ADALIMUMAB KIT | A-S MEDICATION SOLUTIONS 5009044870

Administer by subcutaneous injection (2) Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis ( 2.1 ): 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 ( 2.2 ): 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 ( 2.3 ): 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 ( 2.4 ): 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. Discontinue in patients without evidence of clinical remission by eight weeks (Day 57). Pediatric Patients 5 Years of Age and Older: Pediatric Weight Recommended Dosage Days 1 through 15 Starting on Day 29* 20 kg (44 lbs)to less than 40 kg (88 lbs) Day 1: 80 mg Day 8: 40 mg Day 15: 40 mg 40 mg every other weekor20 mg every week 40 kg (88 lbs) and greater Day 1: 160 mg (single dose or split over two consecutive days) Day 8: 80 mg Day 15: 80 mg 80 mg every other weekor40 mg every week * Continue the recommended pediatric dosage in patients who turn 18 years of age and who are well-controlled on their HUMIRA regimen. Plaque Psoriasis or Adult Uveitis ( 2.5 ): Adults: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose. Hidradenitis Suppurativa ( 2.6 ): 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

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 HUMIRA was injection site reactions. In placebo-controlled trials, 20% of patients treated with HUMIRA developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of patients receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation. The proportion of patients who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of studies in patients with RA (i.e., Studies RA-I, RA-II, RA-III and RA-IV) was 7% for patients taking HUMIRA and 4% for placebo-treated patients. The most common adverse reactions leading to discontinuation of HUMIRA 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 HUMIRA clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 HUMIRA-treated patients versus a rate of 2.9 per 100 patient-years in 4848 control-treated patients. 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 HUMIRA-treated patients, 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 HUMIRA-treated patients, 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 patients treated with HUMIRA and 7% of placebo-treated patients that had negative baseline ANA titers developed positive titers at week 24. Two patients out of 3046 treated with HUMIRA developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved following discontinuation of therapy. No patients developed lupus nephritis or central nervous system symptoms. The impact of long-term treatment with HUMIRA on the development of autoimmune diseases is unknown. Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of HUMIRA (40 mg SC every other week) in patients with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations 3 x ULN occurred in 3.5% of HUMIRA-treated patients and 1.5% of control-treated patients. Since many of these patients in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between HUMIRA and the liver enzyme elevations is not clear. In a controlled Phase 3 trial of HUMIRA in patients with polyarticular JIA who were 4 to 17 years, ALT elevations 3 x ULN occurred in 4.4% of HUMIRA-treated patients and 1.5% of control-treated patients (ALT more common than AST); liver enzyme test elevations were more frequent among those treated with the combination of HUMIRA and MTX than those treated with HUMIRA alone. In general, these elevations did not lead to discontinuation of HUMIRA treatment. No ALT elevations 3 x ULN occurred in the open-label study of HUMIRA in patients with polyarticular JIA who were 2 to <4 years. In controlled Phase 3 trials of HUMIRA (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 patients with Crohn s Disease with a control period duration ranging from 4 to 52 weeks, ALT elevations 3 x ULN occurred in 0.9% of HUMIRA-treated patients and 0.9% of control-treated patients. In the Phase 3 trial of HUMIRA in pediatric patients with Crohn s disease which evaluated efficacy and safety of two body weight based maintenance dose regimens following body weight based induction therapy up to 52 weeks of treatment, ALT elevations 3 x ULN occurred in 2.6% (5/192) of patients, of whom 4 were receiving concomitant immunosuppressants at baseline; none of these patients discontinued due to abnormalities in ALT tests. In controlled Phase 3 trials of HUMIRA (initial doses of 160 mg and 80 mg on Days 1 and 15 respectively, followed by 40 mg every other week) in adult patients with UC with control period duration ranging from 1 to 52 weeks, ALT elevations 3 x ULN occurred in 1.5% of HUMIRA-treated patients and 1.0% of control-treated patients. In the controlled Phase 3 trial of HUMIRA in patients with pediatric ulcerative colitis (N=93), which evaluated efficacy and safety of a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (N=31) and a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every week (N=32), following body weight based induction doses of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=63), or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=30), ALT elevations 3 X ULN occurred in 1.1% (1/93) of patients. In controlled Phase 3 trials of HUMIRA (initial dose of 80 mg then 40 mg every other week) in patients with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations 3 x ULN occurred in 1.8% of HUMIRA-treated patients and 1.8% of control-treated patients. In controlled trials of HUMIRA (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations 3 x ULN occurred in 0.3% of HUMIRA-treated subjects and 0.6% of control-treated subjects. In controlled trials of HUMIRA (initial doses of 80 mg at Week 0 followed by 40 mg every other week starting at Week 1) in adult patients with uveitis with an exposure of 165.4 PYs and 119.8 PYs in HUMIRA-treated and control-treated patients, respectively, ALT elevations 3 x ULN occurred in 2.4% of HUMIRA-treated patients and 2.4% of control-treated patients. Other Adverse Reactions Rheumatoid Arthritis Clinical Studies The data described below reflect exposure to HUMIRA in 2468 patients, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). HUMIRA was studied primarily in placebo-controlled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most patients received 40 mg HUMIRA every other week [see Clinical Studies ( 14.1 ) ]. Table 1 summarizes reactions reported at a rate of at least 5% in patients treated with HUMIRA 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion. Table 1. Adverse Reactions Reported by 5% of Patients Treated with HUMIRA During Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV) HUMIRA40 mg subcutaneousEvery Other Week Placebo (N=705) (N=690) Adverse Reaction (Preferred Term) Respiratory Upper respiratory infection 17% 13% Sinusitis 11% 9% Flu syndrome 7% 6% Gastrointestinal Nausea 9% 8% Abdominal pain 7% 4% Laboratory Tests* Laboratory test abnormal 8% 7% Hypercholesterolemia 6% 4% Hyperlipidemia 7% 5% Hematuria 5% 4% Alkaline phosphatase increased 5% 3% Other Headache 12% 8% Rash 12% 6% Accidental injury 10% 8% Injection site reaction ** 8% 1% Back pain 6% 4% Urinary tract infection 8% 5% Hypertension 5% 3% * Laboratory test abnormalities were reported as adverse reactions in European trials** Does not include injection site erythema, itching, hemorrhage, pain or swelling Less Common Adverse Reactions in Rheumatoid Arthritis Clinical Studies Other infrequent serious adverse reactions that do not appear in the Warnings and Precautions or Adverse Reaction sections that occurred at an incidence of less than 5% in HUMIRA-treated patients in RA studies were: Body As A Whole: Pain in extremity, pelvic pain, surgery, thorax pain