Nivestim Adverse Reactions

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 tables as follows describe adverse reactions reported from clinical trials and spontaneous reporting. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 3.)

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c. Description of selected adverse reactions: Hypersensitivity: Hypersensitivity-type reactions including anaphylaxis, rash, urticaria, angioedema, dyspnoea and hypotension occurring on initial or subsequent treatment have been reported in clinical studies and in post-marketing experience. Overall, reports were more common after IV administration. In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship. Filgrastim should be permanently discontinued in patients who experience a serious allergic reaction.
Pulmonary adverse events: In clinical studies and the post-marketing setting pulmonary adverse effects including interstitial lung disease, pulmonary oedema, and lung infiltration have been reported in some cases with an outcome of respiratory failure or acute respiratory distress syndrome (ARDS), which may be fatal (see Precautions).
Splenomegaly and splenic rupture: Cases of splenomegaly and splenic rupture have been reported following administration of filgrastim. Some cases of splenic rupture were fatal (see Precautions).
Capillary leak syndrome: Cases of capillary leak syndrome have been reported with granulocyte colony-stimulating factor use. These have generally occurred in patients with advanced malignant diseases, sepsis, taking multiple chemotherapy medications or undergoing apheresis (see Precautions).
Cutaneous vasculitis: Cutaneous vasculitis has been reported in patients treated with filgrastim. The mechanism of vasculitis in patients receiving filgrastim is unknown. During long-term use cutaneous vasculitis has been reported in 2% of SCN patients.
Leucocytosis: Leucocytosis (WBC >50 x 10⁹/L) was observed in 41% of normal donors and transient thrombocytopenia (platelets <100 x 10⁹/L) following filgrastim and leukapheresis was observed in 35% of donors (see Precautions).
Sweets syndrome: Cases of Sweets syndrome (acute febrile neutrophilic dermatosis) have been reported in patients treated with filgrastim.
Pseudogout (chondrocalcinosis pyrophosphate): Pseudogout (chondrocalcinosis pyrophosphate) has been reported in patients with cancer treated with filgrastim.
GvHD: There have been reports of GvHD and fatalities in patients receiving G-CSF after allogeneic bone marrow transplantation (see Precautions and Pharmacology: Pharmacodynamics under Actions).
d. Paediatric population: Data from clinical studies in paediatric patients indicate that the safety and efficacy of filgrastim are similar in both adults and children receiving cytotoxic chemotherapy suggesting no age-related differences in the pharmacokinetics of filgrastim. The only consistently reported adverse event was musculoskeletal pain, which is no different from the experience in the adult population.
There is insufficient data to further evaluate filgrastim use in paediatric subjects.
e. Other special populations: Geriatric use: No overall differences in safety or effectiveness were observed between subjects over 65 years of age compared to younger adult (>18 years of age) subjects receiving cytotoxic chemotherapy and clinical experience has not identified differences in the responses between elderly and younger adult patients. There is insufficient data to evaluate filgrastim use in geriatric subjects for other approved filgrastim indications.
Paediatric SCN patients: Cases of decreased bone density and osteoporosis have been reported in paediatric patients with severe chronic neutropenia receiving chronic treatment with filgrastim.