Ustekinumab

Ustekinumab is a human interleukin-12 and -23 antagonist indicated for the treatment of: Moderate to severe plaque psoriasis in adults and pediatric patients 6 years of age and older who are candidates for phototherapy or systemic therapy. Active psoriatic arthritis in adults and pediatric patients 6 years of age and older. Moderately to severely active Crohn's disease in adults and pediatric patients 2 years of age and older. Moderately to severely active ulcerative colitis in adults and pediatric patients 2 years of age and older.

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 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-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.

Adult Patients with Plaque Psoriasis Subcutaneous Recommended Dosage: Weight Range (kilograms) Recommended Dosage 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 Pediatric Patients 6 Years of Age and Older with Plaque Psoriasis Subcutaneous Recommended Dosage: Weight-based dosing is recommended at the initial dose, 4 weeks later, then every 12 weeks thereafter.

Ustekinumab is contraindicated in patients with clinically significant hypersensitivity to any ustekinumab product or to any of the excipients in Ustekinumab. Clinically significant hypersensitivity to any ustekinumab product or to any of the excipients in 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. 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. Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with Ustekinumab. Initiate treatment of latent TB before administering Ustekinumab. 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.

The following serious adverse reactions are discussed elsewhere in the label: Infections Malignancies Serious Hypersensitivity Reactions Posterior Reversible Encephalopathy Syndrome (PRES) Noninfectious Pneumonia Most common adverse reactions are: Psoriasis and Psoriatic Arthritis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue. Crohn's Disease induction (≥3%): vomiting. maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. Ulcerative Colitis induction (≥3%): nasopharyngitis. maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea.

Concomitant Therapies In trials in subjects with plaque psoriasis the safety of Ustekinumab 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 Ustekinumab. 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 Ustekinumab.

Store Ustekinumab vials and prefilled syringes refrigerated between 2 ºC to 8 ºC (36 ºF to 46 ºF). Do not freeze. If needed, individual prefilled syringes may be stored at room temperature up to 30 °C (86 °F) 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 first removed from the refrigerator on the carton in the space provided. Once a syringe has been stored at room temperature, do not return to the refrigerator. Discard the syringe if not used within 30 days at room temperature storage. Store Ustekinumab vials upright. Keep the product in the original carton to protect from light until the time of use.