Otulfi

Q: Who makes Otulfi?

Otulfi is listed by 1 labeler in the FDA NDC directory, including Fresenius Kabi USA, LLC.

ustekinumab-aauz · Injection, Solution · Subcutaneous, Intravenous

Prescription (Rx) Interleukin-12 Antagonist Interleukin-23 Antagonist

Uses

1 INDICATIONS AND USAGE OTULFI 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) OTULFI 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) OTULFI 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) OTULFI is indicated for the treatment of adult patients with moderately to severely active Crohn's disease. 1.4 Ulcerative Colitis OTULFI is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

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 OTULFI subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter. The recommended dose of OTULFI 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 OTULFI for Subcutaneous Injection in Pediatric Patients 6 Years 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 OTULFI 45 mg/0.5 mL single-dose vials for pediatric patients 6 years of age and older with plaque psoriasis and pediatric patients 6 years of age and older with psoriatic arthritis* weighing less than 60 kg 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 25.5 0.28 35 26.3 0.29 36 27 0.3 37 27.8 0.31 38 28.5 0.32 39 29.3 0.32 40 30 0.33 41 30.8 0.34 42 31.5 0.35 43 32.3 0.36 44 33 0.37 45 33.8 0.37 46 34.5 0.38 47 35.3 0.39 48 36 0.4 49 36.8 0.41 50 37.5 0.42 51 38.3 0.42 52 39 0.43 53 39.8 0.44 54 40.5 0.45 55 41.3 0.46 56 42 0.46 57 42.8 0.47 58 43.5 0.48 59 44.3 0.49 * Refer to 2.2 Psoriatic Arthritis; Subcutaneous Pediatric Dosage Regimen. 2.2 Recommended Dosage in Psoriatic Arthritis Subcutaneous Adult Dosage Regimen
• The recommended dosage is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
• For patients with co-existent moderate-to-severe plaque psoriasis weighing more than 100 kg, the recommended dosage is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. Subcutaneous Pediatric Dosage Regimen Administer OTULFI subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter. The recommended dose of OTULFI for pediatric patients 6 years of age and older with psoriatic arthritis, based on body weight, is shown below ( Table 3 ). Table 3: Recommended Dose of OTULFI for Subcutaneous Injection in Pediatric Patients 6 Years of Age and Older with Psoriatic Arthritis * 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 or more 45 mg greater than 100 kg with co-existent moderate-to-severe plaque psoriasis 90 mg 2.3 Recommended Dosage in Crohn's Disease and Ulcerative Colitis Intravenous Induction Adult Dosage Regimen A single intravenous infusion dose of OTULFI using the weight-based dosage regimen specified in Table 4 [see Instructions for dilution of OTULFI 130 mg vial for intravenous infusion ( 2.5 )] .

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 )

Contraindications

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

Warnings and precautions

• Infections : Serious infections have occurred. Avoid starting OTULFI during any clinically important active infection. If a serious infection or clinically significant infection develops, discontinue OTULFI until the infection resolves. ( 5.1 )
• Theoretical Risk for Particular Infections : Serious infections from mycobacteria, salmonella and Bacillus Calmette-Guerin (BCG) vaccinations have been reported in patients genetically deficient in IL- 12/IL-23. Consider diagnostic tests for these infections as dictated by clinical circumstances. ( 5.2 )
• Tuberculosis (TB) : Evaluate patients for TB prior to initiating treatment with OTULFI. Initiate treatment of latent TB before administering OTULFI. ( 5.3 )
• Malignancies : Ustekinumab products may increase risk of malignancy. The safety of ustekinumab products in patients with a history of or a known malignancy has not been evaluated. ( 5.4 )
• Serious Hypersensitivity Reactions : If a severe or other clinically significant hypersensitivity reaction occurs, discontinue OTULFI immediately and initiate appropriate medical treatment. ( 5.5 )
• Posterior Reversible Encephalopathy Syndrome (PRES) : If PRES is suspected, treat promptly and discontinue OTULFI. ( 5.6 )
• Immunizations: Avoid use of live vaccines in patients during treatment with OTULFI. ( 5.7 )
• Noninfectious Pneumonia : Cases of interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products. If diagnosis is confirmed, discontinue OTULFI and institute appropriate treatment. ( 5.8 ) 5.1 Infections Ustekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab products [see Adverse Reactions ( 6.1 , 6.3 )] . Serious infections requiring hospitalization, or otherwise clinically significant infections, reported in clinical trials included the following:
• Plaque Psoriasis : diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis and urinary tract infections.
• Psoriatic arthritis : cholecystitis.
• Crohn's disease : anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeria meningitis.
• Ulcerative colitis : gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis. Avoid initiating treatment with OTULFI in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of OTULFI in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with OTULFI and discontinue OTULFI for serious or clinically significant infections until the infection resolves or is adequately treated. 5.2 Theoretical Risk for Vulnerability to Particular Infections Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with ustekinumab products may be susceptible to these types of infections. Consider appropriate diagnostic testing (e.g., tissue culture, stool culture, as dictated by clinical circumstances). 5.3 Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis infection prior to initiating treatment with OTULFI. Avoid administering OTULFI to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering OTULFI. Consider anti-tuberculosis therapy prior to initiation of OTULFI in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Closely monitor patients receiving OTULFI for signs and symptoms of active tuberculosis during and after treatment. 5.4 Malignancies Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among subjects who received ustekinumab in clinical trials [see Adverse Reactions ( 6.1 )] . In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy [see Nonclinical Toxicology ( 13 )] . The safety of ustekinumab products has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been post-marketing reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving ustekinumab products who had pre-existing risk factors for developing non-melanoma skin cancer. Monitor all patients receiving OTULFI for the appearance of non-melanoma skin cancer. Closely follow patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment [see Adverse Reactions ( 6.1 )] . 5.5 Serious Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products in clinical trials and postmarketing. Some serious hypersensitivity reactions have occurred during the first intravenous dose of Ustekinumab products [see Adverse Reactions ( 6.1 , 6.3 )] . If a severe or clinically significant hypersensitivity reaction occurs, discontinue OTULFI immediately and initiate appropriate medical treatment [see Contraindications ( 4 )] .

