Cimzia

Tumor Necrosis Factor (TNF)-Alpha Inhibitors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Unopened vials and prefilled syringes should be stored under refrigeration between 2 to 8 degrees C (36 to 46 degrees F); do not freeze. When necessary, the unopened vials may be stored at room temperature under a maximum of 25 degrees C (77 degrees F) for no more than 6 months. The prefilled syringes may be stored up to 25 degree C (77 degrees F) in the original carton for a single period of up to 7 days. If the unopened vials or prefilled syringes are stored at room temperature, they should not be placed back into the refrigerator. Write the expiration date on the carton in the space provided.

Lyophilized powder product reconstitution:
If the certolizumab powder is prescribed, a healthcare professional should prepare and administer the injection(s).
If refrigerated, remove the vials from the refrigerator and allow to sit at room temperature for 30 minutes prior to reconstitution. Do not warm the vials in any other way.
Two vials will be needed to provide a 400 mg dose, as each single-use vial provides approximately 200 mg certolizumab pegol.
Reconstitute each vial by adding 1 mL of Sterile Water for Injection to the vial using the provided 20-gauge needle. Direct the diluent to the wall of the vial rather than directly on the lyophilized product.
Gently swirl the vial for approximately 1 minute; do NOT shake. All of the lyophilized product must come into contact with the diluent. Swirl the vial as gently as possible to avoid creating a foaming effect.
Continue to swirl every 5 minutes as long as non-dissolved particles are seen. Full reconstitution may take up to 30 minutes.
Reconstituted product is a clear to opalescent, colorless to pale yellow liquid with no visible particulates or gels in solution. Discard the solution if particulate matter or discoloration are present.
Storage: The reconstituted solution may be stored at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours. Do NOT freeze. No preservatives are present.
Subcutaneous injection using the reconstituted product:
If the reconstituted product has been refrigerated, allow it to reach room temperature before administering. Do not keep at room temperature for more than 2 hours before administration, as no preservatives are present.
A syringe and a 20-gauge needle are needed for each reconstituted vial. Withdraw the reconstituted solution from the vial into the syringes; if 2 vials (400 mg total) are necessary, use separate syringes and needles. Each syringe will contain 1 mL (200 mg of certolizumab).
Switch the 20-gauge needle to a 23-gauge needle.
Inject the full contents of the 200-mg syringe subcutaneously into the abdomen or thigh. Avoid injecting within 2 inches of the navel, and, if 2 injections are needed, at least 1 inch needs to separate the 2 injection sites. Do not inject into skin that is bruised, tender, red, or hard. Also, do not inject into a scar or stretch mark. If a second syringe is needed to achieve a 400 mg total dose, use a new 23-gauge needle and inject into a separate site. Rotate injection sites between the abdomen and thigh to reduce risk of skin reaction.
Do not try to recap the needle and do not rub the injection site.
Be sure to properly dispose of needles and syringes in an acceptable sharps container.[33930]
Prefilled syringe general information:
After proper training in subcutaneous injection technique, a patient may self-inject with the prefilled syringe if a physician determines that it is appropriate.
Patients using the 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.
The needle shield inside the removable cap of the prefilled syringe contains a derivative of natural rubber latex and should be handled with caution by latex-sensitive individuals.
Administration using prefilled syringe:
Remove the prefilled syringe from the refrigerator and keep it at room temperature for 30 minutes before administration.
Each single-use prefilled syringe contains certolizumab 200 mg/mL. The solution should be clear and colorless to light yellow and essentially free from particles. Do not use the solution if it looks cloudy or if large particulates are present.
Appropriate injection sites are the abdomen or thigh. Avoid injecting within 2 inches of the navel, and, if 2 injections are needed for a 400 mg dose, at least an inch needs to separate the 2 injection sites. Do not inject into skin that is bruised, tender, red, or hard. Do not inject into a scar or stretch mark. Rotate injection sites between the abdomen and thigh to reduce risk of skin reaction.
Remove the needle cover and remove any air by tapping the syringe with the needle pointing upward and pushing the syringe until a drop of liquid appears.
Pinch the skin, and inject the needle at a 45 degree angle using a dart-like motion.
Pull back on the syringe. If blood appears in the syringe, remove the needle and throw away the product. If no blood appears, release the skin and inject the full content of each syringe (1 mL) subcutaneously.
Remove the needle, and do not recap the needle or rub the injection site.
To avoid needle-stick injury, do not attempt to place the needle cap back on the syringe or otherwise recap the needle.
Be sure to properly dispose of needles and syringes in an acceptable puncture-proof container. Do not reuse any of the injection materials.[33930]

