Agencia Lei Va Hong
Full Prescribing Info
Each pre-filled syringe contains 6 mg of pegfilgrastim* in 0.6 mL solution for injection. The concentration is 10 mg/mL based on protein only**.
*Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation with polyethylene glycol (PEG).
**The concentration is 20 mg/mL if the PEG moiety is included.
The potency of this product should not be compared to the potency of another pegylated or non-pegylated protein of the same therapeutic class.
Excipient(s) with known effect: Each pre-filled syringe contains 30 mg sorbitol (E420).
Each pre-filled syringe contains less than 1 mmol (23 mg) sodium (see Precautions).
Excipients/Inactive Ingredients: Sodium acetate*, Sorbitol (E420), Polysorbate 20, Water for injections.
*Sodium acetate is formed by titrating glacial acetic acid with sodium hydroxide.
Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes).
Dosage/Direction for Use
Neulastim therapy should be initiated and supervised by physicians experienced in oncology and/or haematology.
Posology: One 6 mg dose (a single pre-filled syringe) of Neulastim is recommended for each chemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy.
Method of administration: Neulastim is injected subcutaneously. The injections should be given into the thigh, abdomen or upper arm. For instructions on handling of the medicinal product before administration, see Special instructions for disposal and other handling under Cautions for Usage.
Paediatric population: The safety and efficacy of Neulastim in children have not yet been established. Currently available data are described in Adverse Reactions, but no recommendation on a posology can be made.
Patients with renal impairment: No dose change is recommended in patients with renal impairment, including those with end stage renal disease.
Single doses of 300 μg/kg have been administered subcutaneously to a limited number of healthy volunteers and patients with non-small cell lung cancer without serious adverse reactions. The adverse events were similar to those in subjects receiving lower doses of pegfilgrastim.
Hypersensitivity to the active substance or to any of the excipients.
Special Precautions
Limited clinical data suggest a comparable effect on time to recovery of severe neutropenia for pegfilgrastim to filgrastim in patients with de novo acute myeloid leukaemia. However, the long-term effects of Neulastim have not been established in acute myeloid leukaemia; therefore, it should be used with caution in this patient population.
Granulocyte-colony stimulating factor 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 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 (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.
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.
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 G-CSF.
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.
Neulastim contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Neulastim contains less than 1 mmol (23 mg) sodium per 6 mg dose, i.e. essentially 'sodium-free'.
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.
Effects on ability to drive and use machines: Neulastim has no or negligible influence on the ability to drive and use machines.
Use In Pregnancy & Lactation
Pregnancy: There are no or limited amount of data from the use of pegfilgrastim in pregnant women. Studies in animals have shown reproductive toxicity. Neulastim is not recommended during pregnancy and in women of childbearing potential not using contraception.
Breast-feeding: There is insufficient information on the excretion of Neulastim/metabolites 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 Neulastim therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility: Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately 6 to 9 times higher than the recommended human dose (based on body surface area).
Adverse Reactions
Summary of the safety profile: The most frequently reported adverse reactions were bone pain (very common [≥ 1/10]) and musculoskeletal pain (common). Bone pain was generally of mild to moderate severity, transient and could be controlled in most patients with standard analgesics.
Hypersensitivity-type reactions, including skin rash, urticaria, angioedema, dyspnoea, erythaema, flushing, and hypotension occurred on initial or subsequent treatment with Neulastim (uncommon [≥ 1/1,000 to < 1/100]). Serious allergic reactions, including anaphylaxis can occur in patients receiving Neulastim (uncommon) (see Precautions).
Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported as uncommon (≥ 1/1,000 to < 1/100) in cancer patients undergoing chemotherapy following administration of granulocyte-colony stimulating factors; see Precautions and Description of selected adverse reactions as follows.
Splenomegaly, generally asymptomatic, is uncommon.
Splenic rupture including some fatal cases is uncommonly reported following administration of pegfilgrastim (see Precautions).
