Drug: Cimzia

CIMZIA (certolizumab pegol) is a TNF blocker. CIMZIA is a recombinant, humanized antibody Fab' fragment, with specificity for human tumor necrosis factor alpha (TNFα), 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. The Fab' fragment is composed of a light chain with 214 amino acids and a heavy chain with 229 amino acids. The molecular weight of certolizumab pegol is approximately 91 kiloDaltons. CIMZIA is supplied as either a sterile, white, lyophilized powder for solution or as a sterile, solution in a single-use prefilled 1 mL glass syringe for subcutaneous injection. After reconstitution of the lyophilized powder with 1 mL sterile Water for Injection, USP, the resulting pH is approximately 5.2. Each single-use vial provides approximately 200 mg certolizumab pegol, 0.9 mg lactic acid, 0.1 mg polysorbate, and 100 mg sucrose. Each single-use prefilled syringe of CIMZIA delivers 200 mg in 1 mL of solution with a pH of approximately 4.7 for subcutaneous use. Each 1 mL syringe of CIMZIA contains certolizumab pegol (200 mg), sodium acetate (1.36 mg), sodium chloride (7.31 mg), and Water for Injection, USP. CIMZIA is a clear to opalescent solution that is colorless to pale yellow and essentially free from particulates. No preservatives are present.

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Clinical Trials Experience The most serious adverse reactions were:
  • Serious Infections [see WARNINGS AND PRECAUTIONS]
  • Malignancies [see WARNINGS AND PRECAUTIONS]
  • Heart Failure [see WARNINGS AND PRECAUTIONS]
Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug, and may not predict the rates observed in a broader patient population in clinical practice. In premarketing controlled trials of all patient populations combined the most common adverse reactions ( ≥ 8%) were upper respiratory infections (18%), rash (9%) and urinary tract infections (8%). Adverse Reactions Most Commonly Leading to Discontinuation of Treatment in Premarketing Controlled Trials The proportion of patients with Crohn's disease who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for CIMZIA and 7% for placebo. The most common adverse reactions leading to the discontinuation of CIMZIA (for at least 2 patients and with a higher incidence than placebo) were abdominal pain (0.4% CIMZIA, 0.2% placebo), diarrhea (0.4% CIMZIA, 0% placebo), and intestinal obstruction (0.4% CIMZIA, 0% placebo). The proportion of patients with rheumatoid arthritis who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for CIMZIA and 2.5% for placebo. The most common adverse reactions leading to discontinuation of CIMZIA were tuberculosis infections (0.5%); and pyrexia, urticaria, pneumonia, and rash (0.3%). Controlled Studies with Crohn's Disease The data described below reflect exposure to CIMZIA at 400 mg subcutaneous dosing in studies of patients with Crohn's disease. In the safety population in controlled studies, a total of 620 patients with Crohn's disease received CIMZIA at a dose of 400 mg, and 614 subjects received placebo (including subjects randomized to placebo in Study CD2 following open label dosing of CIMZIA at Weeks 0, 2, 4). In controlled and uncontrolled studies, 1,564 patients received CIMZIA at some dose level, of whom 1,350 patients received 400 mg CIMZIA. Approximately 55% of subjects were female, 45% were male, and 94% were Caucasian. The majority of patients in the active group were between the ages of 18 and 64. During controlled clinical studies, the proportion of patients with serious adverse reactions was 10% for CIMZIA and 9% for placebo. The most common adverse reactions (occurring in ≥ 5% of CIMZIA-treated patients, and with a higher incidence compared to placebo) in controlled clinical studies with CIMZIA were upper respiratory infections (e.g. nasopharyngitis, laryngitis, viral infection) in 20% of CIMZIA-treated patients and 13% of placebo-treated patients, urinary tract infections (e.g. bladder infection, bacteriuria, cystitis) in 7% of CIMZIA-treated patients and in 6% of placebo-treated patients, and arthralgia (6% CIMZIA, 4% placebo). Other Adverse Reactions The most commonly occurring adverse reactions in controlled trials of Crohn's disease were described above. Other serious or significant adverse reactions reported in controlled and uncontrolled studies in Crohn's disease and other diseases, occurring in patients receiving CIMZIA at doses of 400 mg or other doses include: Blood and lymphatic system disorders: Anemia, leukopenia, lymphadenopathy, pancytopenia, and