These Highlights Do Not Include All The Information Needed To Use Stelara Safely And Effectively. See Full Prescribing Information For Stelara.

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)] .

Storage

If necessary, the diluted infusion solution may be kept at room temperature up to 25 °C (77 °F) for up to 7 hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 8 hours after the dilution in the infusion bag (cumulative time after preparation including the storage and the infusion period). Do not freeze. Discard any unused portion of the infusion solution.

INSTRUCTIONS FOR USE

STELARA ( stel ar a )

(ustekinumab)

injection, for subcutaneous use

This Instructions for Use contains information on how to inject STELARA using a prefilled syringe.

Read this Instructions for Use before you start using STELARA. A healthcare provider should show you how to prepare and give an injection of STELARA the right way.

If you cannot give the injection:

• ask your healthcare provider to help you, or
• ask someone who has been trained by a healthcare provider to give your injections.

Do not try to inject STELARA until you have been shown how to inject STELARA by a healthcare provider.

Important information You Need to Know Before Injecting STELARA:

• For subcutaneous use only(inject directly under the skin).
• Before you start, check the carton to make sure that it is the right dose. You will have either 45 mg or 90 mg as prescribed by the healthcare provider.
  • If the dose is 45 mg, you will receive one 45 mg prefilled syringe.
  • If the dose is 90 mg, you will receive either one 90 mg prefilled syringe or two 45 mg prefilled syringes. If you receive two 45 mg prefilled syringes for a 90 mg dose, you will need to give two injections, one right after the other.
• Check the expiration date on the prefilled syringe and carton. If the expiration date has passed or if the prefilled syringe has been kept at room temperature up to 86°F (30°C) for longer than a maximum single period of 30 days or if the prefilled syringe has been stored above 86°F (30°C), do not use it. If the expiration date has passed or if the prefilled syringe has been stored above 86°F (30°C) or at room temperature for longer than 30 days, call the healthcare provider or pharmacist, or call 1-800-526-7736 for help.
• Make sure the syringe is not damaged.
• The needle cover on the prefilled syringe contains latex. Do not handle the needle cover on the STELARA prefilled syringe if you are allergic to latex.
• Check the prefilled syringe for any particles or discoloration. The liquid in the prefilled syringe should look clear and colorless to light yellow with a few small clear or white particles.
• Do not use if it is frozen, discolored, cloudy or has large particles. Get a new prefilled syringe.
• Do not shake the prefilled syringe at any time. Shaking the prefilled syringe may damage the STELARA medicine. If the prefilled syringe has been shaken, do not use it. Get a new prefilled syringe.
• To reduce the risk of accidental needle sticks, each prefilled syringe has a needle guard that is automatically activated to cover the needle after you have given the injection. Do not pull back on the plunger at any time.

Storing STELARA prefilled syringes

• Store STELARA prefilled syringes in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Store STELARA prefilled syringes in the original carton to protect from light.
• Do not freeze STELARA prefilled syringes.
• If needed, STELARA prefilled syringe may be stored at room temperature up to 86°F (30°C) 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 removed from the refrigerator on the carton in the space provided.
• After a prefilled syringe has been stored at room temperature, do not return it to the refrigerator.
• Throw away (discard) the prefilled syringe if it is not used within 30 days at room temperature storage.

Keep STELARA and all medicines out of the reach of children.

Gather the supplies you will need to prepare and to give the injection. (See Figure A)

You will need:

• antiseptic wipes
• cotton balls or gauze pads
• adhesive bandage
• your prescribed dose of STELARA (See Figure B)
• FDA-cleared sharps disposal container. See " Step 4: Disposing of the syringes"

Figure A

Figure B

To prevent early activation of the needle safety guard, do not touch the NEEDLE GUARD ACTIVATION CLIPS at any time during use.

Step 1: Preparing the injection

• Choose a well-lit, clean, flat work surface.
• Wash your hands well with soap and warm water.
• Hold the prefilled syringe with the covered needle pointing upward.

Step 2: Preparing the injection site

• Choose an injection site around the stomach area (abdomen), buttocks, upper legs (thighs). If a caregiver is giving the injection, the outer area of the upper arms may also be used. (See Figure C)
• Use a different injection site for each injection. Do not give an injection in an area of the skin that is tender, bruised, red or hard.
• Clean the skin with an antiseptic wipe where you plan to give the injection.
• Do not touch this area again before giving the injection. Let the skin dry before injecting.
• Do not fan or blow on the clean area.

Figure C

*Areas in gray are recommended injection sites.

Step 3: Injecting STELARA

• Remove the needle cover when you are ready to inject STELARA.
• Do not touch the plunger or plunger head while removing the needle cover.
• Hold the body of the prefilled syringe with one hand and pull the needle cover straight off. (see Figure D)
• Put the needle cover in the trash.
• You may also see a drop of liquid at the end of the needle. This is normal.
• Do not touch the needle or let it touch anything.
• Do not use the prefilled syringe if it is dropped without the needle cover in place.

Figure D

• Hold the body of the prefilled syringe in one hand between the thumb and index fingers. (See Figure E)

Figure E

• Do not pull back on the plunger at any time.
• Use the other hand to gently pinch the cleaned area of skin. Hold firmly.
• Use a quick, dart-like motion to insert the needle into the pinched skin at about a 45-degree angle. (See Figure F)

Figure F

• Inject all of the liquid by using your thumb to push in the plunger until the plunger head is completely between the needle guard wings. (See Figure G)

Figure G

• When the plunger is pushed as far as it will go, keep pressure on the plunger head. Take the needle out of the skin and then let go of the skin.
• Slowly take your thumb off the plunger head. This will let the empty syringe move up until the entire needle is covered by the needle guard. (See Figure H)

Figure H

• When the needle is pulled out of the skin, there may be a little bleeding at the injection site. This is normal. You can press a cotton ball or gauze pad to the injection site if needed. Do not rub the injection site. You may cover the injection site with a small adhesive bandage, if necessary.

