Dosing and uses of Cimzia (certolizumab pegol)
Adult dosage forms and strengths
powder for injection
- 200mg/vial
Moderate-to-Severe Crohn Disease
Initial: 400 mg SC as 2 injections of 200 mg each, repeat at 2 and 4 weeks
Maintenance: 400 mg SC q4Weeks
Moderate-to-Severe Rheumatoid Arthritis
Initial: 400 mg SC as 2 injections of 200 mg, repeat at 2 and 4 weeks
Maintenance: 200 mg SC q2Weeks OR 400 mg SC q4Weeks
Active Psoriatic Arthritis
Initial: 400 mg SC as 2 injections of 200 mg, repeat at 2 and 4 weeks
Maintenance: 200 mg SC q2Weeks OR 400 mg SC q4Weeks
Active Ankylosing Spondylitis
Initial: 400 mg SC as 2 injections of 200 mg; repeat at 2 and 4 weeks
Maintenance: 200 mg SC q2Weeks OR 400 mg SC q4weeks
Administration
Remove from refrigerator and allow the vial(s) to sit at room temperature for 30 min before reconstituting; do not warm vial in any other way
Reconstitute 200 mg vial(s) with 1 mL of sterile water for injection, USP using the 20-gauge needle provided; water should be directed at vial wall rather than directly to contents
Gently swirl each vial for about one min without shaking, assuring that all of powder comes in contact with sterile water; avoid creating a foaming effect
Continue swirling every 5 min as long as non-dissolved particles observed; full reconstitution may take as long as 30 min; final reconstituted solution contains 200 mg/mL and should be clear to opalescent, colorless to pale yellow liquid essentially free from particulates
Reconstitute each 200 mg vial with 1 mL sterile water for injection, swirl to dissolve; leave vials undisturbed for up to 30 minutes to fully reconstitute
Do not leave reconstituted solution at room temperature >2 hr; maybe stored for up to 24 hr at 2-8°C (36-46° F) prior to injection; do not freeze
Inject full contents of each syringe SC into separate sites on abdomen or thigh
Pediatric dosage forms and strengths
Safety and efficacy not established
Cimzia (certolizumab pegol) adverse (side) effects
>10%
URI (20%)
Headache (7-18%)
Nasopharyngitis (4-13%)
Nausea (11%)
1-10%
UTI (7%)
Arthralgia (6%)
Serious infections (3%)
Frequency not defined
Opportunistic infections (eg, TB)
Lupus-like syndrome
Malignancies
Immunogenicity
Hypersensitivity
Blood/ lymphatic system disorder
Cardiac disorder
Ocular disorder
Psychiatric disorder (anxiety, bipolar d/o, suicide attempt)
Renal/urinary disorder
Menstrual disorder
Skin and subcutaneous disorder
Postmarketing Reports
Vascular disorder: Systemic vasculitis
Skin: Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and new or worsening psoriasis (all sub-types including pustular and palmoplantar)
Immune System Disorders: Sarcoidosis
Lagophthalmos
Neoplasms benign, malignant and unspecified (including cysts and polyps)
Melanoma, Merkel cell carcinoma (neuroendocrine carcinoma of the skin)
Warnings
Black box warnings
Serious infection risk
- Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
- Patients older than 65 years may be at greater risk
- Discontinue if patient develops serious infection or sepsis
- Reported infections include:
- 1) Active TB, including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat latent infection prior to use
- 2) Invasive fungal infections (eg, histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease; antigen/antibody testing for histoplasmosis may be negative in some patients with active infection; initiate empiric antifungal therapy if severe systemic illness develops
- 3) Other bacterial (eg, Legionella, Listeria), mycobacterial (eg, tuberculosis), and viral (eg, hepatitis B) opportunistic pathogens
Malignancy
- Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with TNF blockers
- Cases of acute and chronic leukemia have been reported in association with post-marketing TNF-blocker use in rheumatoid arthritis (RA) and other indications; patients with RA may be at a higher risk (approximately 2-fold) than the general population for leukemia
- Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer
- Manufacturer required to report all malignancies to FDA in order for complete and consistent analysis
Contraindications
Concomitant live vaccines
Active serious infections
Cautions
Hypersensitivity including anaphylaxis and serious reactions
New-onset psoriasis reported with TNF blockers
Enhanced safety surveillance requirements to capture malignancy data: (see Black box warnings)
May interfere with aPPT tests
Risk of exacerbation of, or new onset demyelinating disease
Cytopenias reported; consider discontinuing drug if occurs
Exacerbation or, or new onset CHF
Melanoma and Merkel cell carcinoma reported; periodic skin examinations recommended for all patients, particularly those with risk factors for skin cancer
Lupus-like syndrome reported; discontinue if syndrome develops
Opportunistic infections
- TNF blockers increase 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 prior to starting treatment and monitor; treatment of latent tuberculosis infection prior to therapy with TNF-blocking agents has been shown to reduce 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 prior to initiating therapy with certolizumab, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG); also consider anti-tuberculosis therapy in patients with a past 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
- Risk of hepatitis B virus reactivation (discontinue if this occurs)
- Discontinue if serious infetion develops
Hepatosplenic T-cell lymphomas (HSTCL)
- Rare postmarketing cases reported primarily in adolescent and young adult patients with Crohn 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)
Pregnancy and lactation
Pregnancy category: B; due to its inhibition of TNF-alpha, administration during pregnancy could affect immune responses in the in utero-exposed newborn and infant
Lactation: not known if excreted in breast milk; discontinue drug or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cimzia (certolizumab pegol)
Mechanism of action
Recombinant humanized anti-human TNF-alpha neutralizing antibody
Pharmacokinetics
Bioavailability: 80%
Peak Plasma Time: 54-171 hr
Vd: 6.4 L
Half-Life: 14 days
Clearance: 17 mL/hr
