Rituxan (Rituximab) Side Effects

Starting any new biologic therapy brings questions, and Rituxan (rituximab) is no exception. If your care team has recommended this treatment, you may be wondering what side effects to expect, which ones are normal, and which ones need prompt attention.

Most people who receive Rituxan tolerate it reasonably well, and it helps when you know what to expect and how to prepare.

Infusion reactions are the most common experience, especially during the first infusion, and most are manageable when caught and addressed early. The possible serious side effects, including infections, hepatitis B reactivation, and a rare brain infection, are less common but important to understand before starting Rituxan.

This guide walks through the key Rituxan side effects, from the most frequently reported to the ones worth watching most closely. If you’re new to infusion therapy and want to understand what to expect, this is a good place to start.

What Is Rituxan (Rituximab) and Who Receives It?

Rituxan (rituximab) is an FDA-approved monoclonal antibody used to treat several serious autoimmune and blood conditions. It targets a protein called CD20, found on the surface of B-cell lymphocytes. By binding to these cells, it signals the immune system to remove them from circulation, reducing the harmful immune activity driving the disease.

Rituximab is used to treat the following conditions:

• Non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL), where patients often receive Rituxan with chemotherapy medicines as part of a combined treatment approach
• Rheumatoid arthritis (RA), when other disease-modifying treatments haven’t worked well enough
• Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)
• Pemphigus vulgaris

Acelpa Health and its affiliated specialty pharmacies—California Specialty Pharmacy (CSP), ContinuumRx (CRx), Hawaii Specialty Pharmacy (HSP), Continuum Health (CH), and Integrated Care Systems (ICS)—support patients across oncology, rheumatology, and other specialty areas with Rituxan treatment.

Before starting Rituxan, your health care provider will run blood tests to check liver function and screen for hepatitis B infection. It’s also important to discuss any vaccines that may be needed, as live vaccines should be avoided during treatment. Completing needed vaccines at least two to four weeks before starting Rituxan (rituximab) gives them time to take effect.

If you’re of childbearing age, it’s also a good idea to discuss pregnancy planning early, as the medication requires contraception during treatment and for several months after the last dose of Rituxan.

Infusion Reactions

Infusion reactions are the most frequently reported side effect with Rituxan (rituximab), particularly during the first infusion. Because the body is encountering the antibody for the first time, the immune system can respond in ways that feel uncomfortable, but these reactions are usually manageable and often improve with each subsequent dose.

Symptoms and Timing

Most infusion reactions come on within the first one to two hours of starting the intravenous infusion. Common symptoms of infusion-related reactions to Rituxan (rituximab) include:

• Fever, chills, or shaking similar to flu symptoms
• Flushing, rash, or itching
• Muscle soreness, aches, or spasms
• Headache
• Nausea, vomiting, or diarrhea
• Swelling of the lower limbs
• Loss of appetite
• Throat tightness or mild shortness of breath
• Chest pain or changes in blood pressure
• Fatigue during or after the infusion, sometimes lasting a day or two

These mild side effects tend to lessen or resolve as the body adjusts to the medication with each dose. Most infusion reactions clear within hours to two days after treatment.

How Your Care Team Manages Reactions

Before the infusion begins, your nurse will give you medicines before your infusion, known as premedications, designed to reduce the likelihood and severity of a reaction. These typically include acetaminophen, an antihistamine (like diphenhydramine), and sometimes a corticosteroid.

The infusion starts slowly, and the rate increases gradually if you’re tolerating it well.

If any symptoms develop, your nurse can slow or pause the infusion until they settle. If you’ve had a reaction to a previous infusion, tell your provider or care team ahead of time so they can adjust the protocol accordingly.

The Split-Dose Approach

Some infusion centers use a split-dose approach for the first Rituxan infusion, particularly for patients considered higher risk for reactions.

In this approach, approximately 20% of the total dose is given on day one and the remaining 80% on day two. This is a site-specific and prescriber-discretion practice used alongside premedication and careful rate titration (it isn’t an FDA label requirement), but it can meaningfully reduce reaction risk for patients who may be more sensitive.

Effects on Blood and Immune Function

Rituxan (rituximab) specifically targets B cells, but its effects on the immune system can be broader and longer-lasting than the infusion itself. Your care team will monitor your blood counts closely throughout treatment and in the months following.

Low White Blood Cell Counts

While Rituxan targets B cells, it can also affect other white blood cell counts over time. Lower white blood cell levels reduce the body’s ability to fight infection, sometimes significantly. These effects can be delayed, appearing weeks to even months after a treatment course, and B cell suppression may persist for up to 12 months after completing treatment.

Signs of infection that should prompt an immediate call to your health care provider include:

• Fever above 100.4°F
• Chills or persistent cough
• Burning with urination
• Any wound that isn’t healing or is getting worse

Good hygiene, avoiding close contact with sick people, and keeping up with regular lab work all help protect you during this period. Your provider may also advise on timing for vaccines before or during treatment while your immune system recovers.

Tumor Lysis Syndrome

Patients receiving Rituxan treatment for cancer may face a specific complication called tumor lysis syndrome. This happens when a large number of cancer cells die rapidly and release their contents into the bloodstream, which can overwhelm the kidneys and cause electrolyte imbalances.

Symptoms to be aware of include:

• Muscle cramps, weakness, or tingling
• Nausea, loss of appetite, and decreased urination
• Irregular heartbeat in more severe cases

Your care team will take steps to prevent tumor lysis syndrome with extra IV fluids and, in some cases, medications to protect kidney function. The risk is highest around the time of the first infusion.

Monitoring Blood Counts Throughout Treatment

Because the adverse effects of Rituxan on blood cells can be delayed and cumulative, regular lab work is a standard part of treatment with Rituxan.

