NEOCYTE Filgrastim 300mcg / mL Solution for IV/SC Injection 1mL 1's

Chemotherapy-induced neutropenia: To prevent occurrence of neutropenia, lessen degree of neutropenia, shorten duration of agranulocytosis, and accelerate restoration of number of granulocytes to reduce danger of combination infection.

 

To be administered by subcutaneous (SC) or intravenous (IV) route only.
Do not administer rhG-CSF injection in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to these agents.
RhG-CSF should NOT be diluted with saline solutions as the product may precipitate.
Inspect parenteral solutions visually for particulate matter and discoloration prior to use. Do not use if particulates or discoloration are observed.
Dosage and administration time of rhG-CSF injection are decided according to intensity of chemotherapy and declining degree of neutrophilic granulocytes as follows: See table.

Laboratory monitoring: Obtain a complete blood count (CBC) and platelet count before instituting rhG-CSF therapy. Monitor these parameters two times a week during therapy.
Discontinue rhG-CSF if the ANC exceeds 10 x 10⁹/L after the expected chemotherapy-induced neutropenia.

Hypersensitivity to rhG-CSF, Escherichia coli-derived proteins or any component of the product.
To increase the dose of cytotoxic chemotherapy beyond established dosage regimens.
Severe congenital neutropenia (Kostmann's syndrome) with abnormal cytogenetics (see Precautions).

 