If the dose is 90 mg, you will receive either one 90 mg prefilled syringe or two 45 mg prefilled syringes. If you receive two 45 mg prefilled syringes for a 90 mg dose, you will need to give a second injection right after the first. Repeat Steps 1 to 3 for the second injection using a new syringe. Choose a different site for the second injection.

Step 4: Disposing of the syringes.

• Put the syringe in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) syringes in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of 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 local or state laws about how to throw away syringes and needles. 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 sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your sharps disposal container.
• If you have any questions, talk to your healthcare provider or pharmacist.

Prefilled Syringe Manufactured by:

Janssen Biotech, Inc., Horsham, PA 19044, USA License No. 1864 at Baxter Pharmaceutical Solutions, Bloomington, IN 47403 and at Cilag AG, Schaffhausen, Switzerland

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 06/2025

© Johnson & Johnson and its affiliates 2025

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.

• ¹
  Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 6.6.2 Regs Research Data, Nov 2009 Sub (1973–2007) - Linked To County Attributes - Total U.S., 1969–2007 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2010, based on the November 2009 submission.

Ustekinumab, a human IgG1κ monoclonal antibody, is a human interleukin-12 and -23 antagonist. Using DNA recombinant technology, ustekinumab is produced in a murine cell line (Sp2/0). The manufacturing process contains steps for the clearance of viruses. Ustekinumab is comprised of 1326 amino acids and has an estimated molecular mass that ranges from 148,079 to 149,690 Daltons.

STELARA ^®(ustekinumab) injection is a sterile, preservative-free, colorless to light yellow solution and may contain a few small translucent or white particles with pH of 5.7– 6.3.

STELARA may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving STELARA [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 STELARA 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 STELARA 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 STELARA and discontinue STELARA for serious or clinically significant infections until the infection resolves or is adequately treated.

STELARA is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among subjects who received STELARA 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 STELARA 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 STELARA who had pre-existing risk factors for developing non-melanoma skin cancer. Monitor all patients receiving STELARA 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)] .

Prior to initiating therapy with STELARA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with STELARA should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment with STELARA or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving STELARA because of the potential risk for shedding from the household contact and transmission to patient.

Non-live vaccinations received during a course of STELARA may not elicit an immune response sufficient to prevent disease.

Of the 6709 subjects exposed to STELARA, 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 STELARA did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in studies of other ustekinumab products.

Approximately 6 to 12.4% of subjects treated with STELARA in clinical trials in subjects with plaque psoriasis and psoriatic arthritis developed antibodies to ustekinumab, which were generally low-titer. In clinical trials in subjects with plaque psoriasis, antibodies to ustekinumab were associated with reduced or undetectable serum ustekinumab concentrations and reduced efficacy. In trials in subjects with plaque psoriasis, the majority of subjects who were positive for antibodies to ustekinumab had neutralizing antibodies.

In clinical trials in subjects with Crohn’s disease and ulcerative colitis, 2.9% and 4.6% of subjects, respectively, developed antibodies to ustekinumab when treated with STELARA for approximately one year. No apparent association between the development of antibodies to ustekinumab and the development of injection site reactions was seen.

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

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)]

STELARA was evaluated in three randomized, double-blind, placebo-controlled clinical trials in adult subjects with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week intravenous induction trials(CD-1 and CD-2) followed by a 44-week subcutaneous randomized withdrawal maintenance trial (CD-3) representing 52 weeks of therapy. Subjects in CD-1 had failed or were intolerant to treatment with one or more TNF blockers, while subjects in CD-2 had failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a TNF blocker.

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 STELARA, an antagonist of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of STELARA 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)] .

STELARA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

STELARA 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)

STELARA was evaluated in two randomized, double-blind, placebo-controlled clinical trials [UC-1 and UC-2 (NCT02407236)] in adult subjects with moderately to severely active ulcerative colitis who had an inadequate response to or failed to tolerate a biologic (i.e., TNF blocker and/or vedolizumab), corticosteroids, and/or 6-MP or AZA therapy. The 8-week intravenous induction trial (UC-1) was followed by the 44-week subcutaneous randomized withdrawal maintenance trial (UC-2) for a total of 52 weeks of therapy.

Disease assessment was based on the Mayo score, which ranged from 0 to 12 and has four subscores that were each scored from 0 (normal) to 3 (most severe): stool frequency, rectal bleeding, findings on centrally-reviewed endoscopy, and physician global assessment. Moderately to severely active ulcerative colitis was defined at baseline (Week 0) as Mayo score of 6 to 12, including a Mayo endoscopy subscore ≥2. An endoscopy score of 2 was defined by marked erythema, absent vascular pattern, friability, erosions; and a score of 3 was defined by spontaneous bleeding, ulceration. At baseline, subjects had a median Mayo score of 9, with 84% of subjects having moderate disease (Mayo score 6–10) and 15% having severe disease (Mayo score 11–12).

Subjects in these trials may have received other concomitant therapies including aminosalicylates, immunomodulatory agents (AZA, 6-MP, or MTX), and oral corticosteroids (prednisone).

STELARA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.

Ustekinumab is a human IgG1қ monoclonal antibody that binds 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 vitromodels, ustekinumab was 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, was shown to be protective.

The safety and efficacy of STELARA was assessed in 927 subjects (PsA STUDY 1, n=615; PsA STUDY 2, n=312), in two randomized, double-blind, placebo-controlled trials in adult subjects 18 years of age and older with active PsA (≥5 swollen joints and ≥5 tender joints) despite nonsteroidal anti-inflammatory (NSAID) or disease modifying antirheumatic (DMARD) therapy. Subjects in these trials had a diagnosis of PsA for at least 6 months. Subjects with each subtype of PsA were enrolled, including polyarticular arthritis with the absence of rheumatoid nodules (39%), spondylitis with peripheral arthritis (28%), asymmetric peripheral arthritis (21%), distal interphalangeal involvement (12%) and arthritis mutilans (0.5%). Over 70% and 40% of the patients, respectively, had enthesitis and dactylitis at baseline.

Subjects were randomized to receive treatment with STELARA 45 mg, 90 mg, or placebo subcutaneously at Weeks 0 and 4 followed by every 12 weeks (q12w) dosing. Approximately 50% of subjects continued on stable doses of MTX (≤25 mg/week). The primary endpoint was the percentage of subjects achieving ACR 20 response at Week 24.

