Nivestim · 4.8 Undesirable effects · 1

HOS-095554 · has-adverse-reaction-information · PDF-Seite 13

a. Summary of the safety profile The most serious adverse reactions that may occur during filgrastim treatment include: anaphylactic reaction, serious pulmonary adverse events (including interstitial pneumonia and ARDS), capillary leak syndrome, severe splenomegaly/splenic rupture, transformation to myelodysplastic syndrome or leukaemia in SCN patients, GvHD in patients receiving allogeneic bone marrow transfer or peripheral blood cell progenitor cell transplant and sickle cell crisis in patients with sickle cell disease. The most commonly reported adverse reactions are pyrexia, musculoskeletal pain (which includes bone pain, back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain, musculoskeletal chest pain, neck pain), anaemia, vomiting, and nausea. In clinical trials in cancer patients musculoskeletal pain was mild or moderate in 10%, and severe in 3% of patients. b. Tabulated summary of adverse reactions The data in the table below describe adverse reactions reported from clinical trials and spontaneous reporting. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. MedDRA Adverse reactions system organ Very common Common Uncommon Rare class (≥ 1/10) (≥ 1/100 to (≥ 1/1 000 to (≥ 1/10 000 to < 1/10) < 1/100) < 1/1 000) Infections and Sepsis infestations Bronchitis Upper respiratory tract infection Urinary tract infection Blood and Thrombocytopenia Splenomegalya Leucocytosisa Splenic rupturea lymphatic Anaemiae Haemoglobin Sickle cell anaemia system decreasede with crisis disorders Extramedullary haematopoiesis Immune system Hypersensitivity Anaphy

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HOS-095550 · has-contraindication-information · PDF-Seite 6

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

HOS-095549 · has-indication-information · PDF-Seite 2

Filgrastim is indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with established cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) and for the reduction in the duration of neutropenia in patients undergoing myeloablative therapy followed by bone marrow transplantation considered to be at increased risk of prolonged severe neutropenia. 2 The safety and efficacy of filgrastim are similar in adults and children receiving cytotoxic chemotherapy. Filgrastim is indicated for the mobilisation of peripheral blood progenitor cells (PBPCs). In patients, children or adults, with severe congenital, cyclic, or idiopathic neutropenia with an absolute neutrophil count (ANC) of ≤ 0.5 × 109/L, and a history of severe or recurrent infections, long-term administration of filgrastim is indicated to increase neutrophil counts and to reduce the incidence and duration of infection-related events. Filgrastim is indicated for the treatment of persistent neutropenia (ANC less than or equal to 1.0 × 109/L) in patients with advanced HIV infection, in order to reduce the risk of bacterial infections when other options to manage neutropenia are inappropriate.

HOS-095552 · has-interaction-information · PDF-Seite 12

The safety and efficacy of filgrastim given on the same day as myelosuppressive cytotoxic chemotherapy have not been definitively established. In view of the sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, the use of filgrastim is not recommended in the period from 24 hours before to 24 hours after chemotherapy. Preliminary evidence from a small number of patients treated concomitantly with filgrastim and 5-Fluorouracil indicates that the severity of neutropenia may be exacerbated. Possible interactions with other haematopoietic growth factors and cytokines have not yet been investigated in clinical trials. Since lithium promotes the release of neutrophils, lithium is likely to potentiate the effect of filgrastim. Although this interaction has not been formally investigated, there is no evidence that such an interaction is harmful.

HOS-095553 · has-pregnancy-information · PDF-Seite 12

Pregnancy There are no or limited amount of data from the use of filgrastim in pregnant women. Studies in animals have shown reproductive toxicity. An increased incidence of embryo loss has been observed in rabbits at high multiples of the clinical exposure and in the presence of maternal toxicity (see section 5.3). There are reports in the literature where the transplacental passage of filgrastim in pregnant women has been demonstrated. Filgrastim is not recommended during pregnancy. Breast-feeding It is unknown whether filgrastim/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from filgrastim therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility Filgrastim did not affect reproductive performance or fertility in male or female rats (see section 5.3). 12

HOS-095551 · 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. Special warnings and precautions across indications Hypersensitivity Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have been reported in patients treated with filgrastim. Permanently discontinue filgrastim in patients with clinically significant hypersensitivity. Do not administer filgrastim to patients with a history of hypersensitivity to filgrastim or pegfilgrastim. Pulmonary adverse effects Pulmonary adverse effects, in particular interstitial lung disease, have been reported after G-CSF administration. Patients with a recent history of lung infiltrates or pneumonia may be at higher risk. The onset of pulmonary signs, such as cough, fever and dyspnoea in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of 6 acute respiratory distress syndrome (ARDS). Filgrastim should be discontinued and appropriate treatment given. Glomerulonephritis Glomerulonephritis has been reported in patients receiving filgrastim and pegfilgrastim. Generally, events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim and pegfilgrastim. Urinalysis monitoring is recommended. Capillary leak syndrome Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported after granulocyte colony-stimulating factor administration, and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care (see section 4.8). Splenomegaly and splenic rupture Generally asymptomatic cases of splenomegaly and cases of splenic rupture have been reported in patients and normal donors following administration of filgrastim. Some cases of splenic rupture were fatal. Therefore, spleen size should be carefully monitored (e.g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in donors and/or patients reporting left upper abdominal or shoulder tip pain. Dose reductions of filgrastim have been noted to slow or stop the progression of splenic enlargement in patients with

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