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  • Fulphila
    / Dexcel


    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Pre-filled Syringe (solution for injection)

    1 X 6 mg/0.6 ml

    full basket chart

    Dosage

    Pegfilgrastim therapy should be initiated and supervised by physicians experienced in oncology and/or hematology.
    Posology
    One 6 mg dose (a single pre-filled syringe) of pegfilgrastim is recommended for each chemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy.
    Method of administration
    Fulphila is injected subcutaneously. The injections should be given into the thigh, abdomen or upper arm.
    Pediatric population

    The safety and efficacy of pegfilgrastim in children has not yet been established.
    Patients with renal impairment

    No dose change is recommended in patients with renal impairment, including those with end-stage renal disease.


    Indications

    Reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy, given at intervals of 14 days or more, for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes).


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    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 in patients with de novo acute myeloid leukemia (AML). However, the long-term effects of pegfilgrastim have not been established in 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 pegfilgrastim have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukemia, and in patients with secondary 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 leukemia from AML.

    The safety and efficacy of pegfilgrastim administration in de novo AML patients aged < 55 years with cytogenetics t (15;17) have not been established.

    The safety and efficacy of pegfilgrastim 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
    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 dyspnea 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 pegfilgrastim should be discontinued at the discretion of the physician and the appropriate treatment given.

    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 characterized by hypotension, hypoalbuminemia, edema 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.

    Splenomegaly and splenic rupture
    Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim. 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 anemia
    Treatment with pegfilgrastim alone does not preclude thrombocytopenia and anemia because full dose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring of platelet count and hematocrit 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 leukemia 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 leukemia (AML) in breast and lung cancer patients. Monitor patients treated in these settings for signs and symptoms of MDS/AML.

    Sickle cell anemia
    Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell trait or sickle cell disease. Therefore, physicians should use caution when prescribing pegfilgrastim 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 × 109/l or greater have been observed in less than 1% of patients receiving pegfilgrastim. 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 × 109/l after the expected nadir, this medicine should be discontinued immediately.

    Hypersensitivity
    Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have been reported in patients treated with pegfilgrastim. Permanently discontinue pegfilgrastim in patients with clinically significant hypersensitivity. Do not administer pegfilgrastim 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 neutralizing 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 pegfilgrastim for the mobilization of blood progenitor cells in patients or healthy donors has not been adequately evaluated.
    Increased hematopoietic 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
    contains 30 mg sorbitol in each pre-filed syringe which is equivalent to 50 mg/ml. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.

    Sodium
    contains less than 1 mmol sodium (23 mg) per 6 mg dose, that is to say, essentially ‘sodium-free’.
    See prescribing information for full details.


    Side Effects

    The most frequently reported adverse reactions were bone pain (very common) 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, dyspnea, erythema, flushing, and hypotension occurred on initial or subsequent treatment with pegfilