ocrevus zunovo

Important safety information

Injection Reactions: Management recommendations for injection reactions depend on the type and severity of the reaction. Permanently discontinue OCREVUS ZUNOVO if a life-threatening injection reaction occurs ( 4 , 5.1 ) Infections: Serious, including life-threatening and fatal, infections have occurred in patients treated with ocrelizumab. Delay OCREVUS ZUNOVO administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with OCREVUS ZUNOVO and after discontinuation, until B-cell repletion ( 5.2 ) Progressive Multifocal Leukoencephalopathy (PML): Withhold OCREVUS ZUNOVO at the first sign or symptom suggestive of PML ( 5.3 ) Reduction in Immunoglobulins: Monitor the level of immunoglobulins at the beginning of treatment. Monitor during and after discontinuation of treatment with OCREVUS ZUNOVO, until B-cell repletion, and especially when recurrent serious infections are suspected. Consider discontinuing OCREVUS ZUNOVO in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins ( 2.1 , 5.4 ) Malignancies: An increased risk of malignancy, including breast cancer, may exist with OCREVUS ZUNOVO ( 5.5 ) Immune-Mediated Colitis: Immune-mediated colitis has been reported in the postmarketing setting. Monitor patients for new or persistent diarrhea or other gastrointestinal symptoms, and evaluate promptly if colitis is suspected ( 5.6 ) Liver Injury: Clinically significant liver injury has occurred. Obtain serum aminotransferases, alkaline phosphatase, and bilirubin levels before initiating OCREVUS ZUNOVO, and during treatment as clinically indicated. Discontinue OCREVUS ZUNOVO in patients with evidence of liver injury in the absence of an alternative etiology ( 5.7 ) 5.1 Injection Reactions OCREVUS ZUNOVO can cause injection reactions, which can be local or systemic. Common symptoms of local injection reactions reported by patients treated with OCREVUS ZUNOVO in multiple sclerosis (MS) clinical trials included erythema, pain, swelling, and pruritus. Common symptoms of systemic injection reactions reported by patients included headache and nausea. In an open-label, active-controlled trial, injection reactions were more frequently reported with the first injection; 49% of patients experienced an injection reaction with the first injection [see Adverse Reactions (6.1) ] . In MS clinical trials where ocrelizumab was administered intravenously, the incidence of infusion reactions in patients [who received methylprednisolone (or an equivalent steroid) and possibly other premedication to reduce the risk of infusion reactions prior to infusion] was 34% to 40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of intravenous ocrelizumab-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization. Symptoms of infusion reactions can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis. Monitor patients during and after injections [see Dosage and Administration (2.4) ] . Inform patients that injection reactions can occur during or within 24 hours of the injection. Reducing the Risk of Injection Reactions and Managing Injection Reactions Administer oral premedication (e.g., dexamethasone or an equivalent corticosteroid, and an antihistamine) at least 30 minutes prior to each OCREVUS ZUNOVO injection to reduce the risk of injection reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered [see Dosage and Administration (2.3) ]. Management recommendations for injection reactions depend on the type and severity of the reaction. For life-threatening injection reactions, immediately and permanently stop OCREVUS ZUNOVO and administer appropriate supportive treatment. For less severe injection reactions, the injection should be interrupted immediately, and the patient should receive symptomatic treatment. The injection should be completed at the healthcare provider's discretion and only after all symptoms have resolved. 5.2 Infections Serious, including life-threatening or fatal, bacterial, viral, parasitic, and fungal infections have been reported in patients receiving ocrelizumab. An increased risk of infections (including serious and fatal bacterial, fungal, and new or reactivated viral infections) has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies. A higher proportion of intravenous ocrelizumab-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of intravenous ocrelizumab-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of intravenous ocrelizumab-treated patients experienced one or more infections compared to 68% of patients on placebo. Intravenous ocrelizumab was not associated with an increased risk of serious infections in MS patients in controlled trials. Ocrelizumab increases the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections [see Adverse Reactions (6.1) ]. Delay OCREVUS ZUNOVO administration in patients with an active infection until the infection is resolved. Respiratory Tract Infections A higher proportion of intravenous ocrelizumab-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of patients treated with intravenous ocrelizumab experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of patients treated with intravenous ocrelizumab experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of patients treated with intravenous ocrelizumab experienced upper respiratory tract infections compared to 43% of patients on placebo, and 10% of patients treated with intravenous ocrelizumab experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis. Herpes In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in patients treated with intravenous ocrelizumab than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the patients treated with intravenous ocrelizumab than in the patients on placebo (2.7% vs. 0.8%). Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving ocrelizumab. Some cases were life-threatening. Serious herpes virus infections may occur at any time during treatment with OCREVUS ZUNOVO. If serious herpes infections occur, OCREVUS ZUNOVO should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered [see Patient Counseling Information (17) ]. Hepatitis B Virus Reactivation Hepatitis B virus (HBV) reactivation has been reported in MS patients treated with ocrelizumab in the postmarketing setting. Fulminant hepatitis, hepatic…