使用说明

强生单抗药物ustekinumab（商品名 Stelara）获FDA和欧盟批准批准上市，单独用药或与甲氨蝶呤（methotrexate）联合用药，用于18岁及以上活动性银屑病关节炎（active Psoriatic arthritis，PsA）及克罗恩病患者的治疗。
批准日期：2013年9月20日  公司：强生制药
STELARA®（优特克诺[ustekinumab]）注射剂 用于皮下或静脉内使用
美国初步批准：2009年
最近的主要变化
适应症和用法，克罗恩病：09/06
剂量与管理：09/06
剂量与管理：09/06
作用机制
Ustekinumab是与IL-12和IL-23细胞因子使用的p40蛋白亚基的特异性结合的人IgG1қ单克隆抗体。 IL-12和IL-23是参与炎性和免疫应答的天然存在的细胞因子，例如自然杀伤细胞激活和CD4+T细胞分化和激活。在体外模型中，ustekinumab显示通过破坏这些细胞因子与共享的细胞表面受体链IL-12Rβ1的相互作用来破坏IL-12和IL-23介导的信号传导和细胞因子级联。细胞因子IL-12和IL-23被认为是作为克罗恩病特征的慢性炎症的重要贡献者。在结肠炎的动物模型中，IL-12和IL-23的p40亚基的遗传缺失或抗体阻断是乌司他丁的靶标，被证明是保护性的。
适用范围及用途
STELARA®是一种人白细胞介素-12和-23拮抗剂，用于治疗成人患者：
中度至重度斑块性银屑病（Ps）谁是光疗或全身治疗的候选人。
活动性银屑病关节炎（PsA），单独或与甲氨蝶呤组合。
中度至严重的克罗恩病（CD）患者
失败或不容忍用免疫调节剂或皮质类固醇治疗，但从未破坏肿瘤坏死因子（TNF）阻滞剂或
失败或不容忍用一种或多种TNF阻断剂治疗。
剂量和管理
牛皮癣推荐成人皮下用量
体重范围（千克）剂量方案
初始和4周后皮下投予小于或等于100kg的45mg，随后每12周皮下投予45mg
最初和4周后皮下施用大于100kg的90mg，随后每12周皮下注射90mg
银屑病关节炎推荐成人皮下用量：
推荐剂量为45mg，最初皮下注射，4周后，随后每12周皮下注射45mg。
对于重度大于100 kg的中重度斑块性银屑病患者，推荐剂量为90mg，最初皮下注射，4周后，随后每12周皮下注射90 mg。
克罗恩病推荐的初始成人静脉注射剂量：
使用基于重量的给药的单次静脉输注：
重量范围（千克）推荐用量
最多55公斤260毫克（2vials）
大于55 kg至85 kg 390mg（3vials）
大于85公斤520毫克（4瓶）
克罗恩病推荐维持成人皮下用量：
在初次静脉内给药后8周皮下注射90mg剂量，然后每8周给药一次。
剂量形式和强度
小切口注射
注射：在单剂量预充式注射器中为45mg/0.5mL或90mg/mL
注射：在单剂量小瓶中为45mg/0.5mL
静脉注射
注射：在单剂量小瓶中130mg/26mL（5mg/mL）溶液
禁忌症
对乌斯卡单抗或任何赋形剂的临床显着超敏反应。
警告和注意事项
感染：发生严重感染。在任何临床上重要的活动性感染中，不要开始STELARA®。如果发生严重感染或临床重大感染，请考虑停止STELARA®直至感染消退。
特异性感染的理论风险：在IL-12/IL-23基因缺陷的患者中已经报道了分枝杆菌，沙门氏菌和卡介苗（BCG）疫苗的严重感染。这些感染的诊断试验应视为临床情况所决定。
结核病（TB）：在用STELARA®开始治疗之前评估患者的结核病。在服用STELARA®之前开始治疗潜伏性TB。
恶性肿瘤：STELARA®可能会增加恶性肿瘤的风险。STELARA®在具有或已知恶性肿瘤病史的患者中的安全性尚未得到评估。
超敏反应：可能会发生过敏反应或其他临床上显着的超敏反应。
可逆性后脑白质综合症（RPLS）：有一例报道。如果怀疑，立即治疗并停止STELARA®。
不良反应
最常见的不良反应是：
牛皮癣（≥3％）：鼻咽炎，上呼吸道感染，头痛，乏力。
克罗恩病，诱导（≥3％）：呕吐。
克罗恩病，维持（≥3％）：鼻咽炎，注射部位红斑，外阴阴道念珠菌病/真菌感染，支气管炎，瘙痒，尿路感染和鼻窦炎。
包装规格/存储和处理
STELARA®（ustekinumab）注射液是无菌，无防腐剂的无色至微黄色溶液。 STELARA®可用于含有45mg或90mg的单剂量预灌注注射器或含有45mg ustekinumab用于皮下使用的单剂量小瓶。每个预充式注射器配备有27号固定½英寸针头，针头安全护罩和包含干燥天然橡胶的针头盖。
STELARA®也可用于含有130mg ustekinumab的单剂量小瓶，用于静脉注射。
皮下使用NDC
45mg/0.5mL 单剂量预灌注注射器57894-060-03
90mg/mL 单剂量预灌注注射器57894-061-03
45mg/0.5mL 单剂量小瓶57894-060-02
静脉注射NDC
130mg/26mL（5mg/mL）单剂量小瓶57894-054-27
存储和稳定性
STELARA®小瓶和预充式注射器必须在2°C至8°C（36°F至46°F）下冷藏。将STELARA®小瓶直立存放。将产品保存在原始纸箱中以防止光直到使用时间。不要冻结不要动摇。
完整说明书附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c77a9664-e3bb-4023-b400-127aa53bca2b
STELARA® (ustekinumab) is indicated for the treatment of adult patients with active psoriatic arthritis. STELARA® can be used alone or in combination with methotrexate (MTX).
STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have:
•failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a tumor necrosis factor (TNF) blocker, or•failed or were intolerant to treatment with one or more TNF blockers.
For plaque psoriasis and psoriatic arthritis:
STELARA®, available as 45 and 90 mg, is a subcutaneous injection intended for use under the guidance and supervision of a physician with patients who will be closely monitored and have regular follow-up. Patients may self-inject with STELARA® after physician approval and proper training. Patients should be instructed to follow the directions provided in the Medication Guide.
For Crohn’s disease:
STELARA® for Intravenous Infusion is available as a 130 mg/26 mL (5 mg/mL) single-dose vial. It must be diluted, prepared, and infused by a healthcare professional for Crohn’s disease.
STELARA®, available as 90 mg, is a subcutaneous injection intended for use under the guidance and supervision of a physician with patients who will be closely monitored and have regular follow-up. Patients may self-inject with STELARA® after physician approval and proper training. Patients should be instructed to follow the directions provided in the Medication Guide.
IMPORTANT SAFETY INFORMATION
Infections
STELARA® (ustekinumab) may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections, some requiring hospitalization, were reported. In patients with psoriasis, serious infections included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis and urinary tract infections. In patients with psoriatic arthritis, serious infections included cholecystitis. In patients with Crohn’s disease, serious or other clinically significant infections included anal abscess, gastroenteritis, ophthalmic herpes, pneumonia, and Listeria meningitis.
