Cyltezo
adalimumab-adbm · Kit
Uses
1 INDICATIONS AND USAGE CYLTEZO is a tumor necrosis factor (TNF) blocker indicated for: Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis . ( 1.1 ) Reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. ( 1.2 ) Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis . (1.3) Reducing signs and symptoms in adult patients with active ankylosing spondylitis . ( 1.4 ) Treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older. ( 1.5 ) Treatment of moderately to severely active ulcerative colitis in adult patients. ( 1.6 ) Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers. Treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. ( 1.7 ) Treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older. ( 1.8 ) Treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older. ( 1.9 ) 1.1 Rheumatoid Arthritis CYLTEZO is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. CYLTEZO can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). 1.2 Juvenile Idiopathic Arthritis CYLTEZO is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. CYLTEZO can be used alone or in combination with methotrexate. 1.3 Psoriatic Arthritis CYLTEZO is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. CYLTEZO can be used alone or in combination with non-biologic DMARDs. 1.4 Ankylosing Spondylitis CYLTEZO is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. 1.5 Crohn's Disease CYLTEZO is indicated for the treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older. 1.6 Ulcerative Colitis CYLTEZO is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. Limitations of Use The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF blockers [see Clinical Studies (14.7) ]. 1.7 Plaque Psoriasis CYLTEZO is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. CYLTEZO should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Warnings and Precautions (5) ] . 1.8 Hidradenitis Suppurativa CYLTEZO is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older. 1.9 Uveitis CYLTEZO is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.
Dosage and administration
Administer by subcutaneous injection ( 2 ) Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis ( 2.2 ): Adults: 40 mg every other week. Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week. Juvenile Idiopathic Arthritis or Pediatric Uveitis ( 2.3 ): Pediatric Weight 2 Years of Age and Older Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week Crohn's Disease ( 2.4 ): Adults: 160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mg every other week starting on Day 29. Pediatric Patients 6 Years of Age and Older: Pediatric Weight Recommended Dosage Days 1 and 15 Starting on Day 29 17 kg (37 lbs) to less than 40 kg (88 lbs) Day 1: 80 mg Day 15: 40 mg 20 mg every other week 40 kg (88 lbs) and greater Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg 40 mg every other week Ulcerative Colitis ( 2.5 ): Adults: 160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15 and 40 mg every other week starting on Day 29. Discontinue in patients without evidence of clinical remission by eight weeks (Day 57). Plaque Psoriasis or Adult Uveitis ( 2.6 ): Adults: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose. Hidradenitis Suppurativa ( 2.7 ): Adults: Day 1: 160 mg (given in one day or split over two consecutive days) Day 15: 80 mg Day 29 and subsequent doses: 40 mg every week or 80 mg every other week Adolescents 12 years of age and older: Adolescent Weight Recommended Dosage 30 kg (66 lbs) to less than 60 kg (132 lbs) Day 1: 80 mg Day 8 and subsequent doses: 40 mg every other week 60 kg (132 lbs) and greater Day 1: 160 mg (given in one day or split over two consecutive days) Day 15: 80 mg Day 29 and subsequent doses: 40 mg every week or 80 mg every other week 2.1 Recommended Tuberculosis Evaluation Prior to initiating CYLTEZO and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis The recommended subcutaneous dosage of CYLTEZO for adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) [see Indications and Usage (1.1 , 1.3 , 1.4) ] is 40 mg administered every other week. Methotrexate (MTX), other non-biologic DMARDs, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with CYLTEZO. In the treatment of RA, some patients not taking concomitant MTX may derive additional benefit from increasing the dosage of CYLTEZO to 40 mg every week or 80 mg every other week. 2.3 Recommended Dosage in Juvenile Idiopathic Arthritis or Pediatric Patients with Uveitis The recommended subcutaneous dosage of CYLTEZO for pediatric patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) or pediatric uveitis [see Indications and Usage (1.2 , 1.9) ] , based on weight, is shown below. MTX, glucocorticoids, NSAIDs, and/or analgesics may be continued during treatment with