Certolizumab Pegol

Certolizumab Pegol is a prescription medication used for treating the symptoms of Crohn’s disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, spondyloarthritis, and plaque psoriasis.

• Certolizumab Pegol is available under the following different brand names: Cimzia

Adult dosage

Injection, lyophilized powder for reconstitution

• 200mg/vial

Injectable solution, single-dose prefilled syringe

• 200mg/mL

Crohn Disease

Adult dosage

• Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks
• Maintenance: 400 mg SC every 4 weeks

Rheumatoid Arthritis

Adult dosage

• Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks
• Maintenance: 200 mg SC every 2 weeks OR 400 mg SC every 4 weeks

Psoriatic Arthritis

Adult dosage

• Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks, followed by 200 mg SC every 2 weeks
• Maintenance: Consider 400 mg SC every 4 weeks

Ankylosing Spondylitis

Adult dosage

• Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks
• Maintenance: 200 mg SC every 2 weeks OR 400 mg SC every 4 weeks

Spondyloarthritis

Adult dosage

• Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks
• Maintenance: 200 mg SC every 2 weeks OR 400 mg SC every 4 weeks

Plaque Psoriasis

Adult dosage

• 400 every other week
• For some patients (below 90 kg), consider starting at 400 mg SC (given as 2 injections of 200 mg each) initially and at Weeks 2 and 4, followed by 200 mg SC every other week

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Certolizumab Pegol include:

• stuffy nose,
• sinus pain,
• stomach pain,
• diarrhea,
• constipation,
• injection site reactions (pain, redness, itching, swelling, or bleeding),
• upper respiratory infections (flu, cold),
• rash, and
• urinary tract infections.

Serious side effects of the Certolizumab Pegol include:

• serious infections,
• malignancies, and
• heart failure.

Rare side effects of the Certolizumab Pegol include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Certolizumab Pegol has severe interactions with the following drugs:
  • adenovirus types 4 and 7 live, oral
  • BCG intravesical live
  • BCG vaccine live
  • influenza virus vaccine quadrivalent, intranasal
  • measles mumps and rubella vaccine, live
  • measles, mumps, rubella, and varicella vaccine, live
  • rotavirus oral vaccine, live
  • smallpox (vaccinia) vaccine, live
  • typhoid vaccine live
  • varicella virus vaccine live
  • yellow fever vaccine
  • zoster vaccine live
• Certolizumab Pegol has serious interactions with at least 24 other drugs.
• Certolizumab Pegol has moderate interactions with at least 43 other drugs.
• Certolizumab Pegol has no noted minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

• Contraindications
• History of hypersensitivity reaction to certolizumab Pegol or any of the excipients; reactions have included angioedema, anaphylactoid reaction, serum sickness, and urticaria

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Certolizumab Pegol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Certolizumab Pegol?”

