Briumvi is used to treat relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. It is given as an intravenous infusion every 6 months by a healthcare provider.

Clinical trials report that Briumvi is superior to teriflunomide at reducing relapses and significantly reducing brain lesions on magnetic resonance imaging (MRI).

• 49 % to 59 % fewer relapses were reported with Briumvi vs teriflunomide in 2 clinical trials.
• Both studies also reported near complete (97%) suppression of brain lesions (T1 Gd+ lesions) per MRI over 2 years.
• Zero relapses were reported in 86% to 87% of people taking Briumvi.

Briumvi (ublituximab-xiiy) gained FDA approval on December 28, 2022. There is no generic or biosimilar.

How does Briumvi work?

Briumvi’s mechanism of action involves targeting and destroying B cells (a type of immune cell) in the body. It does this by binding to a protein called CD20 on the B cells’ surface. By reducing B cells, Briumvi helps mitigate the immune system’s effect on the nervous system, which drives MS symptoms. 

Briumvi belongs to the drug class called CD20 monoclonal antibodies.

Briumvi side effects

The most common Briumvi side effects are:

• infusion reactions, which may include symptoms such as dizziness, nausea, light-headed, itchy, sweaty, headache, chest tightness, back pain, trouble breathing, or swelling in your face;
• cold sores around your mouth (herpes infections), skin sores or blisters, itching, tingling, burning pain in your thigh or lower back;
• cold symptoms such as stuffy nose, sneezing, sore throat;
• pain in your hands and feet;
• sleep problems (insomnia); or
• tiredness.

Serious side effects and warnings

Briumvi can cause the following serious side effects.

Infusion reactions. Infusion reactions are one of the most common side effects of Briumvi. Infusion reactions can be serious and may require you to be hospitalized. You will be monitored during your infusion and may be monitored after each infusion of Briumvi for signs and symptoms of an infusion reaction. Tell your healthcare provider if you get any of these symptoms:

• fever
• itchy skin
• wheezing
• chills
• dizziness
• nausea
• headache
• feeling faint
• abdominal pain
• flu-like symptoms
• swelling of the tongue or throat
• throat irritation
• fast heartbeat
• trouble breathing
• red face or skin
• hives.

These infusion reactions can happen over 24 hours after your infusion. You must call your healthcare provider right away if you get any of the signs or symptoms listed above after each infusion. If you get an infusion reaction, your healthcare provider may need to stop or slow down the rate of your infusion.

Infections. Infections are a common side effect, and upper respiratory tract infections are one of the most common side effects of Briumvi. Briumvi increases your risk of getting infections caused by bacteria or viruses that may be life-threatening or cause death. Tell your healthcare provider if you have an infection or have any of the following signs of infection, including fever, chills, a cough that does not go away, or painful urination. Your healthcare provider should delay your treatment with Briumvi until your infection is gone.

Hepatitis B virus (HBV) reactivation: Before starting treatment with Briumvi, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had a hepatitis B virus infection, the hepatitis B virus may become active again during or after treatment with Briumvi. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems, including liver failure or death. Your healthcare provider will monitor you if you are at risk for hepatitis B virus reactivation during treatment and after you stop receiving Briumvi.

Weakened immune system: Briumvi taken before or after other medicines that weaken the immune system could increase your risk of getting infections.

Progressive Multifocal Leukoencephalopathy (PML): PML may happen with Briumvi. PML is a rare, serious brain infection caused by a virus that may get worse over days or weeks. PML can result in death or severe disability. Tell your healthcare provider right away if you have any new or worsening neurologic signs or symptoms. These symptoms may include weakness on one side of your body, loss of coordination in arms and legs, vision problems, and changes in thinking and memory, which may lead to confusion, and personality changes.

Low immunoglobulins: Briumvi may cause a decrease in some types of antibodies. Your healthcare provider will do blood tests to check your blood immunoglobulin levels.

Briumvi may also cause an allergic reaction. Get emergency medical help if you have signs of an allergic reaction to Briumvi, such as hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

It is not known if Briumvi is safe or effective in children.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects.

Before receiving this medicine

Do not receive Briumvi if you:

• have had a life-threatening allergic reaction to ublituximab, Briumvi, or any of the inactive ingredients in the infusion
• have an active hepatitis B virus (HBV) infection.

Before receiving, tell your healthcare provider about all your medical conditions, including if you:

• have or think you have an infection
• take or plan to take medicines that affect your immune system. These medicines may increase your risk of getting an infection
• have ever had hepatitis B or you are a carrier of the hepatitis B virus
• have had a recent vaccination or are scheduled to receive any vaccinations.
  • Make sure all your vaccinations are up to date before starting Briumvi. You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with Briumvi. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with Briumvi and until your healthcare provider tells you that your immune system is no longer weakened.
  • When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with Briumvi. If you would like to receive any non-live vaccines while you are being treated with Briumvi, talk to your healthcare provider.
  • If you have a baby and you received Briumvi during your pregnancy, it is important to tell your baby’s healthcare provider about receiving Briumvi so they can decide when your baby should be vaccinated.
• are pregnant, think that you might be pregnant, or plan to become pregnant
• are breastfeeding, or plan to breastfeed.

Pregnancy

Briumvi may harm your unborn baby. You should use birth control (contraception) during treatment with Briumvi and for at least 6 months after your last infusion of Briumvi. Talk with your healthcare provider about what birth control method is right for you during this time. You may need to have a negative pregnancy test before each infusion of Briumvi.

Pregnancy Registry. There is a pregnancy registry for women who take Briumvi during pregnancy. If you become pregnant while receiving Briumvi or within 6 months following the last dose of Briumvi, tell your healthcare provider right away. Talk to your healthcare provider about registering with the Briumvi Pregnancy Registry. The purpose of this registry is to collect information about your health and your baby’s health. Either you or your healthcare provider can enroll you in this registry by calling 1-877-411-4546 or visiting www.briumvipregnancyregistry.com.

Breastfeeding

It is not known if Briumvi passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Briumvi.  

How will I receive Briumvi?

Briumvi is given through a needle placed in your vein (intravenous infusion) in your arm.

• Your healthcare provider may do a pregnancy test before each infusion of Briumvi.
• Before treatment with Briumvi, you will receive a corticosteroid and an antihistamine medicine to help reduce the risk of infusion reactions by making them less frequent and less severe.
• You may also receive other medicines to help reduce the risk of an infusion reaction.

Your first dose of Briumvi will last about 4 hours.

• Your second dose of Briumvi will be given 2 weeks after your first dose. This infusion will last about 1 hour.
• Your next doses of Briumvi will be given as 1 infusion every 24 weeks. These infusions will last about 1 hour.  

Dosing information

Dose of Briumvi for Multiple Sclerosis (Adults):

• First Infusion: 150 mg IV over at least 4 hours.
• Second Infusion (2 weeks after the first infusion): 450 mg IV over at least 1 hour.
• Subsequent Infusions (24 weeks after the first infusion and every 24 weeks thereafter): 450 mg IV every 24 weeks over at least 1 hour.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your Briumvi injection.

What should I avoid while receiving Briumvi?

Avoid receiving a “live” vaccine while you are being treated with Briumvi, and for at least 4 weeks before your treatment. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles).

Avoid receiving a “non-live” vaccine for at least 2 weeks before your treatment with Briumvi.

What other drugs will affect Briumvi?

Tell your doctor about all your other medicines, especially:

• Drugs that weaken the immune system, such as cancer medications, steroids, and medicines to prevent organ transplant rejection.

What Is Gazyva?

Gazyva (obinutuzumab) is targeted immunotherapy treatment that works with your immune system to treat specific types of blood cancers. Gazyva is a prescription medicine administered intravenously by a healthcare professional, typically alongside other cancer treatments. Currently, no generic version is available.

FDA-Approved Uses for Gazyva

Gazyva is specifically approved for adults with:

• Chronic lymphocytic leukemia (CLL): For first-time treatment in combination with chlorambucil
• Follicular lymphoma (FL): For patients whose cancer has relapsed or not responded to rituximab-containing regimens, used with bendamustine followed by Gazyva maintenance therapy
• Stage II bulky, III, or IV follicular lymphoma: For first-time treatment, used with chemotherapy first, then as monotherapy if treatment is successful

How Gazyva Works

Gazyva targets a protein called CD20 that appears on both normal and cancerous B-lymphocytes (a type of white blood cell). By binding to this protein, Gazyva:

• Helps your immune system identify and destroy marked cells
• Directly attacks cancer cells
• Preserves stem cells in bone marrow, allowing your body to keep producing healthy blood cells.

