Infliximab (Remicade)

INFLIXIMAB (Remicade) is a chimeric (part mouse, part human) monoclonal antibody that blocks activity of a key biologic response mediator called “tumor necrosis factor alpha (TNF-α). The action of Remicade is to bind to and neutralize TNF-α on the cell membrane as well as soluble TNF- α and to destroy TNF-α producing cell, thus inhibiting inflammation. Remicade is supplied as a sterile, white lyophilized powder for intravenous infusion.

Online Resources

  1. Patient Medication Guide
  2. Full Prescribing Information

FDA-Approved Indications and Dosing

  1. Rheumatoid Arthritis: 3 mg/kg IV at 0, 2 and 6 weeks, then every 8 weeks, in conjunction with methotrexate. Some patients may benefit from doses up to 10 mg/kg or treating as often as every 4 weeks.
  2. Ankylosing Spondylitis: 5 mg/kg IV at 0, 2 and 6 weeks, then every 8 weeks.
  3. Psoriatic Arthritis and Plaque Psoriasis: 5 mg/kg IV at 0, 2 and 6 weeks, then every 8 weeks.
  4. Crohn’s Disease: 5 mg/kg IV at 0, 2 and 6 weeks, then every 8 weeks. Some adult patients may benefit from doses up to10 mg/kg. Approved for use in pediatric patients, 6 years and older.
  5. Ulcerative Colitis: 5 mg/kg IV at 0, 2 and 6 weeks, then every 8 weeks. Approved for use in pediatric patients, 6 years and older.

Contraindications

  1. Infliximab doses greater than 5 mg/kg in patients with moderate to severe heart failure (New York Heart Association Functional Class III/IV).
  2. Previous severe hypersensitivity reaction to infliximab or known hypersensitivity to any component of infliximab or to any murine proteins.

Warning and Precautions

  1. Serious infections – do not administer if active infection is present. Patient greater than 65 years of age, those with comorbid conditions or on concomitant immunosuppressant or corticosteroids may be at greater risk for infection.
    • Bacterial infections – including those due to opportunistic organisms, such as Listeria and Legionella.
    • Tuberculosis – active tuberculosis and reactivation of latent tuberculosis may occur. Test for tuberculosis prior to initiating and during infliximab therapy. See Pre-Infusion Checklist below for tuberculosis screening recommendations.
    • Invasive fungal infections – consider empiric antifungal therapy to prevent systemic illness for those who are on infliximab and who live or have traveled to areas where mycoses are endemic.
    • Reactivation of hepatitis B virus- test HBV infection before starting infliximab and monitor for HBV carriers.
  2. Rare hepatotoxicity leading to death or liver transplantation; monitor for marked liver enzyme elevations and for the presence of jaundice.
  3. Lymphoma and other malignancies have been reported in patients receiving TNF blockers.
  4. New or worsening of heart failure may occur, particularly with infliximab 5 mg/kg/dose or higher.
  5. Hypersensitivity – infusion reactions, including anaphylaxis or serious allergic reactions may occur.
  6. Cytopenias
  7. Demyelinating disease – exacerbation or new onset
  8. Lupus-like syndrome
  9. Live vaccines or therapeutic infectious agents should not be given with concurrent infliximab use.
  10. Drug interactions – avoid use with anakinra or abatacept, which may increase risk of serious infections.

Adverse Reactions

Common:

  1. Infections – Upper respiratory infections and urinary tract infections.
  2. Infusion-related reactions – including pruritus, fevers, chills, chest pain, hypotension or hypertension, dyspnea, anaphylaxis and convulsions. Delayed hypersensitivity reactions consisting of a serum sickness or arthralgia/myalgia with fever or rash may also occur. Patients who are positive for infliximab antibodies are more likely to have an infusion reaction, both of which can be reduced with concomitant immunosuppression.
  3. Headache
  4. Gastrointestinal - nausea, abdominal pain, diarrhea, and dyspepsia.