Treatment with STELARA® should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of STELARA® in patients with a chronic infection or a history of recurrent infection.
Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with STELARA® and consider discontinuing STELARA® for serious or clinically significant infections until the infection resolves or is adequately treated.
Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria, Salmonella, 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® may be susceptible to these types of infections. Appropriate diagnostic testing should be considered, e.g., tissue culture, stool culture, as dictated by clinical circumstances.
Pre-Treatment Evaluation of Tuberculosis (TB)
Evaluate patients for TB prior to initiating treatment with STELARA®. Do not administer STELARA® to patients with active tuberculosis infection. Initiate treatment of latent TB before administering STELARA®. Closely monitor patients receiving STELARA® for signs and symptoms of active TB during and after treatment.
Malignancies
STELARA® is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among patients who received STELARA® in clinical studies. The safety of STELARA® has not been evaluated in patients who have a history of malignancy or who have a known malignancy.
There have been reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving STELARA® who had risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving STELARA®, especially those >60 years or those with a history of PUVA or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC.
Hypersensitivity Reactions
STELARA® is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or excipients. Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA®. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue STELARA®.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS were observed in clinical studies of Crohn’s disease. If RPLS is suspected, administer appropriate treatment and discontinue STELARA®. RPLS is a neurological disorder, which is not caused by an infection or demyelination. RPLS can present with headache, seizures, confusion, and visual disturbances. RPLS has been associated with fatal outcomes.
Immunizations
Prior to initiating therapy with STELARA®, patients should receive all age-appropriate immunizations recommended by current guidelines. Patients being treated with STELARA® should not receive live vaccines. BCG vaccines should not be given during treatment or within one year of initiating or discontinuing STELARA®. Exercise caution when administering live vaccines to household contacts of STELARA® patients, as shedding and subsequent transmission to STELARA® patients may occur. Non-live vaccinations received during a course of STELARA® may not elicit an immune response sufficient to prevent disease.
Concomitant Therapies
The safety of STELARA® in combination with other immunosuppressive agents or phototherapy was not evaluated in clinical studies of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of STELARA®. In Crohn’s disease studies, concomitant use of 6-mercaptopurine, azathioprine, methotrexate and corticosteroids did not appear to influence the overall safety or efficacy of STELARA®.
Allergen Immunotherapy
STELARA® may decrease the protective effect of allergen immunotherapy (decrease tolerance) which 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 allergen immunotherapy, particularly for anaphylaxis.
Most Common Adverse Reactions
The most common adverse reactions (≥3% and higher than that with placebo) in psoriasis clinical trials for STELARA® 45 mg, STELARA® 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively. In psoriatic arthritis (PsA) studies, a higher incidence of arthralgia and nausea was observed in patients treated with STELARA® when compared with placebo (3% vs 1% for both). In Crohn’s disease induction studies, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 8 for STELARA® 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In the Crohn’s disease maintenance study, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 44 were: nasopharyngitis (11% vs 8%), injection site erythema (5% vs 0%), vulvovaginal candidiasis/mycotic infection (5% vs 1%), bronchitis (5% vs 3%), pruritus (4% vs 2%), urinary tract infection (4% vs 2%) and sinusitis (3% vs 2%).

