Stelara

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Stelara

Classes

Antipsoriatic Monoclonal Antibodies and Others
Interleukin-23 (IL-23) Inhibitors

Administration
Injectable Administration

Do not shake the prefilled syringe or vial, as irreparable damage to ustekinumab may occur.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be colorless to slightly yellow and may contain a few small translucent or white particles. Do not use if discolored, cloudy, or if foreign particulate matter is present.

Intravenous Administration

Intravenous infusion preparation
Ustekinumab is administered as an IV infusion only for the induction treatment of Crohn's disease or ulcerative colitis.
Each vial is for single use only.
Calculate the dose and the number of ustekinumab vials needed based on patient weight; each 26 mL vial contains 130 mg of ustekinumab.
The ustekinumab solution must be further diluted prior to infusion.
Withdraw and discard a volume of the 0.9% Sodium Chloride Injection from a 250 mL infusion bag equal to the volume of ustekinumab to be added (e.g., discard 26 mL sodium chloride solution from the bag for each vial of ustekinumab 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 ustekinumab 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. Do not shake.
Storage: If necessary, the diluted infusion solution may be kept at room temperature up to 25 degrees C (77 degrees 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.
 
Intravenous Infusion administration
Infuse the diluted usetkinumab infusion solution over a period of at least 1 hour. Once diluted, the infusion should be completely administered within 8 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 micron).
Do not infuse concomitantly in the same intravenous line with other agents.

Subcutaneous Administration

Only an individual trained in subcutaneous drug delivery should administer the injection.
An adult who is properly trained in injection technique may self-inject using the prefilled syringe or vial, if the prescriber deems the action appropriate. However, the first injection needs to be under the supervision of a qualified healthcare professional.
For pediatric patients, it is recommended that doses be administered by a health care professional.
Injection sites include the front part of the middle thigh, the gluteal or abdominal region, and the outer area of the upper arm. Do not administer where skin is tender, bruised, red, or indurated.
Rotate injection sites. If a second injection is needed because two 45 mg vials or prefilled syringes are used for a 90 mg dose, repeat the injection process with new materials, and use a different injection site.
For the vial, use a 1 mL syringe with a 27-gauge, 0.5-inch needle to withdraw the dose.
Gently pinch the cleaned area of skin and insert the needle at about a 45-degree angle subcutaneously using a quick, dart-like motion. Push the plunger slowly and evenly to deliver the dose, remove the needle, and release the pinched skin. Do not rub the injection site; slight bleeding may occur.
For the prefilled syringe, hold the syringe body and pull off the needle cover. The needle cover of the prefilled syringe contains latex. Persons allergic to natural rubber or latex should not handle the cover of the prefilled syringe.
Gently pinch the cleaned area of skin and insert the needle at about a 45-degree angle subcutaneously using a quick, dart-like motion. Push the plunger in as far as it can go to deliver the dose, remove the needle while maintaining pressure on the plunger head, and release the pinched skin.
Do not rub the injection site; slight bleeding may occur. The needle safety guard will be activated once the pressure on the plunger head is released; do not touch the needle guard activation clips to prevent premature activation of the needle safety guard.
Each single-use vial or single-use prefilled syringe contains 45 mg/0.5 mL or 90 mg/mL of ustekinumab. No preservatives are present; discard any unused portion.
Storage: Store unopened vials and prefilled syringes in the refrigerator between 2 to 8 degrees C (36 to 46 degrees F). Do not freeze or shake. If needed, individual prefilled syringes may be stored at room temperature up to 30 degrees C (86 degrees F) for a maximum single period of up to 30 days; keep in the original carton to protect from light. Once a syringe is stored at room temperature, do not return to the refrigerator. Discard the syringe if not used within 30 days at room temperature storage.

