Filgrastim interacts in the following cases:
Since lithium promotes the release of neutrophils, it 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.
G-CSF can promote growth of myeloid cells in vitro and similar effects may be seen on some non-myeloid cells in vitro.
The safety and efficacy of filgrastim administration in patients with myelodysplastic syndrome or chronic myelogenous leukaemia have not been established. Therefore, filgrastim is not indicated for use in these conditions. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from acute myeloid leukaemia.
In view of limited safety and efficacy data in patients with secondary AML, filgrastim should be administered with caution. The safety and efficacy of filgrastim administration in de novo AML patients aged <55 years with good cytogenetics [t (8; 21), t (15; 17), and inv (16)] have not been established.
White blood cell counts of 100 × 109/L or greater have been observed in less than 5% of patients receiving filgrastim at doses above 0.3 MIU/kg/day (3 μg/kg/day). No undesirable effects directly attributable to this degree of leukocytosis have been reported. However, in view of the potential risks associated with severe leukocytosis, a white blood cell count should be performed at regular intervals during filgrastim therapy. If leukocyte counts exceed 50 × 109/L after the expected nadir, filgrastim should be discontinued immediately. However, during the period of administration of filgrastim for PBPC mobilisation, filgrastim should be discontinued or its dosage should be reduced if the leukocyte counts rise to >70 × 109/L.
Cases of splenomegaly and splenic rupture have been reported uncommonly following administration of filgrastim. Some cases of splenic rupture were fatal. Individuals receiving filgrastim who report left upper abdominal and/or shoulder tip pain should be evaluated for an enlarged spleen or splenic rupture. Dose reductions of filgrastim have been noted to slow or stop the progression of splenic enlargement in patients with severe chronic neutropenia, and in 3% of patients a splenectomy was required.
Treatment with filgrastim alone does not preclude thrombocytopenia and anaemia due to myelosuppressive chemotherapy. Because of the potential of receiving higher doses of chemotherapy (e.g. full doses on the prescribed schedule) the patient may be at greater risk of thrombocytopenia and anaemia. Regular monitoring of platelet count and haematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic agents which are known to cause severe thrombocytopenia.
The use of filgrastim-mobilised PBPCs has been shown to reduce the depth and duration of thrombocytopenia following myelosuppressive or myeloablative chemotherapy.
Thrombocytopenia has been reported very commonly in patients receiving filgrastim. Platelet counts should therefore be monitored closely.
Transient thrombocytopenia (platelets <100 × 109/L) following filgrastim administration and leukapheresis was observed in 35% of subjects studied. Among these, two cases of platelets <50 × 109/L were reported and attributed to the leukapheresis procedure. If more than one leukapheresis is required, particular attention should be paid to donors with platelets <100 × 109/L prior to leukapheresis; in general apheresis should not be performed if platelets are <75 × 109/L.
Leukapheresis should not be performed in donors who are anticoagulated or who have known defects in haemostasis. Filgrastim administration should be discontinued or its dosage should be reduced if the leukocyte counts rise to >70 × 109/L. Donors who receive G-CSFs for PBPC mobilisation should be monitored until haematological indices return to normal.
Transient cytogenetic abnormalities have been observed in normal donors following G-CSF use. The significance of these changes is unknown. Nevertheless, a risk of promotion of a malignant myeloid clone cannot be excluded. It is recommended that the apheresis centre perform a systematic record and tracking of the stem cell donors for at least 10 years to ensure monitoring of long-term safety.
Common but generally asymptomatic cases of splenomegaly and uncommon cases of splenic rupture have been reported in healthy donors and patients following administration of G-CSFs. 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 pain or shoulder tip pain.
In normal donors, dyspnoea has been reported commonly and other pulmonary adverse events (haemoptysis, pulmonary haemorrhage, lung infiltrates, and hypoxia) have been reported uncommonly. In case of suspected or confirmed pulmonary adverse events, discontinuation of treatment with filgrastim should be considered and appropriate medical care given.
Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSF administration. Patients with a recent history of pulmonary 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 Adult Respiratory Distress Syndrome (ARDS). Filgrastim should be discontinued and appropriate treatment given in these cases.
Monitoring of bone density may be indicated in patients with underlying osteoporotic bone diseases who undergo continuous therapy with filgrastim for more than 6 months.
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 has been reported after granulocyte colony-stimulating factor administration, and is characterised by hypotension, hypoalbuminaemia, oedema and hemoconcentration. 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.
There are no or limited 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. There are reports in the literature where the transplacental passage of filgrastim in pregnant women has been demonstrated.
Filgrastim is not recommended during pregnancy.
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 breastfeeding 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.
Filgrastim did not affect reproductive performance or fertility in male or female rats.
Filgrastim may have a minor influence on the ability to drive and use machines.
Dizziness may occur following the administration of filgrastim.
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