Clinical Effectiveness

Clinical trials have demonstrated that CLL patients receiving Gazyva plus chlorambucil experienced:

• Nearly 80% partial or complete response rate (versus 66.3% with rituximab plus chlorambucil)
• Approximately one additional year without cancer progression (26.7 months versus 14.9 months with rituximab plus chlorambucil).

Common Side Effects

The most common side effects of Gazyva are:

• Infusion-related reactions
• Low white blood cell counts (neutropenia)
• Fatigue
• Nausea
• Fever
• Cough.

Serious Side Effects and Warnings

Boxed Warnings

Gazyva carries FDA Boxed Warnings for:

• Hepatitis B Virus (HBV) Reactivation: Can cause liver failure or death in patients with previous HBV infection
• Progressive Multifocal Leukoencephalopathy (PML): A rare, serious brain infection that can be fatal

Additional Serious Risks

• Infusion-Related Reactions (IRRs): May occur during or within 24 hours of infusion
• Severe Allergic Reactions: Including anaphylaxis and serum sickness
• Tumor Lysis Syndrome (TLS): Rapid breakdown of cancer cells causing metabolic complications
• Infections: May be severe or fatal
• Low Blood Cell Counts: Including neutropenia (white cells) and thrombocytopenia (platelets)
• Disseminated Intravascular Coagulation (DIC): A rare but potentially fatal blood clotting disorder.

These are not all the possible side effects of Gazyva. For more information, ask your doctor or pharmacist.

Tell your doctor right away about any side effects you experience. You may report side effects to the FDA at (800) FDA-1088, or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Before receiving Gazyva

Contraindications

Do NOT receive Gazyva if you’ve had an allergic reaction to obinutuzumab or any ingredients in the injection.

Important Disclosures to Your Doctor

Tell your healthcare provider if you:

• Have heart disease
• Have any infection, particularly hepatitis B
• Have lung or breathing problems
• Recently received or plan to receive vaccines
• Take blood-thinning medications
• Are pregnant, planning pregnancy, or breastfeeding.

Pregnancy and Breastfeeding

• Pregnancy: Gazyva may harm unborn babies. Use effective contraception during treatment and for 6 months afterward.
• Breastfeeding: Not recommended during treatment and for 6 months after the last dose due to potential risks to infants.
• Vaccinations: Discuss timing of live virus vaccines for infants if you received Gazyva during pregnancy.

Gazyva Administration and Dosing Schedule

Gazyva is administered as an intravenous infusion in a clinic or infusion center. Most people will complete their Gazyva treatment in about 6 months.

Treatment Format

• 6 treatment cycles of 28 days each (6 months total).
• Gradual dose increases during Cycle 1 to minimize side effects
• For CLL patients: Chlorambucil on Day 1 and Day 15 of each cycle.

Dosing Schedule

Cycle 1:

• Day 1: 100 mg
• Day 2: 900 mg
• Day 8: 1000 mg
• Day 15: 1000 mg

Cycles 2-6:

Day 1: 1000 mg

Preparing for Infusions

One Week Before:

• Review all medications with your doctor
• Discuss blood pressure medications that might need adjustment.

Day of the Infusion:

• Arrange transportation home
• Wear comfortable clothing
• Bring snacks, entertainment, and activities
• Expect to spend most of the day at the facility.

Pre-Medications:

Your doctor may prescribe medications one hour before infusion to reduce side effects:

• Acetaminophen
• Antihistamines
• Steroids.

Ongoing Monitoring

During treatment, your doctor will regularly assess:

• Symptoms
• Lymph node, liver, and spleen size
• Blood counts
• Side effects.

What to Avoid During Treatment

Live vaccines: Do not receive BCG, MMR, MMRV, rotavirus, or varicella vaccines during Gazyva treatment

Manufacturer Information

Gazyva is manufactured by Genentech, a subsidiary of Roche. Genentech is headquartered in South San Francisco, California, while Roche’s global headquarters is in Basel, Switzerland. Other Notable Medications from Genentech/Roche include:

• Avastin (bevacizumab)
• Herceptin (trastuzumab)
• Rituxan (rituximab)
• Tecentriq (atezolizumab)
• Perjeta (pertuzumab)
• Actemra (tocilizumab) for rheumatoid arthritis
• Ocrevus (ocrelizumab) for multiple sclerosis
• Lucentis (ranibizumab) for eye conditions
• Xolair (omalizumab) for asthma and allergies
• Hemlibra (emicizumab) for hemophilia A.

Gazyva Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Gazyva.Gazyva (obinutuzumab) – Genentech, Inc.

What is Kesimpta?

Kesimpta (ofatumumab) is an FDA-approved medicine used to slow the progression and risk of relapses for specific forms of relapsing multiple sclerosis (MS). It is a once-a-month injection given under the skin (subcutaneously) that you can self-administer in your own home.

Kesimpta’s mechanism of action is thought to involve binding to and decreasing numbers of B cells. These are a type of white blood cell called B-lymphocytes that produce antibodies and are more abundant in people with MS, particularly those with active disease. Kesimpta binds to CD20, a protein on the surface of pre-B and mature B cells, triggering the destruction of the cell. Kesimpta will not cure MS but clinical trials show it slows its progression and reduces the rate of relapse.

Kesimpta belongs to the drug class called CD20 monoclonal antibodies. Kesimpta may also be called a selective immunosuppressant.

Kesimpta gained FDA approval on October 26, 2009. There is no Kesimpta generic (more correctly called a biosimilar). 

What is Kesimpta used for?

Kesimpta is used in adults with specific types of relapsing forms of multiple sclerosis (MS) including:

• clinically isolated syndrome (CIS)
• relapsing-remitting MS (RRMS)
• active secondary progressive disease (active SPMS).

Clinical trials have shown Kesimpta starts to work to lower B cells within a week. Symptoms of MS may take a bit longer to resolve.

Important Note:  Arzerra Vs Kesimpta

Although Arzerra contains the same active ingredient as Kesimpta (ofatumumab), they are NOT interchangeable.

• They are used to treat different conditions (Arzerra is used for CLL and Kesimpta is used for MS).
• They are given by different routes of administration (Arzerra is given by intravenous infusion and Kesimpta is given by subcutaneous injection).

Kesimpta side effects

The most common side effects of Kesimpta are:

• upper respiratory tract infections (these are typically viral infections that cause sneezing, nasal congestion, a headache, and a sore throat)
• headache.

Serious side effects and warnings

Kesimpta can cause the following serious side effects.

Infections. Clinical trials have reported serious infections associated with Kesimpta. If you have an active infection, your healthcare provider should delay your treatment until your infection is gone. Kesimpta taken before or after other medicines that weaken the immune system may increase your risk of getting infections. Tell your healthcare provider right away if you have any infections or get any symptoms, including painful and frequent urination, nasal congestion, runny nose, sore throat, fever, chills, cough, or body aches.

Hepatitis B virus (HBV) reactivation. Before starting treatment, your healthcare provider will do blood tests to check for HBV. If you have ever had an HBV infection, the HBV may become active again during or after treatment. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems, including liver failure or death. You should not receive this medicine if you have active hepatitis B liver disease. Your healthcare provider will monitor you for HBV infection during and after you stop using this medicine. Tell your healthcare provider right away if you get worsening tiredness or yellowing of your skin or white part of your eyes during treatment.

Progressive Multifocal Leukoencephalopathy (PML). PML may happen with this medicine. PML is a rare, serious brain infection caused by a virus that may get worse over days or weeks. PML can result in death or severe disability. Tell your healthcare provider right away if you have any new or worsening neurologic signs or symptoms. These may include weakness on one side of your body, loss of coordination in arms and legs, vision problems, and changes in thinking and memory which may lead to confusion and personality changes.

Weakened immune system. Kesimpta taken before or after other medicines that weaken the immune system could increase your risk of getting infections.

Injection-related reactions. Injection-related reactions are a common side effect of Kesimpta. These can happen within 24 hours (1 day) following the first injection and with later injections. There are 2 kinds of reactions:

• at or near the injection site: redness of the skin, swelling, itching and pain. Talk with your healthcare
  provider if you have any of these signs and symptoms.
• those that may happen when certain substances are released in your body: fever, headache, pain in the muscles, chills, tiredness, rash, hives, trouble breathing, swelling of the face, eyelids, lips, mouth, tongue and throat, and feeling faint, or chest tightness. Contact your healthcare provider right away if you experience any of these signs and symptoms, especially if they become worse or you have new severe signs of reactions after subsequent injections. It could be a sign of an allergic reaction, which can be serious.

