Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Yervoy

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HOS-124820 · Präparat HOS-095945

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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Wechselwirkungen · Yervoy

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HOS-124821 · Präparat HOS-095945

Ipilimumab is a human monoclonal antibody that is not metabolised by cytochrome P450 enzymes (CYPs) or other drug metabolizing enzymes.

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Wechselwirkungen · Yervoy

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HOS-124822 · Präparat HOS-095945

21 A drug-interaction study in adults of ipilimumab administered alone and in combination with chemotherapy (dacarbazine or paclitaxel/carboplatin) was conducted evaluating interaction with CYP isozymes (particularly CYP1A2, CYP2E1, CYP2C8, and CYP3A4) in patients with treatment-naive advanced melanoma. No clinically relevant pharmacokinetic drug-drug interaction was observed between ipilimumab and paclitaxel/carboplatin, dacarbazine or its metabolite, 5-aminoimidazole-4-carboxamide (AIC).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): dacarbazine (HOS-089538) carboplatin (HOS-084540) paclitaxel (HOS-087959)

Wechselwirkungen · Yervoy

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HOS-124823 · Präparat HOS-095945

Other forms of interaction

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Wechselwirkungen · Yervoy

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HOS-124824 · Präparat HOS-095945

Corticosteroids The use of systemic corticosteroids at baseline, before starting ipilimumab, should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of ipilimumab. However, systemic corticosteroids or other immunosuppressants can be used after starting ipilimumab to treat immune-related adverse reactions. The use of systemic corticosteroids after starting ipilimumab treatment does not appear to impair the efficacy of ipilimumab.

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Wechselwirkungen · Yervoy

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HOS-124825 · Präparat HOS-095945

Anticoagulants The use of anticoagulants is known to increase the risk of gastrointestinal haemorrhage. Since gastrointestinal haemorrhage is an adverse reaction with ipilimumab (see section 4.8), patients who require concomitant anticoagulant therapy should be monitored closely.

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Nebenwirkungen · Yervoy

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HOS-124826 · Präparat HOS-095945

Ipilimumab as monotherapy (see section 4.2)

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Nebenwirkungen · Yervoy

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HOS-124827 · Präparat HOS-095945

a. Summary of safety profile

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Nebenwirkungen · Yervoy

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HOS-124828 · Präparat HOS-095945

Ipilimumab has been administered to approximately 10 000 patients in a clinical programme evaluating its use with various doses and tumour types. Unless otherwise specified, the data below reflect exposure to ipilimumab at 3 mg/kg in clinical trials of melanoma. In the Phase 3 study MDX010-20, (see section 5.1), patients received a median of 4 doses (range 1-4).

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Nebenwirkungen · Yervoy

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HOS-124829 · Präparat HOS-095945

Ipilimumab is most commonly associated with adverse reactions resulting from increased or excessive immune activity. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of ipilimumab (see section 4.4 for management of immune-related adverse reactions).

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Nebenwirkungen · Yervoy

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HOS-124830 · Präparat HOS-095945

In patients who received 3 mg/kg ipilimumab monotherapy in MDX010-20, the most frequently reported adverse reactions (≥ 10% of patients) were diarrhoea, rash, pruritus, fatigue, nausea, vomiting, decreased appetite, and abdominal pain. The majority were mild to moderate (Grade 1 or 2). Ipilimumab therapy was discontinued for adverse reactions in 10% of patients.

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Nebenwirkungen · Yervoy

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HOS-124831 · Präparat HOS-095945

b. Tabulated list of adverse reactions

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Nebenwirkungen · Yervoy

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HOS-124832 · Präparat HOS-095945

Adverse reactions reported in patients with advanced melanoma who were treated with ipilimumab 3 mg/kg in clinical trials (n = 767) and from post-marketing surveillance are presented in Table 6.

