ustekinumab-aauz

Warnings and Precautions Serious Hypersensitivity Reactions ( 5.5 ) 01/2026

1 INDICATIONS AND USAGE Ustekinumab-aauz is a human interleukin-12 and -23 antagonist indicated for the treatment of: Adult patients with: • moderate to severe plaque psoriasis (PsO) who are candidates for phototherapy or systemic therapy. ( 1.1 ) • active psoriatic arthritis (PsA) . ( 1.2 ) • moderately to severely active Crohn's disease (CD) . ( 1.3 ) • moderately to severely active ulcerative colitis. ( 1.4 ) Pediatric patients 6 years and older with: • moderate to severe plaque psoriasis (PsO) , who are candidates for phototherapy or systemic therapy. ( 1.1 ) • active psoriatic arthritis (PsA) . ( 1.2 ) 1.1 Plaque Psoriasis (PsO) Ustekinumab-aauz is indicated for the treatment of adults and pediatric patients 6 years of age and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. 1.2 Psoriatic Arthritis (PsA) Ustekinumab-aauz is indicated for the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis. 1.3 Crohn's Disease (CD) Ustekinumab-aauz is indicated for the treatment of adult patients with moderately to severely active Crohn's disease. 1.4 Ulcerative Colitis Ustekinumab-aauz is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

2 DOSAGE AND ADMINISTRATION Adult Patients with Plaque Psoriasis Subcutaneous Recommended Dosage ( 2.1 ): Weight Range (kilograms) Dosage less than or equal to 100 kg 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks greater than 100 kg 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks Pediatric Patients 6 Years of Age and Older with Plaque Psoriasis Subcutaneous Recommended Dosage ( 2.1 ): Weight-based dosing is recommended at the initial dose, 4 weeks later, then every 12 weeks thereafter. Weight Range (kilograms) Dose less than 60 kg 0.75 mg/kg 60 kg to 100 kg 45 mg greater than 100 kg 90 mg Psoriatic Arthritis Adult Subcutaneous Recommended Dosage ( 2.2 ): • The recommended dosage is 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks. • For patients with co-existent moderate-to-severe plaque psoriasis weighing greater than 100 kg, the recommended dosage is 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks. Psoriatic Arthritis Pediatric 6 Years of Age and Older Subcutaneous Recommended Dosage ( 2.2 ): Weight-based dosing is recommended at the initial dose, 4 weeks later, then every 12 weeks thereafter. Weight Range (kilograms) Dose less than 60 kg 0.75 mg/kg 60 kg or more 45 mg greater than 100 kg with co-existent moderate-to-severe plaque psoriasis 90 mg Crohn's Disease and Ulcerative Colitis Initial Adult Intravenous Recommended Dose ( 2.3 ): A single intravenous infusion using weight- based dosing: Weight Range (kilograms) Recommended Dose up to 55 kg 260 mg (2 vials) greater than 55 kg to 85 kg 390 mg (3 vials) greater than 85 kg 520 mg (4 vials) Crohn's Disease and Ulcerative Colitis Maintenance Adult Subcutaneous Recommended Dosage ( 2.3 ): A subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then every 8 weeks thereafter. 2.1 Recommended Dosage in Plaque Psoriasis Subcutaneous Adult Dosage Regimen • For patients weighing 100 kg or less, the recommended dosage is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. • For patients weighing more than 100 kg, the recommended dosage is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. In subjects weighing more than 100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects [see Clinical Studies ( 14 )] . Subcutaneous Pediatric Dosage Regimen Administer Ustekinumab-aauz subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter. The recommended dose of Ustekinumab- aauz for pediatric patients 6 years of age and older with plaque psoriasis based on body weight is shown below ( Table 1 ). Table 1: Recommended Dose of Ustekinumab-aauz for Subcutaneous Injection in Pediatric Patients 6Years of Age and Older with Plaque Psoriasis For pediatric patients weighing less than 60 kg, the administration volume for the recommended dose (0.75 mg/kg) is shown in Table 2 ; withdraw the appropriate volume from the single-dose vial. Body Weight of Patient at the Time of Dosing Recommended Dose less than 60 kg 0.75 mg/kg 60 kg to 100 kg 45 mg more than 100 kg 90 mg Table 2: Injection volumes of Ustekinumab-aauz 45 mg/0.5 mL single-dose vials for pediatric patients 6years of age and older with plaque psoriasis and pediatric patients 6years of age and older with psoriatic arthritis* weighing less than 60 kg * Refer to 2.2 Psoriatic Arthritis; Subcutaneous Pediatric Dosage Regimen. Body Weight (kg) at the time of dosing Dose (mg) Volume of injection (mL) 15 11.3 0.12 16 12.0 0.13 17 12.8 0.14 18 13.5 0.15 19 14.3 0.16 20 15.0 0.17 21 15.8 0.17 22 16.5 0.18 23 17.3 0.19 24 18.0 0.20 25 18.8 0.21 26 19.5 0.22 27 20.3 0.22 28 21.0 0.23 29 21.8 0.24 30 22.5 0.25 31 23.3 0.26 32 24 0.27 33 24.8 0.27 34 2 …