Low immunoglobulins. Kesimpta may cause a decrease in some types of antibodies. Your healthcare provider will do blood tests to check your blood immunoglobulin levels.

These are not all the possible side effects of Kesimpta. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA .

Before using Kesimpta

Do not use Kesimpta if you:

• have an active hepatitis B virus infection
• have had an allergic reaction to ofatumumab or a life-threatening injection-related reaction to Kesimpta.

Before using this medicine, tell your healthcare provider about all of your medical conditions, including if you:

• have or think you have an infection including HBV or PML
• have ever taken, currently take, or plan to take medicines that affect your immune system. These medicines could increase your risk of getting an infection
• have had a recent vaccination or are scheduled to receive any vaccinations.
  • You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with this medicine and until your healthcare provider tells you that your immune system is no longer weakened.
  • Whenever possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with Kesimpta.
  • Talk to your healthcare provider about vaccinations for your baby if you used Kesimpta during your pregnancy.
• are pregnant, think you might be pregnant, or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

It is not known if this medicine will harm your unborn baby. Females who can become pregnant should use birth control (contraception) during treatment with this medicine and for 6 months after your last treatment. Talk with your healthcare provider about what birth control method is right for you during this time.

Breastfeeding

 It is not known if this medicine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take this medicine.

How should I use Kesimpta?

See the detailed Instructions for Use that come with the Kesimpta Package Insert for information about how to prepare and inject a dose of this medicine and how to properly throw away (dispose of) used pens or prefilled syringes.

• Use Kesimpta exactly as your healthcare provider tells you to use it.
• Kesimpta is given as an injection under your skin (subcutaneous injection), in your thigh or stomach area (abdomen) by you or a caregiver. A caregiver may also give you an injection in your upper outer arm. See Where and how is Kesimpta injected? for more information.
• Your healthcare provider will show you how to prepare and inject this medicine the right way before you use it for the first time.
• Do not inject into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with moles, scars, or stretch marks.

Kesimpta dosing

• Initial dosing: Kesimpta 20 mg of Kesimpta given by subcutaneous injection at Weeks 0, 1, and 2.
• Subsequent dosing: Kesimpta 20 mg administered monthly starting at week 4.
• There is no injection at Week 3.

What happens if I miss a dose?

If you miss a monthly injection, give it as soon as possible without waiting until the next scheduled dose. After that, use your injections a month apart.

What other drugs will affect Kesimpta?

Tell your doctor about all your other medicines, especially drugs that weaken the immune system such as

• cancer medicine
• steroids
• medicines to prevent organ transplant rejection.

This list is not complete. Other drugs may affect Kesimpta, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal  supplements. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I store Kesimpta?

Store Kesimpta in a refrigerator between 36°F to 46°F (2°C to 8°C). Keep it in the original carton until ready for use to protect it from light.

If needed, Kesimpta may be stored for up to 7 days at room temperature, up to 86°F (30°C ). Write the date taken out of the refrigerator in the space provided on the carton.

If stored below 86°F (30°C), unused Kesimpta may be returned to the refrigerator and must be used within the next 7 days. If this Kesimpta is not used within those 7 days, then discard the medicine.

Do not freeze. Do not shake.

Keep Kesimpta and all medicines out of the reach of children.

What are the ingredients in Kesimpta?

Active ingredient: ofatumumab
Inactive ingredients: Sensoready pen and prefilled syringe: arginine, disodium edetate, polysorbate 80, sodium acetate trihydrate, sodium chloride, and Water for Injection. Hydrochloric acid may be added.

Available as Kesimpta 20 mg/0.4 mL solution in a single-dose prefilled Sensoready Pen and Kesimpta 20 mg/0.4 mL solution in a single-dose prefilled syringe.

Who makes Kesimpta?

Kesimpta is made by Novartis, a multinational pharmaceutical company headquartered in Basel, Switzerland. Novartis was founded in 1996 through the merger of Ciba-Geigy and Sandoz. Some of Novartis’s other notable medications include:

• Entresto (for heart failure)
• Cosentyx (for psoriasis and arthritis)
• Gilenya (for multiple sclerosis)
• Zolgensma (for spinal muscular atrophy)
• Leqvio (for cholesterol management)
• Xolair (for asthma and allergic conditions)
• Tasigna (for leukemia)
• Tafinlar (for melanoma)
• Promacta (for blood disorders)
• Kisqali (for breast cancer).

What is ocrelizumab?

Ocrelizumab is a recombinant humanized monoclonal antibody.

Ocrelizumab intravenous infusion is a prescription medicine used to treat primary progressive multiple sclerosis in adults.

Ocrelizumab is also used to treat relapsing forms of multiple sclerosis in adults (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease).

Warnings

Ocrelizumab may cause a brain infection that can lead to disability or death. Tell your doctor if you have problems with speech, thought, vision, or muscle movement. These symptoms can get worse quickly.

Some side effects may occur during the ocrelizumab infusion or up to 24 hours later. Tell your caregiver if you feel dizzy, nauseated, itchy, or have chest tightness, throat irritation, or trouble breathing.

Ocrelizumab affects your immune system. You may get infections more easily, even serious or fatal infections. Call your doctor if you have a fever, chills, cough, mouth sores, skin sores or blisters, itching, tingling, burning pain, or problems with speech, thought, vision, or muscle movement.

If you’ve ever had hepatitis B, it may become active or get worse while you are using or after you stop using ocrelizumab. You may need frequent liver function tests for several months.

Before taking this medicine

You should not be treated with ocrelizumab if you are allergic to it, or if you have:

• active infection with hepatitis B.

Your doctor may perform tests to make sure you do not have hepatitis B or other infections.

You should not receive any “live” or “live-attenuated” vaccine within the 4 weeks before you start treatment with ocrelizumab. If you need a “non-live” vaccine, you should receive it at least 2 weeks before you start treatment with ocrelizumab.

Also tell your doctor if:

• you have ever had colitis or inflammatory bowel disease;
• you have any type infection;
• you are a carrier of hepatitis B; or
• you have ever used medicine that can weaken your immune system.

Using ocrelizumab may increase your risk of developing certain types of cancer, such as breast cancer. Ask your doctor about your specific risk.

It is not known whether ocrelizumab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 6 months after your last dose.

If you are pregnant, you will need to tell your baby’s doctor if you used ocrelizumab during pregnancy, especially before the baby receives any childhood vaccines.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of ocrelizumab on the baby.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

How is ocrelizumab given?

Ocrelizumab is given as an infusion into a vein. A healthcare provider will give you this injection.

Your first dose of ocrelizumab will be split into 2 separate infusions given 2 weeks apart. The following doses will be given once every 6 months.

Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely using ocrelizumab.

This medicine must be given slowly, and the infusion can take from 2 to 3.5 hours to complete.

You may be given other medications to help prevent serious side effects of ocrelizumab.

You will be watched closely for at least 1 hour after receiving ocrelizumab, to make sure you do not have an allergic reaction to the medication.

Ocrelizumab affects your immune system. You may get infections more easily, even serious or fatal infections. You will need frequent medical tests.

If you’ve ever had hepatitis B, this virus may become active or get worse during treatment with ocrelizumab or in the months after you stop using this medicine. You may need frequent liver function tests while using this medicine and for several months after your last dose.

Dosing information

Usual Adult Dose for Multiple Sclerosis:

Initial dose: 300 mg IV followed 2 weeks later by a second 300 mg IV infusion
Maintenance dose: 600 mg IV every 6 months

RECOMMENDED INFUSION RATES:
INFUSION 1: (300 mg of this drug in 250 mL 0.9% sodium chloride injection): Start at 30 mL/hr and increase by 30 mL/hr every 30 minutes to a maximum of 180 mL/hr; duration of 2.5 hours or longer
INFUSION 2 (TWO WEEKS LATER): (300 mg of this drug in 250 mL 0.9% sodium chloride injection): Start at 30 mL/hr and increase by 30 mL/hr every 30 minutes to a maximum of 180 mL/hr; duration of 2.5 hours or longer
SUBSEQUENT INFUSIONS:
-OPTION 1 (600 mg of this drug in 500 mL 0.9% sodium chloride injection): Start at 40 mL/hr and increase by 40 mL/hr every 30 minutes to a maximum of 200 mL/hr; duration of 3.5 hours or longer
OR
-OPTION 2 if no prior serious infusion reaction (600 mg of this drug in 500 mL 0.9% sodium chloride injection): Start at 100 mL/hr for the first 15 minutes and increase to 200 mL/hr for the next 15 minutes; increase to 250 mL/hr for the next 30 minutes; increase to 300 mL/hr for the remaining 60 minutes; duration of 2 hours or longer

Uses:
-For relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
-Primary progressive MS

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your ocrelizumab injection.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while receiving ocrelizumab?

