Riximyo: Uses, Dosage & Side Effects

What Is Riximyo and What Is It Used For?

Riximyo contains the active substance rituximab, a chimeric (mouse/human) monoclonal immunoglobulin G1-kappa antibody produced by recombinant DNA technology in mammalian (Chinese hamster ovary) cell culture. Monoclonal antibodies are engineered proteins that recognize and bind to a single specific target on the surface of cells. Rituximab is engineered to recognize and bind to the CD20 antigen, a transmembrane phosphoprotein expressed on the surface of B lymphocytes during most stages of their development.

CD20 is found on more than 95% of B cells in non-Hodgkin’s lymphoma and chronic lymphocytic leukemia, as well as on normal B lymphocytes. Importantly, CD20 is not expressed on hematopoietic stem cells (the precursors in the bone marrow that produce all blood cells), pro-B cells, normal plasma cells (the antibody-producing cells derived from mature B cells), or any other normal tissue. This restricted expression pattern means that rituximab can selectively deplete mature B cells and malignant B cells while sparing the stem cells needed to regenerate the B-cell pool, allowing the immune system to recover over time.

When rituximab binds to the CD20 antigen on the surface of a B cell, it triggers cell killing through at least four mechanisms: complement-dependent cytotoxicity (CDC), in which proteins of the complement system are activated to punch holes in the target cell; antibody-dependent cellular cytotoxicity (ADCC), in which natural killer cells and macrophages recognize the antibody-coated B cell and destroy it; direct induction of apoptosis (programmed cell death) through intracellular signaling; and sensitization of resistant malignant cells to chemotherapy. The net result is a rapid and profound depletion of circulating B cells, which typically occurs within hours of the first infusion.

Riximyo is a biosimilar of the reference medicine MabThera (marketed as Rituxan in the United States), which was originally approved in 1997 as the first monoclonal antibody for cancer therapy. A biosimilar is a biological medicine that is highly similar to an already authorized biological medicine (the reference medicine) in terms of quality, safety, and efficacy. Because biological medicines are produced by living cells and are more complex than small-molecule drugs, a biosimilar cannot be an exact copy. However, extensive analytical, non-clinical, and clinical comparability studies must demonstrate that there are no clinically meaningful differences. Other approved rituximab biosimilars include Truxima, Rixathon, Blitzima, Ritemvia, Ruxience, and Tuxella.

Riximyo is approved by the European Medicines Agency (EMA) and equivalent rituximab products are approved by the U.S. Food and Drug Administration (FDA) and regulatory authorities worldwide for the following indications in adult patients:

• Non-Hodgkin’s lymphoma (NHL): Riximyo is used in the treatment of CD20-positive B-cell non-Hodgkin’s lymphomas. For previously untreated follicular lymphoma (stage III–IV), it is given in combination with chemotherapy (such as CHOP, CVP, or bendamustine) as induction, followed by rituximab maintenance therapy in responders. It is also used as monotherapy for patients with stage III–IV follicular lymphoma who are resistant to or relapsed after chemotherapy, and as maintenance in relapsed/refractory follicular lymphoma. For CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL), Riximyo is given in combination with CHOP chemotherapy (the R-CHOP regimen), which has been the standard of care for over two decades.
• Chronic lymphocytic leukemia (CLL): Riximyo is used in combination with chemotherapy (typically fludarabine and cyclophosphamide, known as FCR, or bendamustine) for the treatment of patients with previously untreated and relapsed/refractory CLL. Fitness for fludarabine-based regimens depends on age, comorbidities, and renal function.
• Rheumatoid arthritis (RA): Riximyo is used in combination with methotrexate for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or intolerance to disease-modifying antirheumatic drugs (DMARDs), including one or more tumor necrosis factor (TNF) inhibitor therapies. Rituximab has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function in this group.
• Granulomatosis with polyangiitis (GPA, Wegener’s) and microscopic polyangiitis (MPA): Riximyo is used, in combination with glucocorticoids, for the induction of remission in adult patients with severe, active GPA or MPA (ANCA-associated vasculitides). It is also used for maintenance treatment in adults who have achieved remission with induction therapy.
• Pemphigus vulgaris (PV): Riximyo is used for the treatment of adult patients with moderate-to-severe pemphigus vulgaris, a rare and potentially life-threatening autoimmune blistering disease of the skin and mucous membranes. It is typically given with a tapering course of oral corticosteroids.