Adverse Reactions
Severe

new primary malignancy / Delayed / 0.2-1.7
skin cancer / Delayed / 0.2-1.3
leukoencephalopathy / Delayed / 0-1.0
appendicitis / Delayed / Incidence not known
cholecystitis / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
eosinophilic pneumonia / Delayed / Incidence not known

Moderate

antibody formation / Delayed / 2.9-12.4
erythema / Early / 1.0-5.0
candidiasis / Delayed / 3.0
ocular infection / Delayed / Incidence not known
meningitis / Delayed / Incidence not known
depression / Delayed / Incidence not known
dyspnea / Early / Incidence not known
pneumonitis / Delayed / Incidence not known
psoriasis / Delayed / Incidence not known

Mild

infection / Delayed / 3.0-27.0
pharyngitis / Delayed / 3.0-24.0
headache / Early / 5.0-10.0
abdominal pain / Early / 7.0-7.0
influenza / Delayed / 6.0-6.0
fever / Early / 5.0-5.0
injection site reaction / Rapid / 0-5.0
sinusitis / Delayed / 3.0-4.0
fatigue / Early / 3.0-4.0
vomiting / Early / 4.0-4.0
diarrhea / Early / 2.0-4.0
pruritus / Rapid / 1.0-4.0
arthralgia / Delayed / 0-3.0
nausea / Early / 3.0-3.0
back pain / Delayed / 1.0-2.0
dizziness / Early / 1.0-2.0
asthenia / Delayed / 1.0-1.0
myalgia / Early / 0-1.0
ecchymosis / Delayed / 0-1.0
skin irritation / Early / 0-1.0
acne vulgaris / Delayed / 0-1.0
dental caries / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known

Common Brand Names

Stelara

Dea Class

Rx

Description

Interleukin (IL)-12 and IL-23 antagonist; given intravenously and subcutaneously
Used for moderate to severe plaque psoriasis in adult and pediatric patients 6 years and older; also used for adults with active psoriatic arthritis (PsA) or moderate to severely active Crohn's disease or ulcerative colitis
As with other interleukin inhibitors, may increase risk of infection

Dosage And Indications
For the treatment of moderate to severe plaque psoriasis in persons who are candidates for systemic therapy or phototherapy. Subcutaneous dosage Adults weighing more than 100 kg

90 mg subcutaneously at weeks 0 and 4, then 90 mg subcutaneously every 12 weeks. May consider a lower dose of 45 mg; however, greater efficacy is seen with 90 mg/dose. May increase the dose to 90 mg subcutaneously every 8 weeks if an inadequate primary response may be due to insufficient drug exposure (e.g., known subtherapeutic drug concentrations, obesity, relapse during treatment); however, consider the increased risk for infection and adverse reactions.

Adults weighing 100 kg or less

45 mg subcutaneously at weeks 0 and 4, then 45 mg subcutaneously every 12 weeks. May increase the dose to 90 mg subcutaneously every 8 to 12 weeks if an inadequate primary response may be due to insufficient drug exposure (e.g., known subtherapeutic drug concentrations, relapse during treatment); however, consider the increased risk for infection and adverse reactions.

Children and Adolescents 6 to 17 years weighing more than 100 kg

90 mg subcutaneously at weeks 0 and 4, then 90 mg subcutaneously every 12 weeks. Guidelines recommend ustekinumab as an effective therapy in children and adolescents with moderate to severe plaque psoriasis.

Children and Adolescents 6 to 17 years weighing 60 to 100 kg

45 mg subcutaneously at weeks 0 and 4, then 45 mg subcutaneously every 12 weeks. Guidelines recommend ustekinumab as an effective therapy in children and adolescents with moderate to severe plaque psoriasis.

Children and Adolescents 6 to 17 years weighing less than 60 kg

0.75 mg/kg/dose subcutaneously at weeks 0 and 4, then 0.75 mg/kg/dose subcutaneously every 12 weeks. Guidelines recommend ustekinumab as an effective therapy in children and adolescents with moderate to severe plaque psoriasis.

For the treatment of active psoriatic arthritis, including with coexistent moderate to severe plaque psoriasis. For the treatment of active psoriatic arthritis without coexistent plaque psoriasis. Subcutaneous dosage Adults

45 mg subcutaneously at weeks 0 and 4, then 45 mg subcutaneously every 12 weeks. Ustekinumab can be used as monotherapy or in combination with methotrexate.

For the treatment of active psoriatic arthritis with coexistent moderate to severe plaque psoriasis. Subcutaneous dosage Adults weighing more than 100 kg

90 mg subcutaneously at weeks 0 and 4, then 90 mg subcutaneously every 12 weeks. Ustekinumab can be used as monotherapy or in combination with methotrexate.

Adults weighing 100 kg or less

45 mg subcutaneously at weeks 0 and 4, then 45 mg subcutaneously every 12 weeks. Ustekinumab can be used as monotherapy or in combination with methotrexate.

