Tocilizumab (Actemra)

TOCILIZUMAB (Actemra) is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin IgG1κ subclass. Two heavy chain and two light chain polypeptides are linked by intra- and inter-molecular disulfide bonds. Endogenous IL-6 is induced by inflammatory stimuli and mediates a variety of immunological responses. Inhibition of IL-6 receptors by tocilizumab leads to a reduction in cytokine and acute phase reactant production.

Resources from Manufacturer

Patient Medication Guide
Full Prescribing Information
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Rheumatologic Indications

Tocilizumab is indicated for:

  • Adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease Modifying Anti-Rheumatic Drugs (DMARDs).
  • Active Polyarticular Juvenile Idiopathic Arthritis (PJIA) in patients two years of age and older.
  • Active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients two years of age and older.

Dosing

Rheumatoid Arthritis (RA)

  1. Tocilizumab may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an IV infusion or subcutaneous injection.
  2. IV dosing
    • Tocilizumab is given as a 60 minute single intravenous drip infusion.
    • The recommended dosage initial dose is 4 mg/kg every 4 weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response.
  3. SC Dosing
    • Patients weighing less than 100 kg: 162 mg administered subcutaneously every other week, followed by an increase to every week based on clinical response.
    • Patient weighing at or greater than 100 kg: 162 mg administered subcutaneously every week.

Polyarticular Juvenile Idiopathic Arthritis (PJIA)

  1. Tocilizumab may be used alone or in combination with methotrexate.
  2. The recommended dosage given as IV infusion given once every 4 weeks is
    • Patients less than 30 kg weight: 10 mg/kg
    • Patients at or above 30 kg weight: 8 mg/kg

Systemic Juvenile Arthritis

  1. Tocilizumab may be used alone or in combination with methotrexate.
  2. The recommended dose of tocilizumab given once every 2 weeks as an IV infusion is:
    • Patients less than 30 kg weight: 12 mg/kg
    • Patients at or above 30 kg: 8 mg/kg

Contraindications

Known hypersensitivity

Warnings and Precautions

  1. Serious Infections – do not administer tocilizumab during an active infection, including localized infections. If a serious infection develops, interrupt tocilizumab until the infection is controlled.
  2. Gastrointestinal perforation – use with caution in patients who may be at increased risk.
  3. Laboratory monitoring – recommended due to potential consequences of treatment-related changes in neutrophils, platelets, lipids and liver specific enzymes.
  4. Hypersensitivity reactions including anaphylaxis and death.
  5. Demyelinating Disorders—use with caution in patients with preexisting or recent onset demyelinating disorders.
  6. Active Hepatic disease and Hepatic impairment—use is not recommended
  7. Live vaccines – avoid use with tocilizumab.
  8. Pregnancy – may cause fetal harm
  9. Lactation – discontinue drug or nursing

Adverse Reactions

Most common adverse reactions (>5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT and injection site reactions.

Pre-Infusion Checklist

  1. Confirm the following:
    • Negative PPD
    • Positive PPD with negative chest radiograph or at least 4 weeks post-initiation of latent tuberculosis infection treatment
    • Negative hepatitis B serologic tests
    • Absolute neutrophil count (ANC) is not below 2000/mm3, platelet count is not below 100,000/mm3 and ALT or AST is not above 1.5 times the upper limit of normal.
  2. Ask the patient if he/she:
    • Has a current or recent infection or illness.
    • Is taking antibiotics.
    • Has an upcoming surgery.

If the answer is yes to any of these questions, notify the ordering provider before initiating the infusion therapy.

Medication Preparation

Intravenous

  1. Tocilizumab is supplied as a sterile, preservative-free solution for intravenous (IV) infusion in single use vials (80 mg/4 mL, 200 mg/10 mL and 400 mg/20mL).
  2. Do not dilute vials until after successfully obtaining intravenous access.
  3. For adults RA, PJIA and SJIA patients weighing at or above 30 kg, dilute to 100 mL in 0.9% NaCl for intravenous infusion using aseptic technique.
  4. For PJIA and SJIA patients weighing less than 30 kg, dilute to 50 mL in 0.9% NaCl for intravenous infusion using aseptic technique.
  5. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulates and discoloration are noted, the product should not be used. Fully diluted tocilizumab solutions are compatible with polypropylene, polyethylene and polyvinyl chloride infusion bags and polypropylene, polyethylene and glass infusion bottles.
  6. The fully diluted tocilizumab solutions for infusions should be stored at 36 – 46 degrees Fahrenheit or at room temperature for up to 24 hours. The solution should be protected from light.
  7. Tocilizumab solution does not contain preservatives; therefore, unused product remain in the vials should NOT be used.

Subcutaneous

  1. Tocilizumab for subcutaneous administration is supplied as a prefilled syringe which delivers 0.9ml (162 mg) of tocilizumab.
  2. Instruct the patient to remove from the refrigerator approximately 30-60 minutes prior to injection.

Medication Administration and Monitoring

Intravenous

  1. Allow the fully diluted tocilizumab solution to reach room temperature prior to infusion.
  2. The infusion should be administered over 60 minutes, and must be administered with an infusion set. Do not administer as an intravenous push or bolus.
  3. Tocilizumab should not be infused concomitantly in the same intravenous line with other drugs. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of tocilizumab with other drugs.
  4. Obtain vital signs (temperature, blood pressure and pulse) upon arrival, after initiation of the infusion, upon discontinuing the infusion and before the patient departs the facility. However, if the patient has a history of prior acute infusion reaction, monitor vital signs every 10 minutes for 30 minutes and for 30 minutes after the infusion.
  5. Total infusion time is 60 minutes with an additional 15 minutes to flush 20 mL of normal saline to clear the infusion line of medication.

Subcutaneous

  1. Instruct patient to inject into the front of the thigh (preferred), abdomen (except for 2-inch area around the navel), or the outer area of the upper arms (if administered by a caregiver). Rotate injection sites (≥1 inch apart); do not administer into tender, bruised, red, or hard skin.

Managing Infusion Reactions

  1. Acute infusion reaction can occur during the administration of tocilizumab or within 24 hours of infusion. If the patient reports mild reactions (such as flushing, chills, etc.), slow down the infusion rate and assess the patient. Notify the supervising provider of the reaction.
  2. 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 when mild reactions persist despite slowing the infusion, stop the infusion and treat the acute reaction. Tocilizumab should not be given to patients who have experienced anaphylaxis or other severe hypersensitivity and not re-challenged.

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.