What Should You Know Before Receiving Riximyo?

Contraindications

There are specific situations in which Riximyo must not be used. Understanding these absolute contraindications is essential before treatment begins, and your doctor will review your full medical history and conduct a pre-treatment assessment.

• Hypersensitivity: Do not receive Riximyo if you are hypersensitive (allergic) to rituximab, to murine (mouse) proteins, to any other component of rituximab, or to any of the excipients in Riximyo (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injection).
• Active severe infections: Riximyo must not be used in patients with active, severe infections such as tuberculosis, sepsis, or opportunistic infections. B-cell depletion adds to the risk of infection, and ongoing infections should be fully controlled before starting therapy.
• Severely immunocompromised state: Patients in a severely immunocompromised state (for example, due to advanced HIV infection, hypogammaglobulinemia, or prior immunosuppressive therapy) should not receive Riximyo unless the benefits clearly outweigh the risks and under specialist care.
• Severe heart failure (for non-cancer indications): For rheumatoid arthritis and other non-cancer indications, Riximyo is contraindicated in patients with severe heart failure (New York Heart Association class IV) or severe, uncontrolled cardiac disease. In these patients, the balance of benefits and risks is unfavorable.
• Pregnancy: Riximyo should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. Rituximab is an IgG antibody that crosses the placenta, particularly in the second and third trimesters, and can cause transient B-cell depletion in the newborn.

Warnings and Precautions

Before and during treatment with Riximyo, your doctor will assess and monitor you for several important risks:

• Infusion-related reactions (IRRs) and cytokine release syndrome: Severe IRRs typically develop during the first infusion, particularly in patients with high tumor burden. Symptoms range from mild (fever, chills, headache) to severe (severe hypotension, bronchospasm, angioedema, pulmonary edema). Pre-medication with an antihistamine, paracetamol, and – for non-cancer indications – a corticosteroid is mandatory.
• Tumor lysis syndrome (TLS): Rapid lysis of malignant cells after rituximab can cause hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and acute kidney injury. The risk is highest in patients with high tumor burden or bulky disease. Prophylaxis with adequate hydration, allopurinol, or rasburicase is usually given, and renal function and electrolytes are monitored.
• Hepatitis B virus (HBV) reactivation: HBV reactivation, sometimes leading to fulminant hepatitis, liver failure, and death, has been reported. All patients must be screened for HBV (hepatitis B surface antigen and anti-HBc antibody) before starting Riximyo. Patients with evidence of prior or current HBV infection should be managed in consultation with a hepatologist, including prophylactic antiviral therapy and monitoring.
• Progressive multifocal leukoencephalopathy (PML): PML is a rare, serious, often fatal demyelinating disease of the brain caused by reactivation of the JC virus. Cases have been reported with rituximab, especially in patients with autoimmune diseases or prior immunosuppression. New or worsening neurological symptoms – such as confusion, vision changes, weakness on one side of the body, or difficulty speaking – must be reported immediately.
• Severe mucocutaneous reactions: Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, paraneoplastic pemphigus, lichenoid dermatitis, and vesiculobullous dermatitis, have been reported, some fatal. Riximyo must be permanently discontinued if severe mucocutaneous reactions occur.
• Serious infections: Bacterial, viral, and fungal infections (including opportunistic infections such as Pneumocystis jirovecii pneumonia) have been reported, including fatal cases. The risk is higher in patients with advanced disease, prior or concurrent immunosuppressive therapy, or low immunoglobulin levels. Monitor for signs of infection and delay treatment if active infection is present.
• Hypogammaglobulinemia: Prolonged hypogammaglobulinemia (low IgG, IgM, or IgA) can develop with repeated courses and may increase the risk of serious or recurrent infections. Immunoglobulin levels should be monitored in patients receiving long-term or repeated therapy, particularly for autoimmune indications. Immunoglobulin replacement therapy may be required.
• Cardiovascular events: Angina, arrhythmia (including atrial fibrillation and atrial flutter), heart failure, and myocardial infarction have been reported during or following rituximab infusions. Patients with a history of cardiac disease require careful monitoring. Riximyo should be discontinued if serious arrhythmia occurs.
• Gastrointestinal perforation and bowel obstruction: Abdominal pain, gastrointestinal perforation, and bowel obstruction, in some cases fatal, have been reported in patients with non-Hodgkin’s lymphoma receiving rituximab in combination with chemotherapy. Any new or worsening abdominal symptoms should be promptly evaluated.
• Renal toxicity: Acute renal failure has been reported, typically in the setting of tumor lysis syndrome or combination chemotherapy (for example, cisplatin). Renal function and electrolytes should be monitored.
• Vaccinations: The safety and efficacy of vaccination during rituximab therapy has not been studied, and response to most vaccines is reduced due to B-cell depletion. Live attenuated vaccines are not recommended during or after recent treatment. Whenever possible, age-appropriate vaccinations (especially inactivated vaccines such as seasonal influenza and pneumococcal vaccines) should be brought up to date at least 4 weeks before starting Riximyo.
• Skin reactions: Reactivation of latent infections, lichenoid dermatitis, vesiculobullous dermatitis, and serum sickness–like reactions have been reported, particularly in non-cancer indications.