For the treatment of moderately to severely active Crohn's disease. Intravenous dosage (induction) Adults weighing more than 85 kg

520 mg IV as a single dose. Begin the subcutaneous maintenance regimen 8 weeks after the initial IV dose. Guidelines strongly recommend ustekinumab for moderate-to-severe Crohn's disease patients who failed previous treatment with corticosteroids, thiopurines, methotrexate, or TNF-blockers or in those persons who have had no prior exposure to TNF-blockers.

Adults weighing 56 kg to 85 kg

390 mg IV as a single dose. Begin the subcutaneous maintenance regimen 8 weeks after the initial IV dose. Guidelines strongly recommend ustekinumab for moderate-to-severe Crohn's disease patients who failed previous treatment with corticosteroids, thiopurines, methotrexate, or TNF-blockers or in those persons who have had no prior exposure to TNF-blockers.

Adults weighing 55 kg or less

260 mg IV as a single dose. Begin the subcutaneous maintenance regimen 8 weeks after the initial IV dose. Guidelines strongly recommend ustekinumab for moderate-to-severe Crohn's disease patients who failed previous treatment with corticosteroids, thiopurines, methotrexate, or TNF-blockers or in those persons who have had no prior exposure to TNF-blockers.

Adolescents†


6 mg/kg IV as a single dose rounded to the nearest 130 mg (Max: 520 mg). Begin the subcutaneous maintenance regimen 8 weeks after the initial IV dose. Consider ustekinumab in patients who fail to achieve or maintain clinical remission on TNF-blockers.

Children† 2 to 12 years weighing 40 kg or more

6 mg/kg IV as a single dose rounded to the nearest 130 mg (Max: 520 mg). Alternatively, 130 mg and 390 mg IV as a single dose have been studied. Begin the subcutaneous maintenance regimen 8 weeks after the initial IV dose. In a phase 1 induction dose range study, 44 patients (less than 40 kg n = 18; 40 kg or more n = 26; age range: 2 to 17 years, median 13 years) received either low or high dose ustekinumab as IV induction followed by subcutaneous maintenance doses. Low dose was defined as 130 mg (n = 13) and high dose was defined as 390 (n = 13). Both groups had similar clinical response at week 8, but the high dose induction group had a higher percentage of clinical remission at 16 weeks (22% for low dose vs. 29% for high dose). Consider ustekinumab in patients who fail to achieve or maintain clinical remission on TNF-blockers.

Children† 2 to 12 years weighing 10 to less than 40 kg

6 mg/kg IV as a single dose rounded to the nearest 130 mg. Alternatively, 3 mg/kg and 9 mg/kg IV as a single dose have been studied. Begin the subcutaneous maintenance regimen 8 weeks after the initial IV dose. In a phase 1 induction dose range study, 44 patients (less than 40 kg n = 18; 40 kg or more n = 26; age range: 2 to 17 years, median 13 years) received either low or high dose ustekinumab as IV induction followed by subcutaneous maintenance doses. Low dose was defined as 3 mg/kg/dose (n = 10) and high dose was defined as 9 mg/kg/dose (n = 8). Both groups had similar clinical response at week 8, but the high dose induction group had a higher percentage of clinical remission at 16 weeks (22% for low dose vs. 29% for high dose). Consider ustekinumab in patients who fail to achieve or maintain clinical remission on TNF-blockers.

Subcutaneous dosage Adults

90 mg subcutaneously every 8 weeks, starting 8 weeks after the initial IV induction dose. Guidelines support the use of ustekinumab for maintenance of remission in persons with an ustekinumab-induced induction response.

Adolescents†

90 mg subcutaneously every 8 weeks, starting 8 weeks after the initial IV induction dose; dose escalation after a median of 6 months via a shorter dosing interval of 4 to 6 weeks was shown to increase response in patients with loss of or insufficient response. Consider ustekinumab in patients who fail to achieve or maintain clinical remission on TNF-blockers.

Children† 2 to 12 years weighing 40 kg or more

90 mg subcutaneously every 8 weeks, starting 8 weeks after the initial IV induction dose; dose escalation after a median of 6 months via a shorter dosing interval of 4 to 6 weeks was shown to increase response in patients with loss of or insufficient response. Consider ustekinumab in patients who fail to achieve or maintain clinical remission on TNF-blockers.