In PsA STUDY 1 and PsA STUDY 2, 80% and 86% of the subjects, respectively, had been previously treated with DMARDs. In PsA STUDY 1, previous treatment with anti-tumor necrosis factor (TNF)-α agent was not allowed. In PsA STUDY 2, 58% (n=180) of the subjects had been previously treated with TNF blocker, of whom over 70% had discontinued their TNF blocker treatment for lack of efficacy or intolerance at any time.

In trials in subjects with plaque psoriasis the safety of STELARA 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 STELARA. 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 STELARA.

STELARA 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.

• Infections: Serious infections have occurred. Avoid starting STELARA during any clinically important active infection. If a serious infection or clinically significant infection develops, discontinue STELARA 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 STELARA. Initiate treatment of latent TB before administering STELARA. ( 5.3)
• Malignancies: STELARA may increase risk of malignancy. The safety of STELARA 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 STELARA immediately and initiate appropriate medical treatment. (5.5)
• Posterior Reversible Encephalopathy Syndrome (PRES): If PRES is suspected, treat promptly, and discontinue STELARA. ( 5.6)
• Immunizations:Avoid use of live vaccines in patients during treatment with STELARA . ( 5.7)
• Noninfectious Pneumonia: Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of STELARA. If diagnosis is confirmed, discontinue STELARA and institute appropriate treatment. ( 5.8)

STELARA has not been evaluated in patients who have undergone allergy immunotherapy. STELARA 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.

Adult Patients with Plaque Psoriasis Subcutaneous Recommended Dosage ( 2.1) :

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.

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.

Crohn's Disease and Ulcerative Colitis Initial Adult Intravenous Recommended Dose ( 2.3) :

A single intravenous infusion using weight-based dosing:

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.

Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of STELARA. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and in certain cases administration of corticosteroids. If diagnosis is confirmed, discontinue STELARA and institute appropriate treatment [see Postmarketing Experience (6.3)] .

STELARA (ustekinumab) is a colorless to light yellow solution and may contain a few small translucent or white particles.

The following adverse reactions have been reported during post-approval use of STELARA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to STELARA exposure.

Immune system disorders: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, dyspnea, rash, urticaria), including a fatal case that presented with chest tightness and dyspnea during infusion of the first dose.

Infections and infestations:Lower respiratory tract infection (including opportunistic fungal infections and tuberculosis).

Neurological disorders:Posterior Reversible Encephalopathy Syndrome (PRES) .

Respiratory, thoracic, and mediastinal disorders:Interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia.

Skin reactions: Pustular psoriasis, erythrodermic psoriasis, hypersensitivity vasculitis.

STELARA is indicated for the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.

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.

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

STELARA ^®(ustekinumab) injection is a sterile, preservative-free, colorless to light yellow solution and may contain a few small translucent or white particles. It is supplied as individually packaged, single-dose prefilled syringes or single-dose vials.

Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA in clinical trials and postmarketing. Some serious hypersensitivity reactions have occurred during the first intravenous dose of STELARA [see Adverse Reactions (6.1, 6.3)].

If a severe or clinically significant hypersensitivity reaction occurs, discontinue STELARA immediately and initiate appropriate medical treatment [see Contraindications (4)].

Two multicenter, randomized, double-blind, placebo-controlled trials (Ps STUDY 1 and Ps STUDY 2) enrolled a total of 1996 subjects 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded from the trials.

Ps STUDY 1 enrolled 766 subjects and Ps STUDY 2 enrolled 1230 subjects. The trials had the same design through Week 28. In both trials, subjects were randomized in equal proportion to placebo, 45 mg or 90 mg of STELARA. Subjects randomized to STELARA received 45 mg or 90 mg doses, regardless of weight, at Weeks 0, 4, and 16. Subjects randomized to receive placebo at Weeks 0 and 4 crossed over to receive STELARA (either 45 mg or 90 mg) at Weeks 12 and 16.

In both trials, subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline PGA score was marked or severe in 44% of subjects in Ps STUDY 1 and 40% of subjects in Ps STUDY 2. Approximately two-thirds of all subjects had received prior phototherapy, 69% had received either prior conventional systemic or biologic therapy for the treatment of psoriasis, with 56% receiving prior conventional systemic therapy and 43% receiving prior biologic therapy. A total of 28% of subjects had a history of psoriatic arthritis.

In both trials, the endpoints were the proportion of subjects who achieved at least a 75% reduction in PASI score (PASI 75) from baseline to Week 12 and treatment success (cleared or minimal) on the Physician's Global Assessment (PGA). The PGA is a 6-category scale ranging from 0 (cleared) to 5 (severe) that indicates the physician's overall assessment of psoriasis focusing on plaque thickness/induration, erythema, and scaling.

In a 26-week toxicology study, one out of 10 monkeys subcutaneously administered 45 mg/kg ustekinumab twice weekly for 26 weeks had a bacterial infection.

A multicenter, randomized, double blind, placebo-controlled trial (Ps STUDY 3) enrolled 110 pediatric subjects 12 years of age and older with a minimum BSA involvement of 10%, a PASI score greater than or equal to 12, and a PGA score greater than or equal to 3, who were candidates for phototherapy or systemic therapy and whose disease was inadequately controlled by topical therapy.

Subjects were randomized to receive placebo (n = 37), the recommended dose of STELARA (n = 36), or one-half the recommended dose of STELARA (n = 37) by subcutaneous injection at Weeks 0 and 4 followed by dosing every 12 weeks (q12w). The recommended dose of STELARA was 0.75 mg/kg for subjects weighing less than 60 kg, 45 mg for subjects weighing 60 kg to 100 kg, and 90 mg for subjects weighing greater than 100 kg. At Week 12, subjects who received placebo were crossed over to receive STELARA at the recommended dose or one-half the recommended dose.

Of the pediatric subjects, approximately 63% had prior exposure to phototherapy or conventional systemic therapy and approximately 11% had prior exposure to biologics.