Ustekinumab

Pronunciation

(yoo stek in YOO mab)

Index TermsCNTO 1275Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Stelara: 130 mg/26 mL (26 mL) [contains edetate disodium dihydrate, polysorbate 80]

Solution, Subcutaneous [preservative free]:

Stelara: 45 mg/0.5 mL (0.5 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Stelara: 45 mg/0.5 mL (0.5 mL); 90 mg/mL (1 mL) [contains polysorbate 80]

Brand Names: U.S.StelaraPharmacologic CategoryAntipsoriatic AgentInterleukin-12 InhibitorInterleukin-23 InhibitorMonoclonal AntibodyPharmacology

Ustekinumab is a human monoclonal antibody that binds to and interferes with the proinflammatory cytokines, interleukin (IL)-12 and IL-23. Biological effects of IL-12 and IL-23 include natural killer (NK) cell activation, CD4+ T-cell differentiation and activation. Ustekinumab also interferes with the expression of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-inducible protein-10 (IP-10), and interleukin-8 (IL-8). Significant clinical improvement in psoriasis and psoriatic arthritis patients is seen in association with reduction of these proinflammatory signalers.

Distribution

Vd (central compartment): 2.74 L; Vdss: Crohn disease: 4.62 L

Time to Peak

Plasma: 45 mg: 13.5 days; 90 mg: 7 days

Half-Life Elimination

10 to 126 days; Psoriasis: 14.9 ± 4.6 to 45.6 ± 80.2 days; Crohn disease: ~19 days

Special Populations Note

Body weight: When given the same dose, subjects weighing >100 kg had lower median serum concentrations compared with those subjects weighing ≤100 kg. The median trough serum concentrations of ustekinumab in subjects >100 kg in the 90 mg group were comparable with those in subjects ≤100 kg in the 45 mg group.

Use: Labeled Indications

Crohn disease: Treatment of moderately to severely active Crohn disease in adults who have failed or were intolerant to immunomodulatory or corticosteroid therapy, but never failed tumor necrosis factor (TNF) blocker therapy or who have failed or were intolerant to treatment with one or more TNF blockers.

Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in patients ≥12 years of age who are candidates for phototherapy or systemic therapy

Psoriatic arthritis: Treatment of active psoriatic arthritis (as monotherapy or in combination with methotrexate) in adults

Contraindications

Clinically significant hypersensitivity to ustekinumab or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Severe infections such as sepsis, tuberculosis, and opportunistic infections

Dosing: Adult

Crohn disease:

Induction: IV:

≤55 kg: 260 mg as single dose

>55 kg to 85 kg: 390 mg as single dose

>85 kg: 520 mg as single dose

Maintenance: SubQ: 90 mg every 8 weeks; begin maintenance dosing 8 weeks after the IV induction dose.

Plaque psoriasis: SubQ:

Initial and maintenance:

≤100 kg: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter

>100 kg: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter. Note: Doses of 45 mg given to patients >100 kg were also efficacious; however, 90 mg is the recommended dose in these patients due to greater efficacy.

Psoriatic arthritis: SubQ: Note: When used for psoriatic arthritis, may be administered alone or in combination with methotrexate.

Initial and maintenance: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter.

Coexistent psoriatic arthritis and moderate to severe plaque psoriasis in patients >100 kg: Initial and maintenance: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Plaque psoriasis: Children ≥12 years of age and Adolescents: SubQ:

<60 kg: 0.75 mg/kg at 0 and 4 weeks, and then every 12 weeks thereafter

≥60 kg to ≤100 kg: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter

>100 kg: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Reconstitution

IV: After calculating the appropriate dosage and volume of ustekinumab (using 130 mg per 26 mL vials), withdraw an equal volume of fluid from 250 mL bag of NS and discard. Add ustekinumab to the NS bag; final volume of bag should be 250 mL. Gently mix bag.

Administration

IV: Infuse over at least 1 hour; use of IV set with an in-line, low-protein binding filter (0.2 micrometer) required. Do not infuse concomitantly in the same IV line with other agents.

Subcutaneous: Administer by subcutaneous injection into the top of the thigh, abdomen, upper arms, or buttocks. Rotate sites. Do not inject into tender, bruised, erythematous, or indurated skin. Avoid areas of skin where psoriasis is present. Discard any unused portion. Intended for use under supervision of physician; self-injection may occur after proper training.

Storage

Refrigerate vials and prefilled syringes at 2°C to 8°C (36°F to 46°F); do not freeze. Store vials upright. Keep the product in the original carton to protect from light until the time of use. Do not shake. Discard any unused portion. Once diluted, solution for IV infusion may be stored up to 4 hours at room temperature (up to 25°C [77°F]).

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

InFLIXimab: Ustekinumab may enhance the immunosuppressive effect of InFLIXimab. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

>10%:

Infection: Infection (psoriasis: 27% to 72%; severe infection: ≤3%)

Respiratory: Nasopharyngitis (Crohn disease: 11%)

1% to 10%:

Central nervous system: Headache (psoriasis: 5%), fatigue (psoriasis: 3%), dizziness (psoriasis: 2%), depression (psoriasis: 1%)

Dermatologic: Pruritus (2% to 4%), acne vulgaris (Crohn disease: 1%)

Gastrointestinal: Vomiting (Crohn disease: 4%), nausea (psoriatic arthritis: 3%), dental disease (infection; 1%)

Genitourinary: Vaginal mycosis (Crohn disease: ≤5%), vulvovaginal candidiasis (Crohn disease: ≤5%), urinary tract infection (Crohn disease: 4%)

Hematologic & oncologic: Skin carcinoma (nonmelanoma including squamous cell carcinoma; psoriasis: 2%)

Immunologic: Antibody development (≤6%; associated with reduced efficacy in psoriasis patients)

Local: Erythema at injection site (1% to 5%)

Neuromuscular & skeletal: Arthralgia (psoriatic arthritis: 3%), back pain (psoriasis: 2%), weakness (Crohn disease: 1%)

Respiratory: Bronchitis (Crohn disease: 5%), sinusitis (Crohn disease: 3%), pharyngolaryngeal pain (psoriasis: 2%)

Frequency not defined:

Gastrointestinal: Appendicitis, cholecystitis, gastroenteritis

Genitourinary: Perirectal abscess

Infection: Sepsis, viral infection

Neuromuscular & skeletal: Osteomyelitis

Respiratory: Pneumonia

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, bacterial infection, bleeding at injection site, bruising at injection site, cellulitis, diverticulitis, erythrodermic psoriasis, fungal infection, herpes zoster, hypersensitivity reaction, induration at injection site, irritation at injection site, itching at injection site, malignant neoplasm, meningitis due to listeria monocytogenes, ocular herpes simplex, pain at injection site, pustular psoriasis, reversible posterior leukoencephalopathy syndrome, skin rash, swelling at injection site, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: Antibody formation to ustekinumab has been observed with therapy.

