Briumvi

HOS-100271 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most important and frequently reported adverse reactions are IRRs (45.3%) and infections (55.8%). Tabulated list of adverse reactions Table 2 summarises the adverse reactions that have been reported in association with the use of ublituximab. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each System Organ Class and frequency grouping, adverse reactions are presented in order of decreasing frequency. 7 Table 2: Adverse reactions MedDRA System Organ Very common Common Uncommon Class (SOC) Infections and Upper respiratory tract Herpes virus infections, Encephalitis, infestations infections, Lower respiratory tract Meningitis, Respiratory tract infections Meningoencephalitis infections Blood and Neutropenia lymphatic system disorders Musculoskeletal Pain in extremity and connective tissue disorders Injury, poisoning Infusion-related and procedural reactions1 complications 1 Symptoms reported as IRRs within 24 hours of the infusion are described below in ‘Infusion-related reactions’. Description of selected adverse reactions Infusion-related reactions In active-controlled RMS trials, symptoms of IRR included pyrexia, chills, headache, tachycardia, nausea, abdominal pain, throat irritation, erythema, and anaphylactic reaction. IRRs were primarily mild to moderate in severity. The incidence of IRRs in patients treated with ublituximab was 45.3%, with the highest incidence with the first infusion (40.4%). The incidence of IRRs was 8.6% with the second infusion and decreased thereafter. 1.7% of patients experienced IRRs that led to treatment interruption. 0.4% of patients experienced IRRs that were serious. There were no fatal IRRs. Infection In active-controlled RMS trials, the proportion of patients who experienced a serious infection with ublituximab was 5.0% compared to 2.9% in the teriflunomide group. The overall rate of infections in patients treated with ublituximab was si

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HOS-100267 · has-contraindication-information · PDF-Seite 4

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Severe active infection (see section 4.4). • Patients in a severely immunocompromised state (see section 4.4). • Known active malignancies. 4

HOS-100266 · has-indication-information · PDF-Seite 2

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).

HOS-100269 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed. Vaccinations The safety of immunisation with live or live-attenuated vaccines following ublituximab therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment or until B-cell repletion (see sections 4.4 and 5.1). Immunosuppressants It is not recommended to use other immunosuppressives concomitantly with ublituximab except corticosteroids for symptomatic treatment of relapses. When initiating Briumvi after an immunosuppressive therapy, or when initiating an immunosuppressive therapy after Briumvi, the potential for overlapping pharmacodynamic effects should be taken into consideration (see section 5.1 Pharmacodynamic effects). Caution should be exercised when prescribing Briumvi taking into consideration the pharmacodynamics of other disease modifying MS therapies. 6

HOS-100270 · has-pregnancy-information · PDF-Seite 7

Women of child-bearing potential Women of child-bearing potential should use effective contraception while receiving ublituximab and for at least 4 months after the last infusion (see below and sections 5.1 and 5.2). Pregnancy Ublituximab is a monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. There is a limited amount of data from the use of ublituximab in pregnant women. Postponing vaccination with live or live-attenuated vaccines should be considered for neonates and infants born to mothers who have been exposed to ublituximab during pregnancy. No B-cell count data have been collected in neonates and infants exposed to ublituximab and the potential duration of B-cell depletion in neonates and infants is unknown (see section 4.4). Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. Reproductive toxicity was observed in a pre- and post-natal development studies (see section 5.3). Briumvi should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Breast-feeding It is unknown whether ublituximab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, ublituximab could be used during breast-feeding if clinically needed. Fertility Preclinical data reveal no special hazard on reproductive organs based on studies of general toxicity in cynomolgus monkeys (see section 5.3).

HOS-100268 · has-warning-information · PDF-Seite 5

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Infusion-related reactions (IRRs) Symptoms of IRR may include pyrexia, chills, headache, tachycardia, nausea, abdominal pain, throat irritation, erythema, and anaphylactic reaction (see section 4.8). Patients should premedicate with a corticosteroid and an antihistamine to reduce the frequency and severity of IRRs (see section 4.2). The addition of an antipyretic (e.g., paracetamol) may also be considered. Patients treated with ublituximab should be observed during infusions. Patients should be monitored for at least one hour after the completion of the first two infusions. Subsequent infusions do not require monitoring post-infusion unless IRR and/or hypersensitivity has been observed. Physicians should inform patients that IRRs can occur up to 24 hours after the infusion. For guidance regarding posology for patients experiencing IRR symptoms, see section 4.2. Infection Administration must be delayed in patients with an active infection until the infection is resolved. It is recommended to verify the patient’s immune status before dosing since severely immunocompromised patients (e.g. significant neutropenia or lymphopenia) should not be treated (see sections 4.3 and 4.8). Ublituximab has the potential for serious, sometimes life-threatening or fatal, infections (see section 4.8). Most of the serious infections that occurred in controlled clinical trials in relapsing forms of multiple sclerosis (RMS) resolved. There were 3 infection-related deaths that occurred, all in patients treated with ublituximab; the infections leading to death were post-measles encephalitis, pneumonia, and post- operative salpingitis following an ectopic pregnancy. Progressive multifocal leukoencephalopathy (PML) John Cunningham virus (JCV) infection resulting in PML has been observed very rarely in patients treated with anti-CD20 antibodies and mostly associated with risk factors (e.g., patient population, lymphopenia, advanced age, polytherapy with immunosuppressants). Physicians should be vigilant for the early signs and symptoms of PML, which can include any new onset, or worsening of neurological signs or symptoms, as these can be similar to MS disease. If PML is suspected, dosing with ublituximab must be withheld. Evaluation including Magnetic Resonance Imaging (MRI) scan preferably with contra

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