Side effects

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 per patient-years of follow-up). Serious infections were reported in 2.8% of subjects (0.01 per patient-years of follow-up). Malignancies 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), 1.7% of ustekinumab-treated subjects reported malignancies excluding non-melanoma skin cancers (0.60 per hundred patient-years of follow-up). Non-melanoma skin cancer was reported in 1.5% of ustekinumab-treated subjects (0.52 per hundred patient-years of follow-up) [see Warnings and Precautions ( 5.4 )] . The most frequently observed malignancies other than non-melanoma skin cancer during the clinical trials were: prostate, melanoma, colorectal and breast. Malignancies other than non-melanoma skin cancer in ustekinumab-treated subjects during the controlled and uncontrolled portions of trials were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender and race). 1 Pediatric Subjects with Plaque Psoriasis The safety of ustekinumab was assessed in two trials of pediatric subjects with moderate to severe plaque psoriasis. Ps STUDY 3 evaluated safety for up to 60 weeks in 110 pediatric subjects 12 to 17 years old. Ps STUDY 4 evaluated safety for up to 56 weeks in 44 pediatric subjects 6 to 11 years old. The safety profile in pediatric subjects was similar to the safety profile from trials in adults with plaque psoriasis. Psoriatic Arthritis The safety of ustekinumab was assessed in 927 subjects in two randomized, double-blind, placebo- controlled trials in adults with active psoriatic arthritis (PsA). The overall safety profile of ustekinumab in subjects with PsA was consistent with the safety profile seen in clinical trials in adult subjects with plaque psoriasis.

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 OTULFI 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 substrateas 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.

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 available data on the effects of ustekinumab products on milk production. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to ustekinumab products are unknown. No adverse effects on the breastfed infant causally related to ustekinumab products have been identified in the published literature or postmarketing experience. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OTULFI and any potential adverse effects on the breastfed child from OTULFI or from the underlying maternal condition. 8.4 Pediatric Use Plaque Psoriasis The safety and effectiveness of OTULFI have been established for the treatment of moderate to severe plaque psoriasis in pediatric patients 6 years of age and older who are candidates for phototherapy or systemic therapy. Use of OTULFI in pediatric patients 12 to less than 17 years of age is supported by evidence from a multicenter, randomized, 60-week trial (Ps STUDY 3) of ustekinumab that included a 12-week, double-blind, placebo-controlled, parallel-group portion, in 110 pediatric subjects 12 years of age and older [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 )] . Use of OTULFI in pediatric patients 6 to 11 years of age is supported by evidence from an open-label, single-arm, efficacy, safety and pharmacokinetics trial (Ps STUDY 4) of ustekinumab in 44 subjects [see Adverse Reactions ( 6.1 ), Pharmacokinetics ( 12.3 )] . The safety and effectiveness of OTULFI have not been established in pediatric patients less than 6 years of age with plaque psoriasis. Psoriatic Arthritis The safety and effectiveness of OTULFI have been established for treatment of psoriatic arthritis in pediatric patients 6 years of age and older.

