Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Propharma Group The Netherlands B.V., Schipholweg 73, 2316ZL Leiden, The Netherlands
Briumvi is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features (see section 5.1).
Treatment should be initiated and supervised by specialised physicians experienced in the diagnosis and treatment of neurological conditions and who have access to appropriate medical support to manage severe reactions such as serious infusion-related reactions (IRRs).
The following two premedications must be administered (orally, intravenously, intramuscular, or subcutaneously) prior to each infusion to reduce the frequency and severity of IRRs (see section 4.4 for additional steps to reduce IRRs):
In addition, premedication with an antipyretic (e.g. paracetamol) may also be considered.
The first dose is administered as a 150 mg intravenous infusion (first infusion), followed by a 450 mg intravenous infusion (second infusion) 2 weeks later (see Table 1).
Subsequent doses are administered as a single 450 mg intravenous infusion every 24 weeks (Table 1). The first subsequent dose of 450 mg should be administered 24 weeks after the first infusion.
A minimal interval of 5 months should be maintained between each dose of ublituximab.
If there are signs of a life-threatening or disabling IRR during an infusion, the infusion must be stopped immediately and the patient should receive appropriate treatment. Treatment must be permanently discontinued in these patients (see section 4.4).
If a patient experiences a severe IRR, the infusion should be interrupted immediately and the patient should receive symptomatic treatment. The infusion should be restarted only after all symptoms have resolved. When restarting, the infusion rate should be at half of the infusion rate at the time of onset of the IRR. If the rate is tolerated, the rate should be increased as described in Table 1.
If a patient experiences a mild to moderate IRR, the infusion rate should be reduced to half the rate at the onset of the event. This reduced rate should be maintained for at least 30 minutes. If the reduced rate is tolerated, the infusion rate may then be increased as described in Table 1.
No dose reductions are recommended. In case of dose interruption or infusion rate reduction due to IRR, the total duration of the infusion would be increased, but not the total dose.
If an infusion is missed, it should be administered as soon as possible; administration after a delayed or missed dose should not wait until the next planned dose. The treatment interval of 24 weeks (with a minimum of 5 months) should be maintained between doses (see Table 1).
Based on the limited data available (see section 5.1 and section 5.2), no dose adjustment is considered necessary in patients over 55 years of age.
No dose adjustment is expected to be required for patients with renal impairment (see section 5.2).
No dose adjustment is expected to be required for patients with hepatic impairment (see section 5.2).
The safety and efficacy of Briumvi in children and adolescents aged 0 to 18 years have not yet been established. No data are available.
After dilution, Briumvi is administered as an intravenous infusion through a dedicated line. Infusions should not be administered as an intravenous push or bolus.
Table 1. Dose and schedule:
| Amount and volume | Infusion rate | Duration1 | |
|---|---|---|---|
| First Infusion | 150 mg in 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 in 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)2 | 450 mg in 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 |
1 Infusion duration may take longer if the infusion is interrupted or slowed.
2 The first subsequent infusion should be administered 24 weeks after the first infusion.
Solutions for intravenous infusion are prepared by dilution of the medicinal product into an infusion bag containing sodium chloride 9 mg/ml (0.9%) solution for injection, to a final concentration of 0.6 mg/mL for the first infusion and 1.8 mg/mL for the second infusion and all subsequent infusions.
For instructions on dilution of the medicinal product before administration, see section 6.6.
There is limited clinical trial experience in RMS with doses higher than the approved intravenous dose of ublituximab. The highest dose tested to date in RMS patients is 600 mg (Phase II dose finding study in RMS). The adverse reactions were consistent with the safety profile for ublituximab in the pivotal clinical studies.
There is no specific antidote in the event of an overdose; the infusion should be immediately interrupted and the patient should be observed for IRRs (see section 4.4).
Unopened vial:
3 years.
Diluted solution for intravenous infusion:
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C–8°C and subsequently for 8 hours at room temperature.
From a microbiological point of view, the prepared infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C and subsequently for 8 hours at room temperature, unless dilution has taken place in controlled and validated aseptic conditions.
Store in a refrigerator (2°C–8°C).
Do not shake or freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
6 mL concentrate in a glass vial. Pack size of 1 vial.
Briumvi should be prepared by a healthcare professional using aseptic technique. Do not shake the vial.
The product is intended for single use only.
Do not use the solution if it is discoloured or if it contains foreign particulate matter.
This medicinal product must be diluted before administration. The solution for intravenous administration is prepared by dilution of the product into an infusion bag containing isotonic sodium chloride 9 mg/ml (0.9%) solution for injection.
No incompatibilities between ublituximab and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous administration sets have been observed.
For the first infusion, dilute one vial of product into the infusion bag (150 mg / 250 mL) to a final concentration of approximately 0.6 mg/mL.
For subsequent infusions, dilute three vials of product into the infusion bag (450 mg / 250 mL) to a final concentration of approximately 1.8 mg/mL.
Prior to the start of the intravenous infusion, the content of the infusion bag should be at room temperature (20-25°C).
In case an intravenous infusion cannot be completed the same day, the remaining solution should be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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