USTEKINUMAB Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Concomitant Therapies In trials in subjects with plaque psoriasis the safety of ustekinumab products in combination with immunosuppressive agents or phototherapy has not been evaluated. In trials in subjects with psoriatic arthritis, concomitant MTX use did not appear to influence the safety or efficacy of ustekinumab. In trials in subjects with Crohn's disease (CD-1 and CD-2) and ulcerative colitis (UC-1), immunomodulators (6-MP, AZA, MTX) were used concomitantly in approximately 30% of subjects and corticosteroids were used concomitantly in approximately 40% and 50% of Crohn's disease and ulcerative colitis subjects, respectively. Use of these concomitant therapies did not appear to influence the overall safety or efficacy of ustekinumab.

7.2 CYP450 Substrates The formation of CYP450 enzymes can be suppressed by increased levels of certain cytokines (e.g., IL-1, IL-6, TNFα, IFN) during chronic inflammation. Thus, use of ustekinumab products, antagonists of IL-12 and IL-23, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of USTEKINUMAB-TTWE 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. See the prescribing information of specific CYP substrates. A CYP-mediated drug interaction effect was not observed in subjects with Crohn&apos;s disease <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> .

7.3 Allergen Immunotherapy Ustekinumab products have not been evaluated in patients who have undergone allergy immunotherapy. 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.

Ustekinumab-aauz is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in Ustekinumab-aauz [see Warnings and Precautions ( 5.5 )]. Clinically significant hypersensitivity to ustekinumab products or to any of the excipients in Ustekinumab-aauz. ( 4 )

AND PRECAUTIONS Infections : Serious infections have occurred. Avoid starting USTEKINUMAB-TTWE during any clinically important active infection. If a serious infection or clinically significant infection develops, discontinue USTEKINUMAB-TTWE until the infection resolves. ( 5.1 )

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. ( 5.2 ) Tuberculosis (TB) : Evaluate patients for TB prior to initiating treatment with USTEKINUMAB-TTWE. Initiate treatment of latent TB before administering USTEKINUMAB-TTWE. ( 5.3 ) 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. ( 5.4 )

Serious Hypersensitivity

Reactions : If a severe or other clinically significant hypersensitivity reaction occurs, discontinue USTEKINUMAB-TTWE immediately and initiate appropriate medical treatment. ( 5.5 )

Posterior Reversible Encephalopathy

Syndrome (PRES) : If PRES is suspected, treat promptly and discontinue USTEKINUMAB-TTWE. ( 5.6 ) Immunizations : Avoid use of live vaccines in patients during treatment with USTEKINUMAB-TTWE. ( 5.7 )

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 USTEKINUMAB-TTWE and institute appropriate treatment. ( 5.8 )

5.1 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 , 6.3) ]</span> . 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&apos;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 USTEKINUMAB-TTWE 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 USTEKINUMAB-TTWE 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 USTEKINUMAB-TTWE and discontinue USTEKINUMAB-TTWE for serious or clinically significant infections until the infection resolves or is adequately treated.

5.2 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. Consider appropriate diagnostic testing (e.g., tissue culture, stool culture, as dictated by clinical circumstances).

5.3 Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis infection prior to initiating treatment with USTEKINUMAB-TTWE. Avoid administering USTEKINUMAB-TTWE to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering USTEKINUMAB-TTWE. Consider anti-tuberculosis therapy prior to initiation of USTEKINUMAB-TTWE 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 USTEKINUMAB-TTWE for signs and symptoms of active tuberculosis during and after treatment.

5.4 Malignancies Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among subjects who received ustekinumab in clinical trials <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy <span class="opacity-50 text-xs">[see Nonclinical Toxicology (13) ]</span> . 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 USTEKINUMAB-TTWE 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .

5.5 Serious Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products in clinical trials and postmarketing. Some serious hypersensitivity reactions have occurred during the first intravenous dose of ustekinumab products <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 , 6.3) ]</span> . If a severe or clinically significant hypersensitivity reaction occurs, discontinue USTEKINUMAB-TTWE immediately and initiate appropriate medical treatment <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

5.6 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&apos;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 USTEKINUMAB-TTWE for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue USTEKINUMAB-TTWE.

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

5.8 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. If diagnosis is confirmed, discontinue USTEKINUMAB-TTWE and institute appropriate treatment <span class="opacity-50 text-xs">[see Adverse Reactions (6.3) ]</span> .