Your care team will schedule blood tests before and at intervals after each infusion cycle. These results guide decisions about dosing timing, infection precautions, and when it’s safe to receive vaccines.

Serious Risks

There are also certain possible serious side effects associated with Rixutan (rituximab) use, which should be understood before starting treatment. While these life-threatening side effects are uncommon, knowing what to watch for is essential.

Hepatitis B Reactivation

Hepatitis B virus can remain dormant (inactive) in the liver for years without causing symptoms. Rituxan can trigger reactivation of a previously inactive hepatitis B infection, which can cause serious liver problems, including potentially life-threatening liver damage. This is why screening for both current and past hepatitis B is required before starting Rituxan.

If testing reveals a prior or active infection, your provider will determine whether antiviral medication is needed before and during treatment. In some cases, your health care provider may recommend stopping treatment or delaying the start of Rituxan until the infection is addressed. Monitoring for hepatitis B reactivation continues throughout therapy, not just at the start.

Risk of Serious Infections

Beyond the general immunosuppressive effects of Rituxan, patients face a heightened risk of serious infections, including some caused by bacteria, fungi, and viruses.

Respiratory infections, urinary tract infections, and skin infections are among the more commonly reported issues. The use of Rituxan can make it harder for the body to fight these infections, which is why mentioning them early is so important.

Signs of a serious infection to tell your provider about promptly include persistent fever, a cough that won’t resolve, night sweats, and wounds that worsen rather than heal. You can also report side effects to the FDA at 1-800-FDA-1088. Reporting serious infections and other adverse effects helps track safety data for patients receiving Rituxan.

Progressive Multifocal Leukoencephalopathy (PML)

PML is a rare but serious brain infection caused by the JC virus that has been reported in patients receiving Rituxan and other medications that affect the immune system. While the risk appears low, this is one of the most serious possible side effects of Rituxan, and early recognition is critical.

Symptoms of PML develop gradually and may include:

• Confusion or memory problems
• Difficulty speaking or understanding language
• Vision changes
• Weakness on one side of the body

Any new or unexplained neurological symptoms should be reported to your provider right away. Don’t wait for a scheduled appointment, as stopping treatment with Rituxan promptly may be necessary if PML is suspected.

Pregnancy and Family Planning

Rituxan (rituximab) requires careful planning for anyone who could become pregnant. This medication can cross the placenta and affect the developing baby’s immune function. Women should avoid becoming pregnant during treatment and for at least 12 months after the last dose of Rituxan.

If you become pregnant during treatment, notify your care team immediately. They’ll review your specific situation and discuss next steps.

Because Rituxan may pass into breast milk, most providers recommend avoiding breastfeeding during treatment and for at least 6 months after the last dose.

Talking about these timelines and your family planning goals with your health care provider before starting Rituxan makes coordination much easier and helps you make sure that you have the important side effect information you need before treatment begins.

Staying Ahead of Rituxan Side Effects

Understanding the possible side effects of Rituxan (rituximab) before they even happen puts you in a much stronger position when it comes to managing them.

Completing hepatitis B screening, making sure vaccines are up to date weeks before starting Rituxan, attending all monitoring appointments, and staying in open communication with your care team are the most effective steps you can take.

A simple symptom log between infusion appointments, tracking things like energy levels, any new symptoms, and how long they last, gives your care team useful context and helps identify early changes that may need attention.

Have questions about starting or managing Rituxan treatment? Talk to the team at Acelpa Health and its affiliated pharmacies. We’re ready to help you navigate your treatment with confidence.

Frequently Asked Questions (FAQ):

What are the most common side effects of Rituxan?

Infusion reactions are the most commonly reported side effect of Rituxan, especially with the first dose. Common side effects of Rituxan include fever, chills, rash or itching, flushing, throat tightness, shortness of breath, nausea, chest pain, and changes in blood pressure. Most mild side effects are managed with medicines before your infusion and by adjusting the infusion rate, and they often improve with each subsequent dose.

What are the most serious risks associated with Rituxan?

One of the most serious risks is progressive multifocal leukoencephalopathy (PML), a rare and potentially life-threatening brain infection caused by the JC virus. Other possible serious side effects include hepatitis B reactivation, which can cause serious liver problems, severe infusion reactions, tumor lysis syndrome in cancer patients, and serious infections. Any new or worsening neurological symptoms, difficulty breathing, or signs of liver problems should be evaluated urgently by your health care provider.

How long do Rituxan side effects last?

Most infusion reactions resolve within hours to two days after treatment. Mild fatigue or flu-like symptoms may linger for a few days. Some effects are delayed: low white blood cell counts can appear weeks to months after treatment, and B-cell suppression and elevated infection risk may persist for several months after completing a treatment course. B-cell levels typically begin recovering within 12 months after the last dose.

What is the 20/80 split-dose approach for Rituxan?

Some infusion centers use a split-dose method for the first Rituxan infusion to decrease the chance of reactions in higher-risk patients. Approximately 20% of the total dose is given on day one, with the remaining 80% administered on day two. This is a prescriber-specific practice rather than a label requirement, used alongside premedication and careful rate management. Ask your care team whether this approach applies to your treatment plan.

Can Rituxan cause hepatitis B reactivation?

Yes. In patients who have had hepatitis B in the past, even if it was dormant, receiving Rituxan can cause the virus to become active again and cause serious liver problems. This is why hepatitis B screening is required before the first dose, and monitoring continues throughout treatment. If past exposure is detected, antiviral medications may be prescribed before and during Rituxan treatment. In some situations, your health care provider may delay or stop your Rituxan treatment until the infection is under control.