Warnings

General: The safety and efficacy of rhG-CSF given simultaneously with cytotoxic chemotherapy have not been established. Because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, do not use rhG-CSF 24 hours before to 24 hours after the administration of cytotoxic chemotherapy (see Dosage & Administration).
The efficacy of rhG-CSF has not been evaluated in patients receiving chemotherapy associated with delayed myelosuppression (e.g., nitrosoureas) or with mitomycin C or with myelosuppressive doses of antimetabolites such as 5-fluorouracil.
The safety and efficacy of rhG-CSF have not been evaluated in patients receiving concurrent radiation therapy. Simultaneous use of rhG-CSF with chemotherapy and radiation therapy should be avoided.
Potential Effect on Malignant Cells: RhG-CSF is a growth factor that primarily stimulates production of neutrophils. However, the possibility that rhG-CSF can act as a growth factor for any tumor type cannot be excluded. Randomized studies have demonstrated that treatment with rhG-CSF following chemotherapy for acute myeloid leukemia (AML) does not adversely influence the outcome of treatment. The use of rhG-CSF in chronic myeloid leukemia and myelodysplasia has not been fully investigated, and caution should be exercised in using this drug in patients with such conditions.
Tumor cells may be collected in the leukapheresis product, following peripheral blood progenitor cell mobilization by rhG-CSF. The clinical significance and the effect of reinfusion of tumor cells with the leukapheresis product are still unknown and the possible contribution of clonogenic tumor cells to an eventual relapse has not been determined.
AML has been reported to occur in the natural history of severe chronic neutropenia (SCN) without cytokine therapy. It is not known that, if any, additional risk may be imposed by rhG-CSF therapy.
Cardiovascular Effects: Cardiac events (myocardial infarctions, arrhythmias) have been reported in cancer patients receiving rhG-CSF in clinical studies; the relationship is unknown. However, patients with pre-existing cardiac conditions receiving rhG-CSF should be monitored closely.
Hematologic Effects: The response to rhG-CSF may be diminished in patients with reduced neutrophil precursors such as those previously treated with extensive dose of chemotherapy or radiotherapy.
In studies of rhG-CSF administration following chemotherapy, most reported side effects were consistent with those seen as a result of cytotoxic chemotherapy. As a result of the potential of receiving higher doses of chemotherapy (i.e., full doses on the prescribed schedule), the patients may be at greater risk of thrombocytopenia, anemia and non-hematological consequences of increased chemotherapy doses (please refer to the prescribing information of the specific chemotherapy agents used). Regular monitoring of hematocrit and platelet count is recommended.
Leukocytosis: White blood cell counts of 100 x 10⁹/L or greater were observed in approximately 2% of patients receiving rhG-CSF at doses above 5 mcg/kg body weight/day. There were no reports of adverse events associated with this degree of leukocytosis. In order to avoid the potential complications of excessive leukocytosis, a CBC is recommended two times a week during rhG-CSF therapy (see Dosage & Administration).
Hypersensitivity/Allergic Reactions: Allergic-type reactions occurring on initial or subsequent treatment have been reported in <1 in 4000 patients treated with rhG-CSF. These have generally been characterized by systemic symptoms involving at least 2 body systems, most often skin (rash, urticaria, facial edema), respiratory (wheezing, dyspnea), and cardiovascular (hypotension, tachycardia). Some reactions occurred on initial exposure. Reactions tended to occur within the first 30 minutes after administration and appeared to occur more frequently in patients receiving rhG-CSF IV. Drug should be withdrawn immediately. Rapid resolution of symptoms occurred in most cases after administration of antihistamines, steroids, bronchodilators, and/or epinephrine. Do not rechallenge since symptoms recurred in more than half the patients who were rechallenged.
Cutaneous Vasculitis: Cutaneous vasculitis has been reported in patients treated with rhG-CSF. In most cases, severity of cutaneous vasculitis was moderate or severe. Most of the reports involved patients with SCN receiving long-term rhG-CSF therapy. Symptoms of vasculitis generally developed simultaneously with an increase in the ANC and abated when the ANC decreased. Many patients were able to continue rhG-CSF at a reduced dose.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity. The nature and specificity of these antibodies have not been adequately studied. The possibility exists that an antibody directed against rhG-CSF could cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia.
Acute Respiratory Distress Syndrome (ARDS): ARDS has been reported in patients receiving rhG-CSF, and is postulated to be secondary to an influx of neutrophils to sites of inflammation in the lungs. Patients receiving rhG-CSF who develop fever, lung infiltrates or respiratory distress should be evaluated for the possibility of ARDS. In the event that ARDS occurs, rhG-CSF should be withheld until resolution of ARDS or discontinued. Patients should receive appropriate medical management for this condition.
Special Precautions: Risks associated with increased doses of chemotherapy: Intensified doses of chemotherapeutic agents may lead to increased toxicities associated with these agents, including cardiac, pulmonary, neurologic and dermatologic effects (please refer to the prescribing information of the specific chemotherapy agents used). Increased exposure to alkylating agents, particularly if combined with radiotherapy, is known to be associated with the genesis of secondary malignancies. When considering chemotherapy dose intensification with rhG-CSF support, clinicians should weigh the risk of secondary malignancy against the potential benefits of improved primary disease outcome.
Diagnosis of congenital, cyclic or idiopathic neutropenia: Care should be taken to confirm the diagnosis of congenital, cyclic or idiopathic neutropenia, which may be difficult to distinguish from myelodysplasia, before initiating rhG-CSF therapy. The safety and efficacy of rhG-CSF in the treatment of neutropenia due to other hematopoietic disorders (e.g., myelodysplastic syndrome) have not been established.
It is essential that serial CBCs with differential and platelet counts, and an evaluation of bone marrow morphology and karyotype, be performed prior to initiation of rhG-CSF therapy.
Myelodsyplastic syndrome and AML have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. Cytogenic abnormalities, transformation to myelodysplastic syndrome, and AML have also been observed in patients treated with rhG-CSF for SCN.
Chronic administration: Although the relationship to rhG-CSF is unclear, osteoporosis has been reported in approximately 7% of patients receiving rhG-CSF therapy for up to 4.5 years in clinical trials in patients with SCN. Patients with SCN, particularly those with congenital neutropenia and those with underlying osteoporotic bone disease, should be monitored for the possible occurrence of bone density changes while on long-term rhG-CSF therapy. Other infrequently observed adverse effects included exacerbation of some pre-existing skin disorders (e.g., psoriasis), cutaneous vasculitis (leukocytoclastic), alopecia, hematuria/proteinuria, thrombocytopenia (platelets <50 x 10⁹/L).
Infections causing myelosuppression: Neutropenia may be due to bone marrow infiltrating opportunistic infections such as Mycobacterium avium complex or malignancies such as lymphoma. In patients with known bone marrow infiltrating infection or malignancy, consideration should be given to appropriate therapy for treatment of the underlying condition, in addition to administration of rhG-CSF for treatment of neutropenia.
Carcinogenesis, Mutagenesis, Teratogenicity, Impairment of Fertility: The carcinogenic potential of rhG-CSF has not been studied. RhG-CSF failed to induce bacterial gene mutations in either the presence or absence of a drug metabolizing enzyme system. There is no evidence from studies in rats and rabbits that rhG-CSF is teratogenic. An increased incidence of embryo-loss has been observed in rabbits, but no malformation has been seen. RhG-CSF had no observed effect on the fertility of male or female rats, or on gestation at doses up to 500 mcg/kg body weight.
Use in Children (<18 years old): Although efficacy of rhG-CSF has not been demonstrated in children, safety data indicate that it does not exhibit greater toxicity in children than adults.
Use in Elderly: Randomized, placebo-controlled trials of rhG-CSF have observed no overall differences in safety or effectiveness between patients ≥65 years old and younger subjects, and other clinical experience has not identified differences in the responses between elderly and younger patients.