The endpoints were the proportion of subjects who achieved a PGA score of cleared (0) or minimal (1), PASI 75, and PASI 90 at Week 12. Subjects were followed for up to 60 weeks following first administration of trial agent.

• STELARA is intended for use under the guidance and supervision of a healthcare provider . STELARA should only be administered to patients who will be closely monitored and have regular follow-up visits with a healthcare provider. The appropriate dose should be determined by a healthcare provider using the patient's current weight at the time of dosing. In pediatric patients, it is recommended that STELARA be administered by a healthcare provider. If a healthcare provider determines that it is appropriate, a patient may self-inject or a caregiver may inject STELARA after proper training in subcutaneous injection technique. Instruct patients to follow the directions provided in the Instructions for Use [see Instructions for Use].
• The needle cover on the prefilled syringe contains dry natural rubber (a derivative of latex). The needle cover should not be handled by persons sensitive to latex.
• It is recommended that each injection be administered at a different anatomic location (such as upper arms, gluteal regions, thighs, or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, or indurated. When using the vial, a 1 mL syringe with a 27 gauge, ½ inch needle is recommended.
• Prior to administration, visually inspect STELARA for particulate matter and discoloration. STELARA is a colorless to light yellow solution and may contain a few small translucent or white particles. Do not use STELARA if it is discolored or cloudy, or if other particulate matter is present. STELARA does not contain preservatives; therefore, discard any unused product remaining in the vial and/or syringe.

Evaluate patients for tuberculosis infection prior to initiating treatment with STELARA.

Avoid administering STELARA to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering STELARA. Consider anti-tuberculosis therapy prior to initiation of STELARA 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 STELARA for signs and symptoms of active tuberculosis during and after treatment.

Stelara ^®

(ustekinumab)

Injection

90 mg/mL

For subcutaneous use

Contains one 90 mg/mL syringe

NDC 57894-061-03

Single-dose prefilled syringe - Discard unused portion

The 90 mg prefilled syringe contains:

90 mg ustekinumab, 1 mg L-histidine and L-histidine

monohydrochloride monohydrate, 0.04 mg polysorbate 80,

and 76 mg sucrose to fill a final volume of 1 mL

See package insert for dosing information

Rx only

ATTENTION: Dispense the enclosed Medication

Guide to each patient.

© 2009 Janssen

NDC 57894-054-27

Single-Dose vial

Discard unused portion

Stelara ^®

(ustekinumab)

Injection

130 mg/26 mL

(5 mg/mL)

For Intravenous Infusion Only

Must be diluted

ATTENTION: Dispense

the enclosed Medication

Guide to each patient.

Rx only

janssen

NDC 57894-060-02

Single-dose vial.

Discard unused portion.

Stelara^®

(ustekinumab)

Injection

45 mg/0.5 mL

For Subcutaneous Use

Attention: Dispense the enclosed

Medication Guide to each patient.

Rx only

Each vial contains 0.5 mL

Johnson

& Johnson

Stelara ^®

(ustekinumab)

Injection

45 mg/0.5 mL

For subcutaneous use

Contains one 45 mg/0.5 mL syringe

NDC 57894-060-03

Single-dose prefilled syringe - Discard unused portion

The 45 mg prefilled syringe contains:

45 mg ustekinumab, 0.5 mg L-histidine and L-histidine

monohydrochloride monohydrate, 0.02 mg polysorbate 80,

and 38 mg sucrose to fill a final volume of 0.5 mL

See package insert for dosing information

Rx only

ATTENTION: Dispense the enclosed Medication Guide

to each patient.

© 2009 Janssen

Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis, and Crohn's disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab.

Monitor all patients treated with STELARA for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue STELARA.

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of STELARA. Published literature showed that administration of murine IL-12 caused an anti-tumor effect in mice that contained transplanted tumors and IL-12/IL-23p40 knockout mice or mice treated with anti-IL-12/IL-23p40 antibody had decreased host defense to tumors. Mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone developed UV-induced skin cancers earlier and more frequently compared to wild-type mice. The relevance of these experimental findings in mouse models for malignancy risk in humans is unknown.

No effects on fertility were observed in male cynomolgus monkeys that were administered ustekinumab at subcutaneous doses up to 45 mg/kg twice weekly (45 times the MRHD on a mg/kg basis) prior to and during the mating period. However, fertility and pregnancy outcomes were not evaluated in mated females.

No effects on fertility were observed in female mice that were administered an analogous IL-12/IL-23p40 antibody by subcutaneous administration at doses up to 50 mg/kg, twice weekly, prior to and during early pregnancy.

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 STELARA may be susceptible to these types of infections. Consider appropriate diagnostic testing, (e.g., tissue culture, stool culture, as dictated by clinical circumstances).

STELARA solution for intravenous infusion must be diluted, prepared, and infused by a healthcare professional using aseptic technique.

• Calculate the dose and the number of STELARA vials needed based on patient weight (Table 4). Each 26 mL vial of STELARA contains 130 mg of ustekinumab.
• Withdraw, and then discard a volume of the 0.9% Sodium Chloride Injection, USP from the 250 mL infusion bag equal to the volume of STELARA to be added (discard 26 mL sodium chloride for each vial of STELARA needed, for 2 vials- discard 52 mL, for 3 vials- discard 78 mL, 4 vials- discard 104 mL). Alternatively, a 250 mL infusion bag containing 0.45% Sodium Chloride Injection, USP may be used.
• Withdraw 26 mL of STELARA from each vial needed and add it to the 250 mL infusion bag. The final volume in the infusion bag should be 250 mL. Gently mix.
• Visually inspect the diluted solution before infusion. Do not use if visibly opaque particles, discoloration or foreign particles are observed.
• Infuse the diluted solution over a period of at least one hour. Once diluted, the infusion should be completely administered within eight hours of the dilution in the infusion bag.
• Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.2 micrometer).
• Do not infuse STELARA concomitantly in the same intravenous line with other agents.
• STELARA does not contain preservatives. Each vial is for a one-time use in only one patient. Discard any remaining solution. Dispose any unused medicinal product in accordance with local requirements.