Children† 2 to 12 years weighing 10 kg to less than 40 kg

2 mg/kg/dose (Max: 90 mg) subcutaneously every 8 weeks, starting 8 weeks after the initial IV induction dose; dose escalation after a median of 6 months via a shorter dosing interval of 4 to 6 weeks was shown to increase response in patients with loss of or insufficient response. In a phase 1 induction dose range study, 44 patients (less than 40 kg n = 18; 40 kg or more n = 26; age range: 2 to 17 years, median 13 years) received ustekinumab as IV induction followed by subcutaneous maintenance doses of 2 mg/kg in patients less than 40 kg and 90 mg in patients 40 kg or more every 8 weeks. Clinical remission was achieved in 22% to 29% of patients at week 16. Consider ustekinumab in patients who fail to achieve or maintain clinical remission on TNF-blockers.

For the treatment of moderately to severely active ulcerative colitis. Intravenous dosage Adults weighing more than 85 kg

520 mg IV as a single dose. Begin subcutaneous maintenance dose 8 weeks after the initial intravenous dose. Guidelines strongly recommend ustekinumab for induction of remission in persons with moderately to severely active ulcerative colitis.[64393]

Adults weighing 56 kg to 85 kg

390 mg IV as a single dose. Begin subcutaneous maintenance dose 8 weeks after the initial intravenous dose. Guidelines strongly recommend ustekinumab for induction of remission in persons with moderately to severely active ulcerative colitis.[64393]

Adults weighing 55 kg or less

260 mg IV as a single dose. Begin subcutaneous maintenance dose 8 weeks after the initial intravenous dose. Guidelines strongly recommend ustekinumab for induction of remission in persons with moderately to severely active ulcerative colitis.[64393]

Subcutaneous dosage Adults

90 mg subcutaneously every 8 weeks starting 8 weeks after the initial intravenous induction dose. Guidelines strongly recommend ustekinumab for maintenance of remission in persons with moderately to severely active ulcerative colitis who responded to ustekinumab induction.[64393]

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Abatacept: (Major) Concomitant use of abatacept with biological DMARDs, such as ustekinumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with ustekinumab.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as ustekinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as ustekinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclosporine: (Moderate) Upon initiation of usetkinumab in patients who are receiving cyclosporine, consider monitoring cyclosporine drug concentrations and adjusting the cyclosporine dose if clinically indicated, due to potential changes in CYP450 activity as inflammation is treated. The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF, IFN) during chronic inflammation. Thus, ustekinumab, an antagonist of IL-12 and IL-23, could normalize the formation of CYP450 enzymes, which might affect CYP450 substrates with a narrow therapeutic index.
Intranasal Influenza Vaccine: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Live Vaccines: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Rotavirus Vaccine: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with other biological DMARDs such as ustekinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with other biological DMARDs such as ustekinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as ustekinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Typhoid Vaccine: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as ustekinumab, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Warfarin: (Moderate) The formation of CYP450 enzymes may be altered during chronic inflammation; the formation of CYP450 enzymes could be normalized during ustekinumab receipt. For CYP450 substrates that have a narrow therapeutic index such as warfarin, consider monitoring the warfarin concentration if ustekinumab is initiated or discontinued; warfarin dose adjustment may be needed.
Yellow Fever Vaccine, Live: (Contraindicated) If possible, administer all recommended vaccines before ustekinumab initiation. Ustekinumab recipients may receive inactive vaccines, but the elicited immune response may be insufficient to prevent disease. Do not administer live vaccines to a ustekinumab recipient. Furthermore, do not administer BCG live vaccines for either 1 year before or 1 year after ustekinumab receipt, due to the infectious risk for Mycobacteria. No data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration of other live vaccines to ustekinumab recipients. Cautious administration of ustekinumab to household contacts of ustekinumab recipients may be warranted due to the potential risk for shedding from the household contact and transmission to the patient. Practitioners should also refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

How Supplied

Stelara Intravenous Inj Sol: 1mL, 5mg
Stelara Subcutaneous Inj Sol: 0.5mL, 1mL, 45mg, 90mg

Maximum Dosage
Adults

Psoriasis and Psoriatic Arthritis
Weighing more than 100 kg: 90 mg/dose subcutaneously for plaque psoriasis +/- psoriatic arthritis and 45 mg/dose subcutaneously for psoriatic arthritis alone; maintenance therapy every 12 weeks.
Weighing 100 kg or less: 45 mg/dose subcutaneously; maintenance therapy every 12 weeks.
 