3 DOSAGE FORMS AND STRENGTHS Ustekinumab-aauz is a clear to slightly opalescent and colorless to slightly brown-yellow solution. Subcutaneous Injection • Injection: 45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe • Injection: 45 mg/0.5 mL solution in a single-dose vial Intravenous Infusion • Injection: 130 mg/26 mL (5 mg/mL) solution in a single-dose vial Subcutaneous Injection ( 3 ) • Injection: 45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe • Injection: 45 mg/0.5 mL solution in a single-dose vial Intravenous Infusion ( 3 ) • Injection: 130 mg/26 mL (5 mg/mL) solution in a single-dose vial ( 3 )

4 CONTRAINDICATIONS Ustekinumab-aauz is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in Ustekinumab-aauz [see Warnings and Precautions ( 5.5 )]. Clinically significant hypersensitivity to ustekinumab products or to any of the excipients in Ustekinumab-aauz. ( 4 )

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the label: • Infections [see Warnings and Precautions ( 5.1 )] • Malignancies [see Warnings and Precautions ( 5.4 )] • Serious Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] • Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions ( 5.6 )] • Noninfectious Pneumonia [see Warnings and Precautions ( 5.8 )] Most common adverse reactions are: • Psoriasis and Psoriatic Arthritis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue. ( 6.1 ) • Crohn's Disease, induction (≥3%): vomiting. ( 6.1 ) • Crohn's Disease, maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. ( 6.1 ) • Ulcerative colitis, induction (≥3%): nasopharyngitis ( 6.1 ) • Ulcerative colitis, maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, 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. Adult Subjects with Plaque Psoriasis The safety data reflect exposure to ustekinumab in 3117 adult subjects with plaque psoriasis, including 2414 exposed for at least 6 months, 1855 exposed for at least one year, 1653 exposed for at least two years, 1569 exposed for at least three years, 1482 exposed for at least four years and 838 exposed for at least five years. Table 5 summarizes the adverse reactions that occurred at a rate of at least 1% with higher rates in the ustekinumab groups during the placebo-controlled period of Ps STUDY 1 and Ps STUDY 2 [see Clinical Studies ( 14 )] . Table 5: Adverse Reactions Reported by ≥1% of Subjects with Plaque Psoriasis and at Higher Rates in the ustekinumab groups through Week 12 in Ps STUDY 1 and Ps STUDY 2 ustekinumab Placebo 45 mg 90 mg Subjects treated 665 664 666 Nasopharyngitis 51 (8%) 56 (8%) 49 (7%) Upper respiratory tract infection 30 (5%) 36 (5%) 28 (4%) Headache 23 (3%) 33 (5%) 32 (5%) Fatigue 14 (2%) 18 (3%) 17 (3%) Back pain 8 (1%) 9 (1%) 14 (2%) Dizziness 8 (1%) 8 (1%) 14 (2%) Pharyngolaryngeal pain 7 (1%) 9 (1%) 12 (2%) Pruritus 9 (1%) 10 (2%) 9 (1%) Injection site erythema 3 (<1%) 6 (1%) 13 (2%) Myalgia 4 (1%) 7 (1%) 8 (1%) Depression 3 (<1%) 8 (1%) 4 (1%) Adverse reactions that occurred at rates less than 1% in the controlled period of Ps STUDIES 1 and 2 through week 12 included: cellulitis, herpes zoster, diverticulitis and certain injection site reactions (pain, swelling, pruritus, induration, hemorrhage, bruising, and irritation). One case of PRES occurred during clinical trials in adult subjects with plaque psoriasis [see Warnings and Precautions ( 5.6 )] . Infections In the placebo-controlled period of clinical trials of subjects with plaque psoriasis (average follow-up of 12.6 weeks for subjects receiving placebo and 13.4 weeks for ustekinumab-treated subjects), 27% of ustekinumab-treated subjects reported infections (1.39 per patient-years of follow-up) compared with 24% of subjects receiving placebo (1.21 per patient-years of follow-up). Serious infections occurred in 0.3% of ustekinumab-treated subjects (0.01 per patient-years of follow-up) and in 0.4% of subjects receiving placebo (0.02 per patient-years of follow-up) [see Warnings and Precautions ( 5.1 )] . In the controlled and non-controlled portions of clinical trials in subjects with plaque psoriasis (median follow-up of 3.2 years), representing 8998 patient-years of exposure, 72.3% of ustekinumab-treated subjects reported infections (0.87 …