Uncommon pulmonary adverse reactions including interstitial pneumonia, pulmonary oedema, pulmonary infiltrates and pulmonary fibrosis have been reported. Uncommonly, cases have resulted in respiratory failure or Acute Respiratory Distress Syndrome (ARDS), which may be fatal (see Precautions).
Isolated cases of sickle cell crises have been reported in patients with sickle cell trait or sickle cell disease (uncommon in sickle cell patients) (see Precautions).
Tabulated summary of adverse reactions: The data in the table 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.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Uncommon cases of Sweet's syndrome have been reported, although in some cases underlying haematological malignancies may play a role.
Uncommon events of cutaneous vasculitis have been reported in patients treated with Neulastim. The mechanism of vasculitis in patients receiving Neulastim is unknown.
Injection site reactions, including injection site erythaema (uncommon (≥ 1/1,000 to < 1/100)) as well as injection site pain (common events ≥ 1/100 to < 1/10) have occurred on initial or subsequent treatment with Neulastim.
Common (≥ 1/100 to < 1/10) cases of leukocytosis (White Blood Count [WBC] > 100 x 109/L) have been reported (see Precautions).
Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associated clinical effects, were uncommon; reversible, mild to moderate elevations in lactate dehydrogenase, with no associated clinical effects, were uncommon in patients receiving Neulastim following cytotoxic chemotherapy.
Nausea and headaches were very commonly observed in patients receiving chemotherapy.
Uncommon elevations in liver function tests (LFTs) for ALT (alanine aminotransferase) or AST (aspartate aminotransferase), have been observed in patients after receiving pegfilgrastim following cytotoxic chemotherapy. These elevations are transient and return to baseline.
Common cases of thrombocytopenia have been reported.
Cases of capillary leak syndrome have been reported in the post-marketing setting 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).
Paediatric population: The experience in children is limited. A higher frequency of serious adverse reactions in younger children aged 0-5 years (92%) has been observed compared to older children aged 6-11 and 12-21 years respectively (80% and 67%) and adults. The most common adverse reaction reported was bone pain.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions as per local regulations.
Drug Interactions
Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, Neulastim should be administered at least 24 hours after administration of cytotoxic chemotherapy. In clinical trials, Neulastim has been safely administered 14 days before chemotherapy. Concomitant use of Neulastim with any chemotherapy agent has not been evaluated in patients. In animal models concomitant administration of Neulastim and 5-fluorouracil (5-FU) or other antimetabolites has been shown to potentiate myelosuppression.
Possible interactions with other haematopoietic growth factors and cytokines have not been specifically investigated in clinical trials.
The potential for interaction with lithium, which also promotes the release of neutrophils, has not been specifically investigated. There is no evidence that such an interaction would be harmful.
The safety and efficacy of Neulastim have not been evaluated in patients receiving chemotherapy associated with delayed myelosuppression e.g., nitrosoureas.
Specific interaction or metabolism studies have not been performed, however, clinical trials have not indicated an interaction of Neulastim with any other medicinal products.
Caution For Usage
Special instructions for disposal and other handling: Before administration, Neulastim solution should be inspected visually for particulate matter. Only a solution that is clear and colourless should be injected.
Excessive shaking may aggregate pegfilgrastim, rendering it biologically inactive.
Allow the pre-filled syringe to reach room temperature before injecting.
Any unused product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: This medicinal product must not be mixed with other medicinal products, particularly with sodium chloride solutions.
Store in a refrigerator (2°C-8°C).
Neulastim may be exposed to room temperature (not above 30°C) for a maximum single period of up to 72 hours. Neulastim left at room temperature for more than 72 hours should be discarded.
Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hours does not adversely affect the stability of Neulastim.
Keep the container in the outer carton, in order to protect from light.
ATC Classification
L03AA13 - pegfilgrastim ; Belongs to the class of colony stimulating factors. Used as immunostimulants.
Soln for inj (pre-filled syringe) 6 mg/0.6 mL (clear, colourless) x 1's.
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