Cardiovascular System: Arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia Digestive System: Cholecystitis, cholelithiasis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, hepatic necrosis, vomiting Endocrine System: Parathyroid disorder Hemic And Lymphatic System: Agranulocytosis, polycythemia Metabolic And Nutritional Disorders: Dehydration, healing abnormal, ketosis, paraproteinemia, peripheral edema Musculo-Skeletal System: Arthritis, bone disorder, bone fracture (not spontaneous), bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis, synovitis, tendon disorder Neoplasia: Adenoma Nervous System: Confusion, paresthesia, subdural hematoma, tremor Respiratory System: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion Special Senses: Cataract Thrombosis: Thrombosis leg Urogenital System: Cystitis, kidney calculus, menstrual disorder Juvenile Idiopathic Arthritis Clinical Studies In general, the adverse reactions in the HUMIRA-treated patients in the polyarticular juvenile idiopathic arthritis (JIA) trials (Studies JIA-I and JIA-II) [see Clinical Studies ( 14.2 ) ] were similar in frequency and type to those seen in adult patients [see Warnings and Precautions ( 5 ) , Adverse Reactions ( 6 ) ]. Important findings and differences from adults are discussed in the following paragraphs. In Study JIA-I, HUMIRA was studied in 171 patients who were 4 to 17 years of age, with polyarticular JIA. Severe adverse reactions reported in the study included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis. Serious infections were observed in 4% of patients within approximately 2 years of initiation of treatment with HUMIRA and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster. In Study JIA-I, 45% of patients experienced an infection while receiving HUMIRA with or without concomitant MTX in the first 16 weeks of treatment. The types of infections reported in HUMIRA-treated patients were generally similar to those commonly seen in polyarticular JIA patients who are not treated with TNF blockers. Upon initiation of treatment, the most common adverse reactions occurring in this patient population treated with HUMIRA were injection site pain and injection site reaction (19% and 16%, respectively). A less commonly reported adverse event in patients receiving HUMIRA was granuloma annulare which did not lead to discontinuation of HUMIRA treatment. In the first 48 weeks of treatment in Study JIA-I, non-serious hypersensitivity reactions were seen in approximately 6% of patients and included primarily localized allergic hypersensitivity reactions and allergic rash. In Study JIA-I, 10% of patients treated with HUMIRA who had negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of treatment. No patient developed clinical signs of autoimmunity during the clinical trial. Approximately 15% of patients treated with HUMIRA developed mild-to-moderate elevations of creatine phosphokinase (CPK) in Study JIA-I. Elevations exceeding 5 times the upper limit of normal were observed in several patients. CPK concentrations decreased or returned to normal in all patients. Most patients were able to continue HUMIRA without interruption. In Study JIA-II, HUMIRA was studied in 32 patients who were 2 to <4 years of age or 4 years of age and older weighing <15 kg with polyarticular JIA. The safety profile for this patient population was similar to the safety profile seen in patients 4 to 17 years of age with polyarticular JIA. In Study JIA-II, 78% of patients experienced an infection while receiving HUMIRA. These included nasopharyngitis, bronchitis, upper respiratory tract infection, otitis media, and were mostly mild to moderate in severity. Serious infections were observed in 9% of patients receiving HUMIRA in the study and included dental caries, rotavirus gastroenteritis, and varicella. In Study JIA-II, non-serious allergic reactions were observed in 6% of patients and included intermittent urticaria and rash, which were all mild in severity. Psoriatic Arthritis and Ankylosing Spondylitis Clinical Studies HUMIRA has been studied in 395 patients with psoriatic arthritis (PsA) in two placebo-controlled trials and in an open label study and in 393 patients with ankylosing spondylitis (AS) in two placebo-controlled studies [see Clinical Studies ( 14.3 , 14.4 )]. The safety profile for patients with PsA and AS treated with HUMIRA 40 mg every other week was similar to the safety profile seen in patients with RA, HUMIRA Studies RA-I through IV. Crohn s Disease Clinical Studies Adults: The safety profile of HUMIRA in 1478 adult patients with Crohn s disease from four placebo-controlled and two open-label extension studies [see Clinical Studies ( 14.5 ) ] was similar to the safety profile seen in patients with RA. Pediatric Patients 6 Years to 17 Years: The safety profile of HUMIRA in 192 pediatric patients from one double-blind study (Study PCD-I) and one open-label extension study [see Clinical Studies ( 14.6 ) ] was similar to the safety profile seen in adult patients with Crohn s disease. During the 4-week open label induction phase of Study PCD-I, the most common adverse reactions occurring in the pediatric population treated with HUMIRA were injection site pain and injection site reaction (6% and 5%, respectively). A total of 67% of children experienced an infection while receiving HUMIRA in Study PCD-I. These included upper respiratory tract infection and nasopharyngitis. A total of 5% of children experienced a serious infection while receiving HUMIRA in Study PCD-I. These included viral infection, device related sepsis (catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis. In Study PCD-I, allergic reactions were observed in 5% of children which were all non-serious and were primarily localized reactions. Ulcerative Colitis Clinical Studies Adults: The safety profile of HUMIRA in 1010 adult patients with ulcerative colitis (UC) from two placebo-controlled studies and one open-label extension study [see Clinical Studies ( 14.7 ) ] was similar to the safety profile seen in patients with RA. Pediatric Patients 5 Years to 17 Years: The safety profile of HUMIRA in 93 pediatric patients with ulcerative colitis from one double-blind study and one open-label extension study [see Clinical Studies ( 14.8 ) ] was similar to the safety profile seen in adult patients with ulcerative colitis. Plaque Psoriasis Clinical Studies HUMIRA has been studied in 1696 subjects with plaque psoriasis (Ps) in placebo-controlled and open-label extension studies [see Clinical Studies ( 14.9 ) ]. The safety profile for subjects with Ps treated with HUMIRA was similar to the safety profile seen in subjects with RA with the following exceptions. In the placebo-controlled portions of the clinical trials in Ps subjects, HUMIRA-treated subjects had a higher incidence of arthralgia when compared to controls (3% vs. 1%). Hidradenitis Suppurativa Clinical Studies HUMIRA has been studied in 727 subjects with hidradenitis suppurativa (HS) in three placebo-controlled studies and one open-label extension study [see Clinical Studies ( 14.10 ) ]. The safety profile for subjects with HS treated with HUMIRA weekly was consistent with the known safety profile of HUMIRA. Flare of HS, defined as 25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from HUMIRA treatment following the primary efficacy timepoint in two studies. Uveitis Clinical Studies HUMIRA has been studied in 464 adult patients with uveitis (UV) in placebo-controlled and open-label extension studies and in 90 pediatric patients with uveitis (Study PUV-I) [see Clinical Studies ( 14.11 , 14.12 )] . The safety profile for patients with UV treated with HUMIRA was similar to the safety profile seen in patients with RA.