Do not receive a “live” vaccine while using ocrelizumab or within 4 weeks before you start using ocrelizumab. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Do not receive a “non-live” vaccine while using ocrelizumab or within 2 weeks before you start using this medicine. Non-live vaccines include hepatitis A, polio, rabies, and a yearly flu shot.

Ocrelizumab side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Ocrelizumab may cause a brain infection that can lead to disability or death. Tell your doctor if you have problems with speech, thought, vision, or muscle movement. These symptoms can get worse quickly.

Some side effects may occur during the injection or up to 24 hours later. Tell your caregiver right away if you feel dizzy, tired, nauseated, light-headed, feverish, itchy, warm and tingly, or if you have a skin rash, headache, fast heartbeats, chest tightness, pain or irritation in your throat, or trouble breathing.

Call your doctor at once if you have:

• diarrhea or more frequent bowel movements than usual, or black, tarry, sticky or bloody stools, or stomach pain or tenderness;
• fast heart beats, tiredness;
• headache, nausea, dizziness;
• itchy skin, rash, hives;
• fever, chills, cough;
• throat pain or irritation;
• wheezing, breathing problem, feeling short of breath;
• flushing (sudden warmth, redness, or tingly feeling);
• skin sores, blisters, pus, or oozing;
• cold sores or fever blisters on or around your lips;
• nerve pain (tingling, burning pain, “pins and needles” feeling);
• mood or behavior changes, confusion, memory problems;
• weakness on one side of your body; or
• problems with speech, vision, or muscle movement.

Your ocrelizumab treatments may be delayed or permanently discontinued if you have certain side effects.

Common ocrelizumab side effects may include:

• skin infections;
• reactions to an injection; or
• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What is Ocrevus infusion?

Ocrevus (ocrelizumab) is a treatment for relapsing and progressive multiple sclerosis (MS) to help reduce relapses and slow disability progression. Ocrevus binds and destroys B cells, which are involved in MS progression. Ocrevus is used for primary progressive MS and relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. Ocrevus active ingredient is ocrelizumab.

Multiple sclerosis is a disabling condition caused by your immune system mistakenly attacking and damaging the protective cover (myelin sheath) of nerves in your brain, spinal cord, and optic nerves. B cells and T cells are part of the immune system that causes damage to the myelin sheath.

Ocrevus mechanism of action is believed to be binding to proteins (antigens) called CD20 on the outside of  B cells and destroying them. Fewer B cells in the body mean less damage to the nerves which helps to reduce the number of relapses and brain lesions and to slow the progression of disability. B cells, a type of white blood cell, are part of the immune system that causes MS by damaging the myelin sheath.  Ocrevus is a CD20-directed cytolytic antibody.

Ocrevus infusion is given over a couple of hours, and Ocrevus Zunovo is given as an injection under the skin (subcutaneous injection) for approximately 10 minutes. Both are given twice a year as a maintenance dose by your healthcare professional. 

What is Ocrevus used for?

Ocrevus infusion is an MS medicine FDA approved to be used for:

• relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
• primary progressive MS in adults.

Ocrevus received FDA approval in March 2017; it is given as an infusion. Ocrevus Zunovo became FDA-approved on September 13, 2024. It contains ocrelizumab and hyaluronidase and is given as a subcutaneous injection.

Ocrevus Side Effects

Common Ocrevus infusion side effects

When used for RMS, common Ocrevus side effects are infusion reactions and cold symptoms such as stuffy nose, sneezing, and sore throat, which are symptoms of an upper respiratory tract infection.  These occurred in 10% or more patients and greater than Rebif, 

Common Ocrevus side effects when used for PPMS are lower respiratory tract infections, cold symptoms such as stuffy nose, sneezing, and sore throat, which are symptoms of an upper respiratory tract infection, skin infections, and also infusion reactions.  These occurred ≥10% and > placebo).

Serious Ocrevus infusion side effects

Ocrevus may cause serious allergic reactions, including severe allergic reactions, brain infections (progressive multifocal leukoencephalopathy (PML)), other serious infections, Hepatitis B virus (HBV) reactivation, and decreased immunoglobulins.

Get emergency medical help if you have signs of an allergic reaction, such as hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Ocrevus may cause a brain infection that can lead to disability or death. Tell your doctor if you have problems with speech, thought, vision, or muscle movement. These symptoms can get worse quickly.

Some side effects may occur during the injection or up to 24 hours later. Tell your caregiver right away if you feel dizzy, tired, nauseated, light-headed, feverish, itchy, warm and tingly, or if you have a skin rash, headache, fast heartbeats, chest tightness, pain or irritation in your throat, or trouble breathing.

Call your doctor at once if you have:

• diarrhea or more frequent bowel movements than usual, or black, tarry, sticky or bloody stools, or stomach pain or tenderness;
• fast heartbeats, tiredness;
• headache, nausea, dizziness;
• itchy skin, rash, hives;
• fever, chills, cough;
• throat pain or irritation;
• wheezing, breathing problem, feeling short of breath;
• flushing (sudden warmth, redness, or tingly feeling);
• skin sores, blisters, pus, or oozing;
• cold sores or fever blisters on or around your lips;
• nerve pain (tingling, burning pain, “pins and needles” feeling);
• mood or behavior changes, confusion, memory problems;
• weakness on one side of your body; or
• problems with speech, vision, or muscle movement.

Your Ocrevus treatments may be delayed or permanently discontinued if you have certain side effects.

These are not all the possible side effects of this medication. Call your doctor for medical advice about side effects.

What is the Ocrevus copay card?

With the Ocrevus copay card, you may pay as little as $0, depending on your health insurance plan.  Click on Ocrevus Co-pay Cards and Price Guide for links to the Ocrevus Co-pay Program and the start form.

Warnings

Infusion reactions: Infusion reactions are a side effect of Ocrevus, which can be serious and may require you to be hospitalized. When you receive your Ocrevus infusion you will be monitored for signs and symptoms of an infusion reaction, and infusion will be interrupted or stopped if any symptoms occur, and appropriate supportive treatment will be administered if necessary.

Tell your healthcare provider or nurse if you get any of these symptoms: itchy skin, trouble breathing, nausea, shortness of breath, rash, throat irritation or pain, headache, fatigue, hives, feeling faint, swelling of the throat, fast heartbeat, tiredness, fever, dizziness, coughing or wheezing or redness on your face (flushing), injection site pain, swelling and redness.

Injection reactions can happen during or up to 24 hours after administration. You must call your healthcare provider right away if you get any of the signs or symptoms listed above after each infusion or injection.

Infection: Infections are a common side effect. Ocrevus increase your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Serious infections can happen with Ocrevus, which can be life-threatening or cause death. Tell your healthcare provider if you have an infection or have any of the following signs of infection, including fever, chills, or a cough that does not go away or painful urination. Signs of herpes infection include: cold sores, shingles, genital sores, skin rash, pain, and itching. Signs of more serious herpes infection include: changes in vision, eye redness or eye pain, severe or persistent headache, stiff neck, and confusion. Signs of infection can happen during treatment or after you have received your last dose of Ocrevus. Tell your healthcare provider right away if you have an infection. Your healthcare provider should delay your treatment with Ocrevus until your infection is gone.

Hepatitis B virus (HBV) reactivation: Before starting treatment with ocrelizumab, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had hepatitis B virus infection, the hepatitis B virus may become active again during or after treatment with Ocrevus. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems including liver failure or death. Your healthcare provider will monitor you if you are at risk for hepatitis B virus reactivation during treatment and after you stop receiving Ocrevus.

Weakened immune system: Ocrevus taken before or after other medicines that weaken the immune system could increase your risk of getting infections.

Progressive Multifocal Leukoencephalopathy (PML): PML is a rare brain infection that usually leads to death or severe disability and has been reported with ocrelizumab. Symptoms of PML get worse over days to weeks. It is important that you call your healthcare provider right away if you have any new or worsening neurologic signs or symptoms that have lasted several days, including problems with:

• thinking
• eyesight
• strength
• balance
• weakness on 1 side of your body
• using your arms or legs

Decreased immunoglobulins: Ocrevus may cause a decrease in some types of immunoglobulins. Your healthcare provider will do blood tests to check your blood immunoglobulin levels.

