RITUXAN (rituximab) – Complete Information

RITUXAN is a CD20-directed cytolytic antibody indicated for the treatment of:

• Adult patients with Non-Hodgkin’s Lymphoma (NHL):
  • refractory or relapsed, low grade or follicular, CD20-positive B-cell NHL as a single agent.
  • 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.
  • Non-progressing, low-grade, CD20- positive, B-cell NHL as a single agent after first-line vincristine, cyclophosphamide, and prednisone chemotherapy.
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with (cyclophosphamide, vincristine, doxorubicin, and prednisone) (CHOP) or other anthracycline-based chemotherapy regimens.

• Pediatric patients aged 6 months and older with mature B-cell NHL and mature B-cell acute leukemia (B AL):
  • Previously untreated, advanced stage, CD20-positive, diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mature B-cell acute leukemia (B-AL), or Burkitt-like lymphoma (BLL) in combination with chemotherapy.

• Adult patients with Chronic Lymphocytic Leukemia (CLL):
  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide.

• Rheumatoid Arthritis (RA):
  • in combination with methotrexate in adult patients with moderate to severely active RA who have an inadequate response to one or more TNF antagonist therapies.

• Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA):
  • in adult and pediatric patients 2 years of age and older in combination with glucocorticoids.

• Pemphigus Vulgaris:
  • Moderate to severe Pemphigus Vulgaris (PV) in adult patients.

Before receiving RITUXAN, tell your doctor if you:

• Have had a severe reaction to RITUXAN or on any rituximab products.

• Have a history of heart problems

• Have lung or kidney problems.

• Have had an infection or currently have an infection, or have a weak immune system.

• Have or have had any of the following severe infections:
  • Hepatitis B virus (HBV), Hepatitis C virus (HCV), Cytomegalovirus (CMV), Herpes simplex virus (HSV), Parvovirus B19, Varicella zoster virus (chickenpox or shingles), and West Nile Virus.

• Have had a recent vaccination or are planning to receive vaccinations. You should not receive certain vaccines before or during treatment with RITUXAN.

• If you have any other medical conditions.

• If are pregnant or planning to become pregnant. Talk to your doctor about the risks to your unborn baby if you receive RITUXAN during pregnancy. Females who are able to become pregnant: 
  • You should do a pregnancy test to see if you are pregnant before starting RITUXAN and you should use effective birth control during treatment with RITUXAN and also for 12 months straight after the last dose of RITUXAN. You can talk to your doctor about birth control. Tell your doctor right away if you become pregnant or think that you are pregnant during treatment with RITUXAN.

• If you are breastfeeding or planning to breastfeed. RITUXAN may pass into your breast milk. and make sure to not breastfeed during treatment (for 6 months after your last dose of rituximab).

• If you are taking any medications, prescriptions, over-the-counter medicines, vitamins, and herbal supplements. Especially if you take or have taken:
  • a tumor necrosis factor (TNF) inhibitor medicine, or a disease-modifying anti-rheumatic drug (DMARD).

• RITUXAN is given by infusion through your or your child’s central catheter or through a needle placed in a vein, in your or your child’s arm. Talk to your doctor about how you or your child will receive RITUXAN.

• Your doctor may prescribe medicines before each infusion of RITUXAN to reduce infusion side effects such as fever and chills.

• Your doctor should do blood tests regularly to check for side effects of RITUXAN.

• Before each RITUXAN treatment, your doctor will ask you questions about your or your child’s general health or if you have any symptoms.

• RITUXAN is administered as an intravenous infusion.

• Do not administer as an intravenous push or bolus.

• RITUXAN should only be administered by a doctor with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur.

• The dose for adult and pediatric B-cell NHL is 375 mg/m2.

• The dose for CLL is 375 mg/m2 in the first cycle and 500 mg/m2 in cycles 2-6, in combination with FC, administered every 28 days.

• The dose as a component of the Zevalinâ (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m2.

• The dose for RA in combination with methotrexate is two-1,000 mg infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion.

• The recommended dose for adult patients with active GPA and MPA in combination with glucocorticoids is 375 mg/m2 once weekly for 4 weeks. The follow-up dose for adult patients with GPA and MPA who achieved disease control with induction treatment, in combination with glucocorticoids is two 500 mg infusions separated by two weeks, followed by a 500 mg infusion every 6 months thereafter based on clinical evaluation.