Crohn's Disease and Ulcerative Colitis
Weighing more than 85 kg: 520 mg single dose IV and 90 mg/dose subcutaneously every 8 weeks.
Weighing 56 to 85 kg: 390 mg single dose IV and 90 mg/dose subcutaneously every 8 weeks.
Weighing 55 kg or less: 260 mg single dose IV and 90 mg/dose subcutaneously every 8 weeks.

Geriatric

Psoriasis and Psoriatic Arthritis
Weighing more than 100 kg: 90 mg/dose subcutaneously for plaque psoriasis +/- psoriatic arthritis and 45 mg/dose subcutaneously for psoriatic arthritis alone; maintenance therapy every 12 weeks.
Weighing 100 kg or less: 45 mg/dose subcutaneously; maintenance therapy every 12 weeks.
 
Crohn's Disease and Ulcerative Colitis
Weighing more than 85 kg: 520 mg single dose IV and 90 mg/dose subcutaneously every 8 weeks.
Weighing 56 to 85 kg: 390 mg single dose IV and 90 mg/dose subcutaneously every 8 weeks.
Weighing 55 kg or less: 260 mg single dose IV and 90 mg/dose subcutaneously every 8 weeks.

Adolescents

Weighing more than 100 kg: 90 mg/dose subcutaneously for plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, Crohn's disease or ulcerative colitis.
Weighing 60 to 100 kg: 45 mg/dose subcutaneously for plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, Crohn's disease or ulcerative colitis.
Weighing less than 60 kg: 0.75 mg/kg/dose subcutaneously for plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, Crohn's disease or ulcerative colitis.

Children

6 to 12 years weighing more than 100 kg: 90 mg/dose subcutaneously for plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, Crohn's disease or ulcerative colitis.
6 to 12 years weighing 60 to 100 kg: 45 mg/dose subcutaneously for plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, Crohn's disease or ulcerative colitis.
6 to 12 years weighing less than 60 kg: 0.75 mg/kg/dose subcutaneously for plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, Crohn's disease or ulcerative colitis.
1 to 5 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Ustekinumab is a human IgG monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit, which is part of both interleukin (IL)-12 and IL-23. Both IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. In in vitro models, ustekinumab 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-12R,beta-1. The cytokines IL-12 and IL-23 have also 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 IL-12 p40 and IL-23 p40 was shown to be protective. In a small exploratory study, a decrease was observed in the expression of mRNA of its molecular targets IL-12 and IL-23 in lesional skin biopsies in patients with psoriasis.
 
Normally, CD4+ T cells develop into T helper-1 (Th1) cells under the influence of IL-12. Th1 cells produce interferon gamma and mediate cellular immunity. In addition, IL-12 induces cutaneous lymphocyte antigen (CLA), resulting in T cell homing to the skin. Under the influence of IL-23, CD4+ T cells develop into IL-17 producing T cells (Th17). Th17 cells produce IL-17, IL-17F, IL-6, and TNF-alpha to mediate cellular immunity. Ustekinumab, by disrupting IL-12 and IL-23 signal transduction, suppresses the formation of the proinflammatory Th1 and Th17 cells. In vitro, ustekinumab inhibited IL-12 and IL-23-induced interferon-gamma, IL-17A, TNF-alpha, IL-2, and IL-10 secretion.
 
In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy. In mice deficient in IL-12 or in IL-12 and IL-23, ultraviolet-induced skin cancers developed earlier and more frequently; the relevance of these findings to humans is not known.

