OCREVUS

2 DOSAGE AND ADMINISTRATION Before initiating OCREVUS, screen for Hepatitis B virus 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 OCREVUS by intravenous infusion Start dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion ( 2.3 ) Subsequent doses: 600 mg intravenous infusion every 6 months ( 2.3 ) Must be diluted prior to administration ( 2.3 , 2.6 ) Monitor patients closely during and for at least one hour after infusion ( 2.3 , 2.5 ) 2.1 Assessments Prior to First Dose of OCREVUS Hepatitis B Virus Screening Prior to initiating OCREVUS, perform Hepatitis B virus (HBV) screening. OCREVUS is contraindicated in patients with active HBV confirmed by positive results for HBsAg and anti-HBV tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment [see Warnings and Precautions (5.2) ] . Serum Immunoglobulins Prior to initiating OCREVUS, 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 OCREVUS. 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 OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ] . Liver Function Tests Prior to initiating OCREVUS, obtain serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase, and bilirubin levels [see Warnings and Precautions (5.7) ] . 2.2 Preparation Before Every Infusion Infection Assessment Prior to every infusion of OCREVUS, determine whether there is an active infection. In case of active infection, delay infusion of OCREVUS until the infection resolves [see Warnings and Precautions (5.2) ]. Recommended Premedication Pre-medicate with 100 mg of methylprednisolone (or an equivalent corticosteroid) administered intravenously approximately 30 minutes prior to each OCREVUS infusion to reduce the frequency and severity of infusion reactions [see Warnings and Precautions (5.1) ] . Pre-medicate with an antihistamine (e.g., diphenhydramine) approximately 30-60 minutes prior to each OCREVUS 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 OCREVUS under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions. Initial dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion. Subsequent doses: single 600 mg intravenous infusion every 6 months. Observe the patient for at least one hour after the completion of the infusion [see Warnings and Precautions (5.1) ] . Table 1 Recommended Dose, Infusion Rate, and Infusion Duration for RMS and PPMS Amount and Volume Solutions of OCREVUS for intravenous infusion are prepared by dilution of the drug product into an infusion bag containing 0.9% Sodium Chloride Injection, to a final drug concentration of approximately 1.2 mg/mL. Infusion Rate and Duration Infusion time may take longer if the infusion is interrupted or slowed [see Dosage and Administration (2.5) ] . Initial Dose (two infusions) Infusion 1 300 mg in 250 mL Start at 30 mL per hour Increase by 30 mL per hour every 30 minutes Maximum: 180 mL per hour Duration: 2.5 hours or longer Infusion 2 (2 weeks later) 300 mg in 250 mL Subsequent Doses (one infusion) every 6 months) Administer the first Subsequent Dose 6 months after Infusion 1 of the Initial Dose. Option 1 Infusion of approximately 3.5 hours duration 600 mg in 500 mL Start at 40 mL per hour Increase by 40 mL per hour every 30 minutes Maximum: 200 mL per hour Duration: 3.5 hours or longer OR Option 2 (If no prior serious infusion reaction with any previous OCREVUS infusion) [see Adverse Reactions (6.1) and Clinical Studies (14.3) ] . Infusion of approximately 2 hours duration 600 mg in 500 mL Start at 100 mL per hour for the first 15 minutes Increase to 200 mL per hour for the next 15 minutes Increase to 250 mL per hour for the next 30 minutes Increase to 300 mL per hour for the remaining 60 minutes Duration: 2 hours or longer 2.4 Delayed or Missed Doses If a planned infusion of OCREVUS is missed, administer OCREVUS as soon as possible; do not wait until the next scheduled dose. Reset the dose schedule to administer the next sequential dose 6 months after the missed dose is administered. Doses of OCREVUS must be separated by at least 5 months [see Dosage and Administration (2.3) ] . 2.5 Dose Modifications Because of Infusion Reactions Dose modifications in response to infusion reactions depends on the severity. Life-threatening Infusion Reactions Immediately stop and permanently discontinue OCREVUS 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. If this rate is tolerated, increase the rate as described in Table 1 [see Dosage and Administration (2.3) ] . 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 this rate is tolerated, increase the rate as described in Table 1 [see Dosage and Administration (2.3) ] . This change in rate will increase the total duration of the infusion but not the total dose. 2.6 Preparation and Storage of the Dilute Solution for Infusion Preparation OCREVUS must be prepared by a healthcare professional using aseptic technique. A sterile needle and syringe should be used to prepare the diluted infusion solution. Visually inspect for particulate matter and discoloration prior to administration. Do not use the solution if discolored or if the solution contains discrete foreign particulate matter. Do not shake. Withdraw intended dose and further dilute into an infusion bag containing 0.9% Sodium Chloride Injection, to a final drug concentration of approximately 1.2 mg/mL. Withdraw 10 mL (300 mg) of OCREVUS and inject into 250 mL Withdraw 20 mL (600 mg) of OCREVUS and inject into 500 mL Do not use other diluents to dilute OCREVUS since their use has not been tested. The product contains no preservative and is intended for single use only. Storage of Infusion Solution Prior to the start of the intravenous infusion, the content of the infusion bag should be at room temperature. Use the prepared infusion solution immediately. If not used immediately, store up to 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F) and 8 hours at room temperature up to 25°C (77°F), which includes infusion time. In the event an intravenous infusion cannot be completed the same day, discard the remaining solution. No incompatibilities between OCREVUS and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous (IV) administration sets have been observed. Administration Administer the diluted infusion solution through a dedicated line using an infusion set with a 0.2 or 0.22 micron in-line filter.

See official label

1 INDICATIONS AND USAGE OCREVUS 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 Primary progressive MS, in adults OCREVUS is a CD20-directed cytolytic antibody 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 ( 1 ) Primary progressive MS, in adults ( 1 )