Neulastim Special Precautions

Traceability: In order to improve the traceability of granulocyte-colony stimulating factors (G-CSFs), the trade name of the administered product should be clearly recorded in the patient file.
Limited clinical data suggest a comparable effect on time to recovery of severe neutropenia for pegfilgrastim to filgrastim with de novo acute myeloid leukaemia (see Pharmacology: Pharmacodynamics under Actions). However, the long-term effects of Neulastim have not been established in acute myeloid leukaemia (AML); therefore, it should be used with caution in this patient population.
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 Neulastim have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary Acute Myeloid Leukaemia (AML); therefore, it should not be used in such patients. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from acute myeloid leukaemia.
The safety and efficacy of Neulastim administration in de novo AML patients aged < 55 years with cytogenetics t(15;17) have not been established.
The safety and efficacy of Neulastim have not been investigated in patients receiving high dose chemotherapy. This medicinal product should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimens.
Pulmonary adverse events: Uncommon (≥ 1/1,000 to < 1/100) 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 (see Adverse Reactions).
The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological signs of pulmonary infiltrates, and deterioration in pulmonary function along with increased neutrophil count may be preliminary signs of Acute Respiratory Distress Syndrome (ARDS). In such circumstances, Neulastim should be discontinued at the discretion of the physician and the appropriate treatment given (see Adverse Reactions).
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 has been reported after G-CSF 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 Adverse Reactions).
Splenomegaly and splenic rupture: Uncommon but generally asymptomatic cases of splenomegaly and uncommon cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim (see Adverse Reactions). Therefore, spleen size should be carefully monitored (e.g., clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tip pain.
Thrombocytopenia and anaemia: Treatment with Neulastim alone does not preclude thrombocytopenia and anaemia because full dose myelosuppressive chemotherapy is maintained on the prescribed schedule. 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.
Myelodysplastic syndrome and acute myeloid leukaemia in breast and lung cancer patients.
In the post-marketing observational study setting, pegfilgrastim in conjunction with chemotherapy and/or radiotherapy has been associated with development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) in breast and lung cancer patients (see Adverse Reactions). Monitor patients treated in these settings for signs and symptoms of MDS/AML.
Sickle cell anaemia: Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell trait or sickle cell disease (see Adverse Reactions). Therefore, physicians should use caution when prescribing Neulastim in patients with sickle cell trait or sickle cell disease, should monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of this medicine with splenic enlargement and vaso-occlusive crisis.
Leukocytosis: White blood cell (WBC) counts of 100 x 10⁹/L or greater have been observed in less than 1% of patients receiving Neulastim. No adverse events directly attributable to this degree of leukocytosis have been reported. Such elevation in white blood cells is transient, typically seen 24 to 48 hours after administration and is consistent with the pharmacodynamic effects of this medicine. Consistent with the clinical effects and the potential for leukocytosis, a WBC count should be performed at regular intervals during therapy. If leukocyte counts exceed 50 x 10⁹/L after the expected nadir, this medicine should be discontinued immediately.
Hypersensitivity: Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment has been reported in patients treated with Neulastim. Permanently discontinue Neulastim in patients with clinically significant hypersensitivity. Do not administer Neulastim to patients with a history of hypersensitivity to pegfilgrastim or filgrastim. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days.
Stevens-Johnson syndrome: Stevens-Johnson syndrome (SJS), which can be life-threatening or fatal, has been reported rarely in association with pegfilgrastim treatment. If the patient has developed SJS with the use of pegfilgrastim, treatment with pegfilgrastim must not be restarted in this patient at any time.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of antibodies against pegfilgrastim is generally low. Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present.
Aortitis: Aortitis has been reported after G-CSF administration in healthy subjects and in cancer patients. The symptoms experienced included fever, abdominal pain, malaise, back pain and increased inflammatory markers (e.g. c-reactive protein and white blood cell count). In most cases aortitis was diagnosed by CT scan and generally resolved after withdrawal of GCSF. See also Adverse Reactions.
Other warnings: The safety and efficacy of Neulastim for the mobilisation of blood progenitor cells in patients or healthy donors have not been adequately evaluated.
The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging findings. This should be considered when interpreting bone-imaging results.
Sorbitol: The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
Neulastim contains less than 1 mmol sodium (23 mg) per 6 mg dose, i.e. essentially 'sodium-free'.
Effects on ability to drive and use machines: Neulastim has no or negligible influence on the ability to drive and use machines.