thrombophilia. Cardiac disorders: Angina pectoris, arrhythmias, atrial fibrillation, cardiac failure, hypertensive heart disease, myocardial infarction, myocardial ischemia, pericardial effusion, pericarditis, stroke and transient ischemic attack. Eye disorders: Optic neuritis, retinal hemorrhage, and uveitis. General disorders and administration site conditions: Bleeding and injection site reactions. Hepatobiliary disorders: Elevated liver enzymes and hepatitis. Immune system disorders: Alopecia totalis. Psychiatric disorders: Anxiety, bipolar disorder, and suicide attempt. Renal and urinary disorders: Nephrotic syndrome and renal failure. Reproductive system and breast disorders: Menstrual disorder. Skin and subcutaneous tissue disorders: Dermatitis, erythema nodosum, and urticaria. Vascular disorders: Thrombophlebitis, vasculitis. Controlled Studies with Rheumatoid Arthritis CIMZIA was studied primarily in placebo-controlled trials and in long-term follow-up studies. The data described below reflect the exposure to CIMZIA in 2,367 RA patients, including 2,030 exposed for at least 6 months, 1,663 exposed for at least one year and 282 for at least 2 years; and 1,774 in adequate and well-controlled studies. In placebo-controlled studies, the population had a median age of 53 years at entry; approximately 80% were females, 93% were Caucasian and all patients were suffering from active rheumatoid arthritis, with a median disease duration of 6.2 years. Most patients received the recommended dose of CIMZIA or higher. Table 1 summarizes the reactions reported at a rate of at least 3% in patients treated with CIMZIA 200 mg every other week compared to placebo (saline formulation), given concomitantly with methotrexate. Table 1: Adverse Reactions Reported by ≥ 3% of Patients Treated with CIMZIA Dosed Every Other Week during Placebo-Controlled Period of Rheumatoid Arthritis Studies, with Concomitant Methotrexate.
Adverse Reaction (Preferred Term) Placebo+ MTX# (%)
N =324 CIMZIA 200 mg EOW + MTX(%)
N =640 Upper respiratory tract infection 2 6 Headache 4 5 Hypertension 2 5 Nasopharyngitis 1 5 Back pain 1 4 Pyrexia 2 3 Pharyngitis 1 3 Rash 1 3 Acute bronchitis 1 3 Fatigue 2 3 #EOW = Every other Week, MTX = Methotrexate. Hypertensive adverse reactions were observed more frequently in patients receiving CIMZIA than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs. Patients receiving CIMZIA 400 mg as monotherapy every 4 weeks in rheumatoid arthritis controlled clinical trials had similar adverse reactions to those patients receiving CIMZIA 200 mg every other week. Other Adverse Reactions Other infrequent adverse reactions (occurring in less than 3% of RA patients) were similar to those seen in Crohn's disease patients. Psoriatic Arthritis Clinical Study CIMZIA has been studied in 409 patients with psoriatic arthritis (PsA) in a placebo-controlled trial. The safety profile for patients with PsA treated with CIMZIA was similar to the safety profile seen in patients with RA and previous experience with CIMZIA. Infections The incidence of infections in controlled studies in Crohn's disease was 38% for CIMZIA-treated patients and 30% for placebo-treated patients. The infections consisted primarily of upper respiratory infections (20% for CIMZIA, 13% for placebo). The incidence of serious infections during the controlled clinical studies was 3% per patient-year for CIMZIA-treated patients and 1% for placebo-treated patients. Serious infections observed included bacterial and viral infections, pneumonia, and pyelonephritis. The incidence of new cases of infections in controlled clinical studies in rheumatoid arthritis was 0.91 per patient-year for all CIMZIA-treated patients and 0.72 per patient-year for placebo-treated patients. The infections consisted primarily of upper respiratory tract infections, herpes infections, urinary tract infections, and lower respiratory tract infections. In the controlled rheumatoid arthritis studies, there were more new cases of serious infection adverse reactions in the CIMZIA treatment groups, compared to the placebo groups (0.06 per patient-year for all CIMZIA doses vs. 0.02 per patient-year for placebo). Rates of serious infections in the 200 mg every other week dose group were 0.06 per patient-year and in the 400 mg every 4 weeks dose group were 0.04 per patient-year. Serious infections included tuberculosis, pneumonia, cellulitis, and pyelonephritis. In the placebo group, no serious infection occurred in more than one subject. There is no evidence of increased risk of