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Treatment Name: Rituximab + Hyaluronidase (Rituxan Hycela®)

Rituximab + Hyaluronidase (Rituxan Hycela®) is an Immunotherapy Regimen for Lymphoma, B-cell

How does subcutaneous rituximab hyaluronidase (Rituxan Hycela®) work?

  • Rituximab is an FDA approved 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 destroy the cancer cell
  • Hyaluronidase is a naturally occurring protein in the body that increases the ability of the tissue under the skin to absorb fluid. Hyaluronidase helps absorption of rituximab when given together as an injection under the skin

Goals of therapy:
Cancer patients with B-cell Lymphoma that have symptoms such as fevers, night sweats, and weight loss may benefit from Rituximab Hyaluronidase (subcutaneous Rituxan Hycela). It is a blood cancer treatment injected alone or prescribed with chemotherapy. Rituximab hyaluronidase is often given with the goal of cure, but may be given as maintenance therapy to keep lymphoma in remission.


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  • Rituximab hyaluronidase is injected over 5 to 7 minutes subcutaneously (SC or SubQ or SQ) into the abdomen on Day 1 of each Cycle
  • Injection times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications with acetaminophen (Tylenol®), an antihistamine (Benadryl®), and intravenous (I.V.) fluids, such as hydration, may add more time

Before getting rituximab hyaluronidase by subcutaneous administration, cancer patients receiving this must get at least one full infusion of intravenous Rituxan due to the risk of infusion reactions with the first dose. If no reactions occur, subcutaneous rituximab hyaluronidase may be substituted for I.V. rituximab as a way to reduce the time patients need to spend in an outpatient infusion center. On occasion, it may be given in the hospital if someone is too sick. Patients are observed for side effects for at least 15 minutes after each injection.

How often rituximab hyaluronidase is given is dependent upon the schedule of your chemotherapy regimen.

Click here for the common rituximab hyaluronidase (Rituxan Hycela®) starting doses.

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

Side Effects

In clinical studies, the most commonly reported side effects of rituximab hyaluronidase are shown here. Side effects sometimes have percentage ranges [example: 14 – 32%] because they differed between clinical studies. Additionally, side effects reported with rituximab hyaluronidase depend upon which chemotherapy agents it was combined with:

  • Low white blood cells [neutropenia], (14 - 32%)
  • Nausea, (9 - 32%)
  • Constipation, (5 - 25%)
  • Cough, (5 - 23%)
  • Low red blood cells [anemia], (10 - 21%)
  • Fatigue, (9 - 20%)
  • Diarrhea, (5 - 18%)
  • Weakness, (17%)
  • Injection site reactions [redness, itching, rash, mild pain], (5 - 16%)
  • Tingling or numbness in fingers or toes, (5 - 16%)
  • Sinus infection, (10 - 15%)
  • Fever, (6 - 15%)
  • Stomach pain, (14%)
  • Hair loss, (13 - 14%)
  • Vomiting, (3 - 14%)
  • Headache, (13%)
  • Joint pain, (13%)
  • Neutropenic fever, (8 - 13%)
  • Shortness of breath, (11%)
  • Pneumonia, (5 - 11%)
  • Itching, (10%)
  • Bone pain, (10%)
  • Rash, (10%)
  • Pain in arms or legs, (10%)
  • Sore throat. (9%)

Note: in clinical trials, rituximab hyaluronidase was investigated in combination with chemotherapy (R-CHOP or R-CVP or R-Bendamustine) therefore it is unknown if the reported side effect frequencies are due to combination with chemotherapy or single agent rituximab hyaluronidase. The risk of neutropenic fever may be greater when subcutaneous rituximab is given as compared to I.V. rituximab.

Side effect videos Side Effect Videos
Nausea and VomitingNausea and VomitingConstipationConstipationAnemiaAnemiaFatigue Fatigue DiarrheaDiarrheaPainPainNeutropenic FeverNeutropenic Fever


How often is monitoring needed?
Labs (blood tests) may be checked before each treatment and in-between treatments at the discretion of your doctor. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), uric acid, phosphorous, Lactate Dehydrogenase (LDH), plus any others your doctor may order. Hepatitis B screening and Human Immunodeficiency Virus (HIV) screening may also be done before starting treatment.

How often is imaging needed?
Imaging may be checked before treatment then approximately after every two or three cycles. Imaging may include: computerized tomography (CT) scan or positron emission tomography (PET) scans.

How might blood test results/imaging affect treatment options?
Depending upon the results, your doctor may advise to continue rituximab hyaluronidase as planned, pause treatment, change the dose, or switch to an alternative (different) therapy.

Questions to Ask Your...

A better understanding of your treatments will allow you to ask more questions of your healthcare team. We then hope that with the answers, you will get better results and have greater satisfaction with your care. Because we know it's not always easy to know what questions to ask, we've tried to make it easy for you!