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other adalimumab products may be misleading. There are two assays that have been used to measure anti-adalimumab antibodies. With the ELISA, antibodies to adalimumab could be detected only when serum adalimumab concentrations were < 2 mcg/mL. The ECL assay can detect anti-adalimumab antibody titers independent of adalimumab concentrations in the serum samples. The incidence of anti-adalimumab antibody (AAA) development in patients treated with HUMIRA are presented in Table 2. Table 2: Anti-Adalimumab Antibody Development Determined by ELISA and ECL Assay in Patients Treated with HUMIRA Indications Study Duration Anti-Adalimumab Antibody Incidence by ELISA (n/N) Anti-Adalimumab Antibody Incidence by ECL Assay (n/N) In all patients who received adalimumab In patients with serum adalimumab concentrations < 2 mcg/mL Rheumatoid Arthritisa 6 to 12 months 5% (58/1062) NR NA Juvenile Idiopathic Arthritis (JIA) 4 to 17 years of ageb 48 weeks 16% (27/171) NR NA 2 to 4 years of age or 4 years of age and weighing < 15 kg 24 weeks 7% (1/15)c NR NA Psoriatic Arthritisd 48 weekse 13% (24/178) NR NA Ankylosing Spondylitis 24 weeks 9% (16/185) NR NA Adult Crohn s Disease 56 weeks 3% (7/269) 8% (7/86) NA Pediatric Crohn s Disease 52 weeks 3% (6/182) 10% (6/58) NA Adult Ulcerative Colitis 52 weeks 5% (19/360) 21% (19/92) NA Pediatric Ulcerative Colitis 52 weeks 3% (3/100) 13% (3/23) 33% (33/100)i Plaque Psoriasisf Up to 52 weeksg 8% (77/920) 21% (77/372) NA Hidradenitis Suppurativa 36 weeks 7% (30/461) 28% (58/207)h 61% (272/445)j Non-infectious Uveitis 52 weeks 5% (12/249) 21% (12/57) 40% (99/249)k n: number of patients with anti-adalimumab antibody; NR: not reported; NA: Not applicable (not performed) a In patients receiving concomitant methotrexate (MTX), the incidence of anti-adalimumab antibody was 1% compared to 12% with HUMIRA monotherapy b In patients receiving concomitant MTX, the incidence of anti-adalimumab antibody was 6% compared to 26% with HUMIRA monotherapy c This patient received concomitant MTX d In patients receiving concomitant MTX, the incidence of antibody development was 7% compared to 1% in RA e Subjects enrolled after completing 2 previous studies of 24 weeks or 12 weeks of treatments. f In plaque psoriasis patients who were on HUMIRA monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to adalimumab after retreatment was similar to the rate observed prior to withdrawal g One 12-week Phase 2 study and one 52-week Phase 3 study h Among subjects in the 2 Phase 3 studies who stopped HUMIRA treatment for up to 24 weeks and in whom adalimumab serum levels subsequently declined to <2 mcg/mL (approximately 22% of total subjects studied) i No apparent association between antibody development and safety was observed. The association of antibody development and efficacy outcome was not assessed due to limited number of subjects in each treatment group stratified by anti-adalimumab antibody titer. j No apparent association between antibody development and safety was observed k No correlation of antibody development to safety or efficacy outcomes was observed Rheumatoid Arthritis and Psoriatic Arthritis: Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab using the ELISA during the 6- to 12-month period. No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of HUMIRA is unknown.

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 HUMIRA Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn s disease (CD). 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 HUMIRA 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 HUMIRA, 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 HUMIRA was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 g/mL in cord blood, 4.28-17.7 g/mL in infant serum, and 0-16.1 g/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 g/mL), 7 weeks (1.31 g/mL), 8 weeks (0.93 g/mL), and 11 weeks (0.53 g/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.

The safety and effectiveness of HUMIRA 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 moderately to severely active ulcerative colitis in pediatric patients 5 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. Due to its inhibition of TNF , HUMIRA administered during pregnancy could affect immune response in the in utero-exposed newborn and infant. Data from eight infants exposed to HUMIRA 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 HUMIRA [see Warnings and Precautions ( 5.2 ) ]. Juvenile Idiopathic Arthritis In Study JIA-I, HUMIRA was shown to reduce signs and symptoms of active polyarticular JIA in patients 4 to 17 years of age [see Clinical Studies ( 14.2 ) ]. In Study JIA-II, the safety profile for patients 2 to <4 years of age was similar to the safety profile for patients 4 to 17 years of age with polyarticular JIA [see Adverse Reactions ( 6.1 ) ]. HUMIRA has 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 HUMIRA in 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 HUMIRA have not been established in pediatric patients with JIA less than 2 years of age. Pediatric Crohn s Disease The safety and effectiveness of HUMIRA 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 HUMIRA 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 HUMIRA 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 HUMIRA have not been established in pediatric patients with Crohn s disease less than 6 years of age. Pediatric Ulcerative Colitis The safety and effectiveness of HUMIRA for the treatment of moderately to severely active ulcerative colitis have been established in pediatric patients 5 years of age and older. Use of HUMIRA 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 HUMIRA in 93 pediatric patients (5 years to 17 years of age) [see Adverse Reactions ( 6.1 ) , Clinical Pharmacology ( 12.3 ) , Clinical Studies ( 14.8 ) ]. The adverse reaction profile in patients 5 years to 17 years of age was similar to adults. The effectiveness of HUMIRA has not been established in patients who have lost response or were intolerant to TNF blockers. The safety and effectiveness of HUMIRA have not been established in pediatric patients with ulcerative colitis less than 5 years of age. Pediatric Uveitis The safety and effectiveness of HUMIRA for the treatment of non-infectious uveitis have been established in pediatric patients 2 years of age and older. The use of HUMIRA is supported by evidence from adequate and well-controlled studies of HUMIRA in adults and a 2:1 randomized, controlled clinical study in 90 pediatric patients [see Clinical Studies ( 14.12 ) ]. The safety and effectiveness of HUMIRA have not been established in pediatric patients with uveitis less than 2 years of age. Hidradenitis Suppurativa Use of HUMIRA in pediatric patients 12 years of age and older for HS is supported by evidence from adequate and well-controlled studies of HUMIRA in adult HS patients. Additional population pharmacokinetic modeling and simulation predicted that weight-based dosing of HUMIRA 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 ( 2.6 ) , Clinical Pharmacology ( 12.3 ) , and Clinical Studies ( 14.10 ) ]. The safety and effectiveness of HUMIRA have not been established in patients less than 12 years of age with HS.