7 DRUG INTERACTIONS 7.1 Concomitant Therapies In trials in subjects with plaque psoriasis, the safety of ustekinumab products in combination with immunosuppressive agents or phototherapy has not been evaluated. In trials in subjects with psoriatic arthritis, concomitant MTX use did not appear to influence the safety or efficacy of ustekinumab. In trials in subjects with Crohn’s disease (CD-1 and CD-2) and ulcerative colitis (UC-1) , immunomodulators (6-MP, AZA, MTX) were used concomitantly in approximately 30% of subjects and corticosteroids were used concomitantly in approximately 40% and 50% of Crohn’s disease and ulcerative colitis subjects, respectively. Use of these concomitant therapies did not appear to influence the overall safety or efficacy of ustekinumab. 7.2 CYP450 Substrates The formation of CYP450 enzymes can be suppressed by increased levels of certain cytokines (e.g., IL-1, IL-6, TNFα, IFN) during chronic inflammation. Thus, use of ustekinumab products, antagonists of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of Ustekinumab-aauz in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and adjust the individual dosage of the CYP substrate as needed. See the prescribing information of specific CYP substrates. A CYP-mediated drug interaction effect was not observed in subjects with Crohn’s disease [see Clinical Pharmacology ( 12.3 )] . 7.3 Allergen Immunotherapy Ustekinumab products have not been evaluated in patients who have undergone allergy immunotherapy. Ustekinumab products may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry, published literature and pharmacovigilance in pregnant women have not identified a ustekinumab associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes ( see Data ). There are risks to the mother and the fetus associated with inflammatory bowel disease (IBD) in pregnancy . In animal reproductive and developmental toxicity studies, no adverse developmental effects were observed in offspring after administration of ustekinumab to pregnant monkeys at exposures greater than 100 times the maximum recommended human dose (MRHD). 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 of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with 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 Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Therefore, Ustekinumab products may be present in infants exposed in utero. The potential clinical impact of ustekinumab product exposure in infants exposed in utero should be considered. Data Human Data An observational pregnancy registry conducted by (OTIS)/MotherToBaby in the U.S. and Canada (enrollment between 2013 and 2019) assessed the risk of major birth defects, pattern of major and minor anomalies in live-born infants, miscarriage, and adverse infant outcomes in women with ustekinumab exposure. In the registry study, there were 101 participants and 107 pregnancies with exposure to ustekinumab (88 prospective; 19 retrospective). Most participants had a primary indication of CD (65.4%) or psoriasis (30.8%). The pregnancy registry did not identify a ustekinumab associated risk of major birth defects, pattern of major or minor anomalies, increased risk of miscarriage or adverse infant outcomes. Methodological limitations of the registry include small sample size, lack of an internal comparison group, a mix of prospective and retrospective reports, and unmeasured confounders. The conclusions from the pregnancy registry were consistent with the published literature and pharmacovigilance. Animal Data Ustekinumab was tested in two embryo-fetal development toxicity studies in cynomolgus monkeys. No teratogenic or other adverse developmental effects were observed in fetuses from pregnant monkeys that were administered ustekinumab subcutaneously twice weekly or intravenously weekly during the period of organogenesis. Serum concentrations of ustekinumab in pregnant monkeys were greater than 100 times the serum concentration in patients treated subcutaneously with 90 mg of ustekinumab weekly for 4 weeks. In a combined embryo-fetal development and pre- and post-natal development toxicity study, pregnant cynomolgus monkeys were administered subcutaneous doses of ustekinumab twice weekly at exposures greater than 100 times the MRHD from the beginning of organogenesis to Day 33 after delivery. Neonatal deaths occurred in the offspring of one monkey administered ustekinumab at 22.5 mg/kg and one monkey dosed at 45 mg/kg. No ustekinumab-related effects on functional, morphological, or immunological development were observed in the neonates from birth through six months of age. 8.2 Lactation Risk Summary Limited data from published literature suggests that ustekinumab is present in human breast milk. There are no avail …

