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YESINTEK is a brand name for Ustekinumab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE YESINTEK is a human interleukin-12 and -23 antagonist indicated for the treatment of: Adult patients with: moderate to severe plaque psoriasis (PsO) who are candidates for phototherapy or systemic therapy. ( 1.1 ) active psoriatic arthritis (PsA) . ( 1.2 ) moderately to severely active Crohn’s…
Verbatim from this product's FDA label. Tap a section to expand.
1 ): Weight-based dosing is recommended at the initial dose, 4 weeks later, then every 12 weeks thereafter. 2 ): The recommended dosage is 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks.
For patients with co-existent moderate-to-severe plaque psoriasis weighing greater than 100 kg, the recommended dosage is 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks.
2 ): Weight-based dosing is recommended at the initial dose, 4 weeks later, then every 12 weeks thereafter. 3 ) : A subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then every 8 weeks thereafter. 1 Recommended Dosage in Plaque Psoriasis Subcutaneous Adult Dosage Regimen For patients weighing 100 kg or less, the recommended dosage is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
For patients weighing more than 100 kg, the recommended dosage is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. In subjects weighing more than 100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects [see Clinical Studies (14) ] .
Subcutaneous Pediatric Dosage Regimen Administer YESINTEK subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter. The recommended dose of YESINTEK for pediatric patients 6 years of age and older with plaque psoriasis based on body weight is shown below (Table 1).
75 mg/kg) is shown in Table 2; withdraw the appropriate volume from the vial. 2 Psoriatic Arthritis; Subcutaneous Pediatric Dosage Regimen. 2 Recommended Dosage in Psoriatic Arthritis Subcutaneous Adult Dosage Regimen The recommended dosage is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.
For patients with co-existent moderate-to-severe plaque psoriasis weighing more than 100 kg, the recommended dosage is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. Subcutaneous Pediatric Dosage Regimen Administer YESINTEK subcutaneously at Weeks 0 and 4, then every 12 weeks thereafter.
The recommended dose of YESINTEK for pediatric patients 6 years of age and older with psoriatic arthritis, based on body weight, is shown below (Table 3). 75 mg/kg) is shown in Table 2; withdraw the appropriate volume from the vial.
8) ] Most common adverse reactions are: Psoriasis and Psoriatic Arthritis (≥3%) : nasopharyngitis, upper respiratory tract infection, headache, and fatigue. 1 ) Crohn’s Disease, induction (≥3%) : vomiting. 1 ) Crohn’s Disease, maintenance (≥3%) : nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis.
gov/medwatch. *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product.
, indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. 1 Clinical Trials 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.
Adult Subjects with Plaque Psoriasis The safety data reflect exposure to ustekinumab in 3117 adult subjects with plaque psoriasis, 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 5 summarizes the adverse reactions that occurred at a rate of at least 1% with higher rates in the ustekinumab groups during the placebo-controlled period of Ps STUDY 1 and Ps STUDY 2 [see Clinical Studies (14) ] .
Table 5:
Adverse Reactions, Reported by ≥1% of Subjects with Plaque Psoriasis and at Higher Rates in the ustekinumab groups through Week 12 in Ps STUDY 1 and Ps STUDY 2 Ustekinumab Placebo 45 mg 90 mg Subjects treated 665 664 666 Nasopharyngitis 51 (8%) 56 (8%) 49 (7%) Upper respiratory tract infection 30 (5%) 36 (5%) 28 (4%) Headache 23 (3%) 33 (5%) 32 (5%) Fatigue 14 (2%) 18 (3%) 17 (3%) Back pain 8 (1%) 9 (1%) 14 (2%) Dizziness 8 (1%) 8 (1%) 14 (2%) Pharyngolaryngeal pain 7 (1%) 9 (1%) 12 (2%) Pruritus 9 (1%) 10 (2%) 9 (1%) Injection site erythema 3 (<1%) 6 (1%) 13 (2%) Myalgia 4 (1%) 7 (1%) 8 (1%) Depression 3 (<1%) 8 (1%) 4 (1%) 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).