infection / Delayed / 3.0-3.0
erythema multiforme / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
serum sickness / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
retinal hemorrhage / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
leukemia / Delayed / Incidence not known
skin cancer / Delayed / Incidence not known
lymphoma / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
seizures / Delayed / Incidence not known
uveitis / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
stroke / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
suicidal ideation / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known

antibody formation / Delayed / 7.0-19.0
hypertension / Early / 5.0-5.0
cystitis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
hypotension / Rapid / Incidence not known
anemia / Delayed / Incidence not known
bleeding / Early / Incidence not known
lymphadenopathy / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
psoriasis / Delayed / Incidence not known
erythema / Early / Incidence not known
edema / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
angina / Early / Incidence not known
phlebitis / Rapid / Incidence not known

rash / Early / 9.0-9.0
arthralgia / Delayed / 6.0-6.0
pharyngitis / Delayed / 3.0-5.0
headache / Early / 2.9-5.0
back pain / Delayed / 4.0-4.0
cough / Delayed / 1.1-3.2
injection site reaction / Rapid / 1.7-3.2
fatigue / Early / 3.0-3.0
sinusitis / Delayed / Incidence not known
laryngitis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
syncope / Early / Incidence not known
malaise / Early / Incidence not known
dizziness / Early / Incidence not known
fever / Early / Incidence not known
lichen planus-like eruption / Delayed / Incidence not known
skin discoloration / Delayed / Incidence not known
anxiety / Delayed / Incidence not known

Patients who receive certolizumab are at increased risk for developing serious infections that may result in hospitalization and/or death including tuberculosis (TB), bacterial sepsis, invasive fungal infection (such as histoplasmosis), and infections due to other opportunistic pathogens. Certolizumab pegol should be discontinued if a patient develops a serious infection or sepsis.[33930] Evaluate the risks and benefits of certolizumab before beginning therapy in patients with chronic or recurrent infections or patients with underlying conditions predisposing them to infection.[45593] Patients with a history of recurrent infections with underlying conditions that may predispose them to infections (e.g., patients with advanced or uncontrolled diabetes mellitus, acquired immunodeficiency syndrome (AIDS), malignancy, bone marrow suppression, or immunosuppression) may not be appropriate candidates for certolizumab. Patients greater than 65 years of age or patients taking concomitant immunosuppressants (e.g. corticosteroid therapy or methotrexate) may be at a greater risk of infection. Before initiating certolizumab pegol and periodically during therapy, evaluate all patients for active tuberculosis and test for latent TB infection.[33930] Patients need to be evaluated with a tuberculin skin test both before and during treatment. If tuberculin skin testing is performed for latent TB infection, an induration size of 5 mm or greater should be considered positive even if the patient was vaccinated previously with Bacille Calmette-Guerin. Treatment of latent TB infection should be started before certolizumab initiation, as this has been shown to reduce the risk of tuberculosis reactivation during certolizumab therapy. Consider anti-tuberculosis therapy before certolizumab initiation in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed and in patients who risk factors for tuberculosis infection (e.g., close contact with infected persons or travel to endemic zones) and have a negative test for latent tuberculosis. Cases of active tuberculosis have been reported in patients receiving certolizumab despite previous or concurrent treatment for latent tuberculosis. Some patients previously treated for active tuberculosis have redeveloped tuberculosis during certolizumab treatment. Monitor closely for the development of tuberculosis even in patients who tested negative for latent tuberculosis infection before initiating therapy. Tests for latent tuberculosis infection may be falsely negative while receiving certolizumab. Consider consultation with a physician specializing in tuberculosis management to aid in the decision of whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Strongly consider tuberculosis in patients who develop a new infection during certolizumab treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or in those who have had close contact with a person with active tuberculosis.[33930] Reported serious infections involve multiple organ systems and include bacterial infection (Legionella and Listeria), mycobacterial infection (disseminated tuberculosis or extrapulmonary tuberculosis), fungal infection (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, listeriosis, Pneumocystis jiroveci pneumonia), parasitic infection, viral infection (hepatitis B, influenza), and various opportunistic infections. Patients with invasive fungal infections (i.e., histoplasmosis) may present with disseminated rather than localized disease. Health care providers should be aware that antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Carefully consider the risks associated with certolizumab before initiating therapy in patients who reside in histoplasmosis, blastomycosis, or coccidioidomycosis endemic zones. In patients who develop a severe systemic illness, consider administering empiric antifungal therapy. Educate patients about the symptoms of infection, and closely monitor patients for signs and symptoms of infection during and after certolizumab treatment. If a patient develops a new infection, closely monitor the infection, and discontinue certolizumab if the infection is severe.[33930]