Pharmacokinetics

Ustekinumab is administered subcutaneously and intravenously. Ustekinumab metabolism has not been characterized, but the drug is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. The volume of distribution (Vd) of ustekinumab in the central compartment is 2.7 L in patients with Crohn's disease and 3 L in patients with ulcerative colitis. The total Vd at steady-state is 4.6 L in patients with Crohn's disease and 4.4 L in patients with ulcerative colitis. After subcutaneous administration in psoriasis patients, the mean half-life ranged from 14.9 +/- 4.6 days to 45.6 +/- 80.2 days. In a population pharmacokinetic analysis of ustekinumab, the clearance was 0.19 L/day with an estimated median terminal half-life of approximately 19 days in patients with Crohn's disease and ulcerative colitis.[36889]
 
Affected cytochrome P450 enzymes and drug transporters: Unknown
The effects of interleukins IL-12 or IL-23 on the regulation of CYP450 enzymes were evaluated in an in vitro study using human hepatocytes, which showed that IL-12 and/or IL-23 (at concentrations of 10 ng/mL) did not alter human CYP450 enzyme activities (CYP1A2, 2B6, 2C9, 2C19, 2D6, or 3A4). However, the clinical relevance has not been established. No in vivo drug interaction studies have been conducted with ustekinumab. The formation of CYP450 enzymes can be altered by increased concentrations of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF-alpha, IFN) during chronic inflammation. Thus, ustekinumab, an antagonist of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Monitor the therapeutic effect of any concomitant CYP450 substrates, particularly those with a narrow therapeutic index, when ustekinumab is initiated.[36889]

Intravenous Route

After the recommended intravenous induction dose, the mean peak serum ustekinumab concentration was 125.2 +/- 33.6 mcg/mL in patients with Crohn's disease and 129.1 +/- 27.6 mcg/mL in patients with ulcerative colitis.

Subcutaneous Route

The median time to reach the maximum serum concentration was 13.5 days after a single 45-mg subcutaneous dose and 7 days after a single 90-mg subcutaneous dose to patients with psoriasis. Steady-state serum concentrations were achieved by week 28. After the same dose, lower median ustekinumab concentrations were noted among people who weighed more than 100 kg as compared with concentrations from people who weighed 100 kg or less. For psoriasis patients receiving different doses according to weight, the mean (+/- SD) steady-state trough serum ustekinumab concentrations were 0.69 +/- 0.69 mcg/mL for patients weighing 100 kg or less receiving a 45-mg dose and 0.74 +/- 0.78 mcg/mL for patients weighing more than 100 kg receiving a 90-mg dose. In patients with Crohn's disease and ulcerative colitis receiving subcutaneous maintenance doses of ustekinumab 90 mg starting at week 8 and continuing every 8 weeks thereafter, steady-state was achieved by the start of the second maintenance dose. There was no apparent accumulation in ustekinumab concentration over time when given subcutaneously every 8 weeks. Mean steady-state trough concentration for ustekinumab 90-mg administered every 8 weeks was 2.51 +/- 2.06 mcg/mL in Crohn's patients and 3.3 +/- 2.3 mcg/mL in patients with ulcerative colitis. No apparent accumulation of ustekinumab was noted.[36889]

Pregnancy And Lactation
Pregnancy

Data on the use of ustekinumab during human pregnancy from observational studies, published case reports, and postmarketing surveillance are limited and are insufficient to inform a drug-associated risk. In developmental and reproductive studies involving cynomolgus monkeys, no teratogenic or other adverse developmental effects were observed following administration of ustekinumab resulting in exposures greater than 100 times the human exposure at the maximum recommended human subcutaneous dose (MRHD). In a combined embryo-fetal and pre- and post-natal development toxicity study in which pregnant cynomolgus monkeys received subcutaneous doses of ustekinumab at exposures greater than 100 time the MRHD, neonatal deaths occurred in the offspring of 1 monkey administered ustekinumab at 22.5 mg/kg and in 1 monkey dosed at 45 mg/kg. No effects on functional, morphological, or immunological development were observed in offspring from birth to 6 months of age. Guidelines recommend that ustekinumab be replaced before conception and during pregnancy by other medication until more data regarding the drug's use during pregnancy are available; use ustekinumab during pregnancy only when no other pregnancy-compatible drug can effectively control maternal disease. Current evidence does not indicate an increased rate of congenital malformations; because of limited evidence, however, alternative medications should be considered for treatment throughout pregnancy. If the drug must be used during pregnancy, experts recommend that ustekinumab use be discontinued 8 to 10 weeks before delivery, as transplacental drug transfer is expected later in pregnancy and during delivery. Pediatricians should be informed of any in utero exposure of an infant. Experts recommend avoidance of live vaccines in exposed neonates or infants for at least 9 months following birth or until infant drug levels become undetectable. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to ustekinumab; information about the registry can be obtained at mothertobaby.org/ongoing-study/stelara or by calling 1-877-311-8972.