infections with continued exposure over time [see WARNINGS AND PRECAUTIONS]. Tuberculosis and Opportunistic Infections In completed and ongoing global clinical studies in all indications including 5,118 CIMZIA-treated patients, the overall rate of tuberculosis is approximately 0.61 per 100 patient-years across all indications. The majority of cases occurred in countries with high endemic rates of TB. Reports include cases of miliary, lymphatic, peritoneal, as well as pulmonary TB. The median time to onset of TB for all patients exposed to CIMZIA across all indications was 345 days. In the studies with CIMZIA in RA, there were 36 cases of TB among 2,367 exposed patients, including some fatal cases. Rare cases of opportunistic infections have also been reported in these clinical trials. [see WARNINGS AND PRECAUTIONS]. Malignancies In clinical studies of CIMZIA, the overall incidence rate of malignancies was similar for CIMZIA-treated and control patients. For some TNF blockers, more cases of malignancies have been observed among patients receiving those TNF blockers compared to control patients. [see WARNINGS AND PRECAUTIONS] Heart Failure In placebo-controlled and open-label rheumatoid arthritis studies, cases of new or worsening heart failure have been reported for CIMZIA-treated patients. The majority of these cases were mild to moderate and occurred during the first year of exposure. [see WARNINGS AND PRECAUTIONS]. Autoantibodies In clinical studies in Crohn's disease, 4% of patients treated with CIMZIA and 2% of patients treated with placebo that had negative baseline ANA titers developed positive titers during the studies. One of the 1,564 Crohn's disease patients treated with CIMZIA developed symptoms of a lupus-like syndrome. In clinical trials of TNF blockers, including CIMZIA, in patients with RA, some patients have developed ANA. Four patients out of 2,367 patients treated with CIMZIA in RA clinical studies developed clinical signs suggestive of a lupus-like syndrome. The impact of long-term treatment with CIMZIA on the development of autoimmune diseases is unknown [see WARNINGS AND PRECAUTIONS]. Immunogenicity Patients were tested at multiple time points for antibodies to certolizumab pegol during Studies CD1 and CD2. The overall percentage of antibody positive patients was 8% in patients continuously exposed to CIMZIA, approximately 6% were neutralizing in vitro. No apparent correlation of antibody development to adverse events or efficacy was observed. Patients treated with concomitant immunosuppressants had a lower rate of antibody development than patients not taking immunosuppressants at baseline (3% and 11%, respectively). The following adverse events were reported in Crohn's disease patients who were antibody-positive (N = 100) at an incidence at least 3% higher compared to antibody-negative patients (N = 1,242): abdominal pain, arthralgia, edema peripheral, erythema nodosum, injection site erythema, injection site pain, pain in extremity, and upper respiratory tract infection. The overall percentage of patients with antibodies to certolizumab pegol detectable on at least one occasion was 7% (105 of 1,509) in the rheumatoid arthritis placebo-controlled trials. Approximately one third (3%, 39 of 1,509) of these patients had antibodies with neutralizing activity in vitro. Patients treated with concomitant immunosuppressants (MTX) had a lower rate of antibody development than patients not taking immunosuppressants at baseline. Patients treated with concomitant immunosuppressant therapy (MTX) in RA-I, RA-II, RA-III had a lower rate of neutralizing antibody formation overall than patients treated with CIMZIA monotherapy in RA-IV (2% vs. 8%). Both the loading dose of 400 mg every other week at Weeks 0, 2 and 4 and concomitant use of MTX were associated with reduced immunogenicity. Antibody formation was associated with lowered drug plasma concentration and reduced efficacy. In patients receiving the recommended CIMZIA dosage of 200 mg every other week with concomitant MTX, the ACR20 response was lower among antibody positive patients than among antibody-negative patients (Study RA-I, 48% versus 60%; Study RA-II 35% versus 59%, respectively). In Study RA-III, too few patients developed antibodies to allow for meaningful analysis of ACR20 response by antibody status. In Study RA-IV (monotherapy), the ACR20 response was 33% versus 56%, antibody-positive versus antibody-negative status, respectively. [see CLINICAL PHARMACOLOGY]. No association was seen between antibody development and the development of adverse events. The data reflect the percentage of patients whose test results were considered positive for antibodies to certolizumab pegol in an ELISA, and are highly dependent on the sensitivity and specificity of the assay. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to certolizumab pegol with the incidence of antibodies to other products may be misleading. Hypersensitivity Reactions The following symptoms that could be compatible with hypersensitivity reactions have been reported rarely following CIMZIA administration to patients: angioedema, dermatitis allergic, dizziness (postural), dyspnea, hot flush, hypotension, injection site reactions, malaise, pyrexia, rash, serum sickness, and (vasovagal) syncope [see WARNINGS AND PRECAUTIONS]. Postmarketing Experience The following adverse reactions have been identified during post-approval use of CIMZIA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Vascular disorder: systemic vasculitis has been identified during post-approval use of TNF blockers. Skin: case of severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and new or worsening psoriasis (all sub-types including pustular and palmoplantar) have been identified during post-approval use of TNF blockers. Immune System Disorders: sarcoidosis Read the Cimzia (certolizumab pegol injection) Side Effects Center for a complete guide to possible side effectsLearn More »

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CIMZIA is administered by subcutaneous injection. Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red or hard. When a 400 mg dose is needed (given as two subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen. The solution should be carefully inspected visually for particulate matter and discoloration prior to administration. The solution should be a clear colorless to yellow liquid, essentially free from particulates and should not be used if cloudy or if foreign particulate matter is present. CIMZIA does not contain preservatives; therefore, unused portions of drug remaining in the syringe or vial should be discarded. Crohn's Disease The recommended initial adult dose of CIMZIA is 400 mg (given as two subcutaneous injections of 200 mg) initially, and at Weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks. Rheumatoid Arthritis The recommended dose of CIMZIA for adult patients with rheumatoid arthritis is 400 mg (given as two subcutaneous injections of 200 mg) initially and at Weeks 2 and 4, followed by 200 mg every other week. For maintenance dosing, CIMZIA 400 mg every 4 weeks can be considered [see Clinical Studies]. Psoriatic Arthritis The recommended dose of CIMZIA for adult patients with psoriatic arthritis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at week 2 and 4, followed by 200 mg every other week. For maintenance dosing, CIMZIA 400 mg every 4 weeks can be considered [see Clinical Studies]. Preparation and Administration of CIMZIA Using the Lyophilized Powder for Injection CIMZIA Lyophilized powder should be prepared and administered by a health care professional. CIMZIA is provided in a package that contains everything required to reconstitute and inject the drug [see HOW SUPPLIED/Storage and Handling]. Step-by-step preparation and administration instructions are provided below. Preparation and Storage
  1. CIMZIA should be brought to room temperature before reconstituting.
  2. Use appropriate aseptic technique when preparing and administering CIMZIA.
  3. Reconstitute the vial(s) of CIMZIA with 1 mL of Sterile Water for Injection, USP using the 20-gauge needle provided.
  4. Gently swirl each vial of CIMZIA without shaking, assuring that all of the powder comes in contact with the Sterile Water for Injection.
  5. Leave the vial(s) undisturbed to fully reconstitute, which may take approximately 30 minutes.
  6. The final reconstituted solution contains 200 mg/mL and should be clear to opalescent, colorless to pale yellow liquid essentially free from particulates.
  7. Once reconstituted, CIMZIA can be stored in the vials for up to 24 hours between 2° to 8° C (36° to 46° F) prior to injection. Do not freeze.
Administration
  1. Prior to injecting, reconstituted CIMZIA should be at room temperature but do not leave reconstituted CIMZIA at room temperature for more than two hours prior to administration.
  2. Withdraw the reconstituted solution into a separate syringe for each vial using a new 20gauge needle for each vial so that each syringe contains 1 mL of CIMZIA (200 mg of certolizumab pegol).