Pregnancy and Breastfeeding

Riximyo should be avoided during pregnancy unless the possible benefit outweighs the potential risk. Human IgG antibodies, including rituximab, cross the placenta, particularly in the second and third trimesters. Infants exposed to rituximab in utero may have transient B-cell depletion at birth, which can persist for several months and may affect vaccination schedules. Animal studies have not shown teratogenic effects, but published data on pregnancy outcomes in humans remain limited.

Women of childbearing potential must use effective contraception during treatment and for at least 12 months after the last dose of Riximyo. Tell your doctor immediately if you are pregnant, become pregnant during treatment, or plan to become pregnant in the near future. If pregnancy occurs, the treating team should discuss continuation or adjustment of therapy in a multidisciplinary setting, involving obstetrics and neonatology where appropriate.

It is not known whether rituximab is excreted in human milk, but other human IgG antibodies are. Because of the potential for serious adverse effects in the breastfed infant, breastfeeding is not recommended during Riximyo treatment and for at least 6 months after the last dose.

Children and Adolescents

Riximyo is approved for use in certain pediatric populations. For children aged 6 months to 18 years, rituximab in combination with chemotherapy is approved for previously untreated advanced CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia (B-AL). For children and adolescents aged 2 to 18 years with severe, active granulomatosis with polyangiitis or microscopic polyangiitis, rituximab is approved in combination with glucocorticoids for induction of remission. Safety and efficacy in younger children and in other indications have not been established and should only be considered in specialist care.

Driving and Operating Machinery

Rituximab has no or negligible influence on the ability to drive or use machines, although dizziness and fatigue have been reported. If you experience infusion-related symptoms or any effects on vision, concentration, or reaction speed, you should not drive or operate machinery until they have fully resolved.

Important Information About Ingredients

Each vial of Riximyo contains sodium. A 100 mg/10 mL vial contains approximately 52.6 mg of sodium (equivalent to 2.6% of the WHO-recommended maximum daily sodium intake for an adult), and a 500 mg/50 mL vial contains approximately 263.2 mg of sodium (equivalent to 13.2% of the recommended maximum). This should be taken into consideration in patients on a controlled-sodium diet.

How Does Riximyo Interact with Other Drugs?

Formal drug–drug interaction studies with rituximab have been limited, but important interactions are recognized from clinical trials and post-marketing experience. Rituximab is not metabolized by cytochrome P450 enzymes, so direct pharmacokinetic interactions with most co-medications are minimal. However, pharmacodynamic interactions – where the combined effect of rituximab and another agent increases the risk of adverse events such as infection or immunosuppression – are clinically important. Always provide your healthcare team with a complete list of prescription medications, over-the-counter products, supplements, and herbal remedies before each infusion.

Major Interactions

Minor Interactions

Riximyo can be combined with many chemotherapy regimens (for example R-CHOP, R-CVP, R-bendamustine in lymphoma, or R-FC in chronic lymphocytic leukemia) without clinically meaningful pharmacokinetic interactions with the individual cytotoxic agents. However, the combined immunosuppressive effect increases the risk of neutropenia, infections, and opportunistic pathogens. Prophylactic measures – such as antiviral prophylaxis for HBV carriers, Pneumocystis jirovecii pneumonia (PJP) prophylaxis in selected regimens, and growth factor support for neutropenia – are often required.

