Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Nulojix

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HOS-213607 · Präparat HOS-155150

Transplant recipients who are Epstein-Barr virus (EBV) seronegative or serostatus unknown.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): Epstein-Barr virus (HOS-213608)

Gegenanzeigen · Nulojix

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HOS-213609 · Präparat HOS-155150

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4).

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Wechselwirkungen · Nulojix

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HOS-213610 · Präparat HOS-155150

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.

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Wechselwirkungen · Nulojix

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HOS-213611 · Präparat HOS-155150

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.

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Wechselwirkungen · Nulojix

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HOS-213612 · Präparat HOS-155150

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).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Nulojix

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HOS-213613 · Präparat HOS-155150

Summary of the safety profile

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Nebenwirkungen · Nulojix

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HOS-213614 · Präparat HOS-155150

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.

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Nebenwirkungen · Nulojix

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HOS-213615 · Präparat HOS-155150

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.

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Nebenwirkungen · Nulojix

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HOS-213616 · Präparat HOS-155150

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Nulojix

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HOS-213617 · Präparat HOS-155150

Adverse reactions resulting in interruption or discontinuation of belatacept in ≥ 1% of patients up to Year 3 were renal vein thrombosis and CMV infection.

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Nebenwirkungen · Nulojix

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HOS-213618 · Präparat HOS-155150

Tabulated list of adverse reactions

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Nebenwirkungen · Nulojix

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HOS-213619 · Präparat HOS-155150

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).

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Nebenwirkungen · Nulojix

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HOS-213620 · Präparat HOS-155150

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.

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Nebenwirkungen · Nulojix

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HOS-213621 · Präparat HOS-155150

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, cytomegalovirus (CMV) colitis, polyomavirus-associated nephropathy, genital herpes, staphylococcal infection, endocarditis, tuberculosis*, bronchiectasis, osteomyelitis, strongyloidiasis, blastocystis infection, giardiasis, lymphangitis Neoplasms, benign, malignant and unspecified (incl cysts and polyps)* Common squamous cell carcinoma of skin, basal cell carcinoma, skin papilloma Uncommon EBV associated lymphoproliferative disorder**,lung cancer, rectal cancer, breast cancer, sarcoma, kaposi's sarcoma, prostate cancer, cervix carcinoma, laryngeal cancer, lymphoma, multiple myeloma, transitional cell carcinoma Blood and lymphatic system disorders Very Common anaemia, leukopenia Common thrombocytopenia, neutropenia, leukocytosis, polycythaemia, lymphopenia Uncommon monocytopenia, pure red cell aplasia, agranulocytosis, haemolysis, hypercoagulation Immune system disorders Common blood immunoglobulin G decreased, blood immunoglobulin M decreased Uncommon hypogammaglobulinaemia, seasonal allergy Endocrine disorders Common cushingoid Uncommon adrenal insufficiency Metabolism and nutrition disorders Very Common hypophosphataemia, hypokalaemia, dyslipidaemia, hyperkalaemia, hyperglycaemia, hypocalcaemia Common weight increase, diabetes mellitus, dehydration, weight decrease, acidosis, fluid retention, hypercalcaemia, hypoproteinaemia Uncommon diabetic ketoacidosis, diabetic foot, alkalosis, decreased appetite, vitamin D deficiency Psychiatric disorders Very Common insomnia, anxiety Common depression Uncommon abnormal dreams, mood swings, attention deficit/hyperactivity disorder, libido increased Nervous system disorders Very Common headache Common tremor, paraesthesia, cerebrovascular accident, dizziness, syncope, lethargy, neuropathy peripheral Uncommon encephalitis, Guillain-Barré syndrome*, brain oedema, intracranial pressure increased, encephalopathy, convulsion, hemiparesis, demyelination, facial palsy, dysgeusia, cognitive disorder, memory impairment, migraine, burning sensation, diabetic neuropathy, restless leg syndrome

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Nulojix

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HOS-213622 · Präparat HOS-155150

