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Certolizumab Pegol

Pronunciation: SER-toe-LIZ-oo-mab PEG-ol
Class: Immunomodulator

Trade Names

Cimzia
- Injection, lyophilized powder for solution 200 mg
- Injection, solution 200 mg/mL

Pharmacology

Neutralizes membrane-associated and soluble human tumor necrosis factor alpha (TNF-alpha) in a dose-dependent manner.

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Pharmacokinetics

Absorption

T max is between 54 and 171 h postinjection. Bioavailability is approximately 80%. Mean C max is approximately 43 to 49 mcg/mL.

Distribution

Vd is approximately 6 to 8 L.

Elimination

Terminal elimination half-life is approximately 14 days. Cl is approximately 17 to 21 mL/h.

Special Populations

Renal Function Impairment

Studies have not been performed.

Elderly

Pharmacokinetics were not different between elderly and young adult patients.

Gender

Pharmacokinetics were similar in men and women.

Race

Pharmacokinetics showed no difference between white and Japanese patients.

Body weight

Pharmacokinetic exposure was inversely related to body weight; however, no therapeutic benefit is expected from a weight-adjusted dose regimen.

Indications and Usage

Reduction of signs and symptoms of Crohn disease and maintenance of clinical response in adult patients with moderately to severely active disease who have not responded adequately to conventional therapy; treatment of adults with moderately to severely active rheumatoid arthritis.

Contraindications

None well documented.

Dosage and Administration

Crohn Disease
Adults

Subcutaneous 400 mg, given as 2 injections of 200 mg initially and at wk 2 and 4. In patients obtaining a clinical response, the recommended maintenance dosage is 400 mg every 4 wk.

Rheumatoid Arthritis
Adults

Subcutaneous 400 mg, given as 2 injections of 200 mg initially and at wk 2 and 4, followed by 200 mg every other week. For maintenance dosing, 400 mg every 4 wk may be considered.

General Advice

  • May be used as monotherapy or concomitantly with nonbiological disease-modifying antirheumatic drugs.
  • To facilitate dissolution, bring to room temperature before reconstitution.
  • Reconstitute each vial of certolizumab with 1 mL of sterile water for injection using a syringe with a 20-gauge needle. Gently swirl vial without shaking so that all the lyophilized powder comes into contact with the sterile water for injection.
  • Leave vials undisturbed to fully reconstitute the drug (may take as long as 30 min).
  • Visually inspect solution prior to administration. Do not administer if cloudy or particulate matter is present.
  • Using a new 20-gauge needle for each vial, withdraw the reconstituted solution into a separate syringe for each vial. Switch each 20-gauge needle to a 23-gauge needle and inject the full contents of each syringe subcutaneously into separate sites in the abdomen or thigh.
  • Rotate injection sites and do not administer into areas where the skin is tender, bruised, red, or hard.

Storage/Stability

Store in refrigerator at 36° to 46°F. Do not freeze. Do not leave reconstituted product at room temperature for more than 2 h prior to administration. Once reconstituted, vials may be stored for up to 24 h at 36° to 46°F prior to injection.

Drug Interactions

Abatacept, anakinra, natalizumab, rituximab

Risk of serious infections and neutropenia may be increased. Concurrent use with certolizumab is not recommended.

Live vaccines

Do not coadminister with certolizumab.

Laboratory Test Interactions

May cause erroneously elevated aPTT assay results in patients without coagulation abnormalities. This effect has also been observed with the PTT-LA test from Diagnostic Stago, and the HemosIL APTT-SP liquid and HemosIL lyophilized silica tests from Instrumentation Laboratories.

Adverse Reactions

Cardiovascular

Hypertension (5%); angina pectoris, arrhythmias, atrial fibrillation, cardiac failure, hypertensive heart disease, MI, myocardial ischemia, pericardial effusion, pericarditis, stroke, thrombophlebitis, transient ischemic attack, vasculitis.

CNS

Headache (5%); fatigue (3%); anxiety, bipolar disorder, suicide attempt.