Adalimumab is a tumor necrosis factor blocker. Adalimumab is a recombinant human IgG1 monoclonal antibody created using phage display technology resulting in an antibody with human derived heavy and light chain variable regions and human IgG1:k constant regions. Adalimumab is 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. HUMIRA (adalimumab) injection is supplied as a sterile, preservative-free solution for subcutaneous administration. The drug product is supplied as either a single-dose, prefilled pen (HUMIRA Pen), as a single-dose, 1 mL prefilled glass syringe, or as a single-dose institutional use vial. Enclosed within the pen is a single-dose, 1 mL prefilled glass syringe. The solution of HUMIRA is clear and colorless, with a pH of about 5.2. Each 80 mg/0.8 mL prefilled syringe or prefilled pen delivers 0.8 mL (80 mg) of drug product. Each 0.8 mL of HUMIRA contains adalimumab (80 mg), mannitol (33.6 mg), polysorbate 80 (0.8 mg), and Water for Injection, USP. 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 HUMIRA contains adalimumab (40 mg), mannitol (16.8 mg), polysorbate 80 (0.4 mg), and Water for Injection, USP. Each 40 mg/0.8 mL prefilled syringe, prefilled pen, or single-dose institutional use vial delivers 0.8 mL (40 mg) of drug product. Each 0.8 mL of HUMIRA contains adalimumab (40 mg), citric acid monohydrate (1.04 mg), dibasic sodium phosphate dihydrate (1.22 mg), mannitol (9.6 mg), monobasic sodium phosphate dihydrate (0.69 mg), polysorbate 80 (0.8 mg), sodium chloride (4.93 mg), sodium citrate (0.24 mg) and Water for Injection, USP. Sodium hydroxide is added as necessary to adjust pH. Each 20 mg/0.2 mL prefilled syringe delivers 0.2 mL (20 mg) of drug product. Each 0.2 mL of HUMIRA contains adalimumab (20 mg), mannitol (8.4 mg), polysorbate 80 (0.2 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 HUMIRA contains adalimumab (20 mg), citric acid monohydrate (0.52 mg), dibasic sodium phosphate dihydrate (0.61 mg), mannitol (4.8 mg), monobasic sodium phosphate dihydrate (0.34 mg), polysorbate 80 (0.4 mg), sodium chloride (2.47 mg), sodium citrate (0.12 mg) and Water for Injection, USP. Sodium hydroxide is added as necessary to adjust pH. Each 10 mg/0.1 mL prefilled syringe delivers 0.1 mL (10 mg) of drug product. Each 0.1 mL of HUMIRA contains adalimumab (10 mg), mannitol (4.2 mg), polysorbate 80 (0.1 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 HUMIRA contains adalimumab (10 mg), citric acid monohydrate (0.26 mg), dibasic sodium phosphate dihydrate (0.31 mg), mannitol (2.4 mg), monobasic sodium phosphate dihydrate (0.17 mg), polysorbate 80 (0.2 mg), sodium chloride (1.23 mg), sodium citrate (0.06 mg) and Water for Injection, USP. Sodium hydroxide is added as necessary to adjust pH.

The pharmacokinetics of adalimumab were linear over the dose range of 0.5 to 10 mg/kg following administration of a single intravenous dose (HUMIRA is not approved for intravenous use). Following 20, 40, and 80 mg every other week and every week subcutaneous administration, adalimumab mean serum trough concentrations at steady state increased approximately proportionally with dose in RA patients. The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. Healthy subjects and patients with RA displayed similar adalimumab pharmacokinetics. Adalimumab exposure in patients treated with 80 mg every other week is estimated to be comparable with that in patients treated with 40 mg every week. Absorption The average absolute bioavailability of adalimumab following a single 40 mg subcutaneous dose was 64%. The mean time to reach the maximum concentration was 5.5 days (131 56 hours) and the maximum serum concentration was 4.7 1.6 mcg/mL in healthy subjects following a single 40 mg subcutaneous administration of HUMIRA. Distribution The distribution volume (Vss) ranged from 4.7 to 6.0 L following intravenous administration of doses ranging from 0.25 to 10 mg/kg in RA patients. Elimination The single dose pharmacokinetics of adalimumab in RA patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The systemic clearance of adalimumab is approximately 12 mL/hr. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time in RA patients. Patient Population Rheumatoid Arthritis and Ankylosing Spondylitis: In patients receiving 40 mg HUMIRA every other week, adalimumab mean steady-state trough concentrations were approximately 5 mcg/mL and 8 to 9 mcg/mL, without and with MTX concomitant treatment, respectively. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31 to 96% of those in serum. The pharmacokinetics of adalimumab in patients with AS were similar to those in patients with RA. Psoriatic Arthritis: In patients receiving 40 mg every other week, adalimumab mean steady-state trough concentrations were 6 to 10 mcg/mL and 8.5 to 12 mcg/mL, without and with MTX concomitant treatment, respectively. Plaque Psoriasis: Adalimumab mean steady-state trough concentration was approximately 5 to 6 mcg/mL during HUMIRA 40 mg every other week treatment. Adult Uveitis: Adalimumab mean steady concentration was approximately 8 to 10 mcg/mL during HUMIRA 40 mg every other week treatment. Adult Hidradenitis Suppurativa: Adalimumab trough concentrations were approximately 7 to 8 mcg/mL at Week 2 and Week 4, respectively, after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations at Week 12 through Week 36 were approximately 7 to 11 mcg/mL during HUMIRA 40 mg every week treatment. Adult Crohn s Disease: Adalimumab mean trough concentrations were approximately 12 mcg/mL at Week 2 and Week 4 after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations were 7 mcg/mL at Week 24 and Week 56 during HUMIRA 40 mg every other week treatment. Adult Ulcerative Colitis: Adalimumab mean trough concentrations were approximately 12 mcg/mL at Week 2 and Week 4 after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations were approximately 8 mcg/mL and 15 mcg/mL at Week 52 after receiving a dose of HUMIRA 40 mg every other week and 40 mg every week, respectively. Anti-Drug Antibody Effects on Pharmacokinetics Rheumatoid Arthritis : A trend toward higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies was identified. Pediatric Ulcerative Colitis: Antibodies to adalimumab by ECL assay were associated with reduced serum adalimumab concentrations in pediatric patients with moderately to severely active ulcerative colitis. Hidradenitis Suppurativa: In subjects with moderate to severe HS, antibodies to adalimumab were associated with reduced serum adalimumab concentrations. In general, the extent of reduction in serum adalimumab concentrations is greater with increasing titers of antibodies to adalimumab. Specific Populations Geriatric Patients: A lower clearance with increasing age was observed in patients with RA aged 40 to >75 years. Pediatric Patients: Juvenile Idiopathic Arthritis : 4 years to 17 years of age: The adalimumab mean steady-state trough concentrations were 6.8 mcg/mL and 10.9 mcg/mL in patients weighing <30 kg receiving 20 mg HUMIRA subcutaneously every other week as monotherapy or with concomitant MTX, respectively. The adalimumab mean steady-state trough concentrations were 6.6 mcg/mL and 8.1 mcg/mL in patients weighing 30 kg receiving 40 mg HUMIRA subcutaneously every other week as monotherapy or with MTX concomitant treatment, respectively. 