDs, such as diclofenac or ibuprofen
  • opioids, such as fentanyl or hydrocodone
  • probiotics such as bifidobacterium or lactobacillus
  • rifampin
  • salmeterol
  • sildenafil
  • sleep medications such as eszopiclone or zopiclone
  • terbinafine
  • tramadol
  • vaccinations, such as BCG and Cholera.

Zydelig may also increase the concentration of CYP3A substrates such as darunavir, ebastine, everolimus, ibrutinib, lomitapide, or lovastatin. Avoid coadministration with sensitive substrates.

Note that this list is not all-inclusive and includes only some common medications that may interact with Zydelig. You should refer to the prescribing information for Zydelig for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Zydelig only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: July 12, 2023.