CYLTEZO. Pediatric Weight (2 Years of Age and older) Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week Adalimumab products have not been studied in patients with polyarticular JIA or pediatric uveitis less than 2 years of age or in patients with a weight below 10 kg. 2.4 Recommended Dosage in Crohn's Disease Subcutaneous Adult Dosage Regimen The recommended subcutaneous dosage of CYLTEZO for adult patients with moderately to severely active Crohn's disease (CD) is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) begin a dosage of 40 mg every other week. Aminosalicylates and/or corticosteroids may be continued during treatment with CYLTEZO. Azathioprine, 6-mercaptopurine (6-MP) [see Warnings and Precautions (5.2) ] or MTX may be continued during treatment with CYLTEZO if necessary. Subcutaneous Pediatric Dosage Regimen The recommended subcutaneous dosage of CYLTEZO for pediatric patients 6 years of age and older with moderately to severely active Crohn's disease (CD), based on body weight, is shown below: Pediatric Weight Recommended Dosage Days 1 through 15 Starting on Day 29 17 kg (37 lbs) to less than 40 kg (88 lbs) Day 1: 80 mg Day 15: 40 mg 20 mg every other week 40 kg (88 lbs) and greater Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg 40 mg every other week 2.5 Recommended Dosage in Ulcerative Colitis Subcutaneous Adult Dosage Regimen The recommended subcutaneous dosage of CYLTEZO for adult patients with moderately to severely active ulcerative colitis is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) continue with a dosage of 40 mg every other week. Discontinue CYLTEZO in adult patients without evidence of clinical remission by eight weeks (Day 57) of therapy. Aminosalicylates and/or corticosteroids may be continued during treatment with CYLTEZO. Azathioprine and 6-mercaptopurine (6-MP) [see Warnings and Precautions (5.2) ] may be continued during treatment with CYLTEZO if necessary.
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS CYLTEZO is a clear to slightly opalescent and colorless to slightly yellow solution available as: Injection: Single-dose prefilled pen (CYLTEZO Pen): 40 mg/0.8 mL, 40 mg/0.4 mL ( 3 ) Single-dose prefilled glass syringe: 40 mg/0.8 mL, 40 mg/0.4 mL, 20 mg/0.4 mL, 10 mg/0.2 mL ( 3 ) Pen (CYLTEZO Pen) Injection: 40 mg/0.8 mL in a single-dose pen. Injection: 40 mg/0.4 mL in a single-dose pen. Prefilled Syringe Injection: 40 mg/0.8 mL in a single-dose, 1 mL prefilled glass syringe. Injection: 40 mg/0.4 mL in a single-dose, 1 mL prefilled glass syringe. Injection: 20 mg/0.4 mL in a single-dose, 1 mL prefilled glass syringe. Injection: 10 mg/0.2 mL in a single-dose, 1 mL prefilled glass syringe.
Contraindications
None. None ( 4 )
Warnings and precautions
Serious infections: Do not start CYLTEZO during an active infection. If an infection develops, monitor carefully, and stop CYLTEZO if infection becomes serious. ( 5.1 ) Invasive fungal infections: For patients who develop a systemic illness on CYLTEZO, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic. ( 5.1 ) Malignancies: Incidence of malignancies was greater in adalimumab-treated patients than in controls ( 5.2 ) Anaphylaxis or serious hypersensitivity reactions may occur ( 5.3 ) Hepatitis B virus reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop CYLTEZO and begin anti-viral therapy. ( 5.4 ) Demyelinating disease: Exacerbation or new onset, may occur. ( 5.5 ) Cytopenias, pancytopenia: Advise patients to seek immediate medical attention if symptoms develop, and consider stopping CYLTEZO. ( 5.6 ) Heart failure: Worsening or new onset, may occur. ( 5.8 ) Autoimmunity: Stop CYLTEZO if lupus-like syndrome or autoimmune hepatitis develop. ( 5.9 ) 5.1 Serious Infections Patients treated with adalimumab products, including CYLTEZO, are at 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. The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of CYLTEZO and these biologic products is not recommended in the treatment of patients with RA [see Warnings and Precautions (5.7 , 5.11) and Drug Interactions (7.2) ] . Treatment with CYLTEZO should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment 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; or with underlying conditions that may predispose them to infection. Tuberculosis Cases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving adalimumab products, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating CYLTEZO 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. Prior to initiating CYLTEZO, assess if treatment for latent tuberculosis is needed; and consider an induration of ≥5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG). Consider anti-tuberculosis therapy prior to initiation of CYLTEZO 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. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab products. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Strongly consider tuberculosis in the differential diagnosis in patients who develop a new infection during CYLTEZO 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 Closely monitor patients for the development of signs and symptoms of infection during and after treatment with CYLTEZO, 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 CYLTEZO. Discontinue CYLTEZO if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with CYLTEZO, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy. Invasive Fungal Infections If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider appropriate empiric antifungal therapy, taking into account both the risk for severe fungal infection and the risks of antifungal therapy, while a diagnostic workup is being performed. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions (5.1) ] Malignancies [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Hepatitis B Virus Reactivation [see Warnings and Precautions (5.4) ] Neurologic Reactions [see Warnings and Precautions (5.5) ] Hematological Reactions [see Warnings and Precautions (5.6) ] Heart Failure [see Warnings and Precautions (5.8) ] Autoimmunity [see Warnings and Precautions (5.9) ] Most common adverse reactions (>10%) are: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reaction with adalimumab was injection site reactions. In placebo-controlled trials, 20% of subjects treated with adalimumab developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of subjects receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation. The proportion of subjects who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of studies in subjects with RA (i.e., Studies RA-I, RA-II, RA-III and RA-IV) was 7% for subjects taking adalimumab and 4% for placebo-treated subjects. The most common adverse reactions leading to discontinuation of adalimumab in these RA studies were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%). Infections In the controlled portions of the 39 global adalimumab clinical trials in adult subjects with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 adalimumab-treated subjects versus a rate of 2.9 per 100 patient-years in 4848 control-treated subjects. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis [see Warnings and Precautions (5.1) ]. Tuberculosis and Opportunistic Infections In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS and UV that included 24,605 adalimumab-treated subjects, the rate of reported active tuberculosis was 0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient-years. In a subgroup of 10,113 U.S. and Canadian adalimumab-treated subjects, the rate of reported active TB was 0.05 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal [see Warnings and Precautions (5.1) ]. Autoantibodies In the rheumatoid arthritis controlled trials, 12% of subjects treated with adalimumab and 7% of placebo-treated subjects that had negative baseline ANA titers developed positive titers at week 24. Two subjects out of 3046 treated with adalimumab developed clinical signs suggestive of new-onset lupus-like syndrome. The subjects improved following discontinuation of therapy. No subjects developed lupus nephritis or central nervous system symptoms. The impact of long-term treatment with adalimumab products on the development of autoimmune diseases is unknown. Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in subjects receiving TNF-blockers. In controlled Phase 3 trials of adalimumab (40 mg SC every other week) in subjects with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥3 × ULN occurred in 3.5% of adalimumab-treated subjects and 1.5% of control-treated subjects. Since many of these subjects in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between adalimumab and the liver enzyme elevations is not clear. In a controlled Phase 3 trial of adalimumab in subjects with polyarticular JIA who were 4 to 17 years, ALT elevations ≥3 × ULN occurred in 4.4% of adalimumab-treated subjects and 1.5% of control-treated subjects (ALT more common than AST); liver enzyme test elevations were more frequent among those treated with the combination of adalimumab and MTX than those treated with adalimumab alone. In general, these elevations did not lead to discontinuation of adalimumab treatment. No ALT elevations ≥3 × ULN occurred in the open-label study of adalimumab in subjects with polyarticular JIA who were 2 to <4 years. In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult subjects with Crohn's Disease with a control period duration ranging from 4 to 52 weeks, ALT elevations ≥3 × ULN occurred in 0.9% of adalimumab-treated subjects and 0.9% of control-treated subjects.