Before receiving this medicine

Before receiving Ocrevus, tell your healthcare provider about all of your medical conditions, including if you:

• have or think you have an infection. See “Warnings”
• have ever taken, take, or plan to take medicines that affect your immune system, or other treatments for MS. These medicines could increase your risk of getting an infection.
• have ever had hepatitis B or are a carrier of the hepatitis B virus.
• have a history of inflammatory bowel disease or colitis.
• have had a recent vaccination or are scheduled to receive any vaccinations.

You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with Ocrevus. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with Ocrevus and until your healthcare provider tells you that your immune system is no longer weakened.

When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with Ocrevus. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with Ocrevus talk to your healthcare provider.

Pregnancy 

Tell your healthcare provider if you are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if this medicine will harm your unborn baby. You should use birth control (contraception) during treatment with this medication and for 6 months after your last infusion. Talk with your healthcare provider about what birth control method is right for you during this time.

There is a pregnancy registry for women who take Ocrevus during pregnancy. If you become pregnant while receiving this medication, tell your healthcare provider right away. Talk to your healthcare provider about registering with the Ocrevus Pregnancy Registry. The purpose of this registry is to collect information about your health and your baby’s health. Your healthcare provider can enroll you in this registry by calling 1-833-872-4370 or visiting www.Ocrevuspregnancyregistry.com.

If you have a baby and you received Ocrevus during your pregnancy, it is important to tell your baby’s healthcare provider about receiving this medication so they can decide when your baby should be vaccinated.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Ocrevus passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take this medication.

Who should not receive Ocrevus?

• Do not receive this medication if you have an active hepatitis B virus (HBV) infection.
• Do not receive this medication if you have had a life-threatening allergic reaction to it. Tell your healthcare provider if you have had an allergic reaction to Ocrevus or any of its ingredients in the past. See “What are the ingredients in Ocrevus?” below for a complete list of ingredients.

​​How should I receive Ocrevus?

• Ocrevus is given through a needle placed in your vein (intravenous (IV) infusion) in your arm.
• Before treatment, your healthcare provider will give you a corticosteroid medicine and an antihistamine to help reduce infusion reactions (make them less frequent and less severe). You may also receive other medicines to help reduce infusion reactions. See the Warnings section.
• Your first full dose of Ocrevus will be given as 2 separate infusions, 2 weeks apart. Each infusion will last about 2 hours and 30 minutes.
• Your next doses of this medication will be given as 1 infusion every 6 months. These infusions will last about 2 hours to 3 hours and 30 minutes depending on the infusion rate prescribed by your healthcare provider.

Ocrevus Dosing information

Ocrevus is given by intravenous infusion

Initial Ocrevus dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion

Maintenance Ocrevus doses: 600 mg intravenous infusion every 6 months 

General dosing information:

• Must be diluted before administration.
• You will be monitored closely during and for at least one hour after infusion.
• Before your first treatment you should have hepatitis B virus and quantitative serum immunoglobulin screening 
• Pre-medicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) before each infusion.

Ocrevus J code and billing codes

Ocrevus J code is J2350

Ocrevus is available as Ocrelizumab 300 mg single-dose vial 

NDC code 50242-150-01 (10 digit) or 50242-0150-01 (11 digit)

Multiple sclerosis ICD-10-CM G35

What happens if I miss a dose?

If you miss a dose of Ocrevus, call your healthcare provider and reschedule your appointment to receive your missed dose as soon as possible. Do not wait until your next planned dose. After you receive your missed dose, reschedule your next dose for 6 months after your missed dose. Ocrevus doses must be separated by a minimum of 5 months.

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 healthcare provider about other immunosuppressive or immune-modulating drugs that you have taken or are currently taking.

Ocrevus Package Insert 

Review the Ocrevus Package Insert for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Storage

• Store Ocrevus vials at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light.
• Do not freeze or shake
• Use prepared Ocrevus infusion solution immediately. If not used immediately, store up to 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F) and 8 hours at room temperature up to 25°C (77°F), which includes infusion time. In the event an intravenous infusion cannot be completed the same day, discard the remaining solution.

Keep out of sight and reach of children.

What are the ingredients in Ocrevus?

Active ingredient: ocrelizumab.

Inactive ingredients: glacial acetic acid, polysorbate 20, sodium acetate trihydrate, trehalose dihydrate.

Company

Ocrevus is manufactured by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990.

Ocrevus and Ocrevus Zunovo are manufactured by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990.

Ocrevus Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Ocrevus.Ocrevus (ocrelizumab) – Genentech, Inc.

What is Rituxan?

Rituxan is used to treat certain leukemias and lymphomas and some non-cancer conditions, such as rheumatoid arthritis, polyangiitis, and pemphigus vulgaris. It is given by IV infusion (an infusion into a vein) by a healthcare provider.

Rituxan infusion is not chemotherapy; it is a type of immunotherapy called a targeted cancer treatment.

Rituxan (rituximab) gained FDA approval on November 26, 1997. Rituxan has 3 biosimilars: Riabni, Ruxience, and Truxima. A biosimilar is a biological product that is similar to a reference biologic (usually the originally approved product) and for which there are no clinically meaningful differences in terms of safety, purity, and potency.

FDA approvals and indications

Rituxan is approved to treat:

• Non-Hodgkin’s lymphoma (NHL) in adults.
  • Relapsed or refractory, low-grade or follicular, CD20-positive B-cell NHL as a single agent, or
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy, or
  • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy, or
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with (cyclophosphamide, doxorubicin, vincristine, and prednisone) (CHOP) or other anthracycline-based chemotherapy regimens.
• Mature B-cell Non-Hodgkin’s lymphoma (NHL) and mature B-cell acute leukemia (B-AL) in children 6 months and older.
  • Previously untreated, advanced-stage, CD20-positive, diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL) in combination with chemotherapy.
• Chronic lymphocytic leukemia in adults.
  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC).
• Rheumatoid arthritis (RA) in combination with methotrexate in adult patients with moderately to severely active RA who have inadequate response to one or more TNF antagonist therapies.
• Granulomatosis with Polyangiitis (GPA, Wegener’s granulomatosis) and Microscopic Polyangiitis (MPA) in adults and children 2 years and older, in combination with glucocorticoids.
• Moderate to severe Pemphigus Vulgaris (PV) in adults.

Rituxan is not approved for:

• Children aged less than 2 years with GPA or MPA
• Children less than 6 months of age with mature B-cell NHL and B-AL
• Children with conditions other than GPA, MPA, B-cell NHL, and B-AL.

How Rituxan works

Rituxan is a targeted therapy that attaches to CD20, a protein found on the surface of B cells. As a type of white blood cell in your immune system, B cells normally help fight infections, but they can also contribute to certain diseases. When Rituxan binds to the CD20 protein, it triggers two key mechanisms to destroy these B cells:

1. It activates your body’s complement system, which directly attacks and eliminates the B cells
2. It flags the B cells for destruction by other immune cells in a process called antibody-dependent cell-mediated cytotoxicity.

This targeted elimination of B cells makes Rituxan effective for treating various conditions where B cells play a harmful role, including:

• B-cell cancers such as Non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL)
• Autoimmune disorders such as rheumatoid arthritis, where B cells contribute to inflammation and joint damage.

By precisely targeting problematic B cells, rituximab helps control these conditions while minimizing impact on other parts of the immune system.

Side effects

The most common side effects of Rituxan infusion are:

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

In adults with GPA or MPA, the most common side effects of Rituxan also include:

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

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

• 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 of Rituxan are:

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

These are not all of the possible side effects of Rituxan. Call your doctor for medical advice about side effects. You may report side effects to the FDA .

Serious side effects and warnings

Rituxan carries a Boxed Warning for fatal infusion-related reactions, severe skin reactions, hepatitis B virus reactivation, and a rare brain condition called progressive multifocal leukoencephalopathy (PML).