 

Use In Pregnancy & Lactation

The most commonly reported adverse reactions are mild to moderate musculoskeletal pain occurring in more than 10% of patients. Generally, adverse reactions to rhG-CSF are mild and tolerable, and special treatment is not necessary. The symptoms will disappear after withdrawal.
Gastrointestinal Effects: Nausea, vomiting and abdominal pain are very common. Mucosal inflammation, constipation and diarrhea are common.
Cardiovascular Effects: Sickle cell crisis, sometimes fatal, has been reported (see Precautions). Transient hypotension and vascular disorders including veno-occlusive disease and volume disturbances have also been reported.
Hematologic Effects: Leukocytosis and thrombocytopenia were reported. Thrombocytopenia and anemia are very common in patients with SCN (see Precautions).
Hepatic Effects: Increased gamma-glutamyl transpeptidase and alkaline phosphatase are very common. Hepatomegaly is common in patients with SCN. Increase in aspartate aminotransferase has also been reported.
Central Nervous System Effects: Headache and anorexia are common.
Metabolic Effects: Increased lactate dehydrogenase and uric acid are very common. Decreased glucose and hyperuricemia are very common in patients with SCN. Pseudogout has also been reported in cancer patients.
Musculoskeletal Effects: Chest pain and musculoskeletal pain are common. Osteoporosis is common in patients with SCN. Bone pain and myalgia are very common in patients with SCN and HIV infection. Rheumatoid arthritis, arthritic symptoms exacerbation and arthralgia have also been reported.
Respiratory Effects: ARDS (see Precautions). Cough and pharyngolaryngeal pain are common. Pulmonary edema, interstitial pneumonia, pulmonary infiltrates, hemoptysis, pulmonary hemorrhage, dyspnea, and hypoxia have also been reported.
Dermatologic Effects: Alopecia and skin rash are common. Sweet's syndrome and cutaneous vasculitis are very rare but are common in patients with SCN. Epistaxis has also been reported.
Lymphatic System Effects: Rare cases of splenic rupture (see Warnings). Splenomegaly and other spleen disorders were also reported.
Hypersensitivity (see Precautions): Allergic reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnea, wheezing, tachycardia, and hypotension are very rare.
Genitourinary Effects: Urinary abnormalities (predominantly dysuria) have also been reported. Hematuria and proteinuria have also been reported.
Local Effects: Erythema, swelling or pruritus may occasionally occur at the site of injection. SC injection or infusion may result in minor bruising, inflammation or bleeding, and continuous IV infusion may result in inflammation at the site of administration.
Others: Fatigue and generalized weakness are common.

 

Interactions of rhG-CSF with other cytokines, including hematopoietic growth factors, have been observed in animal studies. The safety, efficacy and possible interactions of rhG-CSF used in combination with other cytokines have not been characterized in clinical trials.
Drug interactions between rhG-CSF and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils, such as lithium, should be used with caution.
Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

Haematopoietic Agents / Supportive Care Therapy