Bekemv · 4.3 Contraindications · 1

HOS-099917 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile Supportive safety data were obtained from 33 clinical studies that included 1 555 patients exposed to eculizumab in complement-mediated disease populations, including PNH, aHUS, refractory generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). The most common adverse reaction was headache, (occurred mostly in the initial phase of dosing), and the most serious adverse reaction was meningococcal infection. Tabulated list of adverse reactions Table 1 gives the adverse reactions observed from spontaneous reporting and in eculizumab completed clinical trials, including PNH, aHUS, refractory gMG and NMOSD studies. Adverse reactions reported at a 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) or not known (cannot be estimated from the available data) frequency with eculizumab, are listed by system organ class and preferred term. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1. Adverse reactions reported in eculizumab clinical trials, including patients with PNH, aHUS, refractory gMG and NMOSD as well as from post marketing experience MedDRA Very Common Uncommon Rare Not known system organ common (≥ 1/100 to (≥ 1/1 000 to (≥ 1/10 000 to (cannot be class (≥ 1/10) < 1/10) < 1/100) < 1/1 000) estimated from the available data) Infections and Pneumonia, Meningococcal Aspergillus infestations Upper infectionb, infectionc, respiratory tract Sepsis, Arthritis infection, Septic shock, bacterialc, Bronchitis, Peritonitis, Genitourinary Nasopharyngitis, Lower respiratory tract gonococcal Urinary tract tract infection, infection, infection, Fungal infection, Haemophilus Oral herpes Viral infection, infection,

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HOS-099913 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to eculizumab or to any of the excipients listed in section 6.1. BEKEMV is contraindicated in subjects with hereditary fructose intolerance (HFI). Prior to initiating treatment HFI should be excluded on age-appropriate clinical grounds (see section 4.4). BEKEMV is contraindicated in babies and children below 2 years of age since they may not yet be diagnosed with hereditary fructose intolerance (HFI) (see section 4.4). BEKEMV therapy must not be initiated in patients (see section 4.4): - with unresolved Neisseria meningitidis infection - who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination.

HOS-099912 · has-indication-information · PDF-Seite 2

BEKEMV is indicated in adults and children for the treatment of - Paroxysmal nocturnal haemoglobinuria (PNH). Evidence of clinical benefit is demonstrated in patients with haemolysis with clinical symptom(s) indicative of high disease activity, regardless of transfusion history (see section 5.1). - Atypical haemolytic uremic syndrome (aHUS) (see section 5.1).

HOS-099915 · has-interaction-information · PDF-Seite 9

No interaction studies have been performed. Based on the potential inhibitory effect of eculizumab on complement-dependent cytotoxicity of rituximab, eculizumab may reduce the expected pharmacodynamic effects of rituximab. Plasma exchange (PE), plasmapheresis (PP) and fresh frozen plasma infusion (PI) have been shown to reduce eculizumab serum levels. A supplemental dose of eculizumab is required in these settings. See section 4.2 for guidance in case of concomitant PE, PP or PI treatment. Concomitant use of eculizumab with intravenous immunoglobulin (IVIg) may reduce effectiveness of eculizumab. Closely monitor for reduced effectiveness of eculizumab. Concomitant use of eculizumab with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of eculizumab. Closely monitor for reduced effectiveness of eculizumab.

HOS-099916 · has-pregnancy-information · PDF-Seite 9

The use of adequate contraception to prevent pregnancy and for at least 5 months after the last dose of treatment with eculizumab should be considered for women of childbearing potential. Pregnancy There are no well-controlled studies in pregnant women treated with eculizumab. Data on a limited number of pregnancies exposed to eculizumab (less than 300 pregnancy outcomes) indicate there is no increased risk of foetal malformation or foetal-neonatal toxicity. However, due to the lack of well- controlled studies, uncertainties remain. Therefore, an individual benefits and risk analysis is recommended before starting and during treatment with eculizumab in pregnant women. Should such a treatment be considered necessary during pregnancy, a close maternal and foetal monitoring according to local guidelines is recommended. Animal reproduction studies have not been conducted with eculizumab (see section 5.3). Human IgG are known to cross the human placental barrier, and thus eculizumab may potentially cause terminal complement inhibition in the foetal circulation. Therefore, BEKEMV should be given to a pregnant woman only if clearly needed. Breast-feeding No effects on the breastfed new-born/infant are anticipated as limited data available suggest that eculizumab is not excreted in human breast milk. However, due to the limitations of the available data, the developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for eculizumab and any potential adverse effects on the breastfed child from eculizumab or from the underlying maternal condition. Fertility No specific study of eculizumab on fertility has been conducted.

HOS-099914 · has-warning-information · PDF-Seite 5

BEKEMV is not expected to affect the aplastic component of anaemia in patients with PNH. Meningococcal infection Due to its mechanism of action, the use of BEKEMV increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving BEKEMV unless the risk of delaying BEKEMV therapy outweighs the risks of developing a meningococcal infection. Patients who initiate BEKEMV treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against all available serogroups including A, C, Y, W 135 and B are recommended in preventing the commonly pathogenic meningococcal serogroups. Patients must be vaccinated and revaccinated according to current national guidelines for vaccination use. Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH) and TMA (aHUS). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination. 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 have been reported in eculizumab-treated patients. Sepsis is a common presentation of meningococcal infections in patients treated with eculizumab (see section 4.8). All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary. Patients should be informed of these signs and symptoms and steps taken to seek medical care immediately. Physicians must discuss the benefits and risks of BEKEMV therapy with patients and provide them with a patient guide and a patient card (see package leaflet for a description). 5 Other systemic infections Due to its mechanism of action, BEKEMV therapy should be administered with caution to patients with active systemic infections. Patients may have increased susceptibility to infections, especially with Neisseria and encapsulated bac

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