Rituxan can cause the following serious side effects:

• Infusion-related reactions. These are a common side effect of R. Serious infusion-related reactions can happen during your or your child’s infusion or within 24 hours after. Your healthcare provider should give you or your child medicines before your Rituxan infusion to decrease the chance of having a severe infusion-related reaction. Tell your healthcare provider or get medical help right away if you or your child gets any of these symptoms during or after an infusion:
  • hives (red itchy welts) or rash
  • shortness of breath, difficulty breathing, or wheezing
  • itching
  • weakness
  • swelling of your lips, tongue, throat, or face
  • dizziness or feeling faint
  • sudden cough
  • 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 or your child gets any of these symptoms at any time during your treatment with Rituxan:
  • painful sores or ulcers on your skin, lips, or in your mouth
  • blisters
  • peeling skin
  • rash
  • pustules.
• Hepatitis B virus (HBV) reactivation. Before you or your child receives Rituxan treatment, your healthcare provider will do blood tests to check for HBV infection. If you or your child has had hepatitis B or is a carrier of the hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure and death. You or your child should not receive Rituxan if you or your child has active hepatitis B liver disease. Your healthcare provider will monitor you or your child for hepatitis B infection during and for several months after you or your child stops receiving Rituxan. Tell your healthcare provider immediately if you or your child gets worsening tiredness, or yellowing of your or your child’s skin or white part of your eyes, during treatment.
• Progressive Multifocal Leukoencephalopathy (PML). PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. 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 or your child has any new or worsening symptoms or if anyone close to you notices these symptoms:
  • confusion
  • dizziness or loss of balance
  • decreased strength or weakness on one side of your body
  • difficulty walking or talking
  • vision problems.
• Tumor Lysis Syndrome (TLS). TLS is caused by the rapid breakdown of cancer cells. TLS can cause you or your child to have:
  • kidney failure and need dialysis treatment
  • an abnormal heart rhythm.

TLS can happen within 12 to 24 hours after an infusion of Rituxan. 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 has any of the following signs or symptoms of TLS:

• • nausea
  • diarrhea
  • vomiting
  • lack of energy.
• Serious infections. Serious infections can happen during and after treatment with Rituxan, and can lead to death. Rituxan 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 Rituxan include bacterial, fungal, and viral infections. After receiving Rituxan, some people have developed low levels of certain antibodies in their blood for a long period (longer than 11 months). Some of these people with low antibody levels developed infections. People with serious infections should not receive Rituxan. Tell your healthcare provider right away if you or your child has any symptoms of infection:
  • fever
  • cold symptoms, such as a 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. Rituxan may cause chest pain, irregular heartbeats, and a heart attack. Your healthcare provider may monitor your or your child’s heart during and after treatment with Rituxan if you or your child has symptoms or heart problems or has a history of heart problems. Tell your healthcare provider right away if you or your child has chest pain or irregular heartbeats during treatment with Rituxan.
• Kidney problems, especially if you or your child are receiving Rituxan for NHL. Rituxan can cause severe kidney problems that can 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 receives Rituxan with chemotherapy medicines. Tell your healthcare provider right away if you or your child has any severe stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.

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

Get emergency medical help if you have signs of an allergic reaction to Rituxan, such as hives, difficulty breathing, swelling in your face or throat, or a severe skin reaction (symptoms may include fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

These are not all of the possible side effects of Rituxan. Call your doctor for medical advice about side effects.

Before taking this medicine

Before you or your child receives Rituxan, 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 Rituxan or a rituximab product
• have a history of heart problems, irregular heartbeat, or chest pain
• have lung, liver, or kidney problems
• have an infection or a weakened immune system
• have or have had any severe infections, including:
  • Hepatitis B virus (HBV)
  • Parvovirus B19
  • Hepatitis C virus (HCV)
  • Varicella zoster virus (chickenpox or shingles)
  • Cytomegalovirus (CMV)
  • West Nile Virus
  • Herpes simplex virus (HSV).
• 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 Rituxan. You should be up-to-date on any needed immunizations before starting treatment with Rituxan.
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Rituxan may harm an unborn baby. Talk to your healthcare provider about the risks to an unborn baby if you or someone you are caring for receives Rituxan during pregnancy. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test to check for pregnancy before starting Rituxan.

Effective birth control (contraception) should be used during treatment with Rituxan and for 12 months after the last dose. Talk to your healthcare provider about effective birth control.

Tell your healthcare provider right away if you or your child becomes pregnant or think you may be pregnant during treatment with Rituxan.

Breastfeeding

Rituxan may pass into your breast milk. It is not safe to breastfeed a baby while you are using this medicine. Do not breastfeed during treatment and for 6 months after your or your child’s last dose of Rituxan.

How is Rituxan administered?

Rituxan is given by infusion through your or your child’s central catheter or a needle placed in a vein (intravenous infusion), in you or your child’s arm. A healthcare provider will give you this injection.

• Your healthcare provider may prescribe medicines before each infusion of Rituxan to reduce infusion side effects such as fever and chills.
• Rituxan is not given daily. Your Rituxan dosing schedule will depend on the condition being treated. Follow your doctor’s dosing instructions very carefully.
• Your healthcare provider should do blood tests regularly to check for side effects of Rituxan.
• Before each Rituxan treatment, your healthcare provider or nurse will ask you questions about your or your child’s general health. Tell your healthcare provider or nurse about any new symptoms.

If you need surgery, tell the surgeon beforehand that you are using this medicine.

Call your doctor at once if you have any of these other side effects, even if they occur several months after you receive Rituxan, or after your treatment ends.

• painful skin or mouth sores, or a severe skin rash with blistering, peeling, or pus;
• redness, warmth, or swelling of the skin;
• severe stomach pain, vomiting, constipation, bloody or tarry stools;
• irregular heartbeats, chest pain or pressure, pain spreading to your jaw or shoulder;
• tiredness or jaundice (yellowing of the skin or eyes);
• signs of infection – fever, chills, cold or flu symptoms, cough, sore throat, mouth sores, headache, earache, pain or burning when you urinate; or
• signs of tumor cell breakdown – confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet, or around your mouth.

What happens if I miss a dose?

Call your doctor if you miss an appointment for your Rituxan infusion.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving Rituxan?

Do not receive a “live” vaccine while receiving Rituxan, and avoid coming into contact with anyone who has recently received a live vaccine.

There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and the nasal flu (influenza) vaccine.

What other drugs will affect Rituxan?

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

• a Tumor Necrosis Factor (TNF) inhibitor medicine such as adalimumab, certolizumab, etanercept, or golimumab, infliximab
• a Disease Modifying Anti-Rheumatic Drug (DMARD) such as leflunomide, methotrexate, or sulfasalazine
• chemotherapy drugs, especially cisplatin.

If you are not sure if your or your child’s medicine is one listed above, ask your healthcare provider. This list is not complete. Other drugs may interact with Rituxan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Rituxan infusion ingredients

Active ingredient: rituximab
Inactive ingredients: polysorbate 80, sodium chloride, sodium citrate dihydrate, and water for injection, USP.

Available as Rituxan injection for infusion, 100 mg/10 mL (10 mg/mL) and 500 mg/50 mL (10 mg/mL) solution in single-dose vials.

Manufacturer

Rituxan (rituximab) is jointly marketed by two pharmaceutical companies, Genentech (a member of the Roche Group) and Biogen.

• Genentech’s headquarters are located in South San Francisco, California, USA.
• Biogen’s headquarters are located in Cambridge, Massachusetts, USA.

The drug was originally developed through a collaboration between these two companies, and they continue to co-market it in the United States, while Roche markets rituximab internationally under various brand names, including MabThera in many countries.

Rituxan Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Rituxan.Rituxan (rituximab) – Genentech, Inc.

What is Rituxan Hycela?

Rituxan Hycela contains a combination of hyaluronidase and rituximab. Hyaluronidase is a genetically designed protein. Rituximab is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Rituxan Hycela is used to treat follicular lymphoma, diffuse large B-cell lymphoma, or chronic lymphocytic leukemia.

Rituxan Hycela is sometimes used together with other cancer medicines.

Rituxan Hycela is usually given only after you have received at least 1 injection of rituximab alone.

Warnings

Do not use Rituxan Hycela if you are pregnant. Avoid getting pregnant for at least 12 months after you stop using this medicine.

Rituxan Hycela may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have problems with speech, thought, vision, or muscle movement.

If you’ve ever had hepatitis B, using Rituxan Hycela can cause this virus to become active or get worse.

Severe skin problems can also occur during treatment with Rituxan Hycela. Call your doctor if you have painful skin or mouth sores, or a severe skin rash with blistering, peeling, or pus.

Some side effects may occur during the injection or within 24 hours afterward. Tell your caregiver right away if you feel itchy, dizzy, weak, light-headed, short of breath, chilled, feverish, or if you have chest pain, wheezing, a sudden cough, or pounding heartbeats or fluttering in your chest.