What Is the Correct Dosage of Riximyo?

Riximyo must always be administered by a healthcare professional as an intravenous infusion in a hospital or specialized clinic that has immediate access to resuscitation facilities. Treatment is directed by a physician experienced in the use of rituximab and in managing the relevant malignant or autoimmune disease. The concentrate is diluted aseptically in 0.9% sodium chloride or 5% glucose to a final concentration of 1–4 mg/mL before infusion. Do not shake the vial or the diluted solution.

Pre-Medication and Monitoring

Before each Riximyo infusion, you will receive the following pre-medications to reduce the risk of infusion-related reactions:

• An antipyretic and analgesic, typically paracetamol (acetaminophen)
• An antihistamine, such as diphenhydramine or an H1-blocker
• A corticosteroid (such as methylprednisolone 100 mg IV), mandatory for non-cancer indications and recommended for cancer indications if not already included in the chemotherapy regimen

During and for at least one hour after each infusion, vital signs (blood pressure, pulse, temperature, respiratory rate, oxygen saturation) are monitored at regular intervals. Resuscitation equipment and medications for treating severe infusion reactions (adrenaline, intravenous corticosteroids, oxygen, bronchodilators) must be immediately available.

Dosing by Indication

How Riximyo Is Given

The required dose of Riximyo is calculated based on indication and, where applicable, body surface area (BSA calculated from height and weight) or body weight. The concentrate is withdrawn under aseptic conditions and diluted into a sodium chloride or glucose infusion bag to a final concentration of 1–4 mg/mL. Do not mix Riximyo with other medicines in the same infusion line. The diluted solution should be administered using a dedicated IV line.

Infusion rate recommendations:

• First infusion: Start at 50 mg/hour. If no reaction occurs, increase by 50 mg/hour every 30 minutes, to a maximum of 400 mg/hour.
• Subsequent infusions: If the first infusion was well tolerated, subsequent infusions may be started at 100 mg/hour and increased by 100 mg/hour every 30 minutes, to a maximum of 400 mg/hour.
• Rapid infusion (lymphoma): In selected patients with non-Hodgkin’s lymphoma who have tolerated two previous standard rituximab infusions without significant reactions and have normal lymphocyte counts, a 90-minute rapid infusion schedule may be used in later cycles.

When Treatment Should Be Interrupted or Stopped

Infusion of Riximyo must be slowed or temporarily interrupted if a mild or moderate infusion-related reaction occurs. Once symptoms have resolved, the infusion can be restarted at half the previous rate. If the symptoms do not resolve, or recur at greater severity, the infusion must be stopped. Permanent discontinuation is required for:

• Severe infusion-related reactions or cytokine release syndrome
• Severe mucocutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Confirmed progressive multifocal leukoencephalopathy (PML)
• Active hepatitis B virus reactivation with clinical hepatitis
• Serious or life-threatening bowel perforation

Missed Dose and Overdose

Because Riximyo is administered in a clinical setting by healthcare professionals, the risk of missing a dose is managed by the medical team. If an appointment is missed, contact the oncology, rheumatology, or dermatology unit as soon as possible so that the schedule can be adjusted. For maintenance regimens, short delays of a few days are generally acceptable, but significant delays should be discussed with the treating physician.

Limited data exist regarding overdose with rituximab. Single doses of up to 1000 mg/m² have been studied, and fixed doses of 1000 mg and 2000 mg have been used in autoimmune indications. In the event of overdose, the infusion must be stopped immediately, and the patient should be monitored closely with supportive care. There is no specific antidote.

What Are the Side Effects of Riximyo?

Like all biological medicines, Riximyo can cause side effects, although not everyone gets them. The frequency and type of side effects depend on the indication, the chemotherapy or immunosuppressive regimen used with rituximab, and the patient’s underlying health. Many side effects are mild and self-limiting; others require dose modification or permanent discontinuation. Report any new or worsening symptoms to your treating team, particularly fever, neurological changes, shortness of breath, severe rash, or jaundice.

