Ustekinumab

Ustekinumab is used for: Plaque Psoriasis, Psoriatic Arthritis, Crohn Disease, Ulcerative Colitis

Plaque Psoriasis Indicated for the treatment of adults and adolescents aged ?12 years with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy <100 kg: 45 mg SC at Weeks 0 and 4, then q12weeks thereafter >100 kg: 90 mg SC at Weeks 0 and 4, then q12weeks thereafter Psoriatic Arthritis Indicated for adults with active psoriatic arthritis alone or in combination with methotrexate 45 mg SC at Weeks 0 and 4, then q12weeks thereafter For patients >100 kg with co-existent moderate-to-severe plaque psoriasis, increase dose to 90 mg SC at Weeks 0 and 4, then q12weeks thereafter Crohn Disease Indicated for adults with moderately to severely active Crohn disease who have Initial weight-based IV dose Single IV dose infused over 1 hr <55 kg: 260 mg IV >55 kg to 85 kg: 390 mg IV >85 kg: 520 mg IV Maintenance SC dose Begin 90 mg SC 8 weeks after the initial IV infusion, then q8wk thereafter Ulcerative Colitis Indicated for adults with moderately to severely active ulcerative colitis Initial weight-based IV dose Single IV dose infused over 1 hr (also see maintenance dose below) <55 kg: 260 mg IV >55 kg to 85 kg: 390 mg IV >85 kg: 520 mg IV Maintenance SC dose Begin 90 mg SC 8 weeks after the initial IV infusion, then q8wk thereafter

Plaque Psoriasis Indicated for treatment of adolescents aged ?12 years with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy <12 years: Safety and efficacy not established >12 years <60 kg: 0.75 mg/kg SC at Weeks 0 and 4, then q12weeks thereafter 60-100 kg: 45 mg SC at at Weeks 0 and 4, then q12weeks thereafter >100 kg: 90 mg SC at Weeks 0 and 4, then q12weeks thereafter

SC Preparation Visually inspect for particulate matter and discoloration Solution should appear clear, colorless to light yellow and may contain a few small translucent or white particles Do not use if it is discolored or cloudy, or if other particulate matter is present Does not contain preservatives; therefore, discard any unused product remaining in the vial and/or syringe SC Administration See full prescribing information for how to use prefilled syringe injector Each injection should be administered at a different anatomic location (eg, upper arms, gluteal regions, thighs, or any quadrant of abdomen) than the previous injection Do not inject into areas where the skin is tender, bruised, erythematous, or indurated When using the single-dose vial, a 27-gauge, 0.5-inch needle is recommended IV Preparation Must be diluted, prepared and infused by a healthcare professional using aseptic technique Calculate dose and the number of ustekinumab vials needed based on patient weight (see Adult Dosing) Each 26 mL vial contains 130 mg of ustekinumab Withdraw, and then discard a volume of the 0.9% NaCl from the 250 mL infusion bag equal to the volume ustekinumab to be added (discard 26 mL NaCl for each vial of needed, for 2 vials- discard 52 mL, for 3 vials- discard 78 mL, 4 vials- discard 104 mL) Withdraw 26 mL 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 Visually inspect the diluted solution before infusion Do not use if visibly opaque particles, discoloration or foreign particles are observed IV Administration Infuse the diluted solution over a period of at least 1 hr Once diluted, the infusion solution may be stored for up to 4 hr prior to infusion Use only an infusion set with an in-line, sterile, nonpyrogenic, low protein-binding filter (pore size 0.2 micrometer) Do not infuse concomitantly in the same IV line with other agents Does not contain preservatives Each vial is for single use only Discard any remaining solution

Hypersensitivity Active serious infection Concomitant live vaccines

Use caution in patients genetically deficient in IL-12/IL-23 Reversible posterior leukoencephalopathy syndrome (RPLS) reported (1 case); if RPLS is suspected, administer appropriate therapy and discontinue treatment Provide age-appropriate immunization prior to initiating therapy Hypersensitivity reactions reported, including anaphylaxis and angioedema Infections Do not administer treatment to patients with active tuberculosis infection; initiate treatment of latent tuberculosis (TB) prior to administering ustekinumab; closely monitor for signs and symptoms of active tuberculosis during and after treatment May increase risk of infections and reactivation of latent infections; serious bacterial, fungal, mycobacterial, and viral infections observed with treatment; evaluate for TB infection before initiating drug Malignancies Increased risk of malignancy Reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients with pre-existing risk factors for developing nonmelanoma skin cancer; monitor all patients for nonmelanoma skin cancer

Pregnancy Limited data on ustekinumab use in pregnant women to inform a drug associated risk In animal reproductive and developmental toxicity studies, no adverse developmental effects were observed after administration of ustekinumab to pregnant monkeys at exposures greater than 100 times the human exposure at the maximum recommended human subcutaneous dose (MRHD) Lactation Data are not available on the presence of ustekinumab in human milk, effects on the breastfed infant, or effects on milk production Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ustekinumab and any potential adverse effects on the breastfed child from ustekinumab or from the underlying maternal condition

Formation of CYP450 enzymes can be altered by increased levels of certain cytokines (eg, IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation; ustekinumab (IL-12 and IL-23 antagonist) may normalize the formation of CYP450 enzyme; monitor therapeutic effects (eg, warfarin) or concentration (eg, cyclosporine) with concomitant CYP450 substrates use (especially narrow therapeutic index drugs) Psoriasis studies the safety of ustekinumab in combination with immunosuppressive agents or phototherapy has not been evaluated; in psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy May decrease the protective effect of allergen immunotherapy Avoid use of live vaccines with ustekinumab BCG vaccines should not be given during treatment or for one year prior to initiating treatment or one year following discontinuation of treatment; use caution when administering live vaccines to household contacts of patients receiving treatment due to the potential risk for shedding from the household contact and transmission to patient

Side effects of Ustekinumab : >10% Upper respiratory infection 1-10% Nasopharyngitis Back pain Cellulitis Depression Diarrhea Fatigue Headache Injection site erythema Myalgia Fatigue Nasal congestion Urticaria Rash Pruritus Antibody formation <1% (selected) Severe infection Malignancy Reversible posterior leukoencephalopathy syndrome

Human IgG1κ monoclonal antibody binds to the p40 protein subunit used by IL-12 and IL-23 cytokines; IL-12 and IL-23 are involved in inflammatory and immune responses (eg, natural killer cell activation, CD4+ T-cell differentiation, and activation)