Kesimpta · 4.3 Contraindications · 1

HOS-099633 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most important and frequently reported adverse reactions are upper respiratory tract infections (39.4%), systemic injection-related reactions (20.6%), local injection-site reactions (10.9%) and urinary tract infections (11.9%) (see section 4.4 and below subsection “Description of selected adverse reactions” for further details). Tabulated list of adverse reactions Adverse reactions that have been reported in association with the use of ofatumumab in pivotal RMS clinical studies and from post-marketing experience are listed by MedDRA system organ class in Table 1. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: 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). 7 Table 1 Tabulated list of adverse reactions Infections and infestations Very common Upper respiratory tract infections1 Urinary tract infections2 Common Oral herpes Immune system disorders Not known Hypersensitivity reactions3 Gastrointestinal disorders Common Nausea, vomiting4 Hepatobiliary disorders Common Hepatic enzymes increased5 General disorders and administration site conditions Very common Injection-site reactions (local) Investigations Common Blood immunoglobulin M decreased Injury, poisoning and procedural complications Very common Injection-related reactions (systemic) 1 Grouping of preferred terms (PTs) was considered for ADR frequency determination and includes the following: nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, pharyngitis, rhinitis, viral upper respiratory infection, tonsillitis, acute sinusitis, pharyngotonsillitis, laryngitis, pharyngitis streptococcal, viral rhinitis, sinusitis bacterial, tonsillitis bacterial, viral pharyngitis, viral tonsillitis, chronic sinusitis, nasal herpes, tracheitis. 2 Grouping of preferred terms (PTs) wa

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HOS-099629 · has-contraindication-information · PDF-Seite 3

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

HOS-099628 · has-indication-information · PDF-Seite 2

Kesimpta 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-099631 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed, as no interactions are expected via cytochrome P450 enzymes, other metabolising enzymes or transporters. Vaccinations The safety of and the ability to generate a primary or anamnestic (recall) response to immunisation with live, live-attenuated or inactivated vaccines during ofatumumab treatment has not been investigated. The response to vaccination could be impaired when B cells are depleted. It is recommended that patients complete immunisations prior to the start of ofatumumab therapy (see section 4.4). Other immunosuppressive or immune-modulating therapies The risk of additive immune system effects should be considered when co-administering immunosuppressive therapies with ofatumumab. When initiating ofatumumab after other immunosuppressive therapies with prolonged immune effects or initiating other immunosuppressive therapies with prolonged immune effects after ofatumumab, the duration and mode of action of these medicinal products should be taken into account because of potential additive immunosuppressive effects (see section 5.1). 5

HOS-099632 · has-pregnancy-information · PDF-Seite 6

Women of childbearing potential Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) while receiving Kesimpta and for 2 months after the last administration of Kesimpta. Pregnancy Data from approximately 400 prospective reports of pregnancies with known outcomes following exposure to ofatumumab during the pre-conception period and/or during the first trimester of pregnancy, do not suggest an increased risk of adverse pregnancy outcomes, including major congenital malformations and foetal/neonatal toxicity; however, the available data are insufficient to draw firm conclusions. Experience with administration during the second and third trimesters of pregnancy is limited. Ofatumumab may cross the placenta and cause foetal B-cell depletion based on findings from animal studies (see section 5.3). No teratogenicity was observed after intravenous administration of ofatumumab to pregnant monkeys during organogenesis. Transient peripheral B-cell depletion and lymphocytopenia have been observed in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. The potential duration of B-cell depletion in infants exposed to ofatumumab in utero, and the impact of B-cell depletion on the safety and effectiveness of vaccines, are unknown (see sections 4.4 and 5.1). Treatment with ofatumumab should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. To help determine the effects of ofatumumab in pregnant women, healthcare professionals are encouraged to report all pregnancy cases and complications that happen during treatment or within 2 months after the last dose of ofatumumab to the marketing authorisation holder, in order to allow monitoring of the outcomes of these pregnancies through the PRegnancy outcomes Intensive Monitoring programme (PRIM). In addition, all adverse pregnancy events should be reported via the national reporting system listed in Appendix V. Lactation There are limited data on the use of ofatumumab in women during lactation. There are no data on the effects of ofatumumab on milk production. In humans, excretion of IgG antibodies in milk occurs during the first few days after birth, which is decreasing to low concentrations soon afterwards. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. An observational study repor

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HOS-099630 · has-warning-information · PDF-Seite 3

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. Systemic injection-related reactions Patients should be informed that systemic injection-related reactions (SIRRs) could occur, generally within 24 hours and predominantly following the first injection (see section 4.8). Symptoms most frequently observed in RMS clinical studies include fever, headache, myalgia, chills, fatigue, nausea and vomiting and were predominantly (99.8%) mild to moderate in severity. There were no life- threatening SIRRs reported in RMS clinical studies (see section 4.8). Additional SIRRs reported in the post-marketing setting include rash, urticaria, dyspnoea and angioedema (e.g. tongue, pharyngeal or laryngeal swelling), and rare cases which were reported as anaphylaxis. While there were some cases which were serious and resulted in discontinuation of ofatumumab treatment, there were also serious cases where patients were able to continue ofatumumab treatment without further incidents. Some SIRR symptoms may be clinically indistinguishable from Type 1 acute hypersensitivity reactions (IgE-mediated). A hypersensitivity reaction may present during any injection, although typically would not present with the first injection. For subsequent injections, more severe symptoms than previously experienced, or new severe symptoms, should prompt consideration of a potential hypersensitivity reaction. Patients with known IgE-mediated hypersensitivity to ofatumumab must not be treated with ofatumumab (see section 4.3). 3 Only limited benefit of premedication with steroids was seen in RMS clinical studies. Injection-related reactions can be managed with symptomatic treatment, should they occur. Therefore, use of premedication is not required. The first injection should be performed under the guidance of an appropriately trained healthcare professional (see section 4.2). Local injection-site reactions Local injection-site reaction symptoms observed in clinical studies included erythema, swelling, itching and pain (see section 4.8). Infections It is recommended to evaluate the patient’s immune status prior to initiating therapy. Based on its mode of action and available clinical experience, ofatumumab has the potential for an increased risk of infections (see section 4.8). Administration should be delayed in pati

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