Rituximab: Side effects, uses, dosage and warning

 

Rituximab Side effects

What is rituximab and its side effects?

Rituximab is a cancer drug that has revolutionized the treatment of non-Hodgkin lymphoma (NHL). It was first approved by the US Food and Drug Administration (FDA) in 1997.

Rituximab is a biological drug called a monoclonal antibody. It works by targeting a protein called CD20, which is found on a type of white blood cell called B cells. NHL and other conditions can affect B cells. It's not clear exactly how rituximab works, but it's known to recruit a patient's own immune system to attack and kill B cells.

Rituximab is available as Rituxan, the original version of rituximab. Biosimilars of rituximab are also available. Biosimilar versions of rituximab are highly similar to Rituxan and are designed to have the same effect on a person, but the biosimilars are not identical. Biosimilars of rituximab include:

  • Riabni (rituximab-arrx) approved in 2020
  • Ruxience (rituximab-pvvr) approved in 2019
  • Truxima (rituximab-abbs) approved in 2018

What is rituximab used for?

The Rituxan brand of rituximab is a prescription medicine used to treat:

  • Adults with NHL: alone or with other chemotherapy medicines.
  • Children 6 months of age and older with mature B-cell NHL and mature B-cell acute leukemia (B-AL): in combination with chemotherapy medicines.
  • Adults with Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.
  • Adults with Rheumatoid Arthritis (RA): with another prescription medicine called methotrexate, to reduce the signs and symptoms of moderate to severe active RA in adults, after treatment with at least one other medicine called a Tumor Necrosis Factor (TNF) antagonist has been used and did not work well enough.
  • Adults and children 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA): with glucocorticoids, to treat GPA and MPA.
  • Adults with Pemphigus Vulgaris (PV): to treat moderate to severe PV.

Rituxan is not indicated in children less than 2 years of age with GPA or MPA, in children less than 6 months of age with mature B-cell NHL and B-AL, or in children with conditions other than GPA, MPA, B-cell NHL and B-AL.

Biosimilar versions of rituximab are also used to treat some of the conditions listed above, but have not been approved to treat all of the same conditions.

Important information

Rituximab can cause serious side effects that can lead to death, including:

  • Infusion-related reactions. Infusion-related reactions are very common side effects of rituximab treatment. Serious infusion-related reactions can happen during your infusion or within 24 hours after your infusion of rituximab. Your healthcare provider should give you medicines before your infusion of rituximab to decrease your chance of having a severe infusion-related reaction. Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an infusion of rituximab:
    • hives (red itchy welts) or rash
    • itching
    • swelling of your lips, tongue, throat or face
    • sudden cough
    • shortness of breath, difficulty breathing, or wheezing
    • weakness
    • dizziness or feel faint
    • palpitations (feel like your heart is racing or fluttering)
    • chest pain
  • Severe skin and mouth reactions. Tell your healthcare provider or get medical help right away if you get any of these symptoms at any time during your treatment with rituximab:
    • painful sores or ulcers on your skin, lips or in your mouth
    • blisters
    • peeling skin
    • rash
    • pustules
  • Hepatitis B virus (HBV) reactivation. Before you receive your rituximab treatment, your healthcare provider will do blood tests to check for HBV infection. If you have had hepatitis B or are a carrier of hepatitis B virus, receiving rituximab could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems including liver failure, and death. You should not receive rituximab if you have active hepatitis B liver disease. Your healthcare provider will monitor you for hepatitis B infection during and for several months after you stop receiving rituximab. Tell your healthcare provider right away if you get worsening tiredness, or yellowing of your skin or white part of your eyes, during treatment with rituximab.
  • Progressive Multifocal Leukoencephalopathy (PML). PML is a rare, serious brain infection caused by a virus that can happen in people who receive rituximab. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML. Tell your healthcare provider right away if you have any new or worsening symptoms or if anyone close to you notices these symptoms:
    • confusion
    • dizziness or loss of balance
    • difficulty walking or talking
    • decreased strength or weakness on one side of your body
    • vision problems
  • See "What are the side effects of rituximab?" below for more information about side effects.

What should I tell my doctor before receiving rituximab?