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)] .

Storage

If necessary, the diluted infusion solution may be kept at room temperature up to 25 °C (77 °F) for up to 7 hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 8 hours after the dilution in the infusion bag (cumulative time after preparation including the storage and the infusion period). Do not freeze. Discard any unused portion of the infusion solution.

INSTRUCTIONS FOR USE

STELARA ( stel ar a )

(ustekinumab)

injection, for subcutaneous use

This Instructions for Use contains information on how to inject STELARA using a prefilled syringe.

Read this Instructions for Use before you start using STELARA. A healthcare provider should show you how to prepare and give an injection of STELARA the right way.

If you cannot give the injection:

• ask your healthcare provider to help you, or
• ask someone who has been trained by a healthcare provider to give your injections.

Do not try to inject STELARA until you have been shown how to inject STELARA by a healthcare provider.

Important information You Need to Know Before Injecting STELARA:

• For subcutaneous use only(inject directly under the skin).
• Before you start, check the carton to make sure that it is the right dose. You will have either 45 mg or 90 mg as prescribed by the healthcare provider.
  • If the dose is 45 mg, you will receive one 45 mg prefilled syringe.
  • If the dose is 90 mg, you will receive either one 90 mg prefilled syringe or two 45 mg prefilled syringes. If you receive two 45 mg prefilled syringes for a 90 mg dose, you will need to give two injections, one right after the other.
• Check the expiration date on the prefilled syringe and carton. If the expiration date has passed or if the prefilled syringe has been kept at room temperature up to 86°F (30°C) for longer than a maximum single period of 30 days or if the prefilled syringe has been stored above 86°F (30°C), do not use it. If the expiration date has passed or if the prefilled syringe has been stored above 86°F (30°C) or at room temperature for longer than 30 days, call the healthcare provider or pharmacist, or call 1-800-526-7736 for help.
• Make sure the syringe is not damaged.
• The needle cover on the prefilled syringe contains latex. Do not handle the needle cover on the STELARA prefilled syringe if you are allergic to latex.
• Check the prefilled syringe for any particles or discoloration. The liquid in the prefilled syringe should look clear and colorless to light yellow with a few small clear or white particles.
• Do not use if it is frozen, discolored, cloudy or has large particles. Get a new prefilled syringe.
• Do not shake the prefilled syringe at any time. Shaking the prefilled syringe may damage the STELARA medicine. If the prefilled syringe has been shaken, do not use it. Get a new prefilled syringe.
• To reduce the risk of accidental needle sticks, each prefilled syringe has a needle guard that is automatically activated to cover the needle after you have given the injection. Do not pull back on the plunger at any time.

Storing STELARA prefilled syringes

• Store STELARA prefilled syringes in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Store STELARA prefilled syringes in the original carton to protect from light.
• Do not freeze STELARA prefilled syringes.
• If needed, STELARA prefilled syringe may be stored at room temperature up to 86°F (30°C) 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 removed from the refrigerator on the carton in the space provided.
• After a prefilled syringe has been stored at room temperature, do not return it to the refrigerator.
• Throw away (discard) the prefilled syringe if it is not used within 30 days at room temperature storage.

Keep STELARA and all medicines out of the reach of children.

Gather the supplies you will need to prepare and to give the injection. (See Figure A)

You will need:

• antiseptic wipes
• cotton balls or gauze pads
• adhesive bandage
• your prescribed dose of STELARA (See Figure B)
• FDA-cleared sharps disposal container. See " Step 4: Disposing of the syringes"

Figure A

Figure B

To prevent early activation of the needle safety guard, do not touch the NEEDLE GUARD ACTIVATION CLIPS at any time during use.

Step 1: Preparing the injection

• Choose a well-lit, clean, flat work surface.
• Wash your hands well with soap and warm water.
• Hold the prefilled syringe with the covered needle pointing upward.

Step 2: Preparing the injection site

• Choose an injection site around the stomach area (abdomen), buttocks, upper legs (thighs). If a caregiver is giving the injection, the outer area of the upper arms may also be used. (See Figure C)
• Use a different injection site for each injection. Do not give an injection in an area of the skin that is tender, bruised, red or hard.
• Clean the skin with an antiseptic wipe where you plan to give the injection.
• Do not touch this area again before giving the injection. Let the skin dry before injecting.
• Do not fan or blow on the clean area.

Figure C

*Areas in gray are recommended injection sites.

Step 3: Injecting STELARA

• Remove the needle cover when you are ready to inject STELARA.
• Do not touch the plunger or plunger head while removing the needle cover.
• Hold the body of the prefilled syringe with one hand and pull the needle cover straight off. (see Figure D)
• Put the needle cover in the trash.
• You may also see a drop of liquid at the end of the needle. This is normal.
• Do not touch the needle or let it touch anything.
• Do not use the prefilled syringe if it is dropped without the needle cover in place.

Figure D

• Hold the body of the prefilled syringe in one hand between the thumb and index fingers. (See Figure E)

Figure E

• Do not pull back on the plunger at any time.
• Use the other hand to gently pinch the cleaned area of skin. Hold firmly.
• Use a quick, dart-like motion to insert the needle into the pinched skin at about a 45-degree angle. (See Figure F)

Figure F

• Inject all of the liquid by using your thumb to push in the plunger until the plunger head is completely between the needle guard wings. (See Figure G)

Figure G

• When the plunger is pushed as far as it will go, keep pressure on the plunger head. Take the needle out of the skin and then let go of the skin.
• Slowly take your thumb off the plunger head. This will let the empty syringe move up until the entire needle is covered by the needle guard. (See Figure H)

Figure H

• When the needle is pulled out of the skin, there may be a little bleeding at the injection site. This is normal. You can press a cotton ball or gauze pad to the injection site if needed. Do not rub the injection site. You may cover the injection site with a small adhesive bandage, if necessary.

If the dose is 90 mg, you will receive either one 90 mg prefilled syringe or two 45 mg prefilled syringes. If you receive two 45 mg prefilled syringes for a 90 mg dose, you will need to give a second injection right after the first. Repeat Steps 1 to 3 for the second injection using a new syringe. Choose a different site for the second injection.