Drug interactions
Abatacept: Increased risk of serious infection. ( 5.1 , 5.11 , 7.2 ) Anakinra: Increased risk of serious infection. ( 5.1 , 5.7 , 7.2 ) Live vaccines: Avoid use with CYLTEZO. ( 5.10 , 7.3 ) 7.1 Methotrexate Adalimumab has been studied in rheumatoid arthritis (RA) patients taking concomitant methotrexate (MTX). Although MTX reduced the apparent clearance of adalimumab, the data do not suggest the need for dose adjustment of either CYLTEZO or MTX [see Clinical Pharmacology (12.3) ] . 7.2 Biological Products In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of CYLTEZO with abatacept or anakinra is not recommended in patients with RA [see Warnings and Precautions (5.7 , 5.11) ] . A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of CYLTEZO and other biologic products for the treatment of RA, PsA, AS, CD, UC, Ps, HS and UV. Concomitant administration of CYLTEZO with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions. 7.3 Live Vaccines Avoid the use of live vaccines with CYLTEZO [see Warnings and Precautions (5.10) ]. 7.4 Cytochrome P450 Substrates The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNFα, IL-6) during chronic inflammation. It is possible for products that antagonize cytokine activity, such as adalimumab products, to influence the formation of CYP450 enzymes. Upon initiation or discontinuation of CYLTEZO in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.
Use in specific populations
8.1 Pregnancy Risk Summary Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn's disease (CD) treated with adalimumab. Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see Data ) . Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in-utero exposed infant (see Clinical Considerations ). In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD) of 40 mg subcutaneous without methotrexate (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester (see Data ) . Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab products in utero [see Use in Specific Populations (8.4) ]. Data Human Data A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab. The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. In an independent clinical study conducted in ten pregnant women with IBD treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of adalimumab was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 mcg/mL in cord blood, 4.28-17.7 mcg/mL in infant serum, and 0-16.1 mcg/mL in maternal serum. In all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/mL), 7 weeks (1.31 mcg/mL), 8 weeks (0.93 mcg/mL), and 11 weeks (0.53 mcg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth. Animal Data In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations. 8.2 Lactation Risk Summary Limited data from case reports in the published literature describe the presence of adalimumab in human milk at infant doses of 0.1% to 1% of the maternal serum concentration. Published data suggest that the systemic exposure to a breastfed infant is expected to be low because adalimumab is a large molecule and is degraded in the gastrointestinal tract. However, the effects of local exposure in the gastrointestinal tract are unknown. There are no reports of adverse effects of adalimumab products on the breastfed infant and no effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CYLTEZO and any potential adverse effects on the breastfed child from CYLTEZO or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of CYLTEZO have not been established in pediatric patients with psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis. The safety and effectiveness of CYLTEZO have been established for: reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 years of age and older.
Pregnancy
8.1 Pregnancy Risk Summary Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn's disease (CD) treated with adalimumab. Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see Data ) . Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in-utero exposed infant (see Clinical Considerations ). In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD) of 40 mg subcutaneous without methotrexate (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester (see Data ) . Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab products in utero [see Use in Specific Populations (8.4) ]. Data Human Data A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab. The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. In an independent clinical study conducted in ten pregnant women with IBD treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of adalimumab was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 mcg/mL in cord blood, 4.28-17.7 mcg/mL in infant serum, and 0-16.1 mcg/mL in maternal serum. In all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/mL), 7 weeks (1.31 mcg/mL), 8 weeks (0.93 mcg/mL), and 11 weeks (0.53 mcg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth. Animal Data In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of CYLTEZO have not been established in pediatric patients with psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis. The safety and effectiveness of CYLTEZO have been established for: reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 years of age and older. the treatment of moderately to severely active Crohn's disease in