Side Effects of Rituximab for CAD

Brian Murphy, Ph.D. avatar

by Brian Murphy, Ph.D. |

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rituximab and side effects

Cold agglutinin disease (CAD) is an autoimmune disorder where the body attacks its red blood cells during exposure to cold temperatures. Rituximab is increasingly used to treat CAD. Here is information about rituximab, and the range of side effects associated with its use.

What is rituximab?

Rituximab (brand names Rituxin in the U.S., MabThera in Europe) is an antibody that attaches to a receptor called CD20 on B-cells, depleting their numbers. B-cells are part of the immune system that produce antibodies. In CAD, B-cells produce antibodies that target the body’s own cells (autoantibodies) — in this case, red blood cells in response to cold. By lowering B-cell levels, rituximab can lessen the loss of red blood cells, and help alleviate symptoms of CAD.

Rituximab is delivered through a number of intravenous (IV) infusions at a medical center where clinical staff can monitor patients for reactions or side effects. It is generally given in a series of four doses, either once a week or once a month depending on whether it is paired with other treatments.

The U.S. Food and Drug Administration (FDA) approved rituximab to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris. Doctors use it off-label to treat CAD.

Side effects of rituximab

Rituximab can cause a number of side effects that vary from minor to severe, and can affect multiple body systems. If you have existing heart, lung, or kidney disease you should not take rituximab, as it could lead to life-threatening complications.

Below are some categories of side effects reported with rituximab, both serious and more general.

Infusion-related reactions

Some patients may experience infusion-related reactions within 24 hours of a rituximab infusion. These reactions can be life-threatening and require urgent medical care. An estimated 80% of fatal reactions occur during the first infusion of rituximab. To reduce the risk of infusion-related reactions, doctors usually give patients an antihistamine or acetaminophen (like Tylenol) prior to infusion.

Possible infusion-related reactions include:

  • Hives (urticaria)
  • Low blood pressure
  • Swelling (angioedema)
  • Lack of oxygen (hypoxia)
  • Airway spasms
  • Fluid around the lungs
  • Heart attack
  • Erratic heartbeat
  • Anaphylactoid (serious allergic) reactions

Reactivation of hepatitis B

If you had a previous hepatitis B infection or are a carrier of this virus, you may be at risk of having the virus reactivated by rituximab. Reactivated hepatitis B can lead to fulminant hepatitis, liver failure, and possible death. You should undergo a test for hepatitis B before treatment with rituximab, and be monitored for symptoms during and after treatment.

Progressive multifocal leukoencephalopathy

Treatment with rituximab weakens your immune system. This can lead to progressive multifocal leukoencephalopathy (PML), a rare and serious brain infection due to infection by the John Cunningham virus.

Skin and mouth reactions

Rituximab may cause severe skin and mouth reactions during and after treatment. These reactions can include sores, ulcers, blisters, rash, and peeling of the skin on the lips and mouth.

Tumor lysis syndrome

CAD has been linked to some forms of cancer, particularly lymphoid malignancies. In addition to targeting B-cells, rituximab can kill certain types of cancer cells. The rapid breakdown of cancer cells releases a large amount of uric acid, potassium, and phosphorus into the blood, potentially leading to tumor lysis syndrome (TLS). This syndrome is marked by damage to the kidneys, especially,  but the heart, brain, muscles, and gastrointestinal tract can also be affected. Possible warning signs of TLS include vomiting, diarrhea, nausea, and lack of energy.

Serious infections

Rituximab weakens the body’s immune system by reducing the number of B-cells. A weakened immune system can leave you more susceptible to contracting serious infections, and less able to fight them. If you have a serious infection, you should not be treated with rituximab. If you are undergoing treatment, you should try to avoid situations that could exposure you to infection — including being vaccinated with an active virus vaccine, or being around people who are sick.

Digestive system issues

Some patients may develop abdominal pain, intestinal blockages, or holes in their digestive tracts. These issues can become life-threatening; inform you doctor if you have pain in the stomach area during treatment with rituximab.

Pregnancy risk

Rituximab can damage a developing fetus, so if you are pregnant or planning a pregnancy, you should not begin treatment with rituximab. If you are currently using it, you should wait 12 months after treatment before trying for pregnancy.

More common side effects

More common side effects of rituximab use can include:

  • Nausea
  • Runny nose
  • Fatigue
  • Headache
  • Swelling of tongue or throat
  • Itching
  • Blurred vision
  • Body aches
  • Discolored stool
  • Increased hunger or thirst
  • Seizures
  • Vomiting
  • Unusual bleeding or bruising
  • Ear congestion
  • Drowsiness


Last updated: Nov. 5, 2020


Cold Agglutinin Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.