Use certolizumab pegol with caution in patients with a history of neoplastic disease. New primary malignancy has been reported in patients treated with TNF blockers such as certolizumab; some cases were fatal. Use of certolizumab by patients with a history of malignancy or current malignancy may be inadvisable. During controlled and open-labeled portions of certolizumab studies of Crohn's disease and other diseases, malignancies (excluding non-melanoma skin cancer) were observed at a rate (95% CI) of 0.5 (0.4, 0.7) per 100 patient-years among 4,650 certolizumab-treated patients versus a rate of 0.6 (0.1, 1.7) per 100 patient-years among 1,319 placebo-treated patients. During certolizumab studies of psoriasis, malignancies (excluding non-melanoma skin cancer) were observed corresponding to an incidence rate of 0.5 (0.2, 1.0) per 100 subject-years among a total of 995 subjects who received certolizumab. The size of the control group and the limited duration of the controlled portions of the studies precludes the ability to draw firm conclusions. Rates in clinical studies for certolizumab cannot be compared to the rates of clinical trials of other TNF blockers and may not predict the rates observed when certolizumab 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. The potential role of TNF blocker therapy in the development of malignancies in adults is not known. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma that has a very aggressive disease course and is usually fatal, have been reported in patients treated with TNF blockers, including certolizumab. The majority of reported TNF blocker cases occurred in adolescent and young adult males with Crohn's disease or ulcerative colitis. Almost all of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine (6-MP) concomitantly with a TNF blocker at or before diagnosis. It is uncertain whether the occurrence of HSTCL is related to the use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. The potential risk of using a TNF blocker in combination with azathioprine or 6MP should be carefully considered. Cases of acute and chronic leukemia have been reported in association with postmarketing 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. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blockers, including certolizumab. Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer.[33930]

The safety and effectiveness of certolizumab pegol in infants and children less than 18 years of age have not been established and the drug is not indicated for pediatric use for any indication. An increased risk of cancer may be associated with the use of TNF blockers in pediatric recipients. Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy at 18 years of age or younger). 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 often observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants. Certolizumab pegol was evaluated for the treatment of pediatric recipients 6 to 17 years of age (n=99) with moderately to severely active Crohn's disease for a period of up to 62 weeks; efficacy was not demonstrated and the study was ended prematurely because of a high number of patient discontinuations.

Cimzia

Rx

TNF-alpha blocker (TNF-blocker) conjugated to polyethylene glycol; for subcutaneous use
Used in adults for rheumatoid arthritis, psoriatic arthritis, Crohn's disease, plaque psoriasis, ankylosing spondylitis, and non-radiographical axial spondyloarthritis
Boxed warning regarding increased risk for serious infection and possible malignancy

