BRIUMVI®▼ (ublituximab)

150 mg concentrate for solution for infusion: Prescribing Information

Presentation: Briumvi concentrate for solution for infusion contains 150 mg ublituximab in 6 mL (25 mg/mL). After dilution, the final concentration is approximately 0.6 mg/mL for the first infusion and 1.8 mg/mL for the second and subsequent infusions. 

Indication: treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features.

Dosage and administration: treatment should be initiated and supervised by specialist 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).

Premedication: 100 mg prednisolone or 10–20 mg dexamethasone (or equivalent) and diphenhydramine must be administered prior to each infusion to reduce the frequency and severity of IRRs. These premedications to be given approximately 30-60 minutes prior to each infusion.

First dose: administered as a 150 mg intravenous infusion through a dedicated line (first infusion).

Second dose: 450 mg intravenous infusion 2 weeks later.

Subsequent doses: first subsequent dose to be administered 24 weeks after the first infusion, as a single 450 mg intravenous infusion, then every 24 weeks. A minimum interval of 5 months should be maintained between doses. Treatment should be stopped immediately if there are signs of a life-threatening or disabling IRR during an infusion, and patients should receive appropriate treatment. In the case of severe IRRs, the infusion should be interrupted immediately, and the patient should receive symptomatic treatment. The infusion should only be restarted after all the symptoms have resolved. When restarting, the infusion rate should be half the infusion rate at the time of onset of the IRR and increased thereafter if tolerated. 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. No dose reductions are recommended. For delayed or missed doses refer to the SmPC.

Special populations: no dose adjustment expected for adults over 55 years of age, patients with renal impairment or hepatic impairment.

Paediatric population: not indicated.

Contraindications: hypersensitivity to the active substance or any excipient; severe active infection; patients in a severely immunocompromised state; known active malignancies.

Warnings and precautions: traceability: the name and batch number of the administered product should be clearly recorded.

IRRs: symptoms include pyrexia, chills, headache, tachycardia, nausea, abdominal pain, throat irritation, erythema, and anaphylactic reaction. Patients should premedicate with a corticosteroid and an antihistamine to reduce the frequency and severity of IRRs. Patients treated with ublituximab should be observed during infusions and for at least 1 hour after the completion of the first two infusions. Physicians should inform patients that IRRs can occur up to 24 hours after infusion.

Infection: administration must be delayed in patients with an active infection until the infection is resolved. It is recommended to verify the patient’s

Progressive multifocal leucoencephalopathy (PML): John Cunningham virus infection resulting in PML has been observed very rarely in patients with anti-CD20 antibodies. Early signs and symptoms of PML include any new onset or worsening of neurological signs or symptoms. If PML is suspected, dosing with ublituximab must be withheld and, if confirmed, treatment must be discontinued permanently. 

Hepatitis B virus (HBV) reactivation: HBV reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has been observed in patients treated with anti-CD20 antibodies. HBV screening should be performed in all patients before initiation of treatment. Patients with active HBV should not be treated with ublituximab.

Vaccinations: vaccination with live-attenuated or live vaccines is not recommended during treatment and not until B-cell repletion, including for infants of mothers treated with ublituximab during pregnancy. All immunisations should be administered at least 4 weeks prior to treatment initiation for live or live-attenuated vaccines and at least 2 weeks prior to treatment initiation for inactivated vaccines.

Interactions: 

Vaccination: vaccination with live-attenuated or live vaccines is not recommended during treatment or until B-cell repletion.

Immunosuppressants: it is not recommended to use other immunosuppressives concomitantly with ublituximab except corticosteroids for symptomatic treatment of relapses. When initiating Briumvi before or after immunosuppressive therapy, the potential for overlapping pharmacodynamic effects should be taken into consideration. Caution should be exercised when prescribing Briumvi, taking into consideration the pharmacodynamics of other disease-modifying MS therapies. 

Fertility, pregnancy and lactation: women of childbearing potential should use effective contraception while receiving ublituximab and for at least 4 months after the last infusion.

Pregnancy: ublituximab is a monoclonal antibody of an immunoglobulin G1 subtype known to cross the placental barrier. Briumvi should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding: it is unknown whether ublituximab is excreted in human milk, a risk cannot be excluded during the first few days after birth. Afterwards, ublituximab could be used during breastfeeding if clinically needed.

Fertility: preclinical data reveal no special hazard on reproductive organs.

Undesirable effects: very common (≥1/10): upper respiratory tract infections, respiratory tract infections, IRRs. Common (≥1/100 to <1/10): herpes virus infections, lower respiratory tract infections, neutropenia, pain in the extremities.

Refer to the SmPC for further details on undesirable effects and interactions.

Legal category: POM. NHS cost: 6 mL vial £2,947.

Marketing authorisation number: PLGB 16869/0029. For further information, please contact: Neuraxpharm UK Ltd, Suite 2, Arlington Flex, Third Floor, Building 1420, Arlington Business Park, Theale, Reading, Berkshire, RG7 4SA.

NXUK/0924/21 Date of preparation: October 2024.