Before you or your child receive rituximab, tell your healthcare provider about all of your or your child's medical conditions, including if you or your child:

  • have had a severe reaction to rituximab or a rituximab product
  • have a history of heart problems, irregular heart beat or chest pain
  • have lung or kidney problems
  • have an infection or weakened immune system.
  • If you have or have had any severe infections including:
    • Hepatitis B virus (HBV)
    • Hepatitis C virus (HCV)
    • Cytomegalovirus (CMV)
    • Herpes simplex virus (HSV
    • Parvovirus B19
    • Varicella zoster virus (chickenpox or shingles)
    • West Nile Virus
  • have had a recent vaccination or are scheduled to receive vaccinations. You or your child should not receive certain vaccines before or during treatment with rituximab.

How should I receive rituximab?

  • Rituximab is given by infusion through your or your child's central catheter or through a needle placed in a vein (intravenous infusion), in your or your child's arm. Talk to your healthcare provider about how you or your child will receive rituximab.
  • Your healthcare provider may prescribe medicines before each infusion of rituximab to reduce infusion side effects such as fever and chills.
  • Your healthcare provider should do blood tests regularly to check for side effects to rituximab.
  • Before each rituximab treatment, your healthcare provider or nurse will ask you questions about your general health. Tell your healthcare provider or nurse about any new symptoms.

Dosing information

  • The dose for adult and pediatric B-cell NHL is 375 mg/m2.
  • The dose for CLL is 375 mg/m2 in the first cycle and 500 mg/m2 in cycles 2–6, in combination with FC, administered every 28 days.
  • The dose as a component of Zevalin (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m2.
  • The dose for RA in combination with methotrexate is two-1,000 mg intravenous infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion .
  • The induction dose for adult patients with active GPA and MPA in combination with glucocorticoids is 375 mg/m2 once weekly for 4 weeks. The follow up dose for adult patients with GPA and MPA who have achieved disease control with induction treatment, in combination with glucocorticoids is two 500 mg intravenous infusions separated by two weeks, followed by a 500 mg intravenous infusion every 6 months thereafter based on clinical evaluation.
  • The induction dose for pediatric patients with GPA and MPA in combination with glucocorticoids is 375 mg/m2 once weekly for 4 weeks. The follow up dose for pediatric patients with GPA and MPA who have achieved disease control with induction treatment, in combination with glucocorticoids is two 250 mg/m2 intravenous infusions separated by two weeks, followed by a 250 mg/m2 intravenous infusion every 6 months thereafter based on clinical evaluation.
  • The dose for PV is two-1,000 mg intravenous infusions separated by 2 weeks in combination with a tapering course of glucocorticoids, then a 500 mg intravenous infusion at Month 12 and every 6 months thereafter or based on clinical evaluation. Dose upon relapse is a 1,000 mg intravenous infusion with considerations to resume or increase the glucocorticoid dose based on clinical evaluation. Subsequent infusions may be no sooner than 16 weeks after the previous infusion (2.7). Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion. Detailed Rituximab dosage information

What are the possible side effects of rituximab?

Rituximab can cause serious side effects, including:

  • See "Important information" above.
  • Tumor Lysis Syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause you or your child to have:
    • kidney failure and the need for dialysis treatment
    • abnormal heart rhythm

      TLS can happen within 12 to 24 hours after an infusion of rituximab. Your healthcare provider may do blood tests to check you or your child for TLS. Your healthcare provider may give you or your child medicine to help prevent TLS.  Tell your healthcare provider right away if you or your child have any of the following signs or symptoms or TLS:
      • nausea
      • vomiting
      • diarrhea
      • lack of energy
  • Serious infections. Serious infections can happen during and after treatment with rituximab, and can lead to death. Rituximab can increase your or your child's risk of getting infections and can lower the ability of your or your child's immune system to fight infections. Types of serious infections that can happen with rituximab include bacterial, fungal, and viral infections. After receiving rituximab, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these people with low antibody levels developed infections. People with serious infections should not receive rituximab. Tell your healthcare provider right away if you or your child have any symptoms of infection:
    • fever
    • cold symptoms, such as runny nose or sore throat that do not go away
    • flu symptoms, such as cough, tiredness, and body aches
    • earache or headache
    • pain during urination
    • cold sores in the mouth or throat
    • cuts, scrapes or incisions that are red, warm, swollen or painful
  • Heart problems. Rituximab may cause chest pain, irregular heartbeats, and heart attack. Your healthcare provider may monitor your or your child's heart during and after treatment with rituximab if you or your child have symptoms or heart problems or have a history of heart problems. Tell your healthcare provider right away if you or your child have chest pain or irregular heartbeats during treatment with rituximab.
  • Kidney problems, especially if you or your child are receiving rituximab for NHL. Rituximab can cause severe kidney problems that lead to death. Your healthcare provider should do blood tests to check how well your or your child's kidneys are working.
  • Stomach and Serious bowel problems that can sometimes lead to death. Bowel problems, including blockage or tears in the bowel can happen if you or your child receive rituximab with chemotherapy medicines. Tell your healthcare provider right away if you or your child have any severe stomach-area (abdomen) pain or repeated vomiting during treatment with rituximab.