• The recommended dose for pediatric patients with GPA and MPA in combination with glucocorticoids is 375 mg/m2 once weekly for 4 weeks. The follow-up dose for pediatric patients with GPA and MPA who achieved disease control with induction treatment, in combination with glucocorticoids is two 250 mg/m2 infusions separated by two weeks, followed by a 250 mg/m2 infusion every 6 months thereafter based on clinical evaluation.

• The dose for Pemphigus Vulgaris is two-1,000 mg infusions separated by 2 weeks in combination with a tapering course of glucocorticoids, then a 500 mg infusion at Month 12 and every 6 months thereafter or based on clinical evaluation. The dose upon relapse is a 1,000 mg infusion with considerations to resume or increase the glucocorticoid dose based on clinical evaluation. Subsequent infusions may be no sooner than 16 weeks after the previous infusion. Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion.

• infusion-related reactions, infections, body aches, tiredness, and nausea.

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

• 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

• Aching joints after receiving an infusion, and frequent upper respiratory tract infections.

• Infusion-related reactions: Infusion-related reactions are very common side effects of RITUXAN. Serious infusion-related reactions can happen within 24 hours after you receive your RITUXAN shot. Your doctor will give you medicines to reduce the serious side effects of RITUXAN. If you experience any of these symptoms from an infusion of RITUXAN, make sure to consult your doctor:
  • Hives or rash
  • Itching
  • Swelling of the face, lips, tongue, and throat
  • Sudden coughing
  • Shortness of breath, difficulty breathing, or wheezing
  • Feeling weakness
  • Dizziness or fainting
  • Palpitations (rising heartbeat), chest pain

• Severe skin and mouth reactions: if you experience any of these symptoms during your treatment with RITUXAN:
  • Ulcers on your skin, painful sores, lips, or in your mouth.
  • peeling of the skin, blisters, rashes, and pustules on the skin.

• Hepatitis B virus Reactivation: before the RITUXAN treatment, your doctor checks if you have HBV infection by conducting a blood test. If you have or had hepatitis B receiving RITUXAN could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems including death. If you get worsening tiredness, yellowing of your skin, or the white part of your eyes during treatment with RITUXAN, contact your doctor. 

• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection that can happen in people who receive RITUXAN. It can result in death or disability. There is no known treatment or cure for PML. Tell your doctor right away if you notice these symptoms:
  • Confusion
  • Dizziness
  • Difficulty in walking or talking
  • Decreased strength or feeling of weakness on one side of your body
  • Vision problems or blurred vision

• Tumor Lysis Syndrome (TLS): It is caused by the fast breakdown of cancer cells. TLS can cause you to have:
  • Kidney failure and the need for dialysis treatment
  • Abnormal heart rhythms can happen within 12 to 24 hours after receiving a dose of RITUXAN. Your doctor may check if you have TLS by conducting a blood test. Your doctor may give you medicine to help prevent TLS. Your doctor will give you medicine if you have experienced any of the following symptoms of TLS:
  • Nausea, vomiting, diarrhea, lack of energy.

• Serious Infections: Serious infections (they include bacterial, fungal, and viral infections) can also happen during and after treatment with RITUXAN, and can lead to death. RITUXAN can increase your risk of getting infections and can weaken the immune system to fight infections. After receiving RITUXAN, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months) and these patients have developed infections. Go to your doctor right away if you experience the following symptoms of infection:
  • Fever
  • Cold symptoms, (such as runny nose or sore throat) that do not go away
  • Flu symptoms
  • Earache, headache, pain during urination
  • Cold sores in the mouth or throat, scrapes, cuts, or incisions that are red, warm, swollen, or painful

• Heart Problems: RITUXAN can cause heart problems (like chest pain, irregular heartbeats, and heart attack). Go to your doctor right away if you experience chest pain or irregular heartbeats during treatment with RITUXAN.

• Kidney Problems: especially if you are receiving RITUXAN for non-Hodgkin’s lymphoma (NHL). RITUXAN can cause severe kidney problems that lead to death. Your doctor should do blood tests to check if your kidneys are working well.

• Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Bowel problems such as blockage or tears in the bowel can happen if you receive RITUXAN with chemotherapy medicines. Go to your doctor right away if you have any abdominal pain or repeated vomiting during treatment with RITUXAN.

Store RITUXAN vials refrigerated at 2°C to 8°C. The RITUXAN vials should be protected from direct sunlight. Do not freeze or shake.

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