Ustekinumab
Ustekinumab Prescribing Information
Ustekinumab 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 Plaque Psoriasis (PsO)Ustekinumab 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.
- active psoriatic arthritis (PsA). ()
1.2 Psoriatic Arthritis (PsA)Ustekinumab is indicated for the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.
- moderately to severely active Crohn's disease (CD). ()
1.3 Crohn's Disease (CD)Ustekinumab is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.
- moderately to severely active ulcerative colitis.()
1.4 Ulcerative ColitisUstekinumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.
Pediatric patients 6 years and older with:
- moderate to severe plaque psoriasis, who are candidates for phototherapy or systemic therapy. ()
1.1 Plaque Psoriasis (PsO)Ustekinumab 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.
- active psoriatic arthritis (PsA). ()
1.2 Psoriatic Arthritis (PsA)Ustekinumab is indicated for the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.
- For patients weighing 100 kg or less, the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
- For patients weighing more than 100 kg, the recommended dose 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
Administer Ustekinumab subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter.
The recommended dose of Ustekinumab for pediatric patients (6–17 years old) with plaque psoriasis based on body weight is shown below (Table 1).
| 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 |
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 (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 |
| Weight Range (kilograms) | Dose |
|---|---|
| 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 |
- For patients weighing 100 kg or less, the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
- For patients weighing more than 100 kg, the recommended dose 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
Administer Ustekinumab subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter.
The recommended dose of Ustekinumab for pediatric patients (6–17 years old) with plaque psoriasis based on body weight is shown below (Table 1).
| 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 |
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 (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 |
| 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 |
- The recommended dose 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 dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks.
Administer Ustekinumab subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter.
The recommended dose of Ustekinumab for pediatric patients (6 to 17 years old) with psoriatic arthritis, based on body weight, is shown below (Table 3).
| Body Weight of Patient at the Time of Dosing | Recommended Dose |
|---|---|
| less than 60 kgFor 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. | 0.75 mg/kg |
| 60 kg or more | 45 mg |
| greater than 100 kg with co-existent moderate-to-severe plaque psoriasis | 90 mg |
- 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.
- The recommended dose 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 dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks.
Administer Ustekinumab subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter.
The recommended dose of Ustekinumab for pediatric patients (6 to 17 years old) with psoriatic arthritis, based on body weight, is shown below (Table 3).
| Body Weight of Patient at the Time of Dosing | Recommended Dose |
|---|---|
| less than 60 kgFor 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. | 0.75 mg/kg |
| 60 kg or more | 45 mg |
| greater than 100 kg with co-existent moderate-to-severe plaque psoriasis | 90 mg |
| 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 |
A single intravenous infusion dose of Ustekinumab using the weight-based dosage regimen specified in Table 4
| Body Weight of Patient at the time of dosing | Dose | Number of 130 mg/26 mL (5 mg/mL) Ustekinumab vials |
|---|---|---|
| 55 kg or less | 260 mg | 2 |
| more than 55 kg to 85 kg | 390 mg | 3 |
| more than 85 kg | 520 mg | 4 |
The recommended maintenance dosage is a subcutaneous 90 mg dose administered 8 weeks after the initial intravenous dose, then every 8 weeks thereafter.
| Weight Range (kilograms) | Recommended Dosage |
|---|---|
| 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) |
A single intravenous infusion dose of Ustekinumab using the weight-based dosage regimen specified in Table 4
| Body Weight of Patient at the time of dosing | Dose | Number of 130 mg/26 mL (5 mg/mL) Ustekinumab vials |
|---|---|---|
| 55 kg or less | 260 mg | 2 |
| more than 55 kg to 85 kg | 390 mg | 3 |
| more than 85 kg | 520 mg | 4 |
The recommended maintenance dosage is a subcutaneous 90 mg dose administered 8 weeks after the initial intravenous dose, then every 8 weeks thereafter.
Ustekinumab is a colorless to light yellow solution and may contain a few small translucent or white particles.
Limited data from observational studies, published case reports, and postmarketing surveillance on the use of Ustekinumab during pregnancy are insufficient to inform a drug associated risk of major birth defects, miscarriage, and other adverse maternal or fetal outcomes. Transport of human IgG antibody across the placenta increases as pregnancy progresses and peaks during the third trimester; therefore, Ustekinumab may be transferred to the developing fetus
Because ustekinumab may theoretically interfere with immune response to infections, consider risks and benefits prior to administering live vaccines to infants exposed to Ustekinumab
The background risk of major birth defects and miscarriage for the indicated population(s) are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Ustekinumab is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or to any of the excipients in Ustekinumab
Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with Ustekinumab
- Infections: Serious infections have occurred. Avoid starting Ustekinumab during any clinically important active infection. If a serious infection or clinically significant infection develops, discontinue Ustekinumab until the infection resolves. ()
5.1 InfectionsUstekinumab may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving Ustekinumab
[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 Ustekinumab 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 Ustekinumab 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 Ustekinumab and discontinue Ustekinumab for serious or clinically significant infections until the infection resolves or is adequately treated.
- 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 Theoretical Risk for Vulnerability to Particular InfectionsIndividuals 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 may be susceptible to these types of infections. Consider appropriate diagnostic testing, (e.g., tissue culture, stool culture, as dictated by clinical circumstances).
- Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with Ustekinumab. Initiate treatment of latent TB before administering Ustekinumab.()
5.3 Pre-treatment Evaluation for TuberculosisEvaluate patients for tuberculosis infection prior to initiating treatment with Ustekinumab.
Avoid administering Ustekinumab to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering Ustekinumab. Consider anti-tuberculosis therapy prior to initiation of Ustekinumab 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 Ustekinumab for signs and symptoms of active tuberculosis during and after treatment.
- Malignancies: Ustekinumab may increase risk of malignancy. The safety of Ustekinumab in patients with a history of or a known malignancy has not been evaluated. ()
5.4 MalignanciesUstekinumab is an immunosuppressant 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 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 who had pre-existing risk factors for developing non-melanoma skin cancer. Monitor all patients receiving Ustekinumab 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)]. - Hypersensitivity Reactions: If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue Ustekinumab. ()
5.5 Hypersensitivity ReactionsHypersensitivity reactions, including anaphylaxis and angioedema, have been reported with Ustekinumab
[see Adverse Reactions (6.1, 6.3)]. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue Ustekinumab. - Posterior Reversible Encephalopathy Syndrome (PRES): If PRES is suspected, treat promptly, and discontinue Ustekinumab. ()
5.6 Posterior Reversible Encephalopathy Syndrome (PRES)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 Ustekinumab for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue Ustekinumab.
- Immunizations:Avoid use of live vaccines in patients during treatment with Ustekinumab. ()
5.7 ImmunizationsPrior to initiating therapy with Ustekinumab, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with Ustekinumab should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment with Ustekinumab 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 Ustekinumab because of the potential risk for shedding from the household contact and transmission to patient.
Non-live vaccinations received during a course of Ustekinumab may not elicit an immune response sufficient to prevent disease.
- Noninfectious Pneumonia: Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of Ustekinumab. If diagnosis is confirmed, discontinue Ustekinumab and institute appropriate treatment. ()
5.8 Noninfectious PneumoniaCases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of Ustekinumab. 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 Ustekinumab and institute appropriate treatment
[see Postmarketing Experience (6.3)].