Choose any healthcare provider below to see common questions that you may want to ask of this person. Then, either print each list to bring to your clinic visits, or copy the questions and send them as a message to your healthcare team through your electronic medical record.

ChemoExperts Tips

  • Premedications such as diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and hydrocortisone (Solu-Cortef®) may be given before rituximab hyaluronidase to help prevent infusion-related side effects. Oral premedications were given in the clinical studies
  • Due to the amount of liquid that is injected, the entire dose of rituximab hyaluronidase must be injected slowly over at least 5 to 7 minutes. Patients will be watched closely for at least 15 minutes after the injections for any reactions
  • Patients and/or caregivers should have a plan in place if a reaction to the injection happens at home. Talk to your doctor about what you should do to prepare
  • Rituximab hyaluronidase should ONLY be injected into the abdomen. No other injection site on the body should be used
  • Do NOT combine any other subcutaneously administered medications, such as insulin or other medications for diabetes, in the same injection site as rituximab hyaluronidase. This will help avoid cutaneous reactions (skin reactions)
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for b-cell lymphoma. Ask your doctor or healthcare professional 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 Rituximab + Hyaluronidase (Rituxan Hycela®), 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 Rituximab + Hyaluronidase (Rituxan Hycela®). Depending upon your income, they may be able to help cover the cost of:

  • Rituximab Hyaluronidase

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 Rituximab + Hyaluronidase (Rituxan Hycela®) 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 Rituximab + Hyaluronidase (Rituxan Hycela®)

Individual Drug Label Information

Rituximab Hyaluronidase (Rituxan Hycela®)

  •​A subcutaneous (SubQ, SQ, SC) injection that is clear or slightly yellow in color 
  • Severe mucocutaneous (skin) reactions can occur and can be fatal
  • Progressive Multifocal Leukoencephalopathy (PML) can occur after taking this drug if there is a certain underlying infection virus infection. This a serious disease of the brain and your doctor will monitor for this if you have a new onset of neurologic symptoms
  • Acetaminophen (Tylenol®) and an antihistamine (e.g. diphenhydramine = Benadryl®) should be given prior to each dose, and may be given by mouth as tablets or capsules 
  • Patients should be screened for hepatitis B as rituximab hyaluronidase 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 hyaluronidase if possible 
  • May cause fetal harm while pregnant. Use effective contraception during therapy and for 12 months following completion of therapy. Do not breastfeed for at least 6 months following the completion of therapy 
General side effects from rituximab hyaluronidase (Hycela®)
  • May cause an infusion reaction, which could include skin reaction, shaking, chills, fever, low blood pressure, shortness of breath, or other symptoms. These reactions may be severe, but are very rarely life-threatening 
  • TLS (Tumor Lysis Syndrome) can occur 12 to 24 hours after a dose is given; your doctor will monitor your blood for this type of situation 
  • May increase the risk of infection. Doctors may prescribe antibiotics or antiviral medications to prevent certain infections associated with rituximab use 
  • Kidney toxicity can occur after a dose of rituximab hyaluronidase. Certain blood tests can help detect if kidney function is being affected by this drug 
  • May cause injection site pain, swelling, or redness 
  • The most common adverse reactions were different depending on what cancer type was being treated 
  • Click on the rituximab hyaluronidase (Rituxan Hycela®) "See DailyMed package insert" link below for reported side effects, possible drug interactions, and other rituximab hyaluronidase prescribing information 

Side Effect Videos

See DailyMed package insert.

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1) Davies A, Merli F, Mihaljević B, et al. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017;4:e272-e282.

2) Lugtenburg P, Avivi I, Berenschot H, et al. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica 2017;102:1913-1922.

Created: November 25, 2017 Updated: December 5, 2018

What is Lymphoma, B-cell?

B-cell Lymphoma is a disease of the white blood cells known as B-lymphocytes which are normally found in lymph nodes, blood, and throughout the body. There are many different types of lymphoma, most of which are rare. Known causes of lymphoma may include immunosuppressive medications, infections such as HIV, while some causes are still unknown. The stage of lymphoma can vary at diagnosis and throughout treatment. The effectiveness of the treatment may depend upon the sub-type of lymphoma and 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 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"

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.

Rituximab hyaluronidase (Rituxan Hycela®) starting recommended dose

  • Rituximab hyaluronidase (Rituxan Hycela®) 1,400 mg/23,400 units subcutaneous injection (SubQ) over 5 minutes into the abdomen

Clinical Studies

1) Davies A, Merli F, Mihaljević B, et al. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017;4:e272-e282.

2) Lugtenburg P, Avivi I, Berenschot H, et al. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica 2017;102:1913-1922.

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