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Nebenwirkungen · Yervoy

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HOS-124833 · Präparat HOS-095945

These reactions are presented by system organ class and by frequency. Frequencies are defined as: 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), not known (cannot be estimated from available post-marketing data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Rates of immune-related adverse reactions in HLA-A2*0201 positive patients who received ipilimumab in MDX010-20 were similar to those observed in the overall clinical programme.

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Nebenwirkungen · Yervoy

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HOS-124834 · Präparat HOS-095945

The safety profile of ipilimumab 3 mg/kg in chemotherapy-naive patients pooled across Phase 2 and 3 clinical trials (N = 75; treated), in treatment-naive patients in two retrospective observational studies (N = 273 and N = 157), and in CA184-169 (N = 362) was similar to that in previously-treated advanced melanoma.

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Nebenwirkungen · Yervoy

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HOS-124835 · Präparat HOS-095945

The safety data for patients with unresectable or metastatic melanoma, treated with ipilimumab (3 mg/kg, with a minimum of 3 year follow-up) and enrolled in multi-national, prospective, observational study CA184143 (N = 1151) were similar to what has been reported in ipilimumab clinical trials for advanced melanoma.

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Nebenwirkungen · Yervoy

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HOS-124836 · Präparat HOS-095945

Table 6: Adverse reactions in patients with advanced melanoma treated with ipilimumab 3 mg/kga Infections and infestations Common sepsisb, urinary tract infection, respiratory tract infection Uncommon septic shockb, pneumonia Neoplasms benign, malignant and unspecified (including cysts and polyps) Common tumour pain Uncommon paraneoplastic syndrome

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Nebenwirkungen · Yervoy

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HOS-124837 · Präparat HOS-095945

23 Blood and lymphatic system disorders Common anaemia, lymphopaenia, thrombocytopaenia, neutropaenia Uncommon haemolytic anaemiab, eosinophilia Not known haemophagocytic lymphohistiocytosise Immune system disorders Uncommon hypersensitivity Very rare anaphylactic reaction Not known solid organ transplant rejectione Endocrine disorders Common hypopituitarism (including hypophysitis)c, hypothyroidismc Uncommon adrenal insufficiencyc, secondary adrenocortical insufficiencyd, hyperthyroidismc, hypogonadism Rare autoimmune thyroiditisd, thyroiditisd Metabolism and nutrition disorders Very common decreased appetite Common dehydration, hypokalaemia, weight decreased, hyponatremia Uncommon alkalosis, hypophosphatemia, tumour lysis syndrome, hypocalcaemiad Rare type 1 diabetes mellitus (including diabetic ketoacidosis)h Psychiatric disorders Common confusional state, depression Uncommon mental status changes, decreased libido Nervous system disorders Common peripheral sensory neuropathy, dizziness, headache, lethargy, cranial neuropathy, brain oedema, peripheral neuropathy Uncommon Guillain-Barré syndromeb,c, meningitis (aseptic), autoimmune central neuropathy (encephalitis)d, syncope, ataxia, tremor, myoclonus, dysarthria Rare myasthenia gravisd Not known myelitis Eye disorders Common blurred vision, eye pain Uncommon uveitisc, vitreous haemorrhage, iritisc, eye oedemad, blepharitisd, reduced visual acuity, foreign body sensation in eyes, conjunctivitis Rare Vogt-Koyanagi-Harada syndromee, serous retinal detachment Cardiac disorders Common arrhythmia, atrial fibrillation Vascular disorders Common hypotension, flushing, hot flush Uncommon vasculitis, angiopathyb, peripheral ischaemia, orthostatic hypotension Rare temporal arteritisd Respiratory, thoracic and mediastinal disorders Common dyspnoea, cough, allergic rhinitis Uncommon respiratory failure, acute respiratory distress syndromeb, lung infiltration, pulmonary oedema, pneumonitis

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Nebenwirkungen · Yervoy

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HOS-124838 · Präparat HOS-095945