pediatric patients 6 years of age and older. the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older. the treatment of non-infectious intermediate, posterior, and panuveitis in pediatric patients 2 years of age and older. A pediatric assessment for CYLTEZO demonstrates that CYLTEZO is safe and effective for pediatric patients in an indication for which Humira (adalimumab) is approved. However, CYLTEZO is not approved for such indication due to marketing exclusivity for Humira (adalimumab). Due to their inhibition of TNFα, adalimumab products administered during pregnancy could affect immune response in the in utero -exposed newborn and infant. Data from eight infants exposed to adalimumab in utero suggest adalimumab crosses the placenta [see Use in Specific Populations (8.1) ] . The clinical significance of elevated adalimumab concentrations in infants is unknown. 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. Post-marketing cases of lymphoma, including hepatosplenic T-cell lymphoma and other malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers including adalimumab products [see Warnings and Precautions (5.2) ] . Juvenile Idiopathic Arthritis The safety and effectiveness of CYLTEZO for the treatment of moderately to severely active polyarticular JIA have been established in pediatric patients 2 years of age and older. Use for this indication is supported by evidence from an adequate and well-controlled study (Study JIA) of adalimumab in patients 4 to 17 years of age [see Clinical Studies (14.2) ] and a safety study (Study JIA-II) of adalimumab in patients 2 to <4 years of age where the safety profile was similar to patients 4 to 17 years of age [see Adverse Reactions (6.1) ] . Adalimumab products have not been studied in patients with polyarticular JIA less than 2 years of age or in patients with a weight below 10 kg. The safety of adalimumab in pediatric patients in the polyarticular JIA trials was generally similar to that observed in adults with certain exceptions [see Adverse Reactions (6.1) ]. The safety and effectiveness of CYLTEZO have not been established in pediatric patients with JIA less than 2 years of age. Pediatric Crohn's Disease The safety and effectiveness of CYLTEZO for the treatment of moderately to severely active Crohn's disease have been established in pediatric patients 6 years of age and older. Use of CYLTEZO for this indication is supported by evidence from adequate and well-controlled studies in adults with additional data from a randomized, double-blind, 52-week clinical study of two dose concentrations of adalimumab in 192 pediatric patients (6 years to 17 years of age) [see Adverse Reactions (6.1) , Clinical Pharmacology (12.2 , 12.3) , Clinical Studies (14.6) ] . The adverse reaction profile in patients 6 years to 17 years of age was similar to adults. The safety and effectiveness of CYLTEZO have not been established in pediatric patients with Crohn's disease less than 6 years of age. Pediatric Uveitis The safety and effectiveness of CYLTEZO for the treatment of non-infectious, intermediate, posterior, and panuveitis have been established in pediatric patients 2 years of age and older. Use of CYLTEZO for this indication is supported by evidence from adequate and well-controlled studies of adalimumab in adults and a 2:1 randomized, controlled clinical study of adalimumab in 90 pediatric patients [see Clinical Studies (14.11) ] . The safety and effectiveness of CYLTEZO have not been established in pediatric patients with uveitis less than 2 years of age. Hidradenitis Suppurativa Use of CYLTEZO in pediatric patients 12 years of age and older for the treatment of moderate to severe HS is supported by evidence from adequate and well-controlled studies of adalimumab in adult HS patients. Additional population pharmacokinetic modeling and simulation predicted that weight-based dosing of adalimumab in pediatric patients 12 years of age and older can provide generally similar exposure to adult HS patients. The course of HS is sufficiently similar in adult and adolescent patients to allow extrapolation of data from adult to adolescent patients. The recommended dosage in pediatric patients 12 years of age or older is based on body weight [see Dosage and Administration (2.7) , Clinical Pharmacology (12.3) , and Clinical Studies (14.9) ] . The safety and effectiveness of CYLTEZO have not been established in patients less than 12 years of age with HS.
Geriatric use
8.5 Geriatric Use In clinical studies of RA (Studies RA-I, RA-II, RA-III, and RA-IV), a total of 519 subjects 65 years of age and older, including 107 subjects 75 years of age and older, received adalimumab. No overall difference in effectiveness was observed between these subjects and younger adult subjects. The frequency of serious infection and malignancy among adalimumab-treated subjects 65 years of age and older was higher than for those less than 65 years of age. Consider the benefits and risks of CYLTEZO in patients 65 years of age and older. In patients treated with CYLTEZO, closely monitor for the development of infection or malignancy [see Warnings and Precautions (5.1 , 5.2) ] .
Overdosage
Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately. Consider contacting the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdose management recommendations.
