Ultomiris · 4.8 Undesirable effects · 1

HOS-098953 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile The most common adverse reactions with ravulizumab are headache (30.6%), upper respiratory tract infection (21.6%), nasopharyngitis (20.4%), diarrhoea (18.7%), pyrexia (17.7%), nausea (15%), arthralgia (14.4%), back pain (13.6%), fatigue (13.3%), abdominal pain (12.3%), dizziness (10.7%) and urinary tract infection (10.7%). The most serious adverse reactions are meningococcal infection (0.7%) including meningococcal sepsis, meningococcal meningitis, encephalitis meningococcal, meningococcal infection (see section 4.4) and disseminated gonococcal infection (0.2%) including disseminated gonococcal infection and gonococcal infection. Tabulated list of adverse reactions Table 7 gives the adverse reactions observed from clinical trials and from post-marketing experience. Adverse reactions are listed by MedDRA System Organ Class (SOC) and frequency, using 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 available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 10 Table 7: Adverse Drug reactions from clinical trials and postmarketing experience MedDRA System Organ Very common Common Uncommon (≥ 1/1,000 Class (≥ 1/10) (≥ 1/100 to to < 1/100) < 1/10) Infections and Urinary tract infectiona Meningococcal infestations Upper respiratory tract infectionb, infection, Nasopharyngitis Disseminated Gonococcal infectionc Immune system Hypersensitivitye Anaphylactic reactiond disorders Nervous system Dizziness, Headache disorders Gastrointestinal Diarrhoea, Vomiting, disorders Nausea, Dyspepsia Abdominal pain Skin and subcutaneous

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HOS-098949 · has-contraindication-information · PDF-Seite 6

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Patients with unresolved Neisseria meningitidis infection at treatment initiation (see section 4.4). • Patients who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination (see section 4.4).

HOS-098948 · has-indication-information · PDF-Seite 2

Paroxysmal nocturnal haemoglobinuria (PNH) Ultomiris is indicated in the treatment of adult and paediatric patients with a body weight of 10 kg or above with PNH: • in patients with haemolysis with clinical symptom(s) indicative of high disease activity. • in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months. Atypical haemolytic uremic syndrome (aHUS) Ultomiris is indicated in the treatment of adult and paediatric patients with a body weight of 10 kg or above with aHUS who are complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab. 2 Generalised myasthenia gravis (gMG) Ultomiris is indicated as an add-on to standard therapy for the treatment of adult patients with gMG who are anti-acetylcholine receptor (AChR) antibody-positive. Neuromyelitis optica spectrum disorder (NMOSD) Ultomiris is indicated in the treatment of adult patients with NMOSD who are anti-aquaporin 4 (AQP4) antibody-positive (see section 5.1).

HOS-098951 · has-interaction-information · PDF-Seite 9

No interaction studies have been performed. Based on the potential inhibitory effect of ravulizumab on complement-dependent cytotoxicity of rituximab, ravulizumab may reduce the expected pharmacodynamic effects of rituximab. Chronic intravenous human immunoglobulin (IVIg) treatment may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as ravulizumab and thereby decrease serum ravulizumab concentrations. See section 4.2 for guidance in case of concomitant PE, PP, or IVIg treatment.

HOS-098952 · has-pregnancy-information · PDF-Seite 9

Women of childbearing potential Women of childbearing potential should use effective contraception methods during treatment and for 8 months after treatment. Pregnancy There are no clinical data from the use of ravulizumab in pregnant women. Nonclinical reproductive toxicology studies were not conducted with ravulizumab (see section 5.3). Reproductive toxicology studies were conducted in mice using the murine surrogate molecule BB5.1, which assessed effect of C5 blockade on the reproductive system. No specific test-article related reproductive toxicities were identified in these studies. Human immunoglobulin G (IgG) are known to cross the human placental barrier, and thus ravulizumab may potentially cause terminal complement inhibition in the foetal circulation. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). In pregnant women the use of ravulizumab may be considered following an assessment of the risks and benefits. Breast-feeding It is unknown whether ravulizumab is excreted into human milk. Nonclinical reproductive toxicology studies conducted in mice with the murine surrogate molecule BB5.1 identified no adverse effect to pups resulting from consuming milk from treated dams. A risk to infants cannot be excluded. Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in nursing infants, breast-feeding should be discontinued during treatment with ravulizumab and for 8 months after treatment. 9 Fertility No specific non-clinical study on fertility has been conducted with ravulizumab. Nonclinical reproductive toxicology studies conducted in mice with a murine surrogate molecule (BB5.1) identified no adverse effect on fertility of the treated females or males.

HOS-098950 · has-warning-information · PDF-Seite 6

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. Serious meningococcal infection Due to its mechanism of action, the use of ravulizumab increases the patient's susceptibility to meningococcal infection/sepsis (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur (see section 4.8). To reduce this risk of infection, all patients must be vaccinated against meningococcal infections at least two weeks prior to initiating ravulizumab unless the risk of delaying ravulizumab therapy outweighs the risk of developing a meningococcal infection. Patients who initiate ravulizumab treatment less than 2 weeks after receiving a meningococcal vaccine, must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against all available serogroups including A, C, Y, W135 and B, are recommended in preventing the 6 commonly pathogenic meningococcal serogroups. Patients must be vaccinated and revaccinated according to current national guidelines for vaccination use. If the patient is being switched from eculizumab treatment, physicians should verify that meningococcal vaccination is current according to national guidelines for vaccination use. Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Cases of serious or fatal meningococcal infections/sepsis have been reported in patients treated with ravulizumab and in patients treated with other terminal complement inhibitors. All patients should be monitored for early signs of meningococcal infection and sepsis, evaluated immediately if infection is suspected, and treated with appropriate antibiotics. Patients should be informed of these signs and symptoms and steps should be taken to seek medical care immediately. Physicians should provide patients with a Patient guide and a Patient card. Immunisation Prior to initiating ravulizumab therapy, it is recommended that patients initiate immunisations according to current immunisation guidelines. Vaccination may further activate complement. As a result, patients with complement-mediated diseases may experience increased signs and symptoms of their underlying disease. Therefore, patients should be closely monitored for

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