Before taking this medicine

To make sure Rituxan Hycela is safe for you, tell your doctor if you have ever had:

• kidney disease;
• lung disease;
• a severe reaction to hyaluronidase or rituximab;
• a weak immune system (caused by disease or by using certain medicines);
• a severe infection such as herpes, shingles, cytomegalovirus, chickenpox, parvovirus, West Nile virus, or hepatitis B or C;
• heart disease, angina (chest pain), or heart rhythm disorder; or
• if you recently received any vaccine, or you are are scheduled to receive a vaccine.

Rituximab may harm an unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 12 months after your last dose. Tell your doctor if you become pregnant.

Do not breastfeed while using this medicine, and for at least 6 months after your last dose.

How is Rituxan Hycela given?

Rituxan Hycela is injected under the skin of your stomach area. This medicine must be injected slowly over 5 to 7 minutes. A healthcare provider will give you this injection.

You will be watched closely for at least 15 minutes after receiving Rituxan Hycela, to make sure you do not have an allergic reaction.

Before each injection, you may be given other medicine to prevent certain side effects. Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

If you have chronic lymphocytic leukemia, you may also need to take medicine to prevent infections. You may need to keep taking this medicine for up to 12 months after your last dose of Rituxan Hycela.

Rituxan Hycela can lower blood cells that help your body fight infections. Your blood will need to be tested often.

If you’ve ever had hepatitis B, using rituximab can cause this virus to become active or get worse. You may need frequent liver function tests while using this medicine and for several months after you stop.

Dosing information

Usual Adult Dose of Rituxan Hycela for Follicular Lymphoma:

Relapsed or Refractory, Follicular Lymphoma: 23,400 Units hyaluronidase human and 1400 mg rituximab subcutaneously once a week for 3 or 7 weeks following a full dose of a rituximab product by IV infusion at week 1 (4 or 8 weeks total)

Retreatment for Relapsed or Refractory, Follicular Lymphoma: 23,400 Units hyaluronidase human and 1400 mg rituximab subcutaneously once a week for 3 weeks following a full dose of a rituximab product by IV infusion at week 1 (4 weeks total)

Previously Untreated, Follicular Lymphoma: 23,400 Units hyaluronidase human and 1400 mg rituximab subcutaneously on Day 1 of Cycles 2 through 8 of chemotherapy (every 21 days), for up to 7 cycles following a full dose of a rituximab product by IV infusion on Day 1 of Cycle 1 of chemotherapy (up to 8 cycles total); in patients with complete or partial response, initiate maintenance treatment 8 weeks following completion of hyaluronidase-rituximab in combination with chemotherapy; administer 23,400 Units hyaluronidase human and 1400 mg rituximab subcutaneously as a single agent every 8 weeks for 12 doses

Non-progressing, Follicular Lymphoma after first line CVP chemotherapy: Following completion of 6 to 8 cycles of CVP chemotherapy and a full dose of a rituximab product by IV infusion at week 1, administer 23,400 Units hyaluronidase human and 1400 mg rituximab subcutaneously once a week for 3 weeks (4 weeks total) at 6 month intervals to a maximum of 16 doses

Comments:
-All patients must receive at least one full dose of a rituximab product by IV infusion before starting therapy with hyaluronidase-rituximab.
-Premedicate before each dose with acetaminophen and an antihistamine. Premedication with a glucocorticoid should also be considered.

Use: For the treatment of adult patients with:
-Relapsed or refractory, follicular lymphoma as a single agent
-Previously untreated follicular lymphoma in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy
-Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy

Usual Adult Dose Rituxan Hycela for Lymphoma:

23,400 Units hyaluronidase human and 1400 mg rituximab subcutaneously on Day 1 of Cycles 2 through 8 of CHOP chemotherapy for up to 7 cycles following a full dose of a rituximab product by IV infusion at Day 1, Cycle 1 of CHOP chemotherapy (up to 6 to 8 cycles total)

Comments:
-All patients must receive at least one full dose of a rituximab product by IV infusion in combination with CHOP chemotherapy before starting therapy with hyaluronidase-rituximab.
-Premedicate before each dose with acetaminophen and an antihistamine. Premedication with a glucocorticoid should also be considered.

Use: For the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL) in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens

Usual Adult Dose for Chronic Lymphocytic Leukemia:

26,800 Units hyaluronidase human and 1600 mg rituximab subcutaneously on Day 1 of Cycles 2 through 6 (every 28 days) for a total of 5 cycles following a full IV dose at Day 1, Cycle 1 (6 cycles total) in combination with fludarabine and cyclophosphamide (FC) chemotherapy

Comments:
-All patients must receive at least one full dose of a rituximab product by IV infusion in combination with CHOP chemotherapy before starting therapy with hyaluronidase-rituximab.
-Premedicate before each dose with acetaminophen and an antihistamine. Premedication with a glucocorticoid should also be considered.

Use: In combination with fludarabine and cyclophosphamide (FC) for the treatment of adult patients with previously untreated and previously treated chronic lymphocytic leukemia (CLL)

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of Rituxan Hycela.

What happens if I overdose?

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving Rituxan Hycela?

Do not receive a “live” vaccine while using Rituxan Hycela. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Rituxan Hycela side effects

Get emergency medical help if you have signs of an allergic reaction to Rituxan Hycela (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Some side effects may occur during the injection (or within 24 hours afterward). Tell your caregiver right away if you feel itchy, dizzy, weak, light-headed, short of breath, chilled, feverish, or if you have chest pain, wheezing, a sudden cough, or pounding heartbeats or fluttering in your chest.

Rituximab may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have problems with speech, thought, vision, or muscle movement.

Serious and sometimes fatal infections may occur during treatment with Rituxan Hycela. Call your doctor right away if you have signs of infection such as:

• fever, sore throat, cold or flu symptoms;
• sores or white patches in your mouth or throat;
• pain or burning when you urinate;
• earaches, headaches; or
• painful skin sores with redness, warmth, or swelling.

Call your doctor at once if you have any of these other side effects, even if they occur several months after your last dose of Rituxan Hycela:

• severe stomach pain, severe vomiting;
• right-sided upper stomach pain, loss of appetite, yellowing of your skin or eyes, and not feeling well;
• little or no urination;
• skin or mouth sores, or a severe skin rash with blistering, peeling, or pus;
• chest pain, irregular heartbeats;
• low red blood cells (anemia) – pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet;
• low white blood cell counts – fever, mouth sores, skin sores, sore throat, cough, trouble breathing; or
• signs of tumor cell breakdown – tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, tingling in your hands and feet or around your mouth.

Common Rituxan Hycela side effects may include:

• low blood cell counts;
• nausea, vomiting, constipation;
• hair loss;
• feeling tired;
• cough; or
• redness where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Rituxan Hycela?

Other drugs may interact with hyaluronidase and rituximab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Rituxan hycela Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Rituxan Hycela.Rituxan Hycela (rituximab and hyaluronidase human) – Genentech, Inc.

What is rituximab?

Rituximab infusion is used to treat certain leukemias and lymphomas and some non-cancer conditions, such as rheumatoid arthritis, polyangiitis, and pemphigus vulgaris, depending on the brand. Brand names include Rituxan, Riabni, Ruxience, and Truxima. Rituximab is given by IV infusion (an infusion into a vein) by a healthcare provider.

Rituximab is not chemotherapy, it is a type of immunotherapy called a targeted cancer treatment.

Rituximab gained FDA approval on November 26, 1997, under the brand name Rituxan. Biosimilars to Rituxan followed, with:

• Truxima (rituximab-abbs), approved on November 28, 2018
• Ruxience (rituximab-pvvr), approved on July 23, 2019
• Riabni (rituximab-arrx), approved on December 17, 2020.

Truxima, Ruxience, and Riabni are not approved for use in children or for pemphigus vulgaris. Only Rituxan can be used in children or for pemphigus vulgaris.

FDA approvals and indications

Rituximab (Rituxan, Truxima, Ruxience, Riabri) is approved to treat:

• Non-Hodgkin’s lymphoma in adults alone or with other chemotherapy medicines
• Chronic lymphocytic leukemia in adults, in combination with the chemotherapy medicines fludarabine and cyclophosphamide
• Rheumatoid arthritis (RA) in adults, in combination with methotrexate, to reduce signs and symptoms of moderate to severely active RA after an inadequate response to treatment with a Tumor Necrosis Factor (TNF) antagonist
• Granulomatosis with Polyangiitis (GPA, Wegener’s granulomatosis) and Microscopic Polyangiitis (MPA) in adults, in combination with glucocorticoids.