2 years to <4 years of age or 4 years of age and older weighing <15 kg: The adalimumab mean steady-state trough adalimumab concentrations were 6.0 mcg/mL and 7.9 mcg/mL in patients receiving HUMIRA subcutaneously every other week as monotherapy or with MTX concomitant treatment, respectively. Pediatric Hidradenitis Suppurativa : Adalimumab concentrations in adolescent patients with HS receiving the recommended dosage regimens are predicted to be similar to those observed in adult subjects with HS based on population pharmacokinetic modeling and simulation. Pediatric Crohn's Disease : Adalimumab mean SD concentrations were 15.7 6.5 mcg/mL at Week 4 following 160 mg at Week 0 and 80 mg at Week 2, and 10.5 6.0 mcg/mL at Week 52 following 40 mg every other week dosing in patients weighing 40 kg. Adalimumab mean SD concentrations were 10.6 6.1 mcg/mL at Week 4 following dosing 80 mg at Week 0 and 40 mg at Week 2, and 6.9 3.6 mcg/mL at Week 52 following 20 mg every other week dosing in patients weighing < 40 kg. Pediatric Ulcerative Colitis : The adalimumab mean steady-state trough concentration was 5.0 3.3 mcg/mL at Week 52 following subcutaneous administration of 0.6 mg/kg (maximum of 40 mg) every other week in pediatric UC patients 5 years to 17 years of age. In patients who received 0.6 mg/kg (maximum of 40 mg) every week, the mean steady-state trough concentration was 15.7 5.6 mcg/mL at Week 52 in pediatric UC patients 5 years to 17 years of age. Male and Female Patients: No gender-related pharmacokinetic differences were observed after correction for a patient s body weight. Healthy subjects and patients with rheumatoid arthritis displayed similar adalimumab pharmacokinetics. Patients with Renal or Hepatic Impairment: No pharmacokinetic data are available in patients with hepatic or renal impairment. Rheumatoid factor or CRP concentrations: Minor increases in apparent clearance were predicted in RA patients receiving doses lower than the recommended dose and in RA patients with high rheumatoid factor or CRP concentrations. These increases are not likely to be clinically important. Drug Interaction Studies: Methotrexate: MTX reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively, in patients with RA [see Drug Interactions ( 7.1 ) ].

HUMIRA (adalimumab) is supplied as a preservative-free, sterile, clear and colorless solution for subcutaneous administration. The following packaging configurations are available. HUMIRA Pen Carton - 40 mg/0.8 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed inch needle, providing 40 mg/0.8 mL of HUMIRA. The needle cover may contain natural rubber latex. The NDC number is 0074-4339-02. HUMIRA Pen Carton - 40 mg/0.4 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 40 mg/0.4 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0554-02. HUMIRA Pen Carton 80 mg/0.8 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 80 mg/0.8 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0124-02. HUMIRA Pen 40 mg/0.8 mL - Starter Package for Crohn's Disease, Ulcerative Colitis or Hidradenitis Suppurativa HUMIRA is supplied in a carton containing 6 alcohol preps and 6 dose trays (Starter Package for Crohn s Disease, Ulcerative Colitis or Hidradenitis Suppurativa). Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed inch needle, providing 40 mg/0.8 mL of HUMIRA. The needle cover may contain natural rubber latex. The NDC number is 0074-4339-06. HUMIRA Pen 80 mg/0.8 mL - Starter Package for Crohn's Disease, Ulcerative Colitis or Hidradenitis Suppurativa HUMIRA is supplied in a carton containing 4 alcohol preps and 3 dose trays (Starter Package for Crohn s Disease, Ulcerative Colitis or Hidradenitis Suppurativa). Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 80 mg/0.8 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0124-03. HUMIRA Pen 80 mg/0.8 mL and 40 mg/0.4 mL - Psoriasis, Uveitis or Adolescent Hidradenitis Suppurativa Starter Package HUMIRA is supplied in a carton containing 4 alcohol preps and 3 dose trays (Psoriasis, Uveitis or Adolescent Hidradenitis Suppurativa Starter Package). One dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 80 mg/0.8 mL of HUMIRA. The other two dose trays each consist of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 40 mg/0.4 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-1539-03. HUMIRA Pen 80 mg/0.8 mL Starter Package for Pediatric Ulcerative Colitis (4 count) HUMIRA is supplied in a carton containing 4 alcohol preps and 4 dose trays (Starter Package for Pediatric Ulcerative Colitis). Each dose tray consists of a single-dose pen, containing a 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 80 mg/0.8 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0124-04. Prefilled Syringe Carton - 40 mg/0.8 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed inch needle, providing 40 mg/0.8 mL of HUMIRA. The needle cover may contain natural rubber latex. The NDC number is 0074-3799-02. Prefilled Syringe Carton - 40 mg/0.4 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 40 mg/0.4 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0243-02. Prefilled Syringe Carton - 20 mg/0.4 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed inch needle, providing 20 mg/0.4 mL of HUMIRA. The needle cover may contain natural rubber latex. The NDC number is 0074-9374-02. Prefilled Syringe Carton - 20 mg/0.2 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 20 mg/0.2 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0616-02. Prefilled Syringe Carton - 10 mg/0.2 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed inch needle, providing 10 mg/0.2 mL of HUMIRA. The needle cover may contain natural rubber latex. The NDC number is 0074-6347-02. Prefilled Syringe Carton - 10 mg/0.1 mL HUMIRA is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 10 mg/0.1 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0817-02. HUMIRA Prefilled Syringe 80 mg/0.8 mL - Pediatric Crohn s Disease Starter Package (3 count) HUMIRA is supplied in a carton containing 4 alcohol preps and 3 dose trays (Pediatric Starter Package). Each dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 80 mg/0.8 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-2540-03. HUMIRA Prefilled Syringe 80 mg/0.8 mL and 40 mg/0.4 mL - Pediatric Crohn s Disease Starter Package (2 count) HUMIRA is supplied in a carton containing 2 alcohol preps and 2 dose trays (Pediatric Starter Package). One dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 80 mg/0.8 mL of HUMIRA. The other dose tray consists of a single-dose, 1 mL prefilled glass syringe with a fixed thin wall, inch needle, providing 40 mg/0.4 mL of HUMIRA. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0067-02. Single-Dose Institutional Use Vial Carton - 40 mg/0.8 mL HUMIRA is supplied for institutional use only in a carton containing a single-dose, glass vial, providing 40 mg/0.8 mL of HUMIRA. The vial stopper is not made with natural rubber latex. The NDC number is 0074-3797-01. Storage and Stability Do not use beyond the expiration date on the container. HUMIRA 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, HUMIRA 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. HUMIRA should be discarded if not used within the 14-day period. Record the date when HUMIRA is first removed from the refrigerator in the spaces provided on the carton and dose tray. Do not store HUMIRA in extreme heat or cold.

Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections Inform patients that HUMIRA 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 HUMIRA [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 HUMIRA 40 mg/0.8 mL Pen and 40 mg/0.8 mL, 20 mg/0.4 mL and 10 mg/0.2 mL prefilled syringe may contain 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 HUMIRA, instruct them in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of HUMIRA [see Instructions for Use ]. For patients who will use the HUMIRA Pen, tell them that they: Will hear a loud click when the plum-colored activator button is pressed. The loud click means the start of the injection. Must keep holding the HUMIRA Pen against their squeezed, raised skin until all of the medicine is injected. This can take up to 15 seconds. Will know that the injection has finished when the yellow marker fully appears in the window view and stops moving. Instruct patients to dispose of their used needles and syringes or used Pen in a FDA-cleared sharps disposal container immediately after use. Instruct patients not to dispose of loose needles and syringes or Pen in their household trash. Instruct patients that if they do not have a 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. AbbVie Inc. North Chicago, IL 60064, U.S.A. US License Number 1889 20083870 2/2024

MEDICATION GUIDE HUMIRA (Hu-MARE-ah) (adalimumab) injection , for subcutaneous use Read the Medication Guide that comes with HUMIRA before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. What is the most important information I should know about HUMIRA? HUMIRA is a medicine that affects your immune system. HUMIRA can lower the ability of your immune system to fight infections. Serious infections have happened in people taking HUMIRA. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some people have died from these infections. Your doctor should test you for TB before starting HUMIRA. Your doctor should check you closely for signs and symptoms of TB during treatment with HUMIRA. You should not start taking HUMIRA if you have any kind of infection unless your doctor says it is okay. Before starting HUMIRA, tell your doctor if you: think you have an infection or have symptoms of an infection such as: fever, sweats, or chills muscle aches cough shortness of breath blood in phlegm warm, red, or painful skin or sores on your body diarrhea or stomach pain burning when you urinate or urinate more often than normal feel very tired weight loss are being treated for an infection. get a lot of infections or have infections that keep coming back. have diabetes. have TB, or have been in close contact with someone with TB. were born in, lived in, or traveled to countries where there is more risk for getting TB. Ask your doctor if you are not sure. live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may happen or become more severe if you use HUMIRA. Ask your doctor if you do not know if you have lived in an area where these infections are common. have or have had hepatitis B. use the medicine ORENCIA (abatacept), KINERET (anakinra), RITUXAN (rituximab), IMURAN (azathioprine), or PURINETHOL (6 mercaptopurine, 6-MP). are scheduled to have major surgery. After starting HUMIRA, call your doctor right away if you have an infection, or any sign of an infection. HUMIRA can make you more likely to get infections or make any infection that you may have worse. Cancer For children and adults taking Tumor Necrosis Factor (TNF)-blockers, including HUMIRA, the chances of getting cancer may increase. There have been cases of unusual cancers in children, teenagers, and young adults using TNF-blockers. People with rheumatoid arthritis (RA), especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma. If you use TNF blockers including HUMIRA your chance of getting two types of skin cancer may increase (basal cell cancer and squamous cell cancer of the skin). These types of cancer are generally not life-threatening if treated. Tell your doctor if you have a bump or open sore that does not heal. Some people receiving TNF blockers including HUMIRA developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn s disease or ulcerative colitis with another medicine called IMURAN (azathioprine) or PURINETHOL (6-mercaptopurine, 6 MP). What is HUMIRA? HUMIRA is a medicine called a Tumor Necrosis Factor (TNF) blocker. HUMIRA is used: To reduce the signs and symptoms of: moderate to severe RA in adults. HUMIRA can be used alone, with methotrexate, or with certain other medicines. moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 2 years and older. HUMIRA can be used alone or with methotrexate. psoriatic arthritis (PsA) in adults. HUMIRA can be used alone or with certain other medicines. ankylosing spondylitis (AS) in adults. moderate to severe hidradenitis suppurativa (HS) in people 12 years and older. T o treat moderate to severe Crohn s disease (CD) in adults and children 6 years of age and older. To treat moderate to severe ulcerative colitis (UC) in adults and children 5 years of age and older. It is not known if HUMIRA is effective in people who stopped responding to or could not tolerate TNF-blocker medicines. To treat moderate to severe chronic (lasting a long time) plaque psoriasis (Ps) in adults who have the condition in many areas of their body and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills). To treat non-infectious intermediate, posterior, and panuveitis in adults and children 2 years of age and older. What should I tell my doctor before taking HUMIRA? HUMIRA may not be right for you. Before starting HUMIRA, tell your doctor about all of your medical conditions, including if you: have an infection. See What is the most important information I should know about HUMIRA? have or have had cancer. have any numbness or tingling or have a disease that affects your nervous system such as multiple sclerosis or Guillain-Barr syndrome. have or had heart failure. have recently received or are scheduled to receive a vaccine. You may receive vaccines, except for live vaccines while using HUMIRA. Children should be brought up to date with all vaccines before starting HUMIRA. are allergic to rubber or latex. Tell your doctor if you have any allergies to rubber or latex. The needle cover for the HUMIRA Pen 40 mg/0.8 mL, HUMIRA 40 mg/0.8 mL prefilled syringe, HUMIRA 20 mg/0.4 mL prefilled syringe, and HUMIRA 10 mg/0.2 mL prefilled syringe may contain natural rubber or latex. The black needle cover for the HUMIRA Pen 80 mg/0.8 mL, HUMIRA 80 mg/0.8 mL prefilled syringe, HUMIRA Pen 40 mg/0.4 mL, HUMIRA 40 mg/0.4 mL prefilled syringe, HUMIRA 20 mg/0.2 mL prefilled syringe, HUMIRA 10 mg/0.1 mL prefilled syringe and the vial stopper on the HUMIRA institutional use vial are not made with natural rubber or latex. are allergic to HUMIRA or to any of its ingredients. See the end of this Medication Guide for a list of ingredients in HUMIRA. are pregnant or plan to become pregnant, breastfeeding or plan to breastfeed. You and your doctor should decide if you should take HUMIRA while you are pregnant or breastfeeding. have a baby and you were using HUMIRA during your pregnancy. Tell your baby s doctor before your baby receives any vaccines. