For US Healthcare Professionals Only
PYZCHIVA is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in PYZCHIVA.
Ustekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections requiring hospitalization or otherwise clinically significant infections were reported. In patients with plaque psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.
Avoid initiating treatment with PYZCHIVA 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 PYZCHIVA 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 PYZCHIVA and discontinue PYZCHIVA for serious or clinically significant infections until the infection resolves or is adequately treated.
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 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).
Evaluate patients for TB infection prior to initiating treatment with PYZCHIVA. Avoid administering PYZCHIVA to patients with active TB infection. Initiate treatment of latent TB prior to administering PYZCHIVA. Closely monitor patients receiving PYZCHIVA for signs and symptoms of active TB during and after treatment.
Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among patients who received ustekinumab in clinical trials. 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 reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving ustekinumab products who had risk factors for developing non‑melanoma skin cancer. Monitor all patients receiving PYZCHIVA, especially those greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy, and those with a history of PUVA treatment, for the appearance of non-melanoma skin cancer.
Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue PYZCHIVA.
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 post-marketing 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 PYZCHIVA for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue PYZCHIVA.
Prior to initiating therapy with PYZCHIVA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with PYZCHIVA should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment, 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 PYZCHIVA products due to the potential risk of shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of PYZCHIVA may not elicit an immune response sufficient to prevent disease.
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 PYZCHIVA and institute appropriate treatment.
Ustekinumab products 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.
The most common adverse reactions (≥3% and higher than that with placebo) in adults from plaque psoriasis clinical trials for ustekinumab 45 mg, ustekinumab 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. The safety profile in pediatric subjects was similar to the safety profile from studies in adults with plaque psoriasis. In psoriatic arthritis (PsA) clinical trials, a higher incidence of arthralgia and nausea was observed in ustekinumab-treated patients when compared with placebo-treated patients (3% vs 1% for both). In the Crohn’s disease induction trials, common adverse reactions (≥3% of patients treated with ustekinumab and higher than placebo) reported through Week 8 for ustekinumab 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In the Crohn’s disease maintenance trial, common adverse reactions (≥3% of patients treated with ustekinumab and higher than placebo) reported through Week 44 for ustekinumab 90 mg subcutaneous injection or placebo 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%). In the ulcerative colitis induction trial, common adverse reactions (≥3% of patients treated with ustekinumab and higher than placebo) reported through Week 8 for ustekinumab 6 mg/kg intravenous single infusion or placebo included nasopharyngitis (7% vs 4%). In the ulcerative colitis maintenance trial, common adverse reactions (≥3% of patients treated with ustekinumab and higher than placebo) reported through Week 44 for ustekinumab 90 mg subcutaneous injection or placebo were 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%).
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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