Description
Adalimumab-adbm is a tumor necrosis factor blocker. Adalimumab-adbm is a recombinant human IgG1 monoclonal antibody produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary (CHO)) expression system and is purified by a process that includes specific viral inactivation and removal steps. It consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons. CYLTEZO (adalimumab-adbm) injection is supplied as a sterile, preservative-free solution of adalimumab-adbm for subcutaneous administration. The drug product is supplied as either a single-dose, prefilled pen (CYLTEZO Pen) or as a single-dose, 1 mL prefilled glass syringe. Enclosed within the pen is a single-dose, 1 mL prefilled glass syringe. The solution of CYLTEZO is clear to slightly opalescent and colorless to slightly yellow, with a pH of about 5.5. Each 40 mg/0.4 mL prefilled syringe or prefilled pen delivers 0.4 mL (40 mg) of drug product. Each 0.4 mL of CYLTEZO contains adalimumab-adbm (40 mg), glacial acetic acid (0.03 mg), polysorbate 80 (0.2 mg), sodium acetate trihydrate (0.47 mg), trehalose dihydrate (30.3 mg), and Water for Injection, USP. Each 40 mg/0.8 mL prefilled syringe or prefilled pen delivers 0.8 mL (40 mg) of drug product. Each 0.8 mL of CYLTEZO contains adalimumab-adbm (40 mg), glacial acetic acid (0.13 mg), polysorbate 80 (0.8 mg), sodium acetate trihydrate (2.4 mg), trehalose dihydrate (65.0 mg), and Water for Injection, USP. Each 20 mg/0.4 mL prefilled syringe delivers 0.4 mL (20 mg) of drug product. Each 0.4 mL of CYLTEZO contains adalimumab-adbm (20 mg), glacial acetic acid (0.06 mg), polysorbate 80 (0.4 mg), sodium acetate trihydrate (1.21 mg), trehalose dihydrate (32.5 mg), and Water for Injection, USP. Each 10 mg/0.2 mL prefilled syringe delivers 0.2 mL (10 mg) of drug product. Each 0.2 mL of CYLTEZO contains adalimumab-adbm (10 mg), glacial acetic acid (0.03 mg), polysorbate 80 (0.2 mg), sodium acetate trihydrate (0.61 mg), trehalose dihydrate (16.3 mg), and Water for Injection, USP.
Mechanism of action
12.1 Mechanism of Action Adalimumab products bind specifically to TNF-alpha and block its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab products also lyse surface TNF expressing cells in vitro in the presence of complement. Adalimumab products do not bind or inactivate lymphotoxin (TNF-beta). TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated concentrations of TNF are found in the synovial fluid of patients with RA, JIA, PsA, and AS and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased concentrations of TNF are also found in psoriasis plaques. In Ps, treatment with CYLTEZO may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism(s) by which adalimumab products exert their clinical effects is unknown. Adalimumab products also modulate biological responses that are induced or regulated by TNF, including changes in the concentrations of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC 50 of 1-2 × 10 -10 M).
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING CYLTEZO ® (adalimumab-adbm) injection is supplied as a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for subcutaneous administration. The following packaging configurations are available. CYLTEZO ® Pen Prefilled Pen Contents Number of Units/Carton NDC number *Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed ½ inch needle, providing 40 mg/0.8 mL of CYLTEZO. The needle cap contains natural rubber latex. **Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed ½ inch needle, providing 40 mg/0.4 mL of CYLTEZO. The needle cap contains natural rubber latex. 40 mg/0.8 mL 2 dose trays* and 2 alcohol preps 2 0597-0375-97 40 mg/0.4 mL 2 dose trays** and 2 alcohol preps 2 0597-0495-50 CYLTEZO ® Prefilled Syringe Contents* Number of Units/Carton NDC number *Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed, ½ inch needle. The needle cap contains natural rubber latex. 10 mg/0.2 mL 2 dose trays and 2 alcohol preps 2 0597-0400-89 20 mg/0.4 mL 2 dose trays and 2 alcohol preps 2 0597-0405-80 40 mg/0.4 mL 2 dose trays and 2 alcohol preps 2 0597-0485-20 40 mg/0.8 mL 2 dose trays and 2 alcohol preps 2 0597-0370-82 Storage and Stability Do not use beyond the expiration date on the container. CYLTEZO must be refrigerated at 36°F to 46°F (2°C to 8°C). DO NOT FREEZE. Do not use if frozen even if it has been thawed. Store in original carton until time of administration to protect from light. If needed, for example when traveling, CYLTEZO may be stored at room temperature up to a maximum of 77°F (25°C) for a period of up to 14 days, with protection from light. CYLTEZO should be discarded if not used within the 14-day period. Record the date when CYLTEZO is first removed from the refrigerator in the spaces provided on the carton and dose tray. Do not store CYLTEZO in extreme heat or cold.