Step 4: Disposing of the syringes.

• Put the syringe in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) syringes in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of 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 local or state laws about how to throw away syringes and needles. 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 sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your sharps disposal container.
• If you have any questions, talk to your healthcare provider or pharmacist.

Prefilled Syringe Manufactured by:

Janssen Biotech, Inc., Horsham, PA 19044, USA License No. 1864 at Baxter Pharmaceutical Solutions, Bloomington, IN 47403 and at Cilag AG, Schaffhausen, Switzerland

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 06/2025

© Johnson & Johnson and its affiliates 2025

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.

• ¹
  Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 6.6.2 Regs Research Data, Nov 2009 Sub (1973–2007) - Linked To County Attributes - Total U.S., 1969–2007 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2010, based on the November 2009 submission.

Ustekinumab, a human IgG1κ monoclonal antibody, is a human interleukin-12 and -23 antagonist. Using DNA recombinant technology, ustekinumab is produced in a murine cell line (Sp2/0). The manufacturing process contains steps for the clearance of viruses. Ustekinumab is comprised of 1326 amino acids and has an estimated molecular mass that ranges from 148,079 to 149,690 Daltons.

STELARA ^®(ustekinumab) injection is a sterile, preservative-free, colorless to light yellow solution and may contain a few small translucent or white particles with pH of 5.7– 6.3.

STELARA may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving STELARA [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 STELARA 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 STELARA 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 STELARA and discontinue STELARA for serious or clinically significant infections until the infection resolves or is adequately treated.

STELARA is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among subjects who received STELARA 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 STELARA 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 STELARA who had pre-existing risk factors for developing non-melanoma skin cancer. Monitor all patients receiving STELARA 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)] .

Prior to initiating therapy with STELARA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with STELARA should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment with STELARA or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving STELARA because of the potential risk for shedding from the household contact and transmission to patient.

Non-live vaccinations received during a course of STELARA may not elicit an immune response sufficient to prevent disease.

Of the 6709 subjects exposed to STELARA, 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 STELARA did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in studies of other ustekinumab products.

Approximately 6 to 12.4% of subjects treated with STELARA in clinical trials in subjects with plaque psoriasis and psoriatic arthritis developed antibodies to ustekinumab, which were generally low-titer. In clinical trials in subjects with plaque psoriasis, antibodies to ustekinumab were associated with reduced or undetectable serum ustekinumab concentrations and reduced efficacy. In trials in subjects with plaque psoriasis, the majority of subjects who were positive for antibodies to ustekinumab had neutralizing antibodies.

In clinical trials in subjects with Crohn’s disease and ulcerative colitis, 2.9% and 4.6% of subjects, respectively, developed antibodies to ustekinumab when treated with STELARA for approximately one year. No apparent association between the development of antibodies to ustekinumab and the development of injection site reactions was seen.

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

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)]

STELARA was evaluated in three randomized, double-blind, placebo-controlled clinical trials in adult subjects with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week intravenous induction trials(CD-1 and CD-2) followed by a 44-week subcutaneous randomized withdrawal maintenance trial (CD-3) representing 52 weeks of therapy. Subjects in CD-1 had failed or were intolerant to treatment with one or more TNF blockers, while subjects in CD-2 had failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a TNF blocker.

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 STELARA, an antagonist of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of STELARA 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)] .

STELARA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

STELARA 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)

STELARA was evaluated in two randomized, double-blind, placebo-controlled clinical trials [UC-1 and UC-2 (NCT02407236)] in adult subjects with moderately to severely active ulcerative colitis who had an inadequate response to or failed to tolerate a biologic (i.e., TNF blocker and/or vedolizumab), corticosteroids, and/or 6-MP or AZA therapy. The 8-week intravenous induction trial (UC-1) was followed by the 44-week subcutaneous randomized withdrawal maintenance trial (UC-2) for a total of 52 weeks of therapy.

Disease assessment was based on the Mayo score, which ranged from 0 to 12 and has four subscores that were each scored from 0 (normal) to 3 (most severe): stool frequency, rectal bleeding, findings on centrally-reviewed endoscopy, and physician global assessment. Moderately to severely active ulcerative colitis was defined at baseline (Week 0) as Mayo score of 6 to 12, including a Mayo endoscopy subscore ≥2. An endoscopy score of 2 was defined by marked erythema, absent vascular pattern, friability, erosions; and a score of 3 was defined by spontaneous bleeding, ulceration. At baseline, subjects had a median Mayo score of 9, with 84% of subjects having moderate disease (Mayo score 6–10) and 15% having severe disease (Mayo score 11–12).

Subjects in these trials may have received other concomitant therapies including aminosalicylates, immunomodulatory agents (AZA, 6-MP, or MTX), and oral corticosteroids (prednisone).

STELARA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.

Ustekinumab is a human IgG1қ monoclonal antibody that binds 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 vitromodels, ustekinumab was 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, was shown to be protective.

The safety and efficacy of STELARA was assessed in 927 subjects (PsA STUDY 1, n=615; PsA STUDY 2, n=312), in two randomized, double-blind, placebo-controlled trials in adult subjects 18 years of age and older with active PsA (≥5 swollen joints and ≥5 tender joints) despite nonsteroidal anti-inflammatory (NSAID) or disease modifying antirheumatic (DMARD) therapy. Subjects in these trials had a diagnosis of PsA for at least 6 months. Subjects with each subtype of PsA were enrolled, including polyarticular arthritis with the absence of rheumatoid nodules (39%), spondylitis with peripheral arthritis (28%), asymmetric peripheral arthritis (21%), distal interphalangeal involvement (12%) and arthritis mutilans (0.5%). Over 70% and 40% of the patients, respectively, had enthesitis and dactylitis at baseline.

Subjects were randomized to receive treatment with STELARA 45 mg, 90 mg, or placebo subcutaneously at Weeks 0 and 4 followed by every 12 weeks (q12w) dosing. Approximately 50% of subjects continued on stable doses of MTX (≤25 mg/week). The primary endpoint was the percentage of subjects achieving ACR 20 response at Week 24.