5 WARNINGS AND PRECAUTIONS Infections: Serious infections have occurred. Avoid starting YESINTEK during any clinically important active infection. If a serious infection or clinically significant infection develops, discontinue YESINTEK until the infection resolves.
1 ) 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.
2 ) Tuberculosis (TB) : Evaluate patients for TB prior to initiating treatment with YESINTEK. Initiate treatment of latent TB before administering YESINTEK. 3) Malignancies: Ustekinumab products may increase risk of malignancy. The safety of ustekinumab products in patients with a history of or a known malignancy has not been evaluated.
4) Serious Hypersensitivity Reactions: If a severe or other clinically significant hypersensitivity reaction occurs, discontinue YESINTEK immediately and initiate appropriate medical treatment. 5) Posterior Reversible Encephalopathy Syndrome (PRES): If PRES is suspected, treat promptly, and discontinue YESINTEK.
6) Immunizations : Avoid use of live vaccines in patients during treatment with YESINTEK. 7) Noninfectious Pneumonia: Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products.
If diagnosis is confirmed, discontinue YESINTEK and institute appropriate treatment. 1 Infections Ustekinumab products may increase the risk of infections and reactivation of latent infections. 3) ] . Serious infections requiring hospitalization, or otherwise clinically significant infections, reported in clinical trials included the following: Plaque Psoriasis : diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections.
5) ]. Clinically significant hypersensitivity to ustekinumab products or to any of the excipients in YESINTEK. ( 4 )
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Table 4:
Initial Intravenous Dosage of YESINTEK Body Weight of Patient at the time of dosing Dose Number of 130 mg/26 mL (5 mg/mL) YESINTEK vials 55 kg or less 260 mg 2 more than 55 kg to 85 kg 390 mg 3 more than 85 kg 520 mg 4 Subcutaneous Maintenance Adult Dosage Regimen The recommended maintenance dosage is a subcutaneous 90 mg dose administered 8 weeks after the initial intravenous dose, then every 8 weeks thereafter.
4 General Considerations for Administration YESINTEK is intended for use under the guidance and supervision of a healthcare provider. YESINTEK should only be administered to patients who will be closely monitored and have regular follow-up visits with a healthcare provider.
The appropriate dose should be determined by a healthcare provider using the patient’s current weight at the time of dosing. In pediatric patients, it is recommended that YESINTEK be administered by a healthcare provider. If a healthcare provider determines that it is appropriate, a patient may self-inject or a caregiver may inject YESINTEK after proper training in subcutaneous injection technique.
Instruct patients to follow the directions provided in the Instructions for Use [see Instructions for Use]. 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 vial, a 1 mL syringe with a 27 gauge, ½ inch needle is recommended. Prior to administration, visually inspect YESINTEK for particulate matter and discoloration. YESINTEK is a clear, colorless to pale yellow solution. Do not use YESINTEK if it is discolored or cloudy, or if other particulate matter is present.
YESINTEK does not contain preservatives; therefore, discard any unused product remaining in the vial and/or syringe. 5 Preparation and Administration of YESINTEK 130 mg/26 mL (5 mg/mL) Vial for Intravenous Infusion (Crohn's Disease and Ulcerative Colitis) YESINTEK solution for intravenous infusion must be diluted, prepared and infused by a healthcare professional using aseptic technique.
Calculate the dose and the number of YESINTEK vials needed based on patient weight (Table 4). Each 26 mL vial of YESINTEK contains 130 mg of ustekinumab-kfce. 9% Sodium Chloride Injection, USP from the 250 mL infusion bag equal to the volume of YESINTEK to be added (discard 26 mL sodium chloride for each vial of YESINTEK needed, for 2 vials- discard 52 mL, for 3 vials- discard 78 mL, 4 vials- discard 104 mL).
45% Sodium Chloride Injection, USP may be used. Withdraw 26 mL of YESINTEK 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. Infuse the diluted solution over a period of at least one hour. Once diluted, the infusion should be completely administered within four hours of the dilution in the infusion bag.
2 micrometer). Do not infuse YESINTEK concomitantly in the same intravenous line with other agents. YESINTEK does not contain preservatives. Each vial is for a one-time use in only one patient. Discard any remaining solution. Dispose any unused medicinal product in accordance with local requirements.
