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Treatment Name: Idelalisib (Zydelig®) + Rituximab

Idelalisib (Zydelig®) + Rituximab is a Chemotherapy Regimen for Chronic Lymphocytic Leukemia (CLL)

How does idelalisib (Zydelig®) + rituximab work?
Idelalisib works by turning off a protein called PI3K (phosphatidylinositol 3-kinase), which stops cancerous b-lymphocytes from growing and dividing plus kills the cancer cells.

Rituximab is an antibody that is designed to target and bind to a protein on the surface of cancerous b-cells. When rituximab binds to this protein, it helps your immune system find and destroy the cancer cell. Rituximab is known as immunotherapy.

Goals of therapy:
Idelalisib + rituximab is given to alleviate symptoms of CLL such as enlarged lymph nodes, enlarged liver or spleen, or symptoms of abnormal bone marrow function, such as frequent infection. It is not commonly given with the goal of cure, but may help patients live longer.


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  • Rituximab intravenous (I.V.) infusion once every two weeks for ten weeks, then once every month for 3 months. The time of infusion varies depending on tolerability
  • Usual idelalisib starting dose: 150 mg oral tablet by mouth twice daily

Estimated total infusion time for this treatment:

  • Up to six hours for the first treatment of rituximab and as short as two hours for the following treatments if tolerated well
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time

Rituximab is usually given in an outpatient infusion center, allowing the person to go home afterwards while idelalisib is usually taken at home.

Rituximab is given for 8 total treatments while idelalisib is taken until the drug stops working or until unacceptable side effects occur. Duration of therapy depends upon response, tolerability, and number of cycles prescribed.

Click here for the common starting doses of idelalisib + rituximab.

Side Effects

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported idelalisib + rituximab side effects are shown here.

  • Low white blood cells [neutropenia] (55%)
  • Liver injury (35%)
  • Fever (29%)
  • Anemia [low red blood cells] (25%)
  • Fatigue (24%)
  • Nausea (24%)
  • Chills (22%)
  • Diarrhea (19%)
  • Increased bleeding risk [low platelets] (17%)
  • Cough (15%)
  • Infusion reactions (15%)
  • Decreased appetite (12%)
  • Vomiting (12%)
  • Constipation (12%)
  • Shortness of breath (11%)
  • Skin rash (10%)
  • Night sweats (10%)
  • Pneumonia (6%)
  • Neutropenic fever (5%)
  • Bacterial blood infection (4%)
  • Inflammation of the lungs (4%)

On average, 5% of patients in this clinical trial discontinued treatment due to unacceptable side effects.

Side effect videos Side Effect Videos
Neutropenic FeverNeutropenic FeverAnemiaAnemiaFatigue Fatigue Nausea and VomitingNausea and VomitingDiarrheaDiarrheaPainPainConstipationConstipation


How often is monitoring needed?
Labs (blood tests) may be checked before treatment, every two weeks for 12 weeks, then every four weeks for 12 weeks, then every six weeks until stable. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked before treatment then approximately every 8 to 12 weeks. Imaging may include: magnetic resonance imaging (MRI) or computerized tomography (CT) scans of the neck, chest, abdomen, and pelvis.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue idelalisib + rituximab as planned, change the doses, or delay or switch therapy.

ChemoExperts Tips

  • Severe diarrhea can occur in as high as 20% of patients and typically does not respond to conventional anti-diarrheal medications such as loperamide (Imodium®). If you are experiencing 3 to 4 or more bowel movements a day, contact your doctor as uncontrolled diarrhea can lead to dehydration and significant blood electrolyte abnormalities
  • Although rare, serious lung injuries can occur. Report and new or increasing shortness of breath, cough, wheezing, or chest pain to your doctor as these could be signs of lung injury and may need treatment with corticosteroids such as prednisone or methylprednisolone (Solu-Medrol®)
  • A very rare fungal infection known as pneumocystis jirovecii (PJP) in the lungs have been reported. Medications such as sulfamethoxazole/trimethoprim (Bactrim®) may be used while on idelalisib to prevent this type of infection
  • Pre-medications may be given before rituximab to help avoid infusion related reactions, these include: diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and hydrocortisone (Solu-Cortef®)
  • The first dose of rituximab is often the most difficult, or takes the longest to infuse. It may lead to fever, shaking, and chills even if “pre-medications” are given to help prevent these side effects. Side effects generally go away when the rituximab is stopped. It may be restarted at a slower rate. Most patients are able to receive the entire dose, although it may take longer. If rituximab is well tolerated, it may be infused over 90 minutes
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for CLL. Ask your doctor if any studies are currently enrolling in your area. If not, go to to search for other centers offering study medications

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Idelalisib (Zydelig®) + Rituximab, we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Idelalisib (Zydelig®) + Rituximab. Depending upon your income, they may be able to help cover the cost of:

  • Idelalisib
  • Rituximab

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Idelalisib (Zydelig®) + Rituximab and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with Idelalisib (Zydelig®) + Rituximab

Individual Drug Label Information

Idelalisib (Zydelig®)

  • ​Is an oral 100 mg or 150 mg tablet 
  • Serious diarrhea can occur. If you are having 3 to 4 or more bowel movements a day, contact your doctor 
  • May cause liver injury. Labs to monitor liver function will be tested often. Contact your doctor immediately if you experience yellowing of the skin or eyes, very dark urine, or unexplained abdominal pain 
  • Life threatening infections can occur. Monitor your temperature often 
  • Notify your doctor if you are experiencing new shortness of breath or cough as this could be a sign of a serious lung injury from idelalisib 
  • Can be taken with or without food. Swallow tablet whole and do not crush 
  • If you miss a dose, you still may take the dose if less than six hours has passed from the scheduled dosing time. If more than six hours has passed from the scheduled dosing time, skip the missed dose and take the next dose as scheduled. DO NOT double the dose to make up for the missed dose 
  • Store at room temperature and in the original container 
  • Dosage adjustments may be required if serious side effects are experienced 
  • May interact with certain antifungal and seizure medications. Ask your doctor or pharmacist to review your medications for any possible interactions  
  • May interact with grapefruit and grapefruit juice causing increased blood levels of idelalisib. This could increase your risk of experiencing side effects. Avoid eating grapefruit and drinking anything containing grapefruit juice during treatment  
  • Avoid therapy with St. Johns Wort as it will decrease blood levels of idelalisib. This could decrease the effectiveness 
  • May cause fetal harm. It is recommend that women of reproductive potential use contraception during therapy and for at least one month after stopping treatment 
General side effects from idelalisib (Zydelig®) 
  • Low red blood cells, white blood cells, and platelets are common 
  • Skin rash or more serious skin reaction may occur 
  • Decreased appetite and weight loss 
  • Nausea and vomiting 
  • Constipation 
  • Night sweats 
  • Fluid retention 
  • Click on the idelalisib (Zydelig®) package insert below for all reported side effects and possible drug interactions  

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaFatigue Fatigue ConstipationConstipationPainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Rituximab (Rituxan®, Truxima®, Ruxience®)

  • Rituximab is an intravenous infusion
  • Acetaminophen (Tylenol®) and antihistamines (e.g. diphenhydramine = Benadryl®) should be given prior to each dose
  • Patients should be screened for hepatitis B as rituximab can cause a re-activation of this infection
  • May cause vaccines to work less well. It is advised that vaccines be given two to four weeks prior to rituximab if possible
General Rituximab Side Effects
  • May cause an infusion reaction, which could include skin reaction, shaking, chills, fever, or shortness of breath. These reactions may be severe, but are very rarely life-threatening
  • Infusion reactions does not usually happen after the first dose, but are possible
  • May increase the risk of infection. Your doctor may prescribe antibiotics to prevent certain infections associated with rituximab use
  • Click on the rituximab package insert below for reported side effects and potential drug Interactions
See DailyMed package insert.

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1. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370:997-1007.

2. Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370:1008-1018.

Created: April 24, 2017 Updated: October 17, 2018

What is Chronic Lymphocytic Leukemia (CLL)?

Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia diagnosed in adults. It is a cancer of the B-lymphocyte. In rare cases, CLL may be hereditary, but most causes are unknown. The stage of CLL can vary at diagnosis and throughout treatment. Stages of CLL include Rai stage 0, I, II, III, or IV. Many therapies are not curative, however, newer therapies are able to suppress the cancer for many months or even years.

As depicted in the picture, CLL may affect lymph nodes, the spleen, bone marrow, and the blood.

CLL may affect lymph nodes, the spleen, bone marrow, and the blood

Medications for CLL may include intravenous infusions, oral tablets or capsules, or a combination of IV and oral medications. Patients may be diagnosed with CLL without having any symptoms. Others may go to their doctor with symptoms of fatigue, a large spleen, or decreased appetite. The effectiveness of the treatment may depend upon the stage at diagnosis.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.

What is an Antibody?

An antibody is a small protein shaped like a “Y” that can attach to specific things in the blood, such as a cancer cell.
  • Once an antibody binds to something, your immune system may attempt to get rid of it.
  • Antibodies may also work by binding to the cancer cell surface and prevent other things from binding to the cancer cell that help it survive. Without the ability to bind growth factors, cancer cells may be forced to die"

Common Starting Doses

  • Rituximab 375 mg/m2 intravenous (I.V.) infusion once, then 500 mg/m2 I.V. infusion once every two weeks for four more doses, then once monthly for 3 months (eight total doses)
  • Idelalisib 150 mg oral tablet by mouth twice daily

Note: Individual doses may vary based on your Doctor's recommendation, or drug availability

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

14) Serum calcium