9 Eye disorders Common cataract, ocular hyperaemia, vision blurred Uncommon retinitis, conjunctivitis, eye inflammation, keratitis, photophobia, eyelid oedema Ear and labyrinth disorders Common vertigo, ear pain, tinnitus Uncommon hypoacusis Cardiac disorders Common tachycardia, bradycardia, atrial fibrillation, cardiac failure, angina pectoris, left ventricular hypertrophy Uncommon acute coronary syndrome, atrioventricular block second degree, aortic valve disease, arrhythmia supraventricular Vascular disorders Very Common hypertension, hypotension Common shock, infarction, haematoma, lymphocele, angiopathy, arterial fibrosis Uncommon venous thrombosis, arterial thrombosis, thrombophlebitis, arterial stenosis, intermittent claudication, flushing Respiratory, thoracic and mediastinal disorders Very Common dyspnoea, cough Common pulmonary oedema, wheezing, hypocapnea, orthopnoea, epistaxis, oropharyngeal pain Uncommon acute respiratory distress syndrome, pulmonary hypertension, pneumonitis, haemoptysis, bronchopneumopathy, painful respiration, pleural effusion, sleep apnoea syndrome, dysphonia, oropharyngeal blistering Gastrointestinal disorders Very Common diarrhoea, constipation, nausea, vomiting, abdominal pain Common dyspepsia, aphthous stomatitis, abdominal hernia Uncommon gastrointestinal disorder, pancreatitis, large intestinal ulcer, melaena, gastroduodenal ulcer, rectal haemorrhage, small intestinal obstruction, cheilitis, gingival hyperplasia, salivary gland pain, faeces discoloured Hepatobiliary disorders Common cytolytic hepatitis, liver function test abnormal Uncommon cholelithiasis, hepatic cyst, hepatic steatosis Skin and subcutaneous tissue disorders Common acne, pruritis, alopecia, skin lesion, rash, night sweats, hyperhidrosis Uncommon psoriasis, hair growth abnormal, onychoclasis, penile ulceration, swelling face, trichorrhexis Musculoskeletal and connective tissue disorders Very Common arthralgia, back pain, pain in extremity Common myalgia, muscular weakness, bone pain, joint swelling, intervertebral disc disorder, joint lock, muscle spasms, osteoarthritis Uncommon bone metabolism disorder, osteitis, osteolysis, synovitis Renal and urinary disorders Very Common proteinuria, blood creatinine increased, dysuria, haematuria Common renal tubular necrosis, renal vein thrombosis*, renal artery stenosis, glycosuria, hydronephrosis, vesicoureteric reflux, urinary incontinence, urinary retention, nocturia Uncommon renal artery thrombosis*, nephritis, nephrosclerosis, renal tubular atrophy, cystitis haemorrhagic, kidney fibrosis

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Nulojix

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HOS-213623 · Präparat HOS-155150

10 Reproductive system and breast disorders Uncommon epididymitis, priapism, cervical dysplasia, breast mass, testicular pain, vulval ulceration, atrophic vulvovaginitis, infertility, scrotal oedema Congenital, familial and genetic disorders Common hydrocele Uncommon hypophosphatasia General disorders and administration site conditions Very Common oedema peripheral, pyrexia Common chest pain, fatigue, malaise, impaired healing Uncommon infusion related reaction*, irritability, fibrosis, inflammation, disease recurrence, feeling hot, ulcer Investigations Common c-reactive protein increased, blood parathyroid hormone increased Uncommon pancreatic enzymes increased, troponin increased, electrolyte imbalance, prostate- specific antigen increased, blood uric acid increased, urine output decreased, blood glucose decreased, CD4 lymphocytes decreased Injury, poisoning and procedural complications Very Common graft dysfunction Common chronic allograft nephropathy (CAN), incisional hernia Uncommon transplant failure, transfusion reaction, wound dehiscence, fracture, tendon rupture, procedural hypotension, procedural hypertension, post-procedural haematoma, procedural pain, procedural headache, contusion * See section “Description of selected adverse reactions”. ** Includes all events reported over a median of 3.3 years in the newly transplanted patient Phase 3 studies, and a median of approximately 7 years in the newly transplanted patient Phase 2 study.

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Nebenwirkungen · Nulojix

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HOS-213624 · Präparat HOS-155150

Long-term extension in Study 1 and Study 2 Of the 1209 randomised and newly transplanted patients in the two Phase 3 studies (see section 5.1), 761 patients continued after Year 3 in a long-term extension period for up to an additional 4 years and continued to receive the study drug according to their original treatment assignment. As compared to the results from the initial 3 years, no new adverse reactions or increasing incidence of adverse reactions (listed above from the initial 3-year period) were detected during the 4-year long-term open label extension.

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Nebenwirkungen · Nulojix

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HOS-213625 · Präparat HOS-155150

Conversion Studies 1 and 2 The overall safety profile of belatacept in the two conversion studies was consistent with the known safety profile in the existing clinical population from the studies in newly transplanted patients presented in Table 2 above.

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Nebenwirkungen · Nulojix

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HOS-213626 · Präparat HOS-155150

Description of selected adverse reactions

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Nebenwirkungen · Nulojix

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HOS-213627 · Präparat HOS-155150

Malignancies and post-transplant lymphoproliferative disease In the newly transplanted patient trials, Year 1 and 3 frequencies of malignancies are shown in Table 3, except for cases of PTLD which are presented at 1 year and > 3 years (median days of follow- up were 1,199 days for belatacept MI, 1,206 days for belatacept LI, and 1,139 days for ciclosporin). The Year 3 frequency of malignant neoplasms, excluding non-melanoma skin cancers, was similar in the belatacept LI and ciclosporin groups and higher in the belatacept MI group. PTLD occurred at a higher rate in both belatacept treatment groups versus ciclosporin (see section 4.4). Non-melanoma skin cancers occurred less frequently with the belatacept LI regimen than with the ciclosporin or belatacept MI regimens.

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