Certolizumab Pegol (Cimzia)

CERTOLIZUMAB PEGOL (Cimzia) is a recombinant, humanized antibody to a Fab’ fragment, with specificity for human TNF-α; it is conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). The Fab’ fragment is manufactured in E. coli and is subsequently subjected to purification and conjugation to PEG2MAL40K, to generate certolizumab pegol.

Online Resources

  1. Patient Medication Guide and Prescribing Information
  2. Full Prescribing Information PDF

Indications and Dosing

FDA-Approved Indications and Dosing

  1. Adult Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: 400 mg subcutaneously initially and then repeat at weeks 2 and 4, followed by 200 mg every other week; 400 mg every 4 weeks can be considered for maintenance dosing
  2. Adult Crohn's disease: 400 mg subcutaneously initially and then repeat at weeks 2 and 4. If response occurs, follow with 400 mg every 4 weeks

Contraindications

  • None

Warnings and Precautions

  1. Serious infections – Most patients had underlying conditions predisposing them to infection or were taking concomitant immunosuppressants, such as methotrexate or corticosteroids. Cimzia should be discontinued for serious infections or sepsis.
    • Bacterial infections – consider opportunistic pathogens, such as Legionella and Listeria
    • Invasive fungal infections – consider empiric antifungal therapy to prevent systemic illness for those who reside or have traveled to areas where mycoses are endemic
    • Active Tuberculosis – Cimzia may reactivate latent tuberculosis. Test for tuberculosis prior to initiating and during Cimzia (see below)
    • Reactivation of hepatitis B virus- test for HBV viral load before starting certolizumab pegol and monitor HBV carriers
  2. Anaphylaxis or serous allergic reactions may occur
  3. New or worsening of heart failure may occur
  4. Demyelinating disease – exacerbations or new onset of demyelinating disease may occur.
  5. Cytopenias and pancytopenias – advise patients to seek immediate medical attention
  6. Lupus-like syndrome – stop Cimzia
  7. Lymphoma and other malignancies have been reported in patients receiving TNF blockers
  8. Drug Interactions
    • Other biological DMARDs – may result in increased risk for serious infections
    • Live vaccines – avoid with Cimzia
    • Activated partial thromboplastin time (aPTT) – Cimzia may interfere with the accuracy of this test

Common Adverse Reactions

  1. Infections – Upper respiratory infections, urinary tract infections
  2. Rash

Rare Adverse Reactions

  1. Opportunistic infections – bacterial, fungal and viral infections, shingles
  2. Hypersensitivity reactions
  3. Coronary artery ischemia
  4. Heart failure
  5. Leukopenia, neutropenia, and thrombocytopenia
  6. Hepatotoxicity
  7. Demyelinating disease
  8. Neurologic reactions – rare cases of seizures, optic neuritis and peripheral neuropathy
  9. Autoimmunity resulting in autoantibodies and rarely, lupus-like syndrome

Pre-Administration 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:
      1. 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-
      2. 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-
      3. 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. 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 certolizumab pegol).

Medication Preparation

  1. Certolizumab pegol is available in lyophilized vials for reconstitution or pre-filled syringes that are ready for administration.
  2. Certolizumab pegol 200 mg lyophilized vials
    • Reconstitute each lyophilized vial of certolizumab pegol using appropriate aseptic technique, with 1 ml of sterile water for injection and a syringe with a 20-gauge needle. Gently swirl each vial of certolizumab pegol without shaking so that all of the lyophilized powder comes into contact with the diluent. Certolizumab pegol vials should be brought to room temperature before reconstituting to facilitate dissolution.
    • Leave the vials undisturbed to facilitate drug dissolution (this may take as long as 30 minutes). Reconstituted certolizumab pegol has a concentration of approximately 200 mg/ml. Once reconstituted, certolizumab pegol is a clear opalescent, colorless to pale yellow liquid. The solution should be carefully inspected visually for particulate matter and discoloration. Certolizumab pegol should not be used if the dissolved solution appears cloudy or if foreign particulate matter is present. Certolizumab pegol does not contain preservative; therefore, unused portions of drug remaining in the syringe or vial should be discarded.
    • Reconstituted certolizumab pegol should be at room temperature prior to injection. Do not leave reconstituted certolizumab pegol at room temperature for more than 2 hours prior to administration. Once reconstituted, certolizumab pegol can be stored in the vials for up to 24 hours at 2o to 8oC (36o to 46oF) prior to injection. Do not freeze.

Medication Administration and Monitoring

  1. Using a new 20-gauge (reconstitution) needle for each vial, withdraw the reconstituted solution into a separate syringe for each vial, so that each syringe contains 1 ml of certolizumab pegol (200 mg of certolizumab pegol). Using a new 23-gauge (dosing) needle, and inject the full contents of each syringe subcutaneously into the thigh or abdomen. Separate sites should be used for each 200 mg injection for a certolizumab pegol 400 mg dose.
  2. Certolizumab pegol 200 mg pre-filled syringes (ready-for-administration): a patient may self-inject certolizumab pegol with the manufacturer’s prefilled syringe if the treating provider determines that it is appropriate, with medical follow-up, as necessary, after proper training in subcutaneous injection technique. Patients using certolizumab pegol should be instructed to inject the full amount in the syringe (1 ml), according to the directions provided in the Patient Instructions for Use [see FDA approved Patient Mediation Guide].
  3. Monitoring should include the following:
    • All patients must be evaluated for both active and inactive (latent) tuberculosis infections and reactivation of hepatitis B virus.
    • Monitor patients closely for signs and symptoms of infections during and after treatment.
    • Monitor patients closely for signs and symptoms of heart failure.
    • Monitor patients for signs and symptoms of allergic reactions
    • Monitor patients for new or worsening neurological problems such as multiple sclerosis, Guillain-Barre syndrome, and seizures.

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