Rituximab (Rituxan)

RITUXIMAB (Rituxan) is a genetically engineered chimeric murine/human monoclonal IgG, kappa antibody directed against the CD20 antigen. CD20 is expressed on the majority of B-cells, but the antigen is not found on hematopoietic stem cells, pro-B-cells, normal plasma cells or other normal tissue. B cells are believed to play a role in the pathogenesis of RA and associated chronic synovitis. Administration of Rituxan results in a rapid and sustained depletion of circulating and tissue-based B cells. Rituxan is a sterile, clear, colorless, preservative-free liquid concentrate for intravenous administration. It is supplied at a concentration of 10 mg/ml in either 100 mg (10 ml) or 500 mg (50 ml) single-use vials.

Online Resources

  1. Patient Medication Guide
  2. Full Prescribing Information

FDA – Approved Indications and Dosing

  1. Rheumatoid Arthritis: in combination with methotrexate is two-1000mg IV infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks.
  2. Granulomatosis with Polyangiitis (GPS) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA): In combination with glucocorticoids is 375 mg/m2 once weekly for 4 weeks.
  3. Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia.

Contraindications

Hypersensitivity to any component, murine proteins.

Warning and Precautions

  1. Infections: Withhold infusion
  2. Cardiac arrhythmias and angina: Discontinue infusions
  3. Bowel obstruction and perforation: Evaluate for abdominal pain, vomiting, or related symptoms
  4. Live virus vaccines: Do not administer live virus vaccines prior or during rituximab treatment

Adverse Reactions

Common:

  1. Upper respiratory tract infection, nasopharyngitis, urinary tract infections, and bronchitis
  2. Nausea and diarrhea
  3. Headache
  4. Muscle spasms
  5. Anemia
  6. Peripheral edema

Rare:

  1. Fatal infusion reactions within 24 hours of rituximab infusion
  2. Severe mucocutaneous reactions
  3. Hepatitis B virus (HBV) reactivation
  4. Progressive multifocal leukoencepalopathy

Pre-Infusion Checklist

1. Tuberculosis screening

  • Verify that latent tuberculosis infection screening has been performed:
    • Detailed history of patient tuberculosis exposure risk factors.
    • Confirm the following:
      • Negative tuberculin skin test/PPD (<5mm induration) and/or Negative Interferon Gamma Release Assay (Quantiferon or T.Spot.TB test). Consider chest x-ray in patients with TB risk factors but negative screening tests. OR
      • Positive tuberculin skin test/PPD or positive Quantiferon/T.Spot.TB test with negative chest x-ray. Consider infectious disease consult and/or treating with INH if tuberculosis history risk factors are present (extrapulmonary TB maybe present). OR
      • Patient is at least 4 weeks post initiation of INH or other TB therapy.
    • Consider repeating screening tests if a patient has subsequently traveled to TB endemic countries or there has been a change in risk factors for TB exposure.

2. Hepatitis B screening

  • Verify negative hepatitis B screening.

3. Ask patient if they:

  • Are taking any antibiotics
  • Have any upcoming surgeries.
  • Have a history of asthma. If yes, have inhaler instructions been given?
  • Are taking anti-hypertensive medications. If yes, has the patient been given instructions to hold their anti-hypertensive before rituximab infusions?
  • Are pregnant or breastfeeding.
  • Have recently received vaccines / live vaccines prior to initiating rituximab.

If the answer is yes to any of these questions, review with ordering provider.