Cautions

• Hypersensitivity includes anaphylaxis and serious reactions (see Contraindications)
• May interfere with aPPT tests
• The needle shield inside the removable cap of the prefilled syringe contains a derivative of natural rubber latex which may cause an allergic reaction in individuals sensitive to latex
• Therapy has been associated with rare cases of new-onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis, and with peripheral demyelinating disease, including Guillain-Barré syndrome; exercise caution in considering use in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with the drug
• Treatment may result in the formation of autoantibodies and rarely, in the development of a lupus-like syndrome; if a patient develops symptoms suggestive of a lupus-like syndrome following treatment, discontinue treatment
• Cases of worsening congestive heart failure (CHF) and new-onset CHF were reported; therapy has not been formally studied in patients with CHF; however, in clinical studies in patients with CHF with another TNF blocker, worsening congestive heart failure (CHF) and increased mortality due to CHF were observed; exercise caution in patients with heart failure and monitor them carefully
• Hematological Reactions
  • Pancytopenia, including aplastic anemia, was reported with TNF blockers; adverse reactions to the hematologic system, including medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) reported
  • The causal relationship between these events remains unclear
  • although no high-risk group has been identified, exercise caution in patients who have ongoing, or a history of, significant hematologic abnormalities
  • Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (eg, persistent fever, bruising, bleeding, pallor) while on treatment
  • Consider discontinuation of therapy in patients with confirmed significant hematologic abnormalities
• Increased risk of serious infections
• Also, see Black Box Warnings
• An increased risk of serious infections was seen in clinical studies of other TNF-blocking agents used in combination with anakinra or abatacept, with no added benefit; no formal drug interaction studies were performed with rituximab or natalizumab; concomitant use of certolizumab Pegol with anakinra, abatacept, rituximab, or natalizumab is not recommended
• A higher risk of serious infections was also observed in combination with DMARDs; because of the nature of adverse events seen with combination therapy, used in combination with other biological DMARDs is not recommended
• Hepatitis B Virus Reactivation
  • The use of TNF blockers has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus; patients concomitantly receiving immunosuppressives, which may also contribute to HBV reactivation
  • Test patients for HBV infection before initiating treatment; patients who test positive for HBV infection
  • Closely monitor patients who are carriers of HBV and require treatment for clinical and laboratory signs of active HBV infection throughout therapy and several months following termination of therapy
  • In patients who develop HBV reactivation, discontinue treatment and initiate effective anti-viral therapy with appropriate supportive treatment
  • Exercise caution when considering resumption of therapy in this situation and monitor patients closely
• Opportunistic infections
  • TNF blockers increase the risk for opportunistic infections, (eg, TB, invasive fungal infections); for patients who develop systemic infections, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic
  • Coadministration with anakinra increases this risk
  • Test for latent TB before starting treatment and monitor; treatment of latent tuberculosis infection before therapy with TNF-blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy; induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis needed before initiating therapy with certolizumab, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG); also consider anti-tuberculosis therapy in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection
  • Discontinue if serious infection develops
• Malignancy risk
  • Enhanced safety surveillance requirements to capture malignancy data: (see Black Box Warnings)
  • In the controlled portions of clinical studies of some TNF blockers, more cases of malignancies have been observed among patients receiving TNF blockers compared to control patients
  • Melanoma and Merkel cell carcinoma
    • Melanoma and Merkel cell carcinoma were reported with TNF-antagonists, including certolizumab Pegol
    • Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer
• Hepatosplenic T-cell lymphomas (HSTCL)
  • Rare postmarketing cases were reported primarily in adolescent and young adult patients with Crohn's disease and ulcerative colitis treated with TNF blockers
  • Reports have also included a patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
  • HSTCL is an aggressive, rare type of T-cell lymphoma (usually fatal)
  • Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-mercaptopurine, although there have been cases reported receiving azathioprine or mercaptopurine alone
  • The following HSTCL cases have been identified in the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), and mercaptopurine (3)
• Drug interaction overview
  • An increased risk of serious infections was seen in clinical studies of other TNF-blocking agents used in combination with anakinra or abatacept, with no added benefit; no formal drug interaction studies were performed with rituximab or natalizumab; concomitant use of certolizumab Pegol with anakinra, abatacept, rituximab, or natalizumab is not recommended
  • Patients treated may receive vaccinations, except for live or live-attenuated vaccines; no data is available on the response to live vaccinations or secondary transmission of infection by live vaccines in patients receiving therapy

Pregnancy and Lactation

• Pregnancy exposure registry monitors pregnancy outcomes in women exposed to the drug during pregnancy; MotherToBaby pregnancy studies conducted by the Organization of Teratology Information Specialists (OTIS); OTIS Autoimmune Diseases Study at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/
• Due to its inhibition of TNFalpha, certolizumab Pegol administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant; the clinical significance of low levels is unknown for in utero-exposed infants; additional data available from one exposed infant suggest that may be eliminated at a slower rate in infants than in adults
• Limited data from the ongoing pregnancy registry on the use of drugs in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes
• Contraception
  • Consider adequate contraception for women of childbearing potential
  • For women planning pregnancy, consider adequate contraception for 5 months after the last dose due to its elimination rate
• Lactation
  • In a clinical study, minimal transfer of certolizumab Pegol from plasma to breast milk was observed
  • The percentage of maternal certolizumab Pegol dose that was reaching an infant during 24 hours was estimated to be 0.04-0.3% In addition, since certolizumab Pegol is a protein that is degraded in the gastrointestinal tract after oral administration, absolute bioavailability is expected to be very low in a breastfed infant; can be used during breastfeeding