2.1 Dosing

STELARA® is administered by subcutaneous injection.

• 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.
• 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)].

The safety and efficacy of STELARA® have not been eva luated beyond two years.

2.2 General Considerations for Administration

STELARA® is intended for subcutaneous administration under the supervision of a physician.

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.

STELARA® should only be administered by a healthcare provider. STELARA® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

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.

• 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.
• Inject STELARA® subcutaneously as recommended [see Dosage and Administration (2.2)].
• 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.
  
  
• 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:
  
  
• Used syringes should be placed in a puncture-resistant container.

5.1Infections

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 development program. These serious infections included cellulitis, diverticulitis, osteomyelitis, viral infections, gastroenteritis, pneumonia, and urinary tract infections.

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.

5.5 Hypersensitivity Reactions

Serious allergic reactions, including angioedema and possible anaphylaxis, have been reported post-marketing. If an anaphylactic or other serious allergic reaction occurs, discontinue STELARA® and institute appropriate therapy [see Adverse Reactions (6.2)].

5.6 Reversible Posterior Leukoencephalopathy Syndrome

One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed during the clinical development program which included 3523 STELARA®-treated subjects. 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, STELARA® should be discontinued and appropriate treatment administered.

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

The safety of STELARA® in combination with other immunosuppressive agents or phototherapy has not been eva luated. 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)].

5.9 Theoretical Risk of Immunotherapy

STELARA® has not been eva luated in patients who have undergone allergy immunotherapy. STELARA® may decrease the protective effect of allergy immunotherapy and 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 allergy immunotherapy, particularly for anaphylaxis.