briumvi

Important safety information

Infusion Reactions : Management recommendations for infusion reactions depend on the type and severity of the reaction. Permanently discontinue BRIUMVI if a life-threatening or disabling infusion reaction occurs ( 2.3 , 5.1 ). Infections : Serious, including life-threatening and fatal infections, have occurred. Delay BRIUMVI 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 BRIUMVI and after discontinuation, until B-cell repletion ( 5.2 ). Reduction in Immunoglobulins : Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with BRIUMVI, until B-cell repletion, and especially when recurrent serious infections are suspected. Consider discontinuing BRIUMVI in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins ( 2.1 , 5.4 ). Fetal Risk : May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 6 months after stopping BRIUMVI ( 5.3 , 8.1 , 8.3 ). Liver Injury : Clinically significant liver injury has occurred. Obtain serum aminotransferases, alkaline phosphatase, and bilirubin levels before initiating BRIUMVI, and during treatment as clinically indicated. Discontinue BRIUMVI in patients with evidence of liver injury in the absence of an alternative etiology ( 5.5 ). 5.1 Infusion Reactions BRIUMVI can cause infusion reactions, which can include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and an anaphylactic reaction [see Adverse Reactions (6.1) ] . In Studies 1 and 2 [see Clinical Studies (14) ] , patients received methylprednisolone (or an equivalent steroid), an antihistamine, and possibly other pre-medication (i.e., acetaminophen) to reduce the risk of infusion reactions prior to each infusion. The incidence of infusion reactions in Studies 1 and 2 in patients who received treatment with BRIUMVI was 48%, with the highest incidence within 24 hours of the first infusion. In Studies 1 and 2, there were no fatal infusion reactions, but 0.6% of patients treated with BRIUMVI experienced infusion reactions that were serious, some requiring hospitalization. Observe patients treated with BRIUMVI for infusion reactions during the infusion and for at least one hour after the completion of the first two infusions. Post-infusion monitoring of subsequent infusions is at physician discretion unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Reducing the Risk of Infusion Reactions and Managing Infusion Reactions Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions [see Dosage and Administration (2.2) ] . The addition of an antipyretic (e.g., acetaminophen) may also be considered [see Dosage and Administration (2.2) ]. Management recommendations for infusion depend on the type and severity of the reaction. For life-threatening infusion reactions, stop the infusion immediately, permanently discontinue BRIUMVI, and provide appropriate supportive treatment [see Dosage and Administration (2.5) ] . For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment. 5.2 Infections Serious, including life-threatening or fatal, bacterial and viral infections have been reported in patients receiving BRIUMVI. An increased risk of infections, including serious and fatal bacterial, fungal, and new or reactivated viral infections, has been observed during and following completion of treatment with other anti-CD20 B-cell depleting therapies. In Studies 1 and 2, the overall rate of infections in MS patients treated with BRIUMVI was 56% compared to 54% in patients who were treated with teriflunomide. The rate of serious infections was higher in patients treated with BRIUMVI compared to patients treated with teriflunomide (5% vs 3%, respectively). There were 3 infection-related deaths that occurred in controlled clinical trials in patients with relapsing forms of multiple sclerosis (RMS), all in patients treated with BRIUMVI; the infections leading to death were post-measles encephalitis, pneumonia, and post-operative salpingitis following an ectopic pregnancy. In Studies 1 and 2, the most common infections reported in patients treated with BRIUMVI included upper respiratory tract infection (45%) and urinary tract infection (10%). Delay BRIUMVI administration in patients with an active infection until the infection is resolved. Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants When initiating BRIUMVI after an immunosuppressive therapy or initiating an immunosuppressive therapy after BRIUMVI, consider the potential for increased immunosuppressive effects [see Drug Interactions (7.1) and Clinical Pharmacology (12.2) ] . BRIUMVI has not been studied in combination with other MS therapies. Hepatitis B Virus (HBV) Reactivation HBV reactivation occurred in an MS patient treated with BRIUMVI in clinical trials. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with BRIUMVI. Do not start treatment with BRIUMVI in patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult a liver disease expert before starting and during treatment. Progressive Multifocal Leukoencephalopathy (PML) PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. JCV infection resulting in PML has been observed in patients treated with anti-CD20 antibodies, including BRIUMVI, and other MS therapies. At the first sign or symptom suggestive of PML, withhold BRIUMVI and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients. If PML is confirmed, treatment with BRIUMVI should be discontinued. Vaccinations Administer all…