  3. Replace the 20-gauge needle(s) on the syringes with a 23-gauge(s) for administration.
  4. Inject the full contents of the syringe(s) subcutaneously into thigh or abdomen. Where a 400 mg dose is required, two injections are required, therefore, separate sites should be used for each 200 mg injection.
Preparation and Administration of CIMZIA Using the Prefilled Syringe After proper training in subcutaneous injection technique, a patient may self-inject with the CIMZIA Prefilled Syringe if a physician determines that it is appropriate. Patients using the CIMZIA Prefilled Syringe should be instructed to inject the full amount in the syringe (1 mL), according to the directions provided in the Instructions for Use booklet. Monitoring to Assess Safety Before initiation of therapy with CIMZIA, all patients must be evaluated for both active and inactive (latent) tuberculosis infection. The possibility of undetected latent tuberculosis should be considered in patients who have immigrated from or traveled to countries with a high prevalence of tuberculosis or had close contact with a person with active tuberculosis. Appropriate screening tests (e.g. tuberculin skin test and chest x-ray) should be performed in all patients. Concomitant Medications CIMZIA may be used as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs). In rheumatoid arthritis clinical studies, patients on CIMZIA therapy also took concomitant methotrexate (MTX) with the recommended CIMZIA dose of 200 mg every other week. In the psoriatic arthritis clinical study, oral corticosteroids, DMARDs (methotrexate, leflunomide, sulfasalazine,) and NSAIDs were permitted as concomitant therapy. CIMZIA should not be used in combination with biological DMARDs or other tumor necrosis factor (TNF) blocker therapy.

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Use with Anakinra, Abatacept, Rituximab, and Natalizumab An increased risk of serious infections has been seen in clinical studies of other TNF-blocking agents used in combination with anakinra or abatacept, with no added benefit. Formal drug interaction studies have not been performed with rituximab or natalizumab. Because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of CIMZIA in these combinations. There is not enough information to assess the safety and efficacy of such combination therapy. Therefore, the use of CIMZIA in combination with anakinra, abatacept, rituximab, or natalizumab is not recommended [see WARNINGS AND PRECAUTIONS]. Live Vaccines Do not give live (including attenuated) vaccines concurrently with CIMZIA [see WARNINGS AND PRECAUTIONS]. Laboratory Tests Interference with certain coagulation assays has been detected in patients treated with CIMZIA. Certolizumab pegol may cause erroneously elevated activated partial thromboplastin time (aPTT) assay results in patients without coagulation abnormalities. This effect has been observed with the PTT-Lupus Anticoagulant (LA) test and Standard Target Activated Partial Thromboplastin time (STA-PTT) Automate tests from Diagnostica Stago, and the HemosIL APTT-SP liquid and HemosIL lyophilized silica tests from Instrumentation Laboratories. Other aPTT assays may be affected as well. Interference with thrombin time (TT) and prothrombin time (PT) assays has not been observed. There is no evidence that CIMZIA therapy has an effect on in vivo coagulation. Read the Cimzia Drug Interactions Center for a complete guide to possible interactions Learn More »

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Crohn's Disease CIMZIA is indicated for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. Rheumatoid Arthritis CIMZIA is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). Psoriatic Arthritis CIMZIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA).

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None. Last reviewed on RxList: 10/14/2013
This monograph has been modified to include the generic and brand name in many instances.

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The maximum tolerated dose of certolizumab pegol has not been established. Doses of up to 800 mg subcutaneous and 20 mg/kg intravenous have been administered without evidence of dose-limiting toxicities. In cases of overdosage, it is recommended that patients be monitored closely for any adverse reactions or effects, and appropriate symptomatic treatment instituted immediately.

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Dosage Forms And Strengths
  • Lyophilized Powder for Reconstitution
    Sterile, white, lyophilized powder for reconstitution and then subcutaneous administration. Each single-use vial provides approximately 200 mg of CIMZIA.
  • Prefilled Syringe
    A single-use, 1 mL prefilled glass syringe with a fixed 25 gauge ½ inch thin wall needle, providing 200 mg per 1 mL of CIMZIA.