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctor if you use: ORENCIA (abatacept), KINERET (anakinra), REMICADE (infliximab), ENBREL (etanercept), CIMZIA (certolizumab pegol) or SIMPONI (golimumab), because you should not use HUMIRA while you are also using one of these medicines. RITUXAN (rituximab). Your doctor may not want to give you HUMIRA if you have received RITUXAN (rituximab) recently. IMURAN (azathioprine) or PURINETHOL (6 mercaptopurine, 6-MP). Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine. How should I take HUMIRA? HUMIRA is given by an injection under the skin. Your doctor will tell you how often to take an injection of HUMIRA. This is based on your condition to be treated. Do not inject HUMIRA more often than you were prescribed. See the Instructions for Use inside the carton for complete instructions for the right way to prepare and inject HUMIRA. Make sure you have been shown how to inject HUMIRA before you do it yourself. You can call your doctor or 1-800-4HUMIRA (1-800-448-6472) if you have any questions about giving yourself an injection. Someone you know can also help you with your injection after they have been shown how to prepare and inject HUMIRA. Do not try to inject HUMIRA yourself until you have been shown the right way to give the injections. If your doctor decides that you or a caregiver may be able to give your injections of HUMIRA at home, you should receive training on the right way to prepare and inject HUMIRA. Do not miss any doses of HUMIRA unless your doctor says it is okay. If you forget to take HUMIRA, inject a dose as soon as you remember. Then, take your next dose at your regular scheduled time. This will put you back on schedule. In case you are not sure when to inject HUMIRA, call your doctor or pharmacist. If you take more HUMIRA than you were told to take, call your doctor. What are the possible side effects of HUMIRA? HUMIRA can cause serious side effects, including: See What is the most important information I should know about HUMIRA? Serious Infections. Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with HUMIRA and during treatment with HUMIRA. Even if your TB test is negative your doctor should carefully monitor you for TB infections while you are taking HUMIRA. People who had a negative TB skin test before receiving HUMIRA have developed active TB. Tell your doctor if you have any of the following symptoms while taking or after taking HUMIRA: cough that does not go away low grade fever weight loss loss of body fat and muscle (wasting) Hepatitis B infection in people who carry the virus in their blood. If you are a carrier of the hepatitis B virus (a virus that affects the liver), the virus can become active while you use HUMIRA. Your doctor should do blood tests before you start treatment, while you are using HUMIRA, and for several months after you stop treatment with HUMIRA. Tell your doctor if you have any of the following symptoms of a possible hepatitis B infection: muscle aches feel very tired dark urine skin or eyes look yellow little or no appetite vomiting clay-colored bowel movements fever chills stomach discomfort skin rash Allergic reactions. Allergic reactions can happen in people who use HUMIRA. Call your doctor or get medical help right away if you have any of these symptoms of a serious allergic reaction: hives trouble breathing swelling of your face, eyes, lips or mouth Nervous system problems. Signs and symptoms of a nervous system problem include: numbness or tingling, problems with your vision, weakness in your arms or legs, and dizziness. Blood problems. Your body may not make enough of the blood cells that help fight infections or help to stop bleeding. Symptoms include a fever that does not go away, bruising or bleeding very easily, or looking very pale. New heart failure or worsening of heart failure you already have. Call your doctor right away if you get new worsening symptoms of heart failure while taking HUMIRA, including: shortness of breath sudden weight gain swelling of your ankles or feet Immune reactions including a lupus-like syndrome. Symptoms include chest discomfort or pain that does not go away, shortness of breath, joint pain, or a rash on your cheeks or arms that gets worse in the sun. Symptoms may improve when you stop HUMIRA. Liver problems. Liver problems can happen in people who use TNF-blocker medicines. These problems can lead to liver failure and death. Call your doctor right away if you have any of these symptoms: feel very tired poor appetite or vomiting skin or eyes look yellow pain on the right side of your stomach (abdomen) Psoriasis. Some people using HUMIRA had new psoriasis or worsening of psoriasis they already had. Tell your doctor if you develop red scaly patches or raised bumps that are filled with pus. Your doctor may decide to stop your treatment with HUMIRA. Call your doctor or get medical care right away if you develop any of the above symptoms. Your treatment with HUMIRA may be stopped. The most c ommon side effects of HUMIRA include: injection site reactions: redness, rash, swelling, itching, or bruising. These symptoms usually will go away within a few days. Call your doctor right away if you have pain, redness or swelling around the injection site that does not go away within a few days or gets worse. upper respiratory infections (including sinus infections). headaches. rash. These are not all the possible side effects with HUMIRA. Tell your doctor if you have any side effect that bothers you or that does not go away. Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store HUMIRA? Store HUMIRA in the refrigerator at 36 F to 46 F (2 C to 8 C). Store HUMIRA in the original carton until use to protect it from light. Do not freeze HUMIRA. Do not use HUMIRA if frozen, even if it has been thawed. Refrigerated HUMIRA may be used until the expiration date printed on the HUMIRA carton, dose tray, Pen or prefilled syringe. Do not use HUMIRA after the expiration date. If needed, for example when you are traveling, you may also store HUMIRA at room temperature up to 77 F (25 C) for up to 14 days. Store HUMIRA in the original carton until use to protect it from light. Throw away HUMIRA if it has been kept at room temperature and not been used within 14 days. Record the date you first remove HUMIRA from the refrigerator in the spaces provided on the carton and dose tray. Do not store HUMIRA in extreme heat or cold. Do not use a Pen or prefilled syringe if the liquid is cloudy, discolored, or has flakes or particles in it. Do not drop or crush HUMIRA. The prefilled syringe is glass. Keep HUMIRA, injection supplies, and all other medicines out of the reach of children. General information about the safe and effective use of HUMIRA. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use HUMIRA for a condition for which it was not prescribed. Do not give HUMIRA to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about HUMIRA. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about HUMIRA that is written for health professionals. What are the ingredients in HUMIRA? Active ingredient: adalimumab HUMIRA Pen 40 mg/0.8 mL, HUMIRA 40 mg/0.8 mL prefilled syringe, HUMIRA 20 mg/0.4 mL prefilled syringe, HUMIRA 10 mg/0.2 mL prefilled syringe, and HUMIRA 40 mg/0.8 mL institutional use vial: Inactive ingredients: citric acid monohydrate, dibasic sodium phosphate dihydrate, mannitol, monobasic sodium phosphate dihydrate, polysorbate 80, sodium chloride, sodium citrate and Water for Injection. Sodium hydroxide is added as necessary to adjust pH. HUMIRA Pen 80 mg/0.8 mL, HUMIRA 80 mg/0.8 mL prefilled syringe, HUMIRA Pen 40 mg/0.4 mL, HUMIRA 40 mg/0.4 mL prefilled syringe, HUMIRA 20 mg/0.2 mL prefilled syringe and HUMIRA 10 mg/0.1 mL prefilled syringe: Inactive ingredients: mannitol, polysorbate 80, and Water for Injection. Manufactured by: AbbVie Inc., North Chicago, IL 60064, U.S.A.For more information go to www.HUMIRA.com or you can enroll in a patient support program by calling 1-800-4HUMIRA (1-800-448-6472).US License Number 1889 This Medication Guide has been approved by the U.S. Food and Drug Administration.20066566 Revised: 02/2021

INSTRUCTIONS FOR USE HUMIRA (Hu-MARE-ah) (adalimumab) 80 mg/0.8 mL, 40 mg/0.4 mL, 20 mg/0.2 mL and 10 mg/0.1 mL Single-Dose Prefilled Syringe Before Injecting: Your healthcare provider should show you how to use HUMIRA before you use it for the first time. Call your healthcare provider or 1-800-4HUMIRA (1-800-448-6472) if you need help. Important Information You Need to Know Before Injecting HUMIRA Do not use the prefilled syringe and call your healthcare provider or pharmacist if: Liquid is cloudy, discolored, or has flakes or particles in it Expiration date has passed Liquid has been frozen (even if thawed) or left in direct sunlight The prefilled syringe has been dropped or crushed Keep the needle cover on until right before your injection. How should I store HUMIRA? Store HUMIRA in the refrigerator between 36 F to 46 F (2 C to 8 C). Store HUMIRA in the original carton until use to protect it from light. Do not freeze Refrigerated HUMIRA may be used until the expiration date printed on the HUMIRA carton, dose tray or prefilled syringe. If needed, for example when you are traveling, you may also store HUMIRA at room temperature up to 77 F (25 C) for up to 14 days. Throw away HUMIRA if it has been kept at room temperature and not used within 14 days. Record the date you first remove HUMIRA from the refrigerator in the spaces provided on the carton and dose tray. Do not store HUMIRA in extreme heat or cold. Keep HUMIRA, injection supplies, and all other medicines out of reach of children. Read Instructions on All Pages Before Using the HUMIRA Single-Dose Prefilled Syringe Take HUMIRA out of the refrigerator. Leave HUMIRA at room temperature for 15 to 30 minutes before injecting. Do not remove the needle cover while allowing HUMIRA to reach room temperature Do not warm HUMIRA in any other way. For example, do not warm it in a microwave or in hot water. Do not use the prefilled syringe if liquid has been frozen (even if thawed) Check expiration date on the prefilled syringe label. Do not use the prefilled syringe if expiration date has passed. Place the following on a clean, flat surface: 1 single-dose prefilled syringe and alcohol swab 1 cotton ball or gauze pad (not included) Puncture-resistant sharps disposal container (not included). See Step 9 at the end of this Instructions for Use for instructions on how to throw away (dispose of) your prefilled syringe Wash and dry your hands. Choose an injection site: On the front of your thighs or Your abdomen (belly) at least 2 inches from your navel (belly button) Different from your last injection site Wipe the injection site in a circular motion with the alcohol swab. Do not inject through clothes Do not inject into skin that is sore, bruised, red, hard, scarred, has stretch marks, or areas with psoriasis plaques Hold the prefilled syringe in one hand. Gently pull the needle cover straight off with the other hand. Throw the needle cover away Do not touch the needle with your fingers or let the needle touch anything Hold the prefilled syringe with the needle facing up. Hold the prefilled syringe at eye level with one hand so you can see the air in the prefilled syringe Using your other hand, slowly push the plunger in to push the air out through the needle. You may see a drop of liquid at the end of the needle. This is normal. Hold the body of the prefilled syringe in one hand between the thumb and index fingers. Hold the prefilled syringe in your hand like a pencil. Do not pull back on the plunger at any time. Gently squeeze the area of cleaned skin at your injection site with your other hand. Hold the skin firmly. Insert the needle into the skin at about a 45-degree angle using a quick, dart-like motion. After the needle is in, let go of the skin. Slowly push the plunger all the way in until all of the liquid is injected and the prefilled syringe is empty. When the injection is completed, slowly pull the needle out of the skin while keeping the prefilled syringe at the same angle. After completing the injection, place a cotton ball or gauze pad on the skin of the injection site. Do not rub Slight bleeding at the injection site is normal How should I dispose of the used HUMIRA prefilled syringe? Put your used needles, syringes, and sharps in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in the household trash. If you do not have a FDA-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, 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. When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA s website at: http://www.fda.gov/safesharpsdisposal. Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container. The needle cover, alcohol swab, cotton ball or gauze pad, dose tray, and packaging may be placed in your household trash. Questions About Using the HUMIRA Single-Dose Prefilled Syringe What if I have not received in-person training from a healthcare provider? Call your healthcare provider or 1-800-4HUMIRA (1-800-448-6472) or visit www.HUMIRA.com if you need help What if I do not have an FDA-cleared sharps disposal container or proper household container? Call 1-800-4HUMIRA (1-800-448-6472) for a free FDA-cleared sharps disposal container Always keep the prefilled syringe and the sharps disposal container out of the reach of children. Keep a record of the dates and locations of your injections. To help remember when to take HUMIRA, mark your calendar ahead of time. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised 02/2021 Manufactured by AbbVie Inc. North Chicago, IL 60064 U.S.A.US License Number 1889 20069914

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