BRIUMVI

2 DOSAGE AND ADMINISTRATION Before initiating BRIUMVI, screen for Hepatitis B virus (HBV) and obtain serum quantitative immunoglobulins, aminotransferases, alkaline phosphatase, and bilirubin ( 2.1 ). Pre-medicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion ( 2.2 ). Administer BRIUMVI by intravenous infusion. First Infusion: 150 mg intravenous infusion ( 2.3 ) Second Infusion: 450 mg intravenous infusion two weeks after the first infusion ( 2.3 ) Subsequent Infusions: 450 mg intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter ( 2.3 ) Must be diluted in 0.9% Sodium Chloride Injection, USP prior to administration ( 2.3 , 2.6 ). Monitor patients closely during 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 ( 2.3 , 5.1 ). 2.1 Assessments Prior to First Dose of BRIUMVI Hepatitis B Virus Screening Prior to initiating BRIUMVI, perform Hepatitis B virus (HBV) screening. BRIUMVI is contraindicated in patients with active HBV confirmed by positive results for Hepatitis B surface antigen [HBsAg] and anti-HBV tests. For patients who are negative for HBsAg and positive for Hepatitis B core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment with BRIUMVI [see Warnings and Precautions (5.2) ] . Serum Immunoglobulins Prior to initiating BRIUMVI, perform testing for quantitative serum immunoglobulins [see Warnings and Precautions (5.4) ]. For patients with low serum immunoglobulins, consult immunology experts before initiating treatment with BRIUMVI. Vaccinations Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of BRIUMVI for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of BRIUMVI for non-live vaccines [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ] . Liver Function Tests Prior to initiating BRIUMVI, obtain serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase, and bilirubin levels [see Warnings and Precautions (5.5) ] . 2.2 Assessment and Premedication Before Every Infusion Infection Assessment Prior to every infusion of BRIUMVI, determine whether there is an active infection. In case of active infection, delay infusion of BRIUMVI until the infection resolves [see Warnings and Precautions (5.2) ] . Recommended Premedication Pre-medicate with 100 mg of methylprednisolone administered intravenously (or an equivalent oral dosage or equivalent corticosteroid) approximately 30 minutes prior to each BRIUMVI infusion to reduce the frequency and severity of infusion reactions [see Warnings and Precautions (5.1) ] . Pre-medicate with an antihistamine (e.g., diphenhydramine) administered orally or intravenously approximately 30-60 minutes prior to each BRIUMVI infusion to further reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered. 2.3 Recommended Dosage and Dose Administration Administer BRIUMVI under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions, such as serious infusion reactions. First Infusion: 150 mg intravenous infusion Second Infusion: 450 mg intravenous infusion administered two weeks after the first infusion Subsequent Infusions: 450 mg intravenous infusion administered 24 weeks after the first infusion and every 24 weeks thereafter Observe the patient 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 [see Warnings and Precautions (5.1) ]. Table 1: Recommended Dose, Infusion Rate, and Infusion Duration for MS Dose (mg) and Volume (mL) of BRIUMVI Volume (mL) of 0.9% Sodium Chloride Injection, USP Withdraw and discard the required volume of 0.9% Sodium Chloride Injection, USP from the infusion bag following the preparation instructions in Preparation and Administration (2.6). Infusion Rate (mL/hour) Duration Infusion duration may take longer if the infusion is interrupted or slowed. First Infusion 150 mg (6 mL) 250 mL Start at 10 mL per hour for the first 30 minutes Increase to 20 mL per hour for the next 30 minutes Increase to 35 mL per hour for the next hour Increase to 100 mL per hour for the remaining 2 hours 4 hours Second Infusion (2 weeks later) 450 mg (18 mL) 250 mL Start at 100 mL per hour for the first 30 minutes Increase to 400 mL per hour for the remaining 30 minutes 1 hour Subsequent Infusions (once every 24 weeks) Administer the first subsequent infusion 24 weeks after the first infusion. 450 mg (18 mL) 250 mL Start at 100 mL per hour for the first 30 minutes Increase to 400 mL per hour for the remaining 30 minutes 1 hour 2.4 Delayed or Missed Doses If a planned infusion of BRIUMVI is missed, administer BRIUMVI as soon as possible; do not wait until the next scheduled infusion. Reset the infusion schedule to administer the next sequential infusion 24 weeks after the missed infusion is administered. Infusions of BRIUMVI must be separated by at least 5 months. 2.5 Dosage Modifications Because of Infusion Reactions Dose modifications in response to infusion reactions depend on the severity. Life-Threatening Infusion Reactions Immediately stop infusion and permanently discontinue BRIUMVI if there are signs of a life-threatening or disabling infusion reaction [see Warnings and Precautions (5.1) ] . Provide appropriate supportive treatment. Severe Infusion Reactions Immediately interrupt the infusion and administer appropriate supportive treatment, as necessary [see Warnings and Precautions (5.1) ] . Restart the infusion only after all symptoms have resolved. When restarting, begin at half of the infusion rate at the time of onset of the infusion reaction [see Dosage and Administration (2.3) ] . If this rate is tolerated, increase the rate as described in Table 1. This change in rate will increase the total duration of the infusion but not the total dose. Mild to Moderate Infusion Reactions Reduce the infusion rate to half the rate at the onset of the infusion reaction and maintain the reduced rate for at least 30 minutes [see Warnings and Precautions (5.1) ] . If the reduced rate is tolerated, increase the rate as described in Table 1. This change in rate will increase the total duration of the infusion but not the total dose. 2.6 Preparation and Administration Preparation Only use 0.9% Sodium Chloride Injection, USP to dilute BRIUMVI. BRIUMVI must be prepared by a healthcare professional using aseptic technique. Prepare the solution for infusion as follows: BRIUMVI should be a clear to opalescent, colorless to slightly yellow solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use the solution if discolored or if the solution contains discrete foreign particulate matter. Preparation of Solution for First Infusion: Prepare infusion bag for First Infusion (150 mg) using one vial (150 mg/6 mL) of BRIUMVI. Withdraw 6 mL 0.9% Sodium Chloride Injection, USP from the 250 mL infusion bag and discard. Withdraw 6 mL BRIUMVI solution from the vial. Add 6 mL (150 mg) BRIUMVI into the infusion bag containing 0.9% Sodium Chloride Injection, USP. Preparation of Solution for Second Infusion and Subsequent Infusions: Prepare infusion bag for Second Infusion (450 mg) and Subsequent Infusions (450 mg) using three vials (150 mg/6 mL) of BRIUMVI. Withdraw 18 mL 0.9% Sodium Chloride Injection, USP from the 250 mL infusion bag and discard. Withdraw 18 mL BRIUMVI solution from the vials (6 mL/vial). Add 18 mL (450 mg) BRIUMVI into the infusion bag containing 0.9% Sodium Chloride Injection, USP. Mix diluted solution by gentle inversion. Do not shake. Administration of Infusion Solution Prior to the start of the intravenous infusion, the contents of the infusion bag should be at room temperature [see Dosage and Administration (2.7) ] . Administer the diluted infusion solution through a dedicated line. No incompatibilities between BRIUMVI and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous (IV) administration sets have been observed. 2.7 Storage Instructions for the Prepared Infusion Solution Use the prepared infusion solution immediately. If the diluted solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours. Do not freeze. If the diluted solution is stored refrigerated, allow it to equilibrate to room temperature prior to administration (approximately 2 hours). The diluted solution can be stored for an additional 8 hours at room temperature up to 25°C (77°F), which includes the equilibration time and infusion time.

See official label

1 INDICATIONS AND USAGE BRIUMVI is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.