Storage And Handling Storage and Stability Refrigerate intact carton between 2 to 8 °C (36 to 46 °F). Do not freeze. Do not separate contents of carton prior to use. Do not use beyond expiration date, which is located on the drug label and carton. Protect solution from light. Lyophilized Powder for Reconstitution NDC 50474-700-62 Pack Content Qtv. Item 2 Type I glass vials with rubber stopper and overseals each containing 200 mg of lyophilized CIMZIA for reconstitution. 2 2 mL Type I glass vials containing 1 mL sterile Water for Injection 2 3 mL plastic syringes 4 20 gauge luer-lock needles (1 inch) 2 23 gauge luer-lock needles (1 inch) 8 Alcohol swabs Prefilled Syringe NDC 50474-710-79 2 alcohol swabs and 2 single use prefilled glass syringes with a fixed 25 ½ gauge thin-wall needle, each containing 200 mg (1 mL) of CIMZIA. Prefilled Syringe Starter Kit NDC 50474-710-81 6 alcohol swabs and 6 single use prefilled glass syringes with a fixed 25 ½ gauge thin-wall needle. The Starter Kit contains 3 sets of 2 prefilled syringes to provide sufficient drug supply for the initial 3 induction doses at the start of treatment. Each prefilled syringe contains 200 mg (1 mL) of CIMZIA. Product manufactured by: UCB, Inc. 1950 Lake Park Drive Smyrna, GA 30080. Revised: 09/2013 Last reviewed on RxList: 10/14/2013
This monograph has been modified to include the generic and brand name in many instances.

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Risk of Serious Infections (see BOXED WARNING) Patients treated with CIMZIA are at an increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease. Treatment with CIMZIA should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (e.g. corticosteroids or methotrexate) may be at a greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients:
  • with chronic or recurrent infection
  • who have been exposed to tuberculosis
  • with a history of an opportunistic infection
  • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis
  • with underlying conditions that may predispose them to infection
Tuberculosis Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving CIMZIA, including patients who have previously received treatment for latent or active tuberculosis. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating CIMZIA and periodically during therapy. Treatment of latent tuberculosis infection prior to 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 is needed prior to initiating CIMZIA, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG). Anti-tuberculosis therapy should also be considered prior to initiation of CIMZIA 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. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision of whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Tuberculosis should be strongly considered in patients who develop a new infection during CIMZIA treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis. Monitoring Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with CIMZIA. CIMZIA should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with CIMZIA should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated. Invasive FungalInfections For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and risks of antifungal therapy. Malignancies 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. During controlled and open-labeled portions of CIMZIA studies of Crohn's disease and other diseases, malignancies (excluding non-melanoma skin cancer) were observed at a rate (95% confidence interval) of 0.5 (0.4, 0.7) per 100 patient-years among 4,650 CIMZIA-treated patients versus a rate of 0.6 (0.1, 1.7) per 100 patient-years among 1,319 placebo-treated patients. The size of the control group and limited duration of the controlled portions of the studies precludes the ability to draw firm conclusions. Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which CIMZIA is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous post-marketing reports. In the controlled portions of clinical trials of all the TNF blockers, more cases of lymphoma have been observed among patients receiving TNF blockers compared to control patients. In controlled studies of CIMZIA for Crohn's disease and other investigational uses, there was one case of lymphoma among 2,657 Cimzia-treated patients and one case of Hodgkin's lymphoma among 1,319 placebo-treated patients. In the CIMZIA RA clinical trials (placebo-controlled and open label) a total of three cases of lymphoma were observed among 2,367 patients. This is approximately 2-fold higher than expected in the general population. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. Rates in clinical studies for CIMZIA cannot be compared to the rates of clinical trials of other TNF blockers and may not predict the rates observed when CIMZIA is used in a broader patient population. Patients with Crohn's disease that require chronic exposure to immunosuppressant therapies may be at higher risk than the general population for the development of lymphoma, even in the absence of TNF blocker therapy [see ADVERSE REACTIONS]. The potential role of TNF blocker therapy in the development of malignancies in adults is not known. Cases of acute and chronic leukemia have been reported in association with post-marketing TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia. Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer. Heart Failure Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including CIMZIA. CIMZIA 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 [see ADVERSE REACTIONS]. Hypersensitivity Reactions The following symptoms that could be compatible with hypersensitivity reactions have been reported rarely following CIMZIA administration to patients: angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria. If such reactions occur, discontinue further administration of CIMZIA and institute appropriate therapy. There are no data on the risks of using CIMZIA in patients who have experienced a severe hypersensitivity reaction towards another TNF blocker; in these patients caution is needed [see ADVERSE REACTIONS]. Hepatitis B Virus Reactivation Use of TNF blockers, including CIMZIA, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Test patients for HBV infection before initiating treatment with CIMZIA. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Patients who are carriers of HBV and require treatment with CIMZIA should be closely monitored 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 CIMZIA and initiate effective anti-viral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of CIMZIA therapy in this situation and monitor patients closely. Neurologic Reactions Use of TNF blockers, of which CIMZIA is a member, 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 the use of CIMZIA 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 CIMZIA [see ADVERSE REACTIONS]. Hematological Reactions Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Adverse reactions of the hematologic system, including medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) have been infrequently reported with CIMZIA [see ADVERSE REACTIONS]. The causal relationship of these events to CIMZIA remains unclear. Although no high risk group has been identified, exercise caution in patients being treated with CIMZIA 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 (e.g., persistent fever, bruising, bleeding, pallor) while on CIMZIA. Consider discontinuation of CIMZIA therapy in patients with confirmed significant hematologic abnormalities. Use with Biological Disease-Modifying Antirheumatic Drugs (Biological DMARDs) Serious infections were seen in clinical studies with concurrent use of anakinra (an interleukin-1 antagonist) and another TNF blocker, etanercept, with no added benefit compared to entanercept alone. A higher risk of serious infections was also observed in combination use of TNF blockers with abatacept and rituximab. Because of the nature of the adverse events seen with this combination therapy, similar toxicities may also result from the use of CIMZIA in this combination. Therefore, the use of CIMZIA in combination with other biological DMARDs is not recommended [see DRUG INTERACTIONS]. Autoimmunity Treatment with CIMZIA 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 with CIMZIA, discontinue treatment [see ADVERSE REACTIONS]. Immunizations Patients treated with CIMZIA may receive vaccinations, except for live or live attenuated vaccines. No data are available on the response to live vaccinations or the secondary transmission of infection by live vaccines in patients receiving CIMZIA. In a placebo-controlled clinical trial of patients with rheumatoid arthritis, no difference was detected in antibody response to vaccine between CIMZIA and placebo treatment groups when the pneumococcal polysaccharide vaccine and influenza vaccine were administered concurrently with CIMZIA. Similar proportions of patients developed protective levels of anti-vaccine antibodies between CIMZIA and placebo treatment groups; however patients receiving CIMZIA and concomitant methotrexate had a lower humoral response compared with patients receiving CIMZIA alone. The clinical significance of this is unknown. Immunosuppression Since TNF mediates inflammation and modulates cellular immune responses, the possibility exists for TNF blockers, including CIMZIA, to affect host defenses against infections and malignancies. The impact of treatment with CIMZIA on the development and course of malignancies, as well as active and/or chronic infections, is not fully understood [see ADVERSE REACTIONS]. The safety and efficacy of CIMZIA in patients with immunosuppression has not been formally evaluated. Patient Counseling Information See FDA-approved patient labeling (Medication Guide) Advise patients of the potential risks and benefits of CIMZIA therapy. Be sure that patients receive the Medication Guide and allow them time to read it prior to starting CIMZIA therapy and to review it periodically. Any questions resulting from the patient's reading of the Medication Guide should be discussed. Because caution should be exercised in prescribing CIMZIA to patients with clinically important active infections, advise patients of the importance of informing their health care providers about all aspects of their health. Immunosuppression Inform patients that CIMZIA may lower the ability of the immune system to fight infections. Instruct patients of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis and reactivation of hepatitis B virus infections. Counsel patients about the possible risk of lymphoma and other malignancies while receiving CIMZIA. Allergic Reactions Advise