Storage If necessary, the diluted infusion solution may be kept at room temperature up to 25°C (77°F) for up to 4 hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 4 hours after the dilution in the infusion bag (cumulative time after preparation including the storage and the infusion period).
Do not freeze. Discard any unused portion of the infusion solution.
6 )]. 21 per patient-years of follow-up). 1 )]. 87 per patient-years of follow-up). 01 per patient-years of follow-up). 60 per hundred patient-years of follow-up). 4 )]. The most frequently observed malignancies other than non-melanoma skin cancer during the clinical trials were: prostate, melanoma, colorectal and breast.
S. population according to the SEER database (adjusted for age, gender and race). 1 Pediatric Subjects with Plaque Psoriasis The safety of ustekinumab was assessed in two trials of pediatric subjects with moderate to severe plaque psoriasis.
Ps STUDY 3 evaluated safety for up to 60 weeks in 110 pediatric subjects 12 to 17 years old. Ps STUDY 4 evaluated safety for up to 56 weeks in 44 pediatric subjects 6 to 11 years old. The safety profile in pediatric subjects was similar to the safety profile from trials in adults with plaque psoriasis.
Psoriatic Arthritis The safety of ustekinumab was assessed in 927 subjects in two randomized, double-blind, placebo-controlled trials in adults with active psoriatic arthritis (PsA). The overall safety profile of ustekinumab in subjects with PsA was consistent with the safety profile seen in clinical trials in adult subjects with plaque psoriasis.
A higher incidence of arthralgia, nausea, and dental infections was observed in ustekinumab-treated subjects when compared with placebo-treated subjects (3% vs. 1% for arthralgia and 3% vs. 1% for nausea; 1% vs. 6% for dental infections) in the placebo-controlled portions of the PsA clinical trials.
Crohn’s Disease The safety of ustekinumab was assessed in 1407 subjects with moderately to severely active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] greater than or equal to 220 and less than or equal to 450) in three randomized, double-blind, placebo-controlled, parallel-group, multicenter trials.
These 1407 subjects included 40 subjects who received a prior investigational intravenous ustekinumab formulation but were not included in the efficacy analyses. 3)]. Subjects who were responders in either trial CD-1 or CD-2 were randomized to receive a subcutaneous maintenance regimen of either 90 mg ustekinumab every 8 weeks, or placebo for 44 weeks in trial CD-3.
4) ]. The overall safety profile of ustekinumab was consistent with the safety profile seen in the clinical trials in adult subjects with plaque psoriasis and psoriatic arthritis. Common adverse reactions in trials CD-1 and CD-2 and in trial CD-3 are listed in Tables 6 and 7, respectively.
4%).
Table 7:
Common Adverse Reactions Through Week 44 in Trial CD-3 occurring in ≥3% of Ustekinumab -Treated Subjects and Higher Than Subjects Receiving Placebo Placebo N=133 Ustekinumab 90 mg subcutaneous maintenance dose every 8 weeks N=131 Nasopharyngitis 8% 11% Injection site erythema 0 5% Vulvovaginal candidiasis/mycotic infection 1% 5% Bronchitis 3% 5% Pruritus 2% 4% Urinary tract infection 2% 4% Sinusitis 2% 3% Infections In subjects with Crohn's disease, serious or other clinically significant infections included anal abscess, gastroenteritis, and pneumonia.
1) ] . 58 events per hundred patient-years) developed non-melanoma skin cancer. 27 events per hundred patient-years) and in none of the placebo-treated subjects. Hypersensitivity Reactions Including Anaphylaxis In CD trials, two subjects reported hypersensitivity reactions following ustekinumab administration.
1% of subjects receiving subcutaneous ustekinumab). 08% of subjects receiving intravenous ustekinumab). 5 )] . 5) ] . The overall safety profile of ustekinumab in subjects with ulcerative colitis was consistent with the safety profile seen across all approved indications.
