Nulojix · 4.3 Contraindications · 1

HOS-155157 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile The adverse reaction profile associated with immunosuppressive agents is often difficult to establish due to the underlying disease and the concurrent use of multiple medicinal products. In trials conducted to support use in newly transplanted patients, the most common serious adverse reactions (≥ 2%) reported with belatacept in both regimens (more intensive [MI] and less intensive [LI]) cumulative up to Year 3 were urinary tract infection, CMV infection, pyrexia, increased blood creatinine, pyelonephritis, diarrhoea, gastroenteritis, graft dysfunction, leukopenia, pneumonia, basal cell carcinoma, anaemia, dehydration. The most commonly reported adverse reactions (≥ 20%) among patients treated with both belatacept- based regimens (MI and LI) up to Year 3 are diarrhoea, anaemia, urinary tract infection, peripheral oedema, constipation, hypertension, pyrexia, nausea, graft dysfunction, cough, vomiting, leukopenia, hypophosphataemia, and headache. Adverse reactions resulting in interruption or discontinuation of belatacept in ≥ 1% of patients up to Year 3 were renal vein thrombosis and CMV infection. Tabulated list of adverse reactions Presented in Table 2, by system organ classification and frequency categories, is the list of adverse reactions with at least a suspected causal relationship, reported in newly transplanted patient clinical trials cumulatively up to Year 3 and pooled for both belatacept regimens (MI and LI). The frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100). Within each frequency category adverse reactions are presented in order of decreasing seriousness. 8 Table 2: Adverse reactions in newly transplanted patient clinical trials Infections and infestations Very Common urinary tract infection, upper respiratory infection, cytomegalovirus infection*, bronchitis Common sepsis, pneumonia, influenza, gastroenteritis, herpes zoster, sinusitis, herpes simplex, oral candidiasis, pyelonephritis, onychomycosis, BK virus infection, respiratory tract infection, candidiasis, rhinitis, cellulitis, wound infection, localised infection, herpes virus infection, fungal infection, fungal skin infection Uncommon progressive multifocal leukoencephalopathy*, cerebral fungal infection,

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HOS-155153 · has-contraindication-information · PDF-Seite 4

Transplant recipients who are Epstein-Barr virus (EBV) seronegative or serostatus unknown. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4).

HOS-155152 · has-indication-information · PDF-Seite 2

NULOJIX, in combination with corticosteroids and a mycophenolic acid (MPA), is indicated for prophylaxis of graft rejection in adult recipients of a renal transplant (see section 5.1 for data on renal function).

HOS-155155 · has-interaction-information · PDF-Seite 7

Belatacept is a fusion protein that is not expected to be metabolised by the cytochrome P450 enzymes (CYPs) and UDP-glucuronosyltransferases (UGTs). Belatacept appears not to have any relevant direct effects on cytokine levels in liver transplant recipients or in healthy volunteers. Belatacept is therefore not expected to affect cytochrome P450 enzymes via effects on cytokines. Belatacept is not expected to interrupt the enterohepatic recirculation of MPA. At a given dose of MMF, MPA exposure is approximately 40% higher with belatacept coadministration than with ciclosporin coadministration. Immunosuppressant therapy may affect response to vaccination. Therefore, during treatment with belatacept, vaccinations may be less effective although this has not been studied in clinical trials. The use of live vaccines should be avoided (see section 4.4).

HOS-155156 · has-pregnancy-information · PDF-Seite 7

Women of childbearing potential/Contraception in males and females Women of childbearing potential should use effective contraception during treatment with belatacept and up to 8 weeks after the last dose of treatment since the potential risk to embryonic/foetal development is unknown. Pregnancy There are no adequate data from use of belatacept in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to embryonal/foetal development at doses up to 16-fold and 19-fold a human 10 mg/kg dose based on AUC. In a pre- and postnatal development study in rats, limited changes in immune function were observed at 19-fold a human 10 mg/kg dose based on AUC (see section 5.3). Belatacept should not be used in pregnant women unless clearly necessary. Breast-feeding Studies in rats have shown excretion of belatacept in milk. It is unknown whether belatacept is excreted in human milk (see section 5.3). Women should not breast-feed while on treatment with a belatacept-based regimen. Fertility There are no data on use of belatacept and effect on fertility in humans. In rats, belatacept had no undesirable effects on male or female fertility (see section 5.3).

HOS-155154 · has-warning-information · PDF-Seite 4

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. Post-transplant lymphoproliferative disorder (PTLD) In Phase 2 and 3 studies (3 studies) in newly transplanted patients, the incidence of PTLD was higher in belatacept-treated patients than in ciclosporin-treated patients (see section 4.8). Belatacept-treated transplant recipients who are EBV seronegative are at an increased risk for PTLD compared with those who are EBV positive (see section 4.8). EBV serology should be ascertained before starting administration of belatacept. Transplant recipients who are EBV seronegative or serostatus unknown should not receive belatacept (see section 4.3). In addition to EBV seronegative status, other known risk factors for PTLD include cytomegalovirus (CMV) infection and T-cell-depleting therapy, which was more commonly used to treat acute rejection in belatacept-treated patients in Phase 3 clinical studies (see section 5.1). PTLD in belatacept-treated patients most often presented in the central nervous system (CNS). Physicians should consider PTLD in the differential diagnosis in patients with new or worsening neurologic, cognitive or behavioural signs or symptoms. Infections Use of immunosuppressants, including belatacept, can increase susceptibility to infection, including fatal infections, opportunistic infections, tuberculosis, and herpes (see progressive multifocal leukoencephalopathy (PML) warning below and also section 4.8). CMV prophylaxis is recommended for at least 3 months after transplantation, particularly for patients at increased risk for CMV infection. Pneumocystis pneumonia prophylaxis is recommended for at least 6 months following transplantation. Tuberculosis was more frequently observed in patients receiving belatacept than ciclosporin in clinical studies (see section 4.8). The majority of cases of tuberculosis occurred in patients who currently live or previously lived in countries with a high prevalence of tuberculosis. Patients should be evaluated for tuberculosis and tested for latent infection prior to initiating belatacept. Adequate treatment of latent tuberculosis infection should be instituted prior to belatacept use. 4 Progressive multifocal leukoencephalopathy PML is a rare, often rapidly progressive and fatal, opportunistic infection of the CNS that is cau

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