12.1 Mechanism of Action Ustekinumab products are human IgG1қ monoclonal antibodies that bind with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. In in vitro models, ustekinumab products were shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12Rβ1. The cytokines IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn's disease and ulcerative colitis. In animal models of colitis, genetic absence or antibody blockade of the p40 subunit of IL-12 and IL-23, the target of ustekinumab products was shown to be protective.

11 DESCRIPTION Ustekinumab-aauz, a human IgG1κ monoclonal antibody, is a human interleukin-12 and -23 antagonist. Using DNA recombinant technology, ustekinumab-aauz is produced in a Chinese hamster ovary (CHO) cell line. The manufacturing process contains steps for the clearance of viruses. Ustekinumab-aauz is comprised of 1326 amino acids and has an estimated molecular mass that ranges from 148,079 to 149,690 Daltons. Ustekinumab-aauz injection is a sterile, preservative-free, clear to slightly opalescent, and colorless to slightly brown-yellow solution with pH of 5.7- 6.3. Ustekinumab-aauz for Subcutaneous Use Available as 45 mg of ustekinumab-aauz in 0.5 mL and 90 mg of ustekinumab-aauz in 1 mL, supplied as a sterile solution in a single-dose prefilled syringe with a 29 gauge fixed 1⁄2 inch needle and as 45 mg of ustekinumab in 0.5 mL in a single-dose 3 mL Type I glass with a coated stopper. The syringe is fitted with a passive needle guard and a needle cover that is not made with natural rubber (latex). Each 0.5 mL prefilled syringe or vial delivers 45 mg ustekinumab-aauz, histidine (0.512 mg), Polysorbate 80 (0.02 mg), sucrose (38 mg) and hydrochloric acid (to adjust pH). Each 1 mL prefilled syringe delivers 90 mg ustekinumab-aauz, histidine (1.024 mg), Polysorbate 80 (0.04 mg), sucrose (76 mg) and hydrochloric acid (to adjust pH). Ustekinumab-aauz for Intravenous Infusion Available as 130 mg of ustekinumab-aauz in 26 mL, supplied as a single-dose 30 mL Type I glass vial with a coated stopper. Each 26 mL vial delivers 130 mg ustekinumab-aauz, edetate disodium (0.47 mg), histidine (20 mg), L-histidine hydrochloride monohydrate (27 mg), methionine (10.4 mg), Polysorbate 80 (10.4 mg) and sucrose (2210 mg).

10 OVERDOSAGE Single doses up to 6 mg/kg intravenously have been administered in clinical trials without dose-limiting toxicity. In case of overdosage, monitor the patient for any signs or symptoms of adverse reactions or effects and institute appropriate symptomatic treatment immediately. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

16 HOW SUPPLIED/STORAGE AND HANDLING Ustekinumab-aauz injection is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly brown-yellow solution. It is supplied as individually packaged, single-dose prefilled syringes or single-dose vials. For Subcutaneous Use Prefilled Syringes • 45 mg/0.5 mL (NDC 65219-862-01) • 90 mg/mL (NDC 65219-866-26) Each prefilled syringe is equipped with a 29 gauge fixed 1⁄2 inch needle, a needle safety guard, and a needle cover that is not made with natural rubber Single-dose Vial • 45 mg/0.5 mL (NDC 65219-864-05) For Intravenous Infusion Single-dose Vial • 130 mg/26 mL (5 mg/mL) (NDC 65219-868-05) Storage and Stability Store Ustekinumab-aauz vials and prefilled syringes refrigerated between 2oC to 8oC (36oF to 46oF). Store Ustekinumab-aauz vials upright. Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake. If needed, individual prefilled syringes may be stored at room temperature up to 30°C (86°F) for a maximum single period of up to 30 days in the original carton to protect from light. Record the date when the prefilled syringe is first removed from the refrigerator on the carton in the space provided. Once a syringe has been stored at room temperature, do not return to the refrigerator. Discard the syringe if not used within 30 days at room temperature storage. Do not use Ustekinumab-aauz after the expiration date on the carton or on the prefilled syringe.