• Hypersensitivity reactions: Hypersensitivity, including anaphylaxis and angioedema, has been reported. Discontinue immediately with signs/symptoms of hypersensitivity reaction and treat appropriately as indicated.

• Infections: May increase the risk for infections or reactivation of latent infections. Serious bacterial, fungal, and viral infections have been observed with use. Avoid use in patients with clinically important active infection until the infection resolves or is successfully treated. Exercise caution when considering use in patients with a history of new/recurrent infections, with conditions that predispose them to infections (eg, diabetes or residence/travel from areas of endemic mycoses), with chronic, latent, or localized infections, or who are genetically deficient in IL-12/IL-23 (IL-12/IL-23 genetic deficiency may predispose patients to disseminated infection). Patients who develop a new infection while undergoing treatment should consult their health care provider and be monitored closely. If a patient develops a serious infection, therapy should be discontinued or withheld until successful resolution of infection.

• Malignancy: May increase the risk for malignancy although the impact on the development and course of malignancies is not fully defined. Rapidly appearing cutaneous squamous cell carcinomas (multiple) have been reported in patients receiving ustekinumab who were at risk for developing nonmelanoma skin cancer. Monitor all patients closely for the development of nonmelanoma skin cancer; closely follow patients >60 years of age, with a history of prolonged immunosuppression, and in patients with a history of PUVA treatment. Use with caution in patients with prior malignancy (use not studied in this population).

• Neurotoxicity: Reversible posterior leukoencephalopathy syndrome (RPLS) has been observed (rare). RPLS symptoms include headache, seizures, confusion, and visual disturbances; may be fatal. Monitor; discontinue ustekinumab if symptoms occur and administer appropriate therapy.

• Tuberculosis: Do not use in patients with active tuberculosis (TB). Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to starting therapy. Treatment of latent TB should be initiated before ustekinumab therapy is used. Consider antituberculosis treatment in patients with a history of latent or active tuberculosis if an adequate prior treatment course cannot be confirmed. During and following treatment, monitor for signs/symptoms of active TB.

Concurrent drug therapy issues:

• Allergen immunotherapy: Use caution in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis; ustekinumab may decrease the protective effect of allergen immunotherapy, which may increase the risk of an allergic reaction to allergen immunotherapy.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Immunosuppressive therapy: Use in combination with other immunosuppressive drugs during psoriasis studies has not been evaluated; use caution. Use in combination with methotrexate during psoriatic arthritis studies did not appear to affect safety or efficacy.

Special populations:

• Patients >100 kg: May require higher dose to achieve adequate serum levels.

Dosage form specific issues:

• Latex: Packaging may contain natural latex rubber.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; inactivated or nonlive vaccines may be given concurrently, but may not elicit a proper immune response. BCG vaccines should not be given 1 year prior to, during, or 1 year following treatment.

• Phototherapy: Use in combination with phototherapy has not been studied; use caution.

Monitoring Parameters

Tuberculosis screening (prior to initiating and periodically during therapy); CBC; ustekinumab-antibody formation; monitor for signs/symptoms of infection, reversible posterior leukoencephalopathy syndrome (RPLS), and squamous cell skin carcinoma

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies; there are limited data related to the use of ustekinumab in human pregnancy. In general, other agents are preferred for the treatment of plaque psoriasis in pregnant women (Hsu 2012).

Data collection to monitor pregnancy and infant outcomes following exposure to ustekinumab is ongoing. Patients may enroll themselves by calling 1-877-311-8972.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinitis, headache, vomiting, common cold symptoms, injection site irritation, or pharyngitis. Have patient report immediately to prescriber signs of infection, signs of posterior reversible encephalopathy syndrome (confusion, not alert, vision changes, seizures, or severe headache), shortness of breath, flushing, angina, severe dizziness, passing out, severe loss of strength and energy, vaginitis, mole changes, or skin growths (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.