Storage
Storage and Stability Do not use beyond the expiration date on the container. CYLTEZO must be refrigerated at 36°F to 46°F (2°C to 8°C). DO NOT FREEZE. Do not use if frozen even if it has been thawed. Store in original carton until time of administration to protect from light. If needed, for example when traveling, CYLTEZO may be stored at room temperature up to a maximum of 77°F (25°C) for a period of up to 14 days, with protection from light. CYLTEZO should be discarded if not used within the 14-day period. Record the date when CYLTEZO is first removed from the refrigerator in the spaces provided on the carton and dose tray. Do not store CYLTEZO in extreme heat or cold.
Patient information
Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections Inform patients that CYLTEZO may lower the ability of their immune system to fight infections. Instruct patients of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections [see Warnings and Precautions (5.1 , 5.2 , 5.4) ] . Malignancies Counsel patients about the risk of malignancies while receiving CYLTEZO [see Warnings and Precautions (5.2) ] . Hypersensitivity Reactions Advise patients to seek immediate medical attention if they experience any symptoms of severe hypersensitivity reactions. Advise latex-sensitive patients that the needle cap of the CYLTEZO Pen and prefilled syringe contains natural rubber latex [see Warnings and Precautions (5.3) , How Supplied/Storage and Handling (16) ] . Other Medical Conditions Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, neurological disease, autoimmune disorders, or cytopenias. Advise patients to report any symptoms suggestive of a cytopenia such as bruising, bleeding, or persistent fever [see Warnings and Precautions (5.5 , 5.6 , 5.8 , 5.9) ] . Instructions on Injection Technique Inform patients that the first injection is to be performed under the supervision of a qualified health care professional. If a patient or caregiver is to administer CYLTEZO, instruct them in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of CYLTEZO [see Instructions for Use ]. For patients who will use the CYLTEZO Pen, tell them that they: Will hear a 'click' when the injection button is pressed. The click indicates the start of the injection. Must keep holding the CYLTEZO Pen against their squeezed, raised skin until all of the medicine is injected. This can take up to 10 seconds. Confirm entire dose was delivered by making sure plunger (seen in window) reached the bottom of the pen. Instruct patients to dispose of their used needles and syringes or used pens in an FDA-cleared sharps disposal container immediately after use. Instruct patients not to dispose of loose needles and syringes or pens in their household trash. Instruct patients that if they do not have an FDA-cleared sharps disposal container, they may use a household container that is made of a heavy-duty plastic, can be closed with a tight-fitting and puncture-resistant lid without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. Instruct patients that when their sharps disposal container is almost full, they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients that there may be state or local laws regarding disposal of used needles and syringes. Refer patients to the FDA's website at http://www.fda.gov/safesharpsdisposal for more information about safe sharps disposal, and for specific information about sharps disposal in the state that they live in. Instruct patients not to dispose of their used sharps disposal container in their household trash unless their community guidelines permit this. Instruct patients not to recycle their used sharps disposal container.
Label text from the FDA structured product label by Boehringer Ingelheim Pharmaceuticals, Inc. (revised May 22, 2026). Long sections are shortened; the complete label is on DailyMed.
Cyltezo NDC products (6)
Frequently asked questions
What is Cyltezo used for?
1 INDICATIONS AND USAGE CYLTEZO is a tumor necrosis factor (TNF) blocker indicated for: Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis . ( 1.1 ) Reducing signs and symptoms of moderately to severely active polyarticular juvenile…
What are the side effects of Cyltezo?
The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions (5.1) ] Malignancies [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Hepatitis B Virus Reactivation [see Warnings and Precautions (5.4) ] Neurologic Reactions [see Warnings and Precautions (5.5) ]… See the full label for the complete list.
Who makes Cyltezo?
Cyltezo is listed by 1 labeler in the FDA NDC directory, including Boehringer Ingelheim Pharmaceuticals, Inc..