400 mg subcutaneously every 2 weeks for 3 doses, then if response occurs, 400 mg subcutaneously every 4 weeks. Guidelines strongly recommend the use of certolizumab pegol to treat Crohn's disease that is resistant to treatment with corticosteroids. Among 331 adults who received certolizumab 400 mg subcutaneously at weeks 0, 2, and 4, then 400 mg subcutaneously every 4 weeks, 35% had a clinical response at week 6, 37% had a clinical response at week 26, and 23% had a clinical response at both time points. Clinical response was defined as at least a 100 point reduction in their Crohn's disease activity index (CDAI) score. In another study, 48% of 215 patients with a clinical response at week 6 were in clinical remission at week 26. A clinical remission was defined as a CDAI score of 150 or less. Continued receipt was required to maintain response. Another study reported a clinical response in patients who had either been nonresponders or intolerant to infliximab.

400 mg subcutaneously every 2 weeks for 3 doses, then 400 mg subcutaneously every 4 weeks led to clinical improvement 2 months after certolizumab initiation; the fistulae appeared closed and nondraining. After 6 months of certolizumab, a control MRI revealed a progressive fibrosis of the fistulae with almost no contrast enhancement. Guidelines state that certolizumab pegol may be effective and strongly recommends that it be considered in treating perianal fistulas in Crohn's disease.

400 mg subcutaneously every other week for 3 doses, then 200 mg subcutaneously every other week as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs). Use of certolizumab with biological DMARDs or other tumor necrosis factor blocker therapy is not recommended. Consider a maintenance dose of 400 mg subcutaneously every 4 weeks. In a study of patients who had an inadequate response to methotrexate, the addition of certolizumab led to an ACR20 response at week 52 in 53% of 393 patients as compared with 13% of methotrexate-only recipients. Further, an ACR70 over a continuous 6-month period was achieved by 13% of certolizumab recipients as compared with 1% of methotrexate-only recipients. A higher dose of 400 mg subcutaneously every 2 weeks did not lead to significantly more patients with ACR responses. In another study of adults who had failed at least 1 DMARD, monotherapy with certolizumab 400 mg subcutaneously every 4 weeks led to an ACR20 response at week 24 in 45.5% of 111 patients. An ACR50 response was obtained by 22.7%, and an ACR70 response was obtained by 5.5% of patients. In contrast, an ACR 20 was obtained by 9.3% of 109 placebo recipients. Guidelines recommend a TNF blocker +/- methotrexate as an option for patients with a disease duration of less than 6 months and high disease activity with poor prognostic feature presence. For patients with established disease, adding or switching to an anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. A switch to a different anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to an anti-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of a non-TNF biologic or with a serious or non-serious adverse event to the drug. The goal is low disease activity or remission.

400 mg subcutaneously every other week.

400 mg subcutaneously every other week. May consider 400 mg subcutaneously at weeks 0, 2, and 4, then 200 mg subcutaneously every other week for some.

400 mg subcutaneously at weeks 0, 2, and 4, then 200 mg subcutaneously every other week or may consider 400 mg subcutaneously every 4 weeks. Certolizumab may be used as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs). Use of certolizumab with biological DMARDs or other tumor necrosis factor blocker therapy is not recommended.

400 mg subcutaneously, given as two 200-mg subcutaneous injections, at weeks 0, 2, and 4, then 200 mg subcutaneously every 2 weeks or 400 mg subcutaneously every 4 weeks as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs). Use of certolizumab with biological DMARDs or other tumor necrosis factor blocker therapy is not recommended. Some patients responded within 1 to 2 weeks of certolizumab initiation, and an Assessment of SpondyloArthritis International Society 20 response at week 24 was achieved by 70% of 400 mg every 4 week recipients, by 68% of 200 mg every 2 week recipients, and by 33% of placebo recipients.

