certolizumab pegol (Rx)

Brand and Other Names:Cimzia
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 200mg/vial

injectable solution, single-dose prefilled syringe

  • 200mg/mL

Crohn Disease

Indicated for reducing signs and symptoms of Crohn disease and maintaining clinical response in patients with moderate to severe active disease who had an inadequate response to conventional therapy

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

Maintenance: 400 mg SC q4Weeks

Rheumatoid Arthritis

Indicated for moderate to severe active rheumatoid arthritis (RA)

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

Maintenance: 200 mg SC q2Weeks OR 400 mg SC q4Weeks

Psoriatic Arthritis

Indicated for active psoriatic arthritis (PsA)

Initial: 400 mg SC (2 injections of 200 mg), repeat at 2 and 4 weeks, followed by 200 mg SC q2Weeks

Maintenance: Consider 400 mg SC q4Weeks

Ankylosing Spondylitis

Indicated for active ankylosing spondylitis (AS)

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

Maintenance: 200 mg SC q2Weeks OR 400 mg SC q4weeks

Spondyloarthritis

Indicated for active nonradiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

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

Maintenance: 200 mg SC q2Weeks OR 400 mg SC q4Weeks

Plaque Psoriasis

Indicated for moderate-to-severe plaque psoriasis (PsO) in patients who are candidates for systemic therapy or phototherapy

400 every other week

For some patients (≤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

Safety and efficacy not established

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Interactions

Interaction Checker

and certolizumab pegol

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            Adverse 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), lichenoid skin reaction

            Immune System Disorders: Sarcoidosis

            Lagophthalmos

            Neoplasms benign, malignant and unspecified (including cysts and polyps)

            Melanoma, Merkel cell carcinoma (neuroendocrine carcinoma of the skin)

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            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
              • 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
              • 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
              • 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

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

            Cautions

            Hypersensitivity including anaphylaxis and serious reactions (see Contraindications)

            May interfere with aPPT tests

            The needle shield inside the removable cap of prefilled syringe contains a derivative of natural rubber latex which may cause an allergic reaction in individuals sensitive to latex

            Risk of exacerbation of, or new onset demyelinating disease

            Exacerbation or new onset CHF reported Lupus-like syndrome reported in association with formation of autoantibodies; discontinue if syndrome develops

            Pancytopenia, including aplastic anemia, reported with TNF blockers

            Increased risk of serious infections

            • Also see Black Box Warnings
            • An increased risk of serious infections 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
            • Hepatitis B Virus Reactivation
              • 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 for 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 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
              • 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 reported with TNF-antagonists, including certolizumab pegol
              • Periodic skin examinations recommended for all patients, particularly those with risk factors for skin cancer
            • 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)

            Drug interaction overview

            • An increased risk of serious infections 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
            • Avoid use of live (including attenuated) vaccines concurrently with certolizumab
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            Pregnancy & Lactation

            Pregnancy

            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; 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 ongoing pregnancy registry on use of drug 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 last dose due to its elimination rate

            Lactation

            In a clinical study, minimal transfer of certolizumab pegol from plasma to breast milk was observed

            Percentage of maternal certolizumab pegol dose that was reaching an infant during a 24 hr period was estimated to 0.04-0.3% In addition, since certolizumab pegol is a protein that is degraded in gastrointestinal tract after oral administration, absolute bioavailability is expected to be very low in a breastfed infant; can be used during breastfeeding

            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.

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            Pharmacology

            Mechanism of Action

            Recombinant humanized antihuman TNF-alpha neutralizing antibody

            Binds to human TNFα with a KD of 90pM; TNF-alpha is a key pro-inflammatory cytokine with a central role in inflammatory processes

            Selectively neutralizes TNF-alpha; cross-reacts poorly with TNF from rodents and rabbits, therefore in vivo efficacy was evaluated using animal models in which human TNF-alpha was the physiologically active molecule

            Absorption

            Peak plasma concentration: 43-49 mcg/mL (RA patients)

            Peak plasma time: 54-171 hr

            Bioavailability: ~80%

            Distribution

            Vd: 4.7-8 L

            Metabolism

            Not studied in humans

            Data from animals indicate that once cleaved from the Fab' fragment the PEG moiety is mainly excreted in urine without further metabolism

            Excretion

            Half-life: 14 days

            Clearance: 17 mL/hr (Crohn disease); 21 mL/hr (RA)

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            Administration

            SC Preparation

            Vials

            • 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, 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

            Syringe

            • Prefilled syringe contains a derivative of natural rubber latex and use caution by latex-sensitive individuals

            SC Administration

            Inject full contents of each syringe SC into separate sites on abdomen or thigh

            Storage

            Unopened vial

            • Refrigerate intact carton between 2-8°C (36-46°F)
            • Do not freeze
            • Do not separate contents of carton prior to use
            • Protect solution from light

            Prefilled syringe

            • Refrigerate intact carton between 2-8°C (36-46°F)
            • Store at room temperature up to 25°C (77°F) in the original carton for a single period of up to 7 days
            • Do not place back in refrigerator; write the date removed from the refrigerator in the space provided on the carton and discard if not used within the 7-day period
            • Do not freeze
            • Do not separate contents of carton prior to use
            • Protect solution from light

            Reconstituted vial

            • Do not leave reconstituted solution at room temperature >2 hr
            • May be stored for up to 24 hr at 2-8°C (36-46°F) prior to injection
            • Do not freeze
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.