The Rituxan brand of rituximab is also approved to treat:

• Mature B-cell Non-Hodgkin’s lymphoma (NHL) and mature B-cell acute leukemia (B-AL) in children 6 months and older, in combination with chemotherapy medicines
• Granulomatosis with Polyangiitis (GPA, Wegener’s granulomatosis) and Microscopic Polyangiitis (MPA) in children 2 years and older, in combination with glucocorticoids
• Moderate to severe pemphigus vulgaris in adults.

Rituximab is not approved for:

• Children aged less than 2 years with GPA or MPA
• Children less than 6 months of age with mature B-cell NHL and B-AL
• Children with conditions other than GPA, MPA, B-cell NHL, and B-AL.

How rituximab works

Rituximab is a targeted therapy that attaches to CD20, a protein found on the surface of B cells. As a type of white blood cell in your immune system, B cells normally help fight infections, but they can also contribute to certain diseases. When rituximab binds to the CD20 protein, it triggers two key mechanisms to destroy these B cells:

1. It activates your body’s complement system, which directly attacks and eliminates the B cells
2. It flags the B cells for destruction by other immune cells in a process called antibody-dependent cell-mediated cytotoxicity.

This targeted elimination of B cells makes rituximab effective for treating various conditions where B cells play a harmful role, including:

• B-cell cancers such as Non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL)
• Autoimmune disorders like rheumatoid arthritis, where B cells contribute to inflammation and joint damage.

By precisely targeting problematic B cells, rituximab helps control these conditions while minimizing impact on other parts of the immune system.

Side effects

The most common side effects of rituximab are:

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

In adults 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 are:

• 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 of rituximab are:

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

These are not all of the possible side effects of rituximab. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Serious side effects and warnings

Rituximab carries a Boxed Warning for fatal infusion-related reactions, severe skin reactions, hepatitis B virus reactivation, and a rare brain condition called progressive multifocal leukoencephalopathy (PML).

Rituximab can cause the following serious side effects:

• Infusion-related reactions. These are very common side effects of rituximab treatment. Serious infusion-related reactions can happen during your or your child’s infusion or within 24 hours after. Your healthcare provider should give you or your child medicines before your rituximab infusion to decrease the chance of having a severe infusion-related reaction. Tell your healthcare provider or get medical help right away if you or your child gets any of these symptoms during or after an infusion:
  • hives (red itchy welts) or rash
  • shortness of breath, difficulty breathing, or wheezing
  • itching
  • weakness
  • swelling of your lips, tongue, throat, or face
  • dizziness or feeling faint
  • sudden cough
  • 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 or your child gets 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 or your child receives rituximab treatment, your healthcare provider will do blood tests to check for HBV infection. If you or your child has had hepatitis B or is a carrier of the 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 or your child should not receive rituximab if you or your child has active hepatitis B liver disease. Your healthcare provider will monitor you or your child for hepatitis B infection during and for several months after you or your child stops receiving rituximab. Tell your healthcare provider immediately if you or your child gets worsening tiredness, or yellowing of your or your child’s skin or white part of your eyes, during treatment.
• 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 or your child has any new or worsening symptoms or if anyone close to you notices these symptoms:
  • confusion
  • dizziness or loss of balance
  • decreased strength or weakness on one side of your body
  • difficulty walking or talking
  • vision problems.
• 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 need dialysis treatment
  • an 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 has any of the following signs or symptoms of TLS:

• • nausea
  • diarrhea
  • vomiting
  • 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 (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 has any symptoms of infection:
  • fever
  • cold symptoms, such as a 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 a heart attack. Your healthcare provider may monitor your or your child’s heart during and after treatment with rituximab if you or your child has symptoms or heart problems or has a history of heart problems. Tell your healthcare provider right away if you or your child has chest pain or irregular heartbeats during treatment with rituximab.
• Kidney problems, especially if you or your child is receiving rituximab for NHL. Rituximab can cause severe kidney problems that can 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 receives rituximab with chemotherapy medicines. Tell your healthcare provider right away if you or your child has 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.

Get emergency medical help if you have signs of an allergic reaction to rituximab, such as hives, difficulty breathing, swelling in your face or throat, or a severe skin reaction (symptoms may include fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

These are not all of the possible side effects of rituximab. Call your doctor for medical advice about side effects.

Before taking this medicine

Before you or your child receives 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, Rituxan, Riabni, Ruxience, Truxima, or any ingredients in the injection
• have a history of heart problems, irregular heartbeat, or chest pain
• have lung, liver, or kidney problems
• have an infection or a weakened immune system
• have or have had any severe infections, including:
  • Hepatitis B virus (HBV)
  • Parvovirus B19
  • Hepatitis C virus (HCV)
  • Varicella zoster virus (chickenpox or shingles)
  • Cytomegalovirus (CMV)
  • West Nile Virus
  • Herpes simplex virus (HSV).
• 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. You should be up-to-date on any needed immunizations before starting treatment with rituximab.
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Rituximab may harm an unborn baby. Talk to your healthcare provider about the risks to an unborn baby if you or someone you are caring for receives rituximab during pregnancy. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test to check for pregnancy before starting rituximab.

Effective birth control (contraception) should be used during treatment with rituximab and for 12 months after the last dose. Talk to your healthcare provider about effective birth control.

Tell your healthcare provider right away if you or your child becomes pregnant or think you may be pregnant during treatment with rituximab.

Breastfeeding

Rituximab may pass into your breast milk. It is not safe to breastfeed a baby while you are using this medicine. Do not breastfeed during treatment and for 6 months after your or your child’s last dose of rituximab.

How is rituximab administered?

Rituximab is given by infusion through your or your child’s central catheter or a needle placed in a vein (intravenous infusion), in your arm or your child’s arm. A healthcare provider will give you this injection.

• Your healthcare provider may prescribe medicines before each infusion of rituximab to reduce infusion side effects such as fever and chills.
• Rituximab is not given daily. Your rituximab dosing schedule will depend on the condition being treated. Follow your doctor’s dosing instructions very carefully.
• Your healthcare provider should do blood tests regularly to check for side effects of rituximab.
• Before each rituximab treatment, your healthcare provider or nurse will ask you questions about your or your child’s general health. Tell your healthcare provider or nurse about any new symptoms.

If you need surgery, tell the surgeon beforehand that you are using this medicine.

Call your doctor at once if you have any of these other side effects, even if they occur several months after you receive rituximab, or after your treatment ends.

• painful skin or mouth sores, or a severe skin rash with blistering, peeling, or pus
• redness, warmth, or swelling of the skin
• severe stomach pain, vomiting, constipation, bloody or tarry stools
• irregular heartbeats, chest pain or pressure, pain spreading to your jaw or shoulder
• tiredness or jaundice (yellowing of the skin or eyes)
• signs of infection – fever, chills, cold or flu symptoms, cough, sore throat, mouth sores, headache, earache, pain or burning when you urinate
• signs of tumor cell breakdown – confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet, or around your mouth.

What happens if I miss a dose?

Call your doctor if you miss an appointment for your rituximab infusion.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving rituximab?

Do not receive a “live” vaccine while receiving rituximab, and avoid coming into contact with anyone who has recently received a live vaccine.

There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and the nasal flu (influenza) vaccine.

What other drugs will affect rituximab?

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

• a Tumor Necrosis Factor (TNF) inhibitor medicine such as adalimumab, certolizumab, etanercept, or golimumab, infliximab
• a Disease Modifying Anti-Rheumatic Drug (DMARD) such as leflunomide, methotrexate, or sulfasalazine
• chemotherapy drugs, especially cisplatin.

If you are not sure if your or your child’s medicine is one listed above, ask your healthcare provider. This list is not complete. Other drugs may interact with rituximab, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Ingredients

Available as an injection for infusion, 100 mg/10 mL (10 mg/mL) and 500 mg/50 mL (10 mg/mL) solution in single-dose vials.

Rituxan

Active ingredient: rituximab
Inactive ingredients: polysorbate 80, sodium chloride, sodium citrate dihydrate, and water for injection, USP.

Truxima

Active ingredient: rituximab-abbs

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

Ruxience

Active ingredient: rituximab-pvvr

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

Riabni

Active ingredient: rituximab-arrx

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

Manufacturer

Manufacturers of rituximab and its biosimilars are:

• Rituxan: Jointly marketed by Genentech (San Francisco, CA) and Biogen (Cambridge, MA)
• Truxima: Celltrion, Inc., Yeonsu-gu, Incheon, Republic of Korea
• Ruxience: Pfizer Ireland Pharmaceuticals, Cork, Ireland 
• Riabni: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA.

Rituximab Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for rituximab.Rituxan (rituximab) – Genentech, Inc.