Dermatologic

Rash (3%); alopecia totalis, dermatitis, erythema nodosum, urticaria; erythema multiforme, new or worsening psoriasis, Stevens-Johnson syndrome, TEN (postmarketing).

EENT

Optic neuritis, retinal hemorrhage, uveitis.

Genitourinary

UTI (7%); menstrual disorder, nephrotic syndrome, renal failure.

Hematologic-Lymphatic

Anemia, bleeding, leukopenia, lymphadenopathy, pancytopenia, thrombophilia.

Hepatic

Elevated liver enzymes, hepatitis.

Hypersensitivity

Antibodies to certolizumab (8%); angioedema.

Local

Injection-site reactions.

Respiratory

Upper respiratory tract infection (20%); nasopharyngitis (5%); acute bronchitis, pharyngitis (3%).

Miscellaneous

Infection (38%); arthralgia (6%); back pain, positive antinuclear antibody titers (4%); pyrexia (3%).

Precautions

Warnings

Infection

Serious and sometimes fatal infections, including tuberculosis (TB) (frequently disseminated or extrapulmonary), invasive fungal infections, and bacterial, viral, and other opportunistic infections, may occur. Most patients who develop these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Evaluate patients for TB risk factors and test for latent TB infection prior to starting and during treatment. Initiate treatment of latent TB infection prior to starting therapy. Discontinue therapy if patient develops a serious infection or sepsis.

Malignancy

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. Certilozumab is not indicated for use in children.


Monitor

Monitor patients for signs and symptoms of infection during and after treatment. Monitor patients for signs and symptoms of active TB, including patients who tested negative for latent TB infection. Evaluate patients at risk for hepatitis B virus (HBV) infection for prior evidence of HBV infection before starting therapy. Closely monitor HBV carriers for clinical and laboratory signs of active HBV infection throughout therapy and for several months after discontinuing treatment. Monitor patients with CHF carefully.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

There is a higher incidence of infection in elderly patients; use with caution.

Hypersensitivity

Angioedema, dermatitis allergic, dizziness (postural), dyspnea, hot flush, hypotension, injection-site reactions, malaria, pyrexia, rash, serum sickness, and syncope (vasovagal) have been reported.

Autoimmunity

Formation of autoantibodies and, rarely, a lupus-like syndrome may occur.

CHF

Worsening and new-onset CHF have been reported with TNF blockers.

Hematologic effects

Rare cases of cytopenia, including leukopenia, pancytopenia (including aplastic anemia), and thrombocytopenia, have been reported.

Hepatitis

Risk of reactivation of HBV in chronic carriers of this virus may be increased. Use with caution in patients identified as HBV carriers.

Immunosuppression

Host defenses against infections and malignancies may be affected.

Malignancies

More cases of malignancies have been observed among patients receiving TNF blockers compared with control patients. Patients with Crohn disease requiring long-term exposure to immunosuppressant therapy may be at increased risk for developing lymphoma, even in the absence of TNF-blocker therapy.

Neurologic effects

Rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease have been reported. Rare cases of neurological disorders, including seizures, optic neuritis, and peripheral neuropathy, have been reported.

Overdosage

Symptoms

Doses of up to 800 mg subcutaneous and 20 mg/kg IV have been administered without serious adverse reactions.

Patient Information

  • Advise patient to review Medication Guide before starting therapy and to review it periodically.
  • Instruct patients to seek immediate medical attention if they experience any symptom of severe allergic reaction.
  • Advise patients to promptly report any signs of new or worsening medical conditions such as heart disease, neurologic disease, autoimmune disorders, or symptoms of cytopenia (including bruising, bleeding, or persistent fever) to health care provider.
  • Instruct patients to contact health care provider if they develop any symptoms of infection, including TB and reactivation of HBV infection.
  • Counsel patients about the possible risk of lymphoma and other malignancies while receiving treatment.

Copyright © 2009 Wolters Kluwer Health.

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