Adverse reactions reported in at least 3% of ustekinumab-treated subjects and at a higher rate than placebo were: Induction (UC-1): nasopharyngitis (7% vs 4%). Maintenance (UC-2): nasopharyngitis (24% vs 20%), headache (10% vs 4%), abdominal pain (7% vs 3%), influenza (6% vs 5%), fever (5% vs.
4%), diarrhea (4% vs 1%), sinusitis (4% vs 1%), fatigue (4% vs 2%), and nausea (3% vs 2%). Infections In subjects with ulcerative colitis, serious or other clinically significant infections included gastroenteritis and pneumonia. 1) ] .
00 events per hundred patient-years) developed non-melanoma skin cancer. 40 events per hundred patient-years). 2 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.
Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of ustekinumab or of other ustekinumab products.
4% of subjects treated with ustekinumab in clinical trials in subjects with plaque psoriasis and psoriatic arthritis developed antibodies to ustekinumab, which were generally low-titer. In clinical trials in subjects with plaque psoriasis, antibodies to ustekinumab were associated with reduced or undetectable serum ustekinumab concentrations and reduced efficacy.
In trials in subjects with plaque psoriasis, the majority of subjects who were positive for antibodies to ustekinumab had neutralizing antibodies. 6% of subjects, respectively, developed antibodies to ustekinumab when treated with ustekinumab for approximately one year.
No apparent association between the development of antibodies to ustekinumab and the development of injection site reactions was seen. 3 Postmarketing Experience The following adverse reactions have been reported during post-approval use of ustekinumab products.
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 ustekinumab product exposure. , anaphylaxis, angioedema, dyspnea, rash, urticaria), including a fatal case that presented with chest tightness and dyspnea during infusion of the first dose.
Infections and infestations:
Lower respiratory tract infection (including opportunistic fungal infections and tuberculosis).
Neurological disorders:
Posterior Reversible Encephalopathy Syndrome (PRES) .
Respiratory, thoracic, and mediastinal disorders:
Interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia .
Skin reactions :
Pustular psoriasis, erythrodermic psoriasis, hypersensitivity vasculitis.
Psoriatic arthritis : cholecystitis. Crohn's disease : anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeria meningitis. Ulcerative colitis : gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.
Avoid initiating treatment with YESINTEK in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of YESINTEK 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 YESINTEK and discontinue YESINTEK for serious or clinically significant infections until the infection resolves or is adequately treated.
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 ustekinumab products may be susceptible to these types of infections.
, tissue culture, stool culture, as dictated by clinical circumstances). 3 Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis infection prior to initiating treatment with YESINTEK. Avoid administering YESINTEK to patients with active tuberculosis infection.
Initiate treatment of latent tuberculosis prior to administering YESINTEK. Consider anti-tuberculosis therapy prior to initiation of YESINTEK in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Closely monitor patients receiving YESINTEK for signs and symptoms of active tuberculosis during and after treatment. 4 Malignancies Ustekinumab products are immunosuppressants and may increase the risk of malignancy. 1) ] . In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy [see Nonclinical Toxicology (13) ] .
The safety of ustekinumab products has not been evaluated 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 ustekinumab products who had pre-existing risk factors for developing non-melanoma skin cancer.
Monitor all patients receiving YESINTEK for the appearance of non-melanoma skin cancer. 1) ] . 5 Serious Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products in clinical trials and postmarketing.
3 )]. If a severe or clinically significant hypersensitivity reaction occurs, discontinue YESINTEK immediately and initiate appropriate medical treatment [see Contraindications ( 4 )] . 6 Posterior Reversible Encephalopathy Syndrome (PRES) Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials.
Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis, and Crohn's disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab product initiation.
A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab products. Monitor all patients treated with YESINTEK for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue YESINTEK.
7 Immunizations Prior to initiating therapy with YESINTEK, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with YESINTEK should avoid receiving live vaccines.
Avoid administering BCG vaccines during treatment with YESINTEK 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 YESINTEK because of the potential risk for shedding from the household contact and transmission to patient.
Non-live vaccinations received during a course of YESINTEK may not elicit an immune response sufficient to prevent disease. 8 Noninfectious Pneumonia Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products.
Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and in certain cases administration of corticosteroids.
3) ] .