Pregnancy

Pediatric use

8.4 Pediatric Use Plaque Psoriasis The safety and effectiveness of OTULFI have been established for the treatment of moderate to severe plaque psoriasis in pediatric patients 6 years of age and older who are candidates for phototherapy or systemic therapy. Use of OTULFI in pediatric patients 12 to less than 17 years of age is supported by evidence from a multicenter, randomized, 60-week trial (Ps STUDY 3) of ustekinumab that included a 12-week, double-blind, placebo-controlled, parallel-group portion, in 110 pediatric subjects 12 years of age and older [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 )] . Use of OTULFI in pediatric patients 6 to 11 years of age is supported by evidence from an open-label, single-arm, efficacy, safety and pharmacokinetics trial (Ps STUDY 4) of ustekinumab in 44 subjects [see Adverse Reactions ( 6.1 ), Pharmacokinetics ( 12.3 )] . The safety and effectiveness of OTULFI have not been established in pediatric patients less than 6 years of age with plaque psoriasis. Psoriatic Arthritis The safety and effectiveness of OTULFI have been established for treatment of psoriatic arthritis in pediatric patients 6 years of age and older. Use of OTULFI in these age groups is supported by evidence from adequate and well controlled trials of ustekinumab in adult subjects with psoriasis and PsA, pharmacokinetic data from adult subjects with psoriasis, adult subjects with PsA and pediatric subjects with psoriasis, and safety data of ustekinumab from two clinical trials in 44 pediatric subjects 6 to 11 years old with psoriasis and 110 pediatric subjects 12 years of age and older with psoriasis. The observed pre-dose (trough) concentrations are generally comparable between adult subjects with psoriasis, adult subjects with PsA and pediatric subjects with psoriasis, and the PK exposure is expected to be comparable between adult and pediatric subjects with PsA [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 , 14.2 , 14.3 )]. The safety and effectiveness of OTULFI have not been established in pediatric patients less than 6 years old with psoriatic arthritis. Crohn's Disease and Ulcerative Colitis The safety and effectiveness of OTULFI have not been established in pediatric patients with Crohn's disease or ulcerative colitis.

Geriatric use

8.5 Geriatric Use Of the 6709 subjects exposed to ustekinumab, a total of 340 were 65 years of age or older (183 subjects with plaque psoriasis, 65 subjects with psoriatic arthritis, 58 subjects with Crohn’s disease and 34 subjects with ulcerative colitis), and 40 subjects were 75 years of age or older. Clinical trials of ustekinumab did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

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.

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. OTULFI (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. OTULFI 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 ½ 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). OTULFI 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).

Mechanism of action

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.

How supplied

(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 65219-824-01)
• 90 mg/mL (NDC 65219-826-26) Each prefilled syringe is equipped with a 29 gauge fixed ½ 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 65219-822-05) For Intravenous Infusion Single-dose Vial
• 130 mg/26 mL (5 mg/mL) (NDC 65219-828-05) Storage and Stability Store OTULFI vials and prefilled syringes refrigerated between 2ºC to 8ºC (36ºF to 46ºF). Store OTULFI 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 OTULFI after the expiration date on the carton or on the prefilled syringe.

Patient information

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections Inform patients that OTULFI may lower the ability of their immune system to fight infections and to contact their healthcare provider immediately if they develop any signs or symptoms of infection [see Warnings and Precautions ( 5.1 )] . Malignancies Inform patients of the risk of developing malignancies while receiving OTULFI [see Warnings and Precautions ( 5.4 )] . Serious Hypersensitivity and Reactions
• Inform patients that serious hypersensitivity reactions have been reported with intravenous and subcutaneous administration of ustekinumab products. Instruct patients to discontinue OTULFI and seek immediate medical attention if they experience any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions ( 5.5 )]. Posterior Reversible Encephalopathy Syndrome (PRES) Inform patients to immediately contact their healthcare provider if they experience signs and symptoms of PRES (which may include headache, seizures, confusion, or visual disturbances) [see Warnings and Precautions ( 5.6 )] . Immunizations Inform patients that OTULFI can interfere with the usual response to immunizations and that they should avoid live vaccines [see Warnings and Precautions ( 5.7 )] . Administration Instruct patients to follow sharps disposal recommendations, as described in the Instructions for Use. Manufactured by: Fresenius Kabi USA, LLC, Lake Zurich, IL 60047, U.S.A, US License Number 2146

Label text from the FDA structured product label by Fresenius Kabi USA, LLC (revised Feb 16, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Ustekinumab in 4 products

Otulfi NDC products (4)

NDC	Strength & form	Labeler	Type
65219-822	Ustekinumab 45 mg/.5mL Injection, Solution	Fresenius Kabi USA, LLC	BLA
65219-824	Ustekinumab 45 mg/.5mL Injection, Solution	Fresenius Kabi USA, LLC	BLA
65219-826	Ustekinumab 90 mg/mL Injection, Solution	Fresenius Kabi USA, LLC	BLA
65219-828	Ustekinumab 130 mg/26mL Solution	Fresenius Kabi USA, LLC	BLA

Frequently asked questions

What is Otulfi used for?

What are the side effects of Otulfi?

Who makes Otulfi?

Otulfi is listed by 1 labeler in the FDA NDC directory, including Fresenius Kabi USA, LLC.