24  Gastrointestinal disorders Very common diarrhoeac, vomiting, nausea, constipation, abdominal pain Common gastrointestinal haemorrhage, colitisb,c, gastroesophageal reflux disease, mucosal inflammationd, gastroenteritis, stomatitis Uncommon gastrointestinal perforationb,c, large intestine perforationb,c, intestinal perforationb,c, peritonitisb, diverticulitis, pancreatitis, enterocolitis, gastric ulcer, large intestinal ulcer, oesophagitis, ileusd, proctitisd Rare pancreatic exocrine insufficiency; coeliac disease Hepatobiliary disorders Common abnormal hepatic function Uncommon hepatic failureb,c, hepatitis, hepatomegaly, jaundice Skin and subcutaneous tissue disorders Very common rashc, pruritusc Common dermatitis, erythema, vitiligo, urticaria, eczemad, alopecia, night sweats, dry skin Uncommon toxic epidermal necrolysisb,c, leukocytoclastic vasculitis, skin exfoliation, hair colour changesd Rare erythema multiformed, psoriasisd, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)d Not known pemphigoid Musculoskeletal and connective tissue disorders Very common musculoskeletal painf Common arthralgia, myalgia, muscle spasms, arthritis Uncommon polymyalgia rheumatica, myositisd, muscular weaknessd Rare polymyositisd Renal and urinary disorders Common renal failureb Uncommon glomerulonephritisc, autoimmune nephritisd, renal tubular acidosis, haematuriad, cystitis noninfectiveg, proteinuriad Reproductive system and breast disorders Uncommon amenorrhea General disorders and administration site conditions Very common fatigue, injection site reaction, pyrexia, oedema, pain Common chills, asthenia, influenza-like illnessd Uncommon multi-organ failureb,c, systemic inflammatory response syndromed, infusion related reaction Investigations Common increased alanine aminotransferasec, increased aspartate aminotransferasec, increased blood alkaline phosphatased, increased blood bilirubin, increased lipasec, Uncommon increased gamma-glutamyltransferased, increased blood creatinine, increased blood thyroid stimulating hormone, decreased blood cortisol, decreased blood corticotrophin, increased blood amylasec, positive antinuclear antibodyd, decreased blood testosterone Rare decreased blood thyroid stimulating hormoned, decreased thyroxined, abnormal blood prolactind Adverse reaction frequencies presented in Table 6 may not be fully attributable to ipilimumab, but may contain contributions from the underlying disease. a Frequencies are based on pooled data from 9 clinical trials investigating the ipilimumab 3 mg/kg dose in melanoma. b Including fatal outcome. c Additional information about these potentially inflammatory adverse reactions is provided in “Description of selected adverse reactions” and section 4.4. Data presented in those sections primarily reflect experience from a Phase 3 study, MDX010-20. d Data outside the 9 completed clinical trials in melanoma were included in frequency determinations. e Post-marketing event (also see section 4.4). f Musculoskeletal pain is a composite term which includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity, and spinal pain. g Reported in clinical studies and in the post-marketing setting. h Type 1 diabetes mellitus that may be associated with diabetic ketoacidosis

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Nebenwirkungen · Yervoy

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HOS-124839 · Präparat HOS-095945

25 Additional adverse reactions not listed in Table 6 have been reported in patients who received other doses (either < or > 3 mg/kg) of ipilimumab in clinical trials of melanoma. These additional reactions occurred at a frequency of < 1% unless otherwise noted: meningism, myocarditis, pericardial effusion, cardiomyopathy, autoimmune hepatitis, erythema nodosum, autoimmune pancreatitis, hyperpituitarism, hypoparathyroidism, infectious peritonitis, episcleritis, scleritis, Raynaud’s phenomenon, palmar-plantar erythrodysaesthesia syndrome, cytokine release syndrome, sarcoidosis, decreased blood gonadotrophin, leukopenia, polycythaemia, lymphocytosis, ocular myositis, and neurosensory hypoacusis.

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