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STELARA (ustekinumab) injection, for subcutaneous
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use STELARA ® safely and effectively. See full prescribing information for STELARA ®.
STELARA ® (ustekinumab) injection, for subcutaneous use
Initial U.S. Approval: 2009
RECENT MAJOR CHANGES
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Indications and Usage, Psoriatic Arthritis (1.2) |
09/2013 |
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Dosage and Administration, Dosing (2.1) |
09/2013 |
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Dosage and Administration (2.2) |
05/2013 |
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Warnings and Precautions, Infections (5.1) |
03/2014 |
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Warnings and Precautions, Hypersensitivity Reactions (5.5) |
09/2013 |
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Warnings and Precautions, Reversible Posterior Leukoencephalopathy Syndrome (5.6) |
03/2014 |
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Warnings and Precautions, Concomitant Therapies (5.8) |
03/2014 |
INDICATIONS AND USAGE
STELARA® is a human interleukin-12 and -23 antagonist indicated for the treatment of adult patients (18 years or older) with
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moderate to severe plaque psoriasis (Ps) who are candidates for phototherapy or systemic therapy. (1.1)
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active psoriatic arthritis (PsA), alone or in combination with methotrexate. (1.2)
DOSAGE AND ADMINISTRATION
STELARA® is administered by subcutaneous injection. (2)
Psoriasis
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For patients weighing ≤100 kg (220 lbs), the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. (2.1)
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For patients weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. (2.1)
Psoriatic Arthritis
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The recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. (2.1).
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For patients with co-existent moderate-to-severe plaque psoriasis weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. (2.1)
DOSAGE FORMS AND STRENGTHS
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Injection: 45 mg/0.5 mL in a single-use prefilled syringe (3)
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Injection: 90 mg/mL in a single-use prefilled syringe (3)
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Injection: 45 mg/0.5 mL in a single-use vial (3)
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Injection: 90 mg/mL in a single-use vial (3)
CONTRAINDICATIONS
Clinically significant hypersensitivity to ustekinumab or to any of the excipients. (4)
WARNINGS AND PRECAUTIONS
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Infections: Serious infections have occurred. Do not start STELARA® during any clinically important active infection. If a serious infection develops, stop STELARA® until the infection resolves. (5.1)
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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. Diagnostic tests for these infections should be considered as dictated by clinical circumstances. (5.2)
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Tuberculosis (TB): eva luate patients for TB prior to initiating treatment with STELARA®. Initiate treatment of latent TB before administering STELARA®. (5.3)
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Malignancies: STELARA® may increase risk of malignancy. The safety of STELARA® in patients with a history of or a known malignancy has not been eva luated. (5.4)
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Anaphylaxis or other clinically significant hypersensitivity reactions may occur. (5.5)
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Reversible Posterior Leukoencephalopathy Syndrome (RPLS): One case was reported. If suspected, treat promptly and discontinue STELARA®. (5.6)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥3% and greater than with placebo): Nasopharyngitis, upper respiratory tract infection, headache, and fatigue. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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Live vaccines: Live vaccines should not be given with STELARA®. (7.1)
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Concomitant therapy: In psoriasis studies, the safety of concomitant use of STELARA® with immunosuppressants or phototherapy has not been eva luated. (7.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 3/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Psoriasis (Ps)
STELARA® is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
1.2 Psoriatic Arthritis (PsA)
STELARA® is indicated for the treatment of adult patients (18 years or older) with active psoriatic arthritis. STELARA® can be used alone or in combination with methotrexate (MTX).
2 DOSAGE AND ADMINISTRATION
2.1 Dosing
STELARA® is administered by subcutaneous injection.
Psoriasis
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For patients weighing ≤100 kg (220 lbs), the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
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For patients weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks.
In subjects weighing >100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects [see Clinical Studies (14)].
Psoriatic Arthritis
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The recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
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For patients with co-existent moderate-to-severe plaque psoriasis weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks.
2.2 General Considerations for Administration
STELARA® is for subcutaneous administration. STELARA® is intended for use under the guidance and supervision of a physician. STELARA® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
After proper training in subcutaneous injection technique, a patient may self inject with STELARA® if a physician determines that it is appropriate. Patients should be instructed to follow the directions provided in the Medication Guide (see Medication Guide).
Prior to administration, STELARA® should be visually inspected for particulate matter and discoloration. STELARA® is colorless to light yellow and may contain a few small translucent or white particles. STELARA® should not be used if it is discolored or cloudy, or if other particulate matter is present. STELARA® does not contain preservatives; therefore, any unused product remaining in the vial and/or syringe should be discarded.
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 single-use vial, a 27 gauge, ½ inch needle is recommended.
2.3 Instructions for Administration of STELARA® Prefilled Syringes Equipped with Needle Safety Guard
Refer to the diagram below for the provided instructions.
To prevent premature activation of the needle safety guard, do not touch the NEEDLE GUARD ACTIVATION CLIPS at any time during use.
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Hold the BODY and remove the NEEDLE COVER. Do not hold the PLUNGER or PLUNGER HEAD while removing the NEEDLE COVER or the PLUNGER may move. Do not use the prefilled syringe if it is dropped without the NEEDLE COVER in place.
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Inject STELARA® subcutaneously as recommended [see Dosage and Administration (2.2)].
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Inject all of the medication by pushing in the PLUNGER until the PLUNGER HEAD is completely between the needle guard wings. Injection of the entire prefilled syringe contents is necessary to activate the needle guard.
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After injection, maintain the pressure on the PLUNGER HEAD and remove the needle from the skin. Slowly take your thumb off the PLUNGER HEAD to allow the empty syringe to move up until the entire needle is covered by the needle guard, as shown by the illustration below:
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Used syringes should be placed in a puncture-resistant container.
3 DOSAGE FORMS AND STRENGTHS
STELARA® solution is colorless to slightly yellow in appearance and contains 90 mg ustekinumab per mL.
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Injection: 45 mg/0.5 mL in a single-use prefilled syringe
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Injection: 90 mg/mL in a single-use prefilled syringe
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Injection: 45 mg/0.5 mL in a single-use vial
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Injection: 90 mg/mL in a single-use vial
4 CONTRAINDICATIONS
Clinically significant hypersensitivity to ustekinumab or to any of the excipients [see Warnings and Precautions (5.5)].
5 WARNINGS AND PRECAUTIONS
5.1 Infections
STELARA® may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections were observed in subjects receiving STELARA® [see Adverse Reactions (6.1)].
STELARA® should not be given to patients with any clinically important active infection. STELARA® should not be administered until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. Exercise caution when considering the use of STELARA® in patients with a chronic infection or a history of recurrent infection.
Serious infections requiring hospitalization occurred in the psoriasis and psoriatic arthritis development programs. In the psoriasis program, serious infections included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis and urinary tract infections. In the psoriatic arthritis program, serious infections included cholecystitis.
5.2 Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients.
It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA® will be susceptible to these types of infections. Appropriate diagnostic testing should be considered, e.g., tissue culture, stool culture, as dictated by clinical circumstances.
5.3 Pre-treatment eva luation for Tuberculosis
eva luate patients for tuberculosis infection prior to initiating treatment with STELARA®.
Do not administer STELARA® to patients with active tuberculosis. 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. Patients receiving STELARA® should be monitored closely for signs and symptoms of active tuberculosis during and after treatment.
5.4 Malignancies
STELARA® is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among subjects who received STELARA® in clinical studies [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 eva luated 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. All patients receiving STELARA® should be monitored for the appearance of non-melanoma skin cancer. Patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment should be followed closely [see Adverse Reactions (6.1)].
5.5 Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported post-marketing. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue STELARA® [see Adverse Reactions (6.3)].
5.6 Reversible Posterior Leukoencephalopathy Syndrome
One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in the clinical trial safety databases for psoriasis and psoriatic arthritis. The subject, who had received 12 doses of STELARA® over approximately two years, presented with headache, seizures and confusion. No additional STELARA® injections were administered and the subject fully recovered with appropriate treatment..
RPLS is a neurological disorder, which is not caused by demyelination or a known infectious agent. RPLS can present with headache, seizures, confusion and visual disturbances. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Fatal outcomes have been reported.
If RPLS is suspected, administer appropriate treatment and discontinue STELARA®.
5.7 Immunizations
Prior to initiating therapy with STELARA®, patients should receive all immunizations appropriate for age as recommended by current immunization guidelines. Patients being treated with STELARA® should not receive live vaccines. BCG vaccines should not be given 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.
5.8 Concomitant Therapies
In psoriasis studies the safety of STELARA® in combination with other immunosuppressive agents or phototherapy has not been eva luated. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of STELARA® [see Drug Interactions (7.2)]. Ultraviolet-induced skin cancers developed earlier and more frequently in mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone [see Nonclinical Toxicology (13)].
