BRIUMVI™ (ublituximab-xiiy) injection
Drug UPDATES: [Drug information (pdf)]
PACKAGE INSERT -Dosing: Click (+) next to Dosage and Administration section (drug info link)
[ 150 mg] [250 mL ] [4 hours - See below]
- 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
- IIncrease to 100 mL per hour for the remaining 2 hours
Second and subsequent infusions:
[ 450 mg] [250 mL ] 1 hour - See below]
Withdraw 18 mL 0.9% Sodium Chloride Injection, USP from the 250 mL infusion bag and discard.
- Start at 100 mL per hour for the first 30 minutes
- Increase to 400 mL per hour for the remaining 30 minutes
- Review assessments Prior to First Dose of BRIUMVI in the dosage and administration section below.
- Review assessment and Premedication Before Every Infusion
- 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.
Ublituximab-xiiy is a recombinant chimeric monoclonal IgG1 antibody with reduced fucose content directed against CD20-expressing B-cells. The molecular weight of the antibody is approximately 147 kDa.
BRIUMVI (ublituximab-xiiy) injection for intravenous infusion is a sterile, clear to opalescent, colorless to slightly yellow, preservative-free solution. Each mL of solution contains 25 mg ublituximab-xiiy, 0.4 mg hydrochloric acid, 0.7 mg polysorbate 80, 9.0 mg sodium chloride, 6.4 mg sodium citrate, and Water for Injection, USP. The pH is 6.5.
The precise mechanism by which ublituximab-xiiy exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ublituximab-xiiy results in cell lysis through mechanisms including antibody-dependent cellular cytolysis and complement-dependent cytolysis.
BRIUMVI 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
- Active hepatitis B virus infection
- History of life-threatening infusion reaction to BRIUMV
- 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). Drug information (pdf)
- 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. 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). Drug information (pdf)
The most common adverse reactions (≥10%) were infusion reactions and upper respiratory tract infections ( 6.1).
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. Drug information (pdf)
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)] . Drug information (pdf)
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.
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior to each infusion with BRIUMVI [see Warnings and Precautions ( 5.3) and Use in Specific Populations ( 8.1, 8.3)]. Drug information (pdf)
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)].
| Dose (mg) and Volume (mL) of BRIUMVI | Volume (mL) of 0.9% Sodium Chloride Injection, USP1 | Infusion Rate (mL/hour) | Duration2 | |
| First Infusion | 150 mg (6 mL) |
250 mL |
|
4 hours |
| Second Infusion (2 weeks later) |
450 mg (18 mL) |
250 mL |
|
1 hour |
| Subsequent Infusions (once every 24 weeks) 3 |
450 mg (18 mL) |
250 mL |
|
1 hour |
|
1. 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). |
|
2. Infusion duration may take longer if the infusion is interrupted or slowed. |
|
3. Administer the first subsequent infusion 24 weeks after the first infusion.
|
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.
Injection: 150 mg/6 mL (25 mg/mL) in a single-dose vial
Store BRIUMVI vials refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze. Do not shake.
Diluted 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.