Your healthcare provider will stop treatment with rituximab if you have severe, serious or life-threatening side effects.

The most common side effects of rituximab include:

  • infusion-related reactions. (see "Important information")
  • infections (may include fever, chills)
  • body aches
  • tiredness
  • nausea

In adult patients with GPA or MPA the most common side effects of rituximab also include:

  • low white and red blood cells
  • swelling
  • diarrhea
  • muscle spasms

In children with B-cell NHL or B-AL who receive rituximab with chemotherapy, the most common side effects include:

  • decreased white blood cells with fever
  • mouth sores
  • inflammation of the upper intestine
  • serious infection throughout the body and organs (sepsis)
  • changes in liver function blood tests
  • low level of potassium in the blood

Other side effects with rituximab include:

  • aching joints during or within hours of receiving an infusion
  • more frequent upper respiratory tract infection

These are not all of the possible side effects with rituximab.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Interactions

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctor if you take or have taken:

  • a Tumor Necrosis Factor (TNF) inhibitor medicine
  • a Disease Modifying Anti-Rheumatic Drug (DMARD)

If you are not sure if your medicine is one listed above, ask your healthcare provider. Rituximab drug interactions

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant. Talk to your healthcare provider about the risks to your or your child's unborn baby if you or your child receive rituximab during pregnancy.
Females who are able to become pregnant:

  • Your healthcare provider should do a pregnancy test to see if you or your child are pregnant before starting rituximab.
  • You or your child should use effective birth control (contraception) during treatment with rituximab and for 12 months after your or your child's last dose of Rrituximab. Talk to your healthcare provider about effective birth control.
  • Tell your healthcare provider right away if you or your child become pregnant or think that you or your child are pregnant during treatment with rituximab.

Tell your doctor if you are breastfeeding or plan to breastfeed. Rituximab may pass into your breast milk. Do not breastfeed during treatment and for 6 months after your or your child's last dose of rituximab.

Storage

Diluted rituximab (Rituxan) solutions for infusion may be stored refrigerated at 2°C to 8°C (36°F to 46°F) for 24 hours. Diluted rituximab solutions for infusion have been shown to be stable for an additional 24 hours at room temperature. However, since rituximab solutions do not contain a preservative, diluted solutions should be stored refrigerated (2°C to 8°C). No incompatibilities between rituximab and polyvinylchloride or polyethylene bags have been observed.

What are the ingredients in rituximab?

Active ingredient: rituximab

Inactive ingredients:

Rituxan: polysorbate 80, sodium chloride, sodium citrate dihydrate, and Water for Injection, USP.

Riabni: polysorbate 80, sodium chloride, sodium citrate dihydrate, and Water for Injection, USP. Hydrochloric acid is used to adjust the buffer solution pH.

Ruxience: edetate disodium dihydrate, L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and Water for Injection, USP.

Truxima: polysorbate 80, sodium chloride, tri-sodium citrate dihydrate, and Water for Injection, USP.

Rituximab products are manufactured by the following companies:

  • Rituxan: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990
  • Riabni: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799
  • Ruxience: Pfizer Ireland Pharmaceuticals Cork, Ireland, P43 X336 U.S.
  • Truxima:CELLTRION, Inc. 20, Academy-ro 51 beon-gil, Yeonsu-gu, Incheon, 22014 Republic of Korea
Important information about Rituximab

Generic name: rituximab, rituximab-arrx, rituximab-pvvr, rituximab-abbs
Brand names: Rituxan, Riabni, Ruxience, Truxima
Dosage form: intravenous (infusion) injection
Drug classes: AntirheumaticsCD20 monoclonal antibodies

Drugs Side Effects 101