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the label:
6.1 Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Psoriasis Clinical Studies
The safety data reflect exposure to STELARA® in 3117 psoriasis subjects, including 2414 exposed for at least 6 months, 1855 exposed for at least one year, 1653 exposed for at least two years, 1569 exposed for at least three years, 1482 exposed for at least four years and 838 exposed for at least five years.
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the STELARA® groups than the placebo group during the placebo-controlled period of Ps STUDY 1 and Ps STUDY 2 [see Clinical Studies (14)].
Adverse reactions that occurred at rates less than 1% in the controlled period of Ps STUDIES 1 and 2 through week 12 included: cellulitis, herpes zoster, diverticulitis and certain injection site reactions (pain, swelling, pruritus, induration, hemorrhage, bruising, and irritation).
One case of RPLS occurred during clinical trials [see Warnings and Precautions (5.6)].
Infections
In the placebo-controlled period of clinical studies of psoriasis subjects (average follow-up of 12.6 weeks for placebo-treated subjects and 13.4 weeks for STELARA®-treated subjects), 27% of STELARA®-treated subjects reported infections (1.39 per subject-year of follow-up) compared with 24% of placebo-treated subjects (1.21 per subject-year of follow-up). Serious infections occurred in 0.3% of STELARA®-treated subjects (0.01 per subject-year of follow-up) and in 0.4% of placebo-treated subjects (0.02 per subject-year of follow-up) [see Warnings and Precautions (5.1)].
In the controlled and non-controlled portions of psoriasis clinical trials (median follow up of 3.2 years), representing 8998 subject-years of exposure, 72.3% of STELARA®-treated subjects reported infections (0.87 per subject-years of follow-up). Serious infections were reported in 2.8% of subjects (0.01 per subject-years of follow-up).
Malignancies
In the controlled and non-controlled portions of psoriasis clinical trials (median follow up of 3.2 years, representing 8998 subject-years of exposure), 1.7% of STELARA®-treated subjects reported malignancies excluding non-melanoma skin cancers (0.60 per hundred subject-years of follow-up). Non-melanoma skin cancer was reported in 1.5% of STELARA®-treated subjects (0.52 per hundred subject-years of follow-up) [see Warnings and Precautions (5.4)]. The most frequently observed malignancies other than non-melanoma skin cancer during the clinical trials were: prostate, melanoma, colorectal and breast. Malignancies other than non-melanoma skin cancer in STELARA®-treated patients during the controlled and uncontrolled portions of studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender and race).1
Psoriatic Arthritis Clinical Studies
The safety of STELARA® was assessed in 927 patients in two randomized, double-blind, placebo-controlled studies in adult patients with active psoriatic arthritis (PsA). The overall safety profile of STELARA® in patients with PsA was consistent with the safety profile seen in psoriasis clinical studies. A higher incidence of arthralgia, nausea, and dental infections was observed in STELARA®-treated patients when compared with placebo-treated patients (3% vs. 1% for arthralgia and 3% vs. 1% for nausea; 1% vs. 0.6% for dental infections) in the placebo-controlled portions of the PsA clinical trials.
6.2 Immunogenicity
Approximately 6% of patients treated with STELARA® in psoriasis and psoriatic arthritis clinical studies developed antibodies to ustekinumab, which were generally low-titer. No apparent association between the development of antibodies to ustekinumab and the development of injection site reactions was seen. No ustekinumab-related serious hypersensitivity reactions were observed in psoriasis and psoriatic arthritis clinical trials. In psoriasis studies, the majority of patients who were positive for antibodies to ustekinumab had neutralizing antibodies.
The data above reflect the percentage of subjects whose test results were positive for antibodies to ustekinumab and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to ustekinumab with the incidence of antibodies to other products may be misleading.
6.3 Post-marketing Experience
Adverse reactions have been reported during post-approval use with 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.
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Immune system disorders: Serious hypersensitivity reactions (including anaphylaxis and angioedema), other hypersensitivity reactions (including rash and urticaria).
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Skin reactions: Pustular psoriasis, erythrodermic psoriasis.
7 DRUG INTERACTIONS
Drug interaction studies have not been conducted with STELARA®.
7.2 Concomitant Therapies
In psoriasis studies the safety of STELARA® in combination with immunosuppressive agents or phototherapy has not been eva luated. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of STELARA®
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