Rare:

  1. Opportunistic infections – bacterial, fungal and viral infections, shingles
  2. Hepatotoxicity – severe liver toxicity, including liver failure and autoimmune hepatitis may occur
  3. Heart failure
  4. Cytopenias – leukopenia, neutropenia, thrombocytopenia, anemia
  5. Demyelinating disease of the central nervous system and Guillain-Barre syndrome
  6. Constipation

Pre-infusion Check List

  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. Confirm that the patient is hepatitis B negative (particularly HepB Surface Antigen).
  3. If patient has a history of moderate to severe heart failure, infliximab has been associated with an exacerbation of heart failure; doses > 5 mg/kg are contraindicated. Close monitoring is recommended.
    • If patient has demyelinating diseases, such as multiple sclerosis, infliximab is contraindicated.
  4. Evaluate patient for: (review affirmative answers with ordering provider)
    • Any current or recent bouts of fever, illness or infection
    • Taking any antibiotics
    • Recent or upcoming surgeries
    • Recent or planned live virus vaccinations (live virus vaccinations are not recommended during therapy with infliximab).

Medication Preparation

The reconstituted infliximab infusion solution should be prepared by a trained medical professional using aseptic technique by the following procedure:

  1. Calculate the dose per providers order, total volume of reconstituted infliximab solution required and the number of infliximab vials needed. Each infliximab vial contains 100 mg of infliximab.
  2. Reconstitute each infliximab vial with 10 mL of Sterile Water using a syringe equipped with a 21-gauge or smaller needle as follows:
    • Insert the syringe needle into the vial through the center of the rubber stopper and direct the stream of Sterile Water gently to the glass wall of the vial.
    • GENTLY swirl the solution by rotating the vial to dissolve the lyophilized powder. Avoid shaking, which may inactivate infliximab. Foaming of the solution is not unusual.
    • Allow the reconstituted solution to stand for 5 minutes. The solution should be colorless to light yellow and opalescent. The solution may develop a few translucent particles.
    • Do not use if the lyophilized cake has not fully dissolved or if opaque particles, discoloration, or other foreign particles are present.
  3. Dilute the total volume of the reconstituted infliximab solution dose to a total volume of 250 mL with sterile 0.9% Sodium Chloride Injection, USP, by withdrawing a volume equal to the volume of reconstituted infliximab from the 0.9% Sodium Chloride Injection, USP, 250 mL bottle or bag.
  4. Slowly add the total volume of reconstituted infliximab solution to the 250 mL infusion bottle or bag. Gently mix.
  5. The infusion solution must be administered over a period of not less than 2 hours utilizing an infusion set with an in-line, sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 μm or less).

No physical biochemical compatibility studies have been conducted to evaluate the co-administration of infliximab with other agents. Infliximab should not be infused concomitantly in the same intravenous line with other agents.

Medication Administration and Monitoring

  1. Vital Signs Monitoring: Obtain vital signs (patient temperature, blood pressure and pulse) upon arrival, after start of medication, 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.
  2. Review Orders and Obtain IV Access:
    • Check for pre-medication orders. Give pre-medications if ordered. Pre-medications may include antihistamines, acetaminophen and/or corticosteroids.
    • Infliximab infusion should be administered over a period of not less than 2 hours. Below is an example of an infusion rate schedule for infliximab diluted in a 250mL volume:
      • 40mL/hr. for 15 minutes, then if tolerated, increase to:
      • 80mL/hr. x 30 minutes, then if tolerate, increase to:
      • 160mL/hr. for the duration of infusion
      • Flush to ensure all medication in the IV tubing is administered.
      • Total infusion time is 2 hours, plus 15 minutes for the flush.

Managing Infusion Reactions

Acute infusion reaction or anaphylaxis can occur at any time during the administration of this agent and include flu-like symptoms, headache, dyspnea, hypotension, transient fever, chills, gastrointestinal symptoms, and skin rashes. If patient reports mild reactions (such as flushing, chills, etc.), stop the infusion and assess patient. 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. Then notify the supervising provider immediately to coordinate next plan of action. For mild reactions, consider adding additional pre-medications for subsequent doses.

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