400 mg subcutaneously, given as two 200-mg subcutaneous injections, at weeks 0, 2, and 4, then 200 mg every 2 weeks or 400 mg every 4 weeks.[33930] Among 159 adults who received certolizumab 400 mg subcutaneously at weeks 0, 2, and 4, then 200 mg subcutaneously every 2 weeks, 47.2% achieved an Ankylosing Spondylitis Disease Activity Score-Major Improvement (ASDAS-MI) at week 52 compared to 7% of placebo recipients (n=158), p<0.0001; patients were allowed to continue therapy with non-biologic medications. ASDAS-MI is defined as a decrease of 2 or greater from baseline in ASDAS or attainment of the lowest ASDAS value.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Adalimumab: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Anakinra: (Major) Avoid the concomitant use of anakinra with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection with no additional clinical benefit. Data suggest a higher rate of serious infections when anakinra and a TNF inhibitor is used in combination with anakinra compared with either drug given alone. Neutropenia (1,000/mcL or less) was observed in 2% of patients receiving the combination. The use of anakinra with a TNF inhibitor in combination did not yield any additional clinical benefit as compared to the use of the TNF inhibitor alone.
Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Antithymocyte Globulin: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Azathioprine: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Basiliximab: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Belimumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Therefore, belimumab use is not recommended in combination with TNF blockers. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Canakinumab: (Major) Avoid concomitant administration of canakinumab with tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Based upon the potential for similar interactions, concomitant administration of canakinumab and TNF inhibitors is not recommended.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclosporine: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Etanercept: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including etanercept, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with etanercept. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Golimumab: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including golimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with golimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Infliximab: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including infliximab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with infliximab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Intranasal Influenza Vaccine: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Live Vaccines: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Methotrexate: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Methylprednisolone: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Natalizumab: (Major) Natalizumab for Crohn's disease should not be used in combination with tumor necrosis factor (TNF) modifiers. Coadministration may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy and other opportunistic infections. Ordinarily, patients with mulitple sclerosis who are receiving chronic TNF-modifier therapy should not be treated with natalizumab.
Prednisolone: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Prednisone: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Rilonacept: (Contraindicated) Concurrent use of rilonacept and tumor necrosis factor (TNF) modifiers is not advised, as the risk of serious infections may be increased. Although concurrent use has not been evaluated in clinical trials, an increased incidence of serious infections and neutropenia has been associated with administration of another drug that blocks IL-1 in combination with TNF inhibitors.
Rituximab: (Major) Avoid the concomitant use of rituximab with certolizumab pegol, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients who received rituximab in combination with a TNF blocker.
Rituximab; Hyaluronidase: (Major) Avoid the concomitant use of rituximab with certolizumab pegol, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients who received rituximab in combination with a TNF blocker.
Rotavirus Vaccine: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Typhoid Vaccine: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vedolizumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Yellow Fever Vaccine, Live: (Contraindicated) Do not administer live vaccines concurrently with certolizumab. No data are available on the response to vaccinations or to the secondary transmission of infection by live vaccines in patients receiving certolizumab. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

Cimzia Subcutaneous Inj Pwd F/Sol: 200mg
Cimzia Subcutaneous Inj Sol: 1mL, 200mg

400 mg/dose subcutaneously.

400 mg/dose subcutaneously.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Certolizumab pegol is a recombinant, pegylated, humanized Fab fragment of an anti-TNFalpha monoclonal antibody that neutralizes membrane-associated and soluble human TNFalpha in a dose-dependent manner. Elevated TNFalpha concentrations have been implicated in the pathology of Crohn's disease. TNFalpha is strongly expressed in bowel wall areas affected by Crohn's disease, and fecal concentrations of TNFalpha have been shown to reflect clinical disease severity. In vitro, certolizumab pegol caused a dose-dependent inhibition of lipopolysaccharide-induced TNFalpha and IL-1beta production in human monocytes. Inhibition of bacterially stimulated cytokine production from macrophages may be a necessary function for efficacy of an anti-TNFalpha agent in Crohn's disease. In contrast, induction of apoptosis, antibody-dependent cell-mediated cytotoxicity, and complement-dependent cytotoxicity may not be required for clinical efficacy of an anti-TNFalpha agent in Crohn's disease. Unlike etanercept, infliximab, and adalimumab, certolizumab pegol does not contain a fragment crystallizable (Fc) region and thus, does not fix complement or cause antibody-dependent cell-mediated cytotoxicity.