patients to seek immediate medical attention if they experience any symptoms of severe allergic reactions. The prefilled syringe components do not contain any latex or dry natural rubber. Other Medical Conditions Advise patients to report any signs of new or worsening medical conditions such as heart disease, neurological disease, or autoimmune disorders. Advise patients to report promptly any symptoms suggestive of a cytopenia such as bruising, bleeding, or persistent fever. Instruction on Prefilled Syringe Self-Injection Technique After proper training by a qualified healthcare professional in subcutaneous injection technique, a patient may self inject with CIMZIA using the Prefilled Syringe if a healthcare provider determines that it is appropriate. A patient's ability to administer CIMZIA subcutaneous injections should be checked to ensure correct administration. Suitable sites for injection include the thigh or abdomen. CIMZIA should be injected when the liquid is at room temperature. Full injection instructions are provided in the Instructions for Use booklet for the Prefilled Syringe, packaged in each CIMZIA Prefilled Syringe kit. To avoid needle-stick injury, patients and healthcare providers should not attempt to place the needle cover back on the syringe or otherwise recap the needle. Be sure to properly dispose of needles and syringes in a puncture-proof container, and instruct patients and caregivers in proper syringe and needle disposal technique. Actively discourage any reuse of the injection materials. Nonclinical Toxicology Carcinogenesis, Mutagenesis, and Impairment of Fertility Long-term animal studies of CIMZIA have not been conducted to assess its carcinogenic potential. Certolizumab pegol was not genotoxic in the Ames test, the human peripheral blood lymphocytes chromosomal aberration assay, or the mouse bone marrow micronucleus assay. Since certolizumab pegol does not cross-react with mouse or rat TNFα, reproduction studies were performed in rats using a rodent anti-murine TNFα pegylated Fab fragment (cTN3 PF), similar to certolizumab pegol. The cTN3 PF had no effects on the fertility and general reproductive performance of male and female rats at intravenous doses up 100 mg/kg, administered twice weekly. Use In Specific Populations Pregnancy Pregnancy Category B Risk Summary Adequate and well-controlled studies with CIMZIA have not been conducted in pregnant women. Certolizumab pegol plasma concentrations obtained from 10 women treated with CIMZIA during pregnancy and their newborn infants demonstrated low placental transfer of certolizumab pegol. CIMZIA may be eliminated at a slower rate in exposed infants than in adult patients. No fetal harm was observed in animal reproduction studies. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIMZIA during pregnancy. To enroll, healthcare providers or patients can call 1-877-311-8972. Human Data In an independent clinical study conducted in 10 pregnant women with Crohn´s disease treated with CIMZIA, certolizumab pegol concentrations were measured in maternal blood as well as in cord and infant blood (n=12) at the day of birth. The last dose of CIMZIA (400 mg for every mother) was given on average 19 days prior to delivery (range 5-42 days). Plasma certolizumab pegol concentrations were < 0.41 –1.66 μg/mL in cord blood, < 0.41 – 1.58 μg/mL in infant blood, and 1.87–59.57 μg/mL in maternal blood. Plasma certolizumab pegol concentrations were lower (by at least 75%) in the infants than in mothers suggesting low placental transfer of certolizumab pegol. In one infant, the plasma certolizumab pegol concentration declined from 1.02 to 0.84 μg /mL over 4 weeks suggesting that CIMZIA may be eliminated at a slower rate in infants than adults. Animal Data Because certolizumab pegol does not cross-react with mouse or rat TNFα, reproduction studies were performed in rats using a rodent anti-murine TNFα pegylated Fab' fragment (cTN3 PF) similar to certolizumab pegol. Reproduction studies have been performed in rats at doses up to 100 mg/kg and have revealed no evidence of impaired fertility or harm to the fetus due to cTN3 PF. Nursing Mothers It is not known whether certolizumab pegol is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CIMZIA, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Due to its inhibition of TNFα, CIMZIA administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant. Although certolizumab pegol levels were low in 12 infants exposed to CIMZIA in utero, the clinical significance of these low levels is unknown. Additional data available from one exposed infant suggests that CIMZIA may be eliminated at a slower rate in infants than in adults. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. Geriatric Use Clinical studies of CIMZIA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Population pharmacokinetic analyses of patients enrolled in CIMZIA clinical studies concluded that there was no apparent difference in drug concentration regardless of age. Because there is a higher incidence of infections in the elderly population in general, use caution when treating the elderly with CIMZIA [see WARNINGS AND PRECAUTIONS]. Last reviewed on RxList: 10/14/2013
This monograph has been modified to include the generic and brand name in many instances.

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