In PsA STUDY 1 and PsA STUDY 2, 80% and 86% of the subjects, respectively, had been previously treated with DMARDs. In PsA STUDY 1, previous treatment with anti-tumor necrosis factor (TNF)-α agent was not allowed. In PsA STUDY 2, 58% (n=180) of the subjects had been previously treated with TNF blocker, of whom over 70% had discontinued their TNF blocker treatment for lack of efficacy or intolerance at any time.

In trials in subjects with plaque psoriasis the safety of STELARA 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 STELARA. 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 STELARA.

STELARA 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.

• Infections: Serious infections have occurred. Avoid starting STELARA during any clinically important active infection. If a serious infection or clinically significant infection develops, discontinue STELARA 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 STELARA. Initiate treatment of latent TB before administering STELARA. ( 5.3)
• Malignancies: STELARA may increase risk of malignancy. The safety of STELARA 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 STELARA immediately and initiate appropriate medical treatment. (5.5)
• Posterior Reversible Encephalopathy Syndrome (PRES): If PRES is suspected, treat promptly, and discontinue STELARA. ( 5.6)
• Immunizations:Avoid use of live vaccines in patients during treatment with STELARA . ( 5.7)
• Noninfectious Pneumonia: Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of STELARA. If diagnosis is confirmed, discontinue STELARA and institute appropriate treatment. ( 5.8)

STELARA has not been evaluated in patients who have undergone allergy immunotherapy. STELARA 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.

Adult Patients with Plaque Psoriasis Subcutaneous Recommended Dosage ( 2.1) :

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.

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.

Crohn's Disease and Ulcerative Colitis Initial Adult Intravenous Recommended Dose ( 2.3) :

A single intravenous infusion using weight-based dosing:

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.

Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of STELARA. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and in certain cases administration of corticosteroids. If diagnosis is confirmed, discontinue STELARA and institute appropriate treatment [see Postmarketing Experience (6.3)] .

STELARA (ustekinumab) is a colorless to light yellow solution and may contain a few small translucent or white particles.

The following adverse reactions have been reported during post-approval use of STELARA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to STELARA exposure.

Immune system disorders: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, dyspnea, rash, urticaria), including a fatal case that presented with chest tightness and dyspnea during infusion of the first dose.

Infections and infestations:Lower respiratory tract infection (including opportunistic fungal infections and tuberculosis).

Neurological disorders:Posterior Reversible Encephalopathy Syndrome (PRES) .

Respiratory, thoracic, and mediastinal disorders:Interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia.

Skin reactions: Pustular psoriasis, erythrodermic psoriasis, hypersensitivity vasculitis.

STELARA is indicated for the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.

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.

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

STELARA ^®(ustekinumab) injection is a sterile, preservative-free, colorless to light yellow solution and may contain a few small translucent or white particles. It is supplied as individually packaged, single-dose prefilled syringes or single-dose vials.

Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA in clinical trials and postmarketing. Some serious hypersensitivity reactions have occurred during the first intravenous dose of STELARA [see Adverse Reactions (6.1, 6.3)].

If a severe or clinically significant hypersensitivity reaction occurs, discontinue STELARA immediately and initiate appropriate medical treatment [see Contraindications (4)].

Two multicenter, randomized, double-blind, placebo-controlled trials (Ps STUDY 1 and Ps STUDY 2) enrolled a total of 1996 subjects 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded from the trials.

Ps STUDY 1 enrolled 766 subjects and Ps STUDY 2 enrolled 1230 subjects. The trials had the same design through Week 28. In both trials, subjects were randomized in equal proportion to placebo, 45 mg or 90 mg of STELARA. Subjects randomized to STELARA received 45 mg or 90 mg doses, regardless of weight, at Weeks 0, 4, and 16. Subjects randomized to receive placebo at Weeks 0 and 4 crossed over to receive STELARA (either 45 mg or 90 mg) at Weeks 12 and 16.

In both trials, subjects in all treatment groups had a median baseline PASI score ranging from approximately 17 to 18. Baseline PGA score was marked or severe in 44% of subjects in Ps STUDY 1 and 40% of subjects in Ps STUDY 2. Approximately two-thirds of all subjects had received prior phototherapy, 69% had received either prior conventional systemic or biologic therapy for the treatment of psoriasis, with 56% receiving prior conventional systemic therapy and 43% receiving prior biologic therapy. A total of 28% of subjects had a history of psoriatic arthritis.

In both trials, the endpoints were the proportion of subjects who achieved at least a 75% reduction in PASI score (PASI 75) from baseline to Week 12 and treatment success (cleared or minimal) on the Physician's Global Assessment (PGA). The PGA is a 6-category scale ranging from 0 (cleared) to 5 (severe) that indicates the physician's overall assessment of psoriasis focusing on plaque thickness/induration, erythema, and scaling.

In a 26-week toxicology study, one out of 10 monkeys subcutaneously administered 45 mg/kg ustekinumab twice weekly for 26 weeks had a bacterial infection.

A multicenter, randomized, double blind, placebo-controlled trial (Ps STUDY 3) enrolled 110 pediatric subjects 12 years of age and older with a minimum BSA involvement of 10%, a PASI score greater than or equal to 12, and a PGA score greater than or equal to 3, who were candidates for phototherapy or systemic therapy and whose disease was inadequately controlled by topical therapy.

Subjects were randomized to receive placebo (n = 37), the recommended dose of STELARA (n = 36), or one-half the recommended dose of STELARA (n = 37) by subcutaneous injection at Weeks 0 and 4 followed by dosing every 12 weeks (q12w). The recommended dose of STELARA was 0.75 mg/kg for subjects weighing less than 60 kg, 45 mg for subjects weighing 60 kg to 100 kg, and 90 mg for subjects weighing greater than 100 kg. At Week 12, subjects who received placebo were crossed over to receive STELARA at the recommended dose or one-half the recommended dose.

Of the pediatric subjects, approximately 63% had prior exposure to phototherapy or conventional systemic therapy and approximately 11% had prior exposure to biologics.