Infusion-Related Reactions (IRRs)

Infusion-related reactions are by far the most common adverse events with rituximab and typically occur during or within 24 hours of the first infusion. Most IRRs are mild to moderate and consist of fever, chills, rigors, flushing, headache, nausea, itching, and transient hypotension. They are often effectively managed by slowing or pausing the infusion, giving additional antihistamines or corticosteroids, and treating symptoms. However, severe – and in rare cases fatal – cytokine release syndrome has been reported, especially in patients with high tumor burden (for example, bulky lymphoma or chronic lymphocytic leukemia). Severe reactions include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, and multi-organ failure.

Side Effects by Frequency

Effects on Laboratory Tests

Riximyo commonly causes changes in blood counts that are monitored during treatment: decreased neutrophils (neutropenia), decreased lymphocytes (lymphopenia), decreased platelets, and decreased hemoglobin. Serum immunoglobulin levels (IgG, IgM) may decline, especially with repeated courses for autoimmune disease. Periodic monitoring of complete blood count, immunoglobulins, and CD19/CD20 B-cell counts is commonly performed to guide treatment decisions and retreatment timing.

Long-Term Considerations

With repeated courses of Riximyo (particularly in rheumatoid arthritis, vasculitis, and pemphigus), there is an accumulating risk of hypogammaglobulinemia and infections, and of impaired vaccine responses. Regular immunoglobulin measurement and proactive vaccination before treatment (where feasible) are important components of long-term care.

If you experience any side effects, including those not mentioned here, tell your doctor, nurse, or pharmacist. You can also report suspected side effects to your national pharmacovigilance authority (for example, the EMA in the European Union, the FDA MedWatch program in the United States, the MHRA Yellow Card Scheme in the United Kingdom, or your national equivalent).

How Should Riximyo Be Stored?

Keep this medicine out of the sight and reach of children. Do not use Riximyo after the expiry date stated on the outer carton and the vial label after “EXP”. The expiry date refers to the last day of that month. Storage and handling are normally managed entirely by the hospital pharmacy and the infusion team.

• Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
• Light protection: Keep the vial in the outer carton in order to protect from light.
• Diluted solution: Should preferably be used immediately after dilution. Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C followed by 12 hours (including the infusion itself) at room temperature (not above 30°C) when diluted with 0.9% sodium chloride or 5% glucose under controlled aseptic conditions. From a microbiological point of view, the diluted solution should be used immediately.
• Inspection: The concentrate is a clear, colorless liquid. The diluted solution is clear and colorless. Do not use if you see any particles, cloudiness, or discoloration.
• Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic and biological medicines. Do not dispose of via wastewater or household waste.

Because Riximyo is prepared and administered in a hospital or clinic, all storage, dilution, labeling, and disposal are handled by trained pharmacy and nursing staff. Patients do not handle Riximyo vials at home.

What Does Riximyo Contain?

Active Substance

The active substance is rituximab, a chimeric mouse/human IgG1-kappa monoclonal antibody against CD20. Each milliliter of concentrate for solution for infusion contains 10 mg of rituximab. After dilution for infusion the final concentration is typically 1–4 mg/mL depending on the ordered dose and infusion bag volume.

• 10 mL vial: Contains 100 mg of rituximab (10 mg/mL).
• 50 mL vial: Contains 500 mg of rituximab (10 mg/mL).

Inactive Ingredients (Excipients)

• Sodium citrate
• Polysorbate 80
• Sodium chloride
• Sodium hydroxide (for pH adjustment)
• Hydrochloric acid (for pH adjustment)
• Water for injection

Appearance and Pack Sizes

Riximyo is a concentrate for solution for infusion. The concentrate is a clear, colorless liquid supplied in a type I glass vial with a butyl rubber stopper and an aluminum seal with a plastic flip-off cap.

• 100 mg/10 mL vials, supplied in packs of 2 vials.
• 500 mg/50 mL vials, supplied in packs of 1 vial.

Not all pack sizes may be marketed in your country.

Manufacturer and Marketing Authorization

Riximyo is manufactured and developed by Sandoz GmbH (a Novartis Group company). The marketing authorization holder for Riximyo in the European Union is Sandoz GmbH, Kundl, Austria. Riximyo was one of the first rituximab biosimilars approved in the European Union, following the EMA’s rigorous biosimilar pathway that requires extensive analytical, non-clinical, and comparative clinical studies against the reference product.