Certolizumab is administered by subcutaneous injection. Pharmacokinetic parameter values observed in patients with Crohn's disease were consistent with values seen in healthy patients. Steady-state concentrations are 0.5—90 mcg/mL for a fixed dose of 400 mg of certolizumab pegol. Steady-state concentrations range from 0.5 to 75 mcg/mL for patients developing anti-certolizumab pegol antibodies. Anti-certolizumab pegol antibodies had more than a 30% effect on Cmax and/or AUC, but a dose adjustment is not required. The terminal elimination phase half-life of certolizumab is approximately 14 days; conjugation with polyethylene glycol delays the elimination of certolizumab from the circulation. The route of elimination of certolizumab pegol has not been studied in humans.

Peak plasma concentrations of certolizumab pegol are obtained 54—171 hours after subcutaneous injection. The bioavailability is approximately 80% (range, 76—88%). Single subcutaneous doses of certolizumab pegol have predictable dose-related plasma concentrations with a linear relationship between the dose administered and the maximum serum concentration and the area under the certolizumab pegol plasma concentration versus time curve. Anti-certolizumab pegol antibodies had more than a 30% effect on Cmax and/or AUC, but a dose adjustment is not required.

Due to the small number of certolizumab pegol-exposed pregnancies with known outcomes (n=54), no meaningful comparisons between the exposed group and control groups may be conducted to determine an association with certolizumab and major birth defects or adverse pregnancy outcomes. Experts suggest that the pregnant patient can continue scheduled certolizumab dosing through pregnancy, due to the low to negligible active placental transport; however, the safety of using the drug throughout pregnancy needs confirmation by extended published reports. Registry data have not found an increase in congenital malformations or other issues from first trimester exposure. A multicenter clinical study was conducted in 16 women treated with certolizumab pegol 200 mg every 2 weeks or 400 mg every 4 weeks during the third trimester of pregnancy for rheumatological diseases or Crohn's disease. The last dose was given on average 11 days prior to delivery (range 1 to 27 days). Certolizumab pegol plasma concentrations were measured from mothers and babies using an assay that can measure certolizumab pegol concentrations at or above 0.032 mcg/mL. Certolizumab pegol plasma concentrations measured in the mothers at delivery (range: 4.96 to 49.4 mcg/mL) were consistent with non-pregnant women's plasma concentrations in other clinical studies. Certolizumab pegol plasma concentrations were not measurable in 13 out of 15 newborns at birth. The concentration of certolizumab pegol in 1 infant was 0.0422 mcg/mL at birth (infant/mother plasma ratio of 0.09%). In a second infant, delivered by emergency Caesarean section, the concentration was 0.485 mcg/mL (infant/mother plasma ratio of 4.49%). At Week 4 and Week 8, all 15 babies had no measurable concentrations. Among 16 exposed babies, 1 serious adverse reaction was reported in a neonate who was treated empirically with intravenous antibiotics due to an increased white blood cell count; blood cultures were negative. The certolizumab pegol plasma concentrations for this infant were not measurable at birth, Week 4, or Week 8. Low placental transfer of certolizumab pegol has been noted in 10 pregnant women with Crohn's disease who received certolizumab; plasma certolizumab pegol concentrations were at least 75% lower in the babies than in mothers. Specifically, on the day of birth, plasma certolizumab pegol concentrations were less than 0.41 to 1.66 mcg/mL in cord blood, less than 0.41 to 1.58 mcg/mL in infant blood, and 1.87 to 59.57 mcg/mL in maternal blood. The last dose of certolizumab was 400 mg for every mother and was given on average 19 days before delivery (range, 5 to 42 days). In animal studies, neither fetal harm nor fertility impairment was observed after administration of a dose up to 100 mg/kg. Due to its inhibition of TNF-alpha, certolizumab administered during pregnancy could affect immune responses in the in utero-exposed neonates and infants. In one infant who was exposed in utero, the plasma certolizumab pegol concentration declined from 1.02 to 0.84 mcg/mL over 4 weeks, which suggests that certolizumab may be eliminated at a slower rate in infants than adults. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to certolizumab pegol; information about the registry can be obtained at mothertobaby.org/ongoing-study/cimzia or by calling 1-877-311-8972.