Medication Preparation

  1. Use appropriate aseptic technique.
    • Clean the port of the 250-mL IV bag of 0.9% sodium chloride, USP, or 5% dextrose in water, USP, with an alcohol wipe. Remove 100 mL of 0.9% sodium chloride, USP, or 5% dextrose in water, USP, and discard, leaving 150 mL in the IV bag.
    • Remove cap from rituximab vial and clean rubber stopper with alcohol wipe.
  2. Carefully withdraw 50 mL (500 mg) from 2 vials of rituximab, for a total of 100 mL. Gentle air injection or push-pull method can be used to ease the withdrawal of rituximab. Discard any unused portion of rituximab.
  3. Dilute the 100 mL (1000 mg) of rituximab into the 150-mL IV solution, yielding a final total volume of 250 mL and a final concentration of 4 mg/mL. Remove and dispose of needle and syringe in compliance with hospital and/or office protocol.
  4. Gently invert IV bag to mix. Do not shake. Inspect for particulate matter and/or discoloration. Label IV bag with patient's name, drug, dose, and date, and then initial it.
  5. Diluted Rituxan solution may be stored at 35-46 degrees Fahrenheit for up to 24 hours. Protect solution from direct sunlight.
  6. Connect an infusion set to the IV bag containing rituximab. Prime the line. Piggyback the set with rituximab into the port closest to the patient in the primary infusion line. Stop the primary infusion line. Rituximab should not be infused concomitantly in the same line with other medications. Though not mandatory for IV infusion, use of an infusion pump can help regulate the administration and dosage of the drug.

Medication Administration and Monitoring

DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.

Recommended dose for RA is rituximab as two-1000mg separated by 2 weeks. Pre-medication should consist of glucocorticoids administered as methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion.

Recommended dose for GPA, Wegener’s granulomatosis, and MPA is rituximab as 375 mg/m2 once weekly for 4 weeks. Glucocorticoids administered as methylprednisolone 1000 mg IV per day for 1 to 3 days followed by oral prednisone are recommended to treat severe vasculitis symptoms.

  1. First Infusion (Day1): Initiate infusion at a rate of 50 mg/hr. In the absence of infusion reaction, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.
  2. Subsequent Infusions: If the patient did not tolerate the first infusion well, start at the same rate as the first infusion (50 mg/hr) and follow directions noted above.
  3. If the patient tolerated the first infusion, initiate subsequent infusions at a rate of 100 mg/hr. In the absence of infusion reaction, increase rate by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr.
  4. Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion rate at one-half the previous rate upon improvement of symptoms.
  5. Push 20cc NS flush into bag once bag is nearly empty to clear all medication in the IV tubing.
  6. Total minimum infusion time for the first infusion is 4 hours and 15 minutes, plus 15 minutes for the flush.
  7. Total minimum infusion time for subsequent infusions is 3 hours and 15 minutes, plus 15 minutes for the flush.

Vital Signs Monitoring

Obtain vital signs (patient temperature, blood pressure and pulse) upon arrival, after start of medication, every 15 minutes for the first hour of the infusion, every 30 minutes thereafter, upon discontinuing infusion and before the patient departs the facility. However, if prior history of an acute infusion reaction, monitor vitals every 10 minutes for 30 minutes then every 30 minutes and for 30 minutes after infusion.

Managing Acute Infusion Reactions

Acute infusion reaction can occur during the administration of this agent. If patient reports mild to moderate reactions such as flushing, chills, and rigors, slow down the infusion rate and assess patient for symptom resolution. For more severe reactions such as hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, fever, chills or anaphylaxis, or where mild reactions persist, stop the infusion and treat the acute reaction (with diphehydramine, acetaminophen, IV normal saline, vasopressors). Then notify the supervising provider immediately to coordinate next plan of action.

Updated: January 2017 - ARHP Practice Committee

DISCLAIMER:The information contained in this biologic reference guide is offered solely for purposes of providing health care professionals with a quick and initial reference. Before prescribing or administering any drug contained in this biologic reference guide, health professionals should read the manufacturer’s complete prescribing information in order to be informed of the various clinical considerations to be taken into account. The American College of Rheumatology is providing this information as a benefit and service in furtherance of its educational mission. By providing this information, ACR is not endorsing or recommending any of the listed companies or any of their drugs or other products. The information contained in the biologic reference guides reflect the conclusions of the individual companies and not those of the ACR which specifically disclaims any responsibility or liability for the use of such information and/or for the performance of any of the drugs listed in this biologic reference guide.

© 2017 American College of Rheumatology