IMULDOSA® (ustekinumab- srlf) injection, for subcutaneous or intravenous use
IMULDOSA® (ustekinumab- srlf) is biosimilar to STELARA® (ustekinumab) 

IMPORTANT SAFETY INFORMATION

IMULDOSA is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in IMULDOSA. 

Infections 

• Ustekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab products.
• 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.
  • 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 IMULDOSA 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 IMULDOSA 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 IMULDOSA and discontinue IMULDOSA 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 (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. Consider appropriate diagnostic testing (e.g., tissue culture, stool culture, as dictated by clinical circumstances). 

Pre-treatment Evaluation for Tuberculosis 

• Evaluate patients for tuberculosis infection prior to initiating treatment with IMULDOSA. Avoid administering IMULDOSA to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering IMULDOSA. Consider anti-tuberculosis therapy prior to initiation of IMULDOSA 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 IMULDOSA for signs and symptoms of active tuberculosis during and after treatment.

Malignancies 

• Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among subjects who received ustekinumab in clinical trials. In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy. 
• 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 IMULDOSA for the appearance of non-melanoma skin cancer. Closely follow patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment. 

Serious Hypersensitivity Reactions 

• Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, discontinue IMULDOSA immediately and initiate appropriate medical treatment. 

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 IMULDOSA for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue IMULDOSA. 

Immunizations 

• Prior to initiating therapy with IMULDOSA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with IMULDOSA should not receive live vaccines. Avoid administering BCG vaccines during treatment with IMULDOSA 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 IMULDOSA because of the potential risk for shedding from the household contact and transmission to patient. 
• Non-live vaccinations received during a course of IMULDOSA may not elicit an immune response sufficient to prevent disease. 

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. If diagnosis is confirmed, discontinue IMULDOSA and institute appropriate treatment. 

Most Common Adverse Reactions 

The most common adverse reactions associated with ustekinumab products are: 

• Psoriasis and Psoriatic Arthritis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue 
• Crohn’s Disease, induction (≥3%): vomiting 
• Crohn’s Disease, maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis 
• Ulcerative colitis, induction (≥3%): nasopharyngitis  U
• lcerative colitis, maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea 

Drug Interactions 

• Upon initiation or discontinuation of IMULDOSA in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and adjust the individual dosage of the CYP substrate as needed. 

INDICATIONS 

IMULDOSA 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 
• active psoriatic arthritis (PsA) 
• moderately to severely active Crohn’s disease (CD) 
• moderately to severely active ulcerative colitis 

Pediatric patients 6 years and older with: 

• moderate to severe plaque psoriasis (PsO), who are candidates for phototherapy or systemic therapy 
• active psoriatic arthritis (PsA) 

To report SUSPECTED ADVERSE REACTIONS, contact Accord BioPharma Inc at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 

IMULDOSA is supplied as single-dose prefilled syringes for subcutaneous use in 45 mg/0.5 mL and 90 mg/mL strengths or as a single-dose vial for intravenous infusion in 130 mg/26 mL (5 mg/mL) strength.