The endpoints were the proportion of subjects who achieved a PGA score of cleared (0) or minimal (1), PASI 75, and PASI 90 at Week 12. Subjects were followed for up to 60 weeks following first administration of trial agent.

• STELARA is intended for use under the guidance and supervision of a healthcare provider . STELARA should only be administered to patients who will be closely monitored and have regular follow-up visits with a healthcare provider. The appropriate dose should be determined by a healthcare provider using the patient's current weight at the time of dosing. In pediatric patients, it is recommended that STELARA be administered by a healthcare provider. If a healthcare provider determines that it is appropriate, a patient may self-inject or a caregiver may inject STELARA after proper training in subcutaneous injection technique. Instruct patients to follow the directions provided in the Instructions for Use [see Instructions for Use].
• The needle cover on the prefilled syringe contains dry natural rubber (a derivative of latex). The needle cover should not be handled by persons sensitive to latex.
• It is recommended that each injection be administered at a different anatomic location (such as upper arms, gluteal regions, thighs, or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, or indurated. When using the vial, a 1 mL syringe with a 27 gauge, ½ inch needle is recommended.
• Prior to administration, visually inspect STELARA for particulate matter and discoloration. STELARA is a colorless to light yellow solution and may contain a few small translucent or white particles. Do not use STELARA if it is discolored or cloudy, or if other particulate matter is present. STELARA does not contain preservatives; therefore, discard any unused product remaining in the vial and/or syringe.

Evaluate patients for tuberculosis infection prior to initiating treatment with STELARA.

Avoid administering STELARA to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering STELARA. Consider anti-tuberculosis therapy prior to initiation of STELARA 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 STELARA for signs and symptoms of active tuberculosis during and after treatment.

Stelara ^®

(ustekinumab)

Injection

90 mg/mL

For subcutaneous use

Contains one 90 mg/mL syringe

NDC 57894-061-03

Single-dose prefilled syringe - Discard unused portion

The 90 mg prefilled syringe contains:

90 mg ustekinumab, 1 mg L-histidine and L-histidine

monohydrochloride monohydrate, 0.04 mg polysorbate 80,

and 76 mg sucrose to fill a final volume of 1 mL

See package insert for dosing information

Rx only

ATTENTION: Dispense the enclosed Medication

Guide to each patient.

© 2009 Janssen

NDC 57894-054-27

Single-Dose vial

Discard unused portion

Stelara ^®

(ustekinumab)

Injection

130 mg/26 mL

(5 mg/mL)

For Intravenous Infusion Only

Must be diluted

ATTENTION: Dispense

the enclosed Medication

Guide to each patient.

Rx only

janssen

NDC 57894-060-02

Single-dose vial.

Discard unused portion.

Stelara^®

(ustekinumab)

Injection

45 mg/0.5 mL

For Subcutaneous Use

Attention: Dispense the enclosed

Medication Guide to each patient.

Rx only

Each vial contains 0.5 mL

Johnson

& Johnson

Stelara ^®

(ustekinumab)

Injection

45 mg/0.5 mL

For subcutaneous use

Contains one 45 mg/0.5 mL syringe

NDC 57894-060-03

Single-dose prefilled syringe - Discard unused portion

The 45 mg prefilled syringe contains:

45 mg ustekinumab, 0.5 mg L-histidine and L-histidine

monohydrochloride monohydrate, 0.02 mg polysorbate 80,

and 38 mg sucrose to fill a final volume of 0.5 mL

See package insert for dosing information

Rx only

ATTENTION: Dispense the enclosed Medication Guide

to each patient.

© 2009 Janssen

Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis, and Crohn's disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab.

Monitor all patients treated with STELARA for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue STELARA.

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of STELARA. Published literature showed that administration of murine IL-12 caused an anti-tumor effect in mice that contained transplanted tumors and IL-12/IL-23p40 knockout mice or mice treated with anti-IL-12/IL-23p40 antibody had decreased host defense to tumors. Mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone developed UV-induced skin cancers earlier and more frequently compared to wild-type mice. The relevance of these experimental findings in mouse models for malignancy risk in humans is unknown.

No effects on fertility were observed in male cynomolgus monkeys that were administered ustekinumab at subcutaneous doses up to 45 mg/kg twice weekly (45 times the MRHD on a mg/kg basis) prior to and during the mating period. However, fertility and pregnancy outcomes were not evaluated in mated females.

No effects on fertility were observed in female mice that were administered an analogous IL-12/IL-23p40 antibody by subcutaneous administration at doses up to 50 mg/kg, twice weekly, prior to and during early pregnancy.

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 STELARA may be susceptible to these types of infections. Consider appropriate diagnostic testing, (e.g., tissue culture, stool culture, as dictated by clinical circumstances).

STELARA solution for intravenous infusion must be diluted, prepared, and infused by a healthcare professional using aseptic technique.

• Calculate the dose and the number of STELARA vials needed based on patient weight (Table 4). Each 26 mL vial of STELARA contains 130 mg of ustekinumab.
• Withdraw, and then discard a volume of the 0.9% Sodium Chloride Injection, USP from the 250 mL infusion bag equal to the volume of STELARA to be added (discard 26 mL sodium chloride for each vial of STELARA needed, for 2 vials- discard 52 mL, for 3 vials- discard 78 mL, 4 vials- discard 104 mL). Alternatively, a 250 mL infusion bag containing 0.45% Sodium Chloride Injection, USP may be used.
• Withdraw 26 mL of STELARA from each vial needed and add it to the 250 mL infusion bag. The final volume in the infusion bag should be 250 mL. Gently mix.
• Visually inspect the diluted solution before infusion. Do not use if visibly opaque particles, discoloration or foreign particles are observed.
• Infuse the diluted solution over a period of at least one hour. Once diluted, the infusion should be completely administered within eight hours of the dilution in the infusion bag.
• Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.2 micrometer).
• Do not infuse STELARA concomitantly in the same intravenous line with other agents.
• STELARA does not contain preservatives. Each vial is for a one-time use in only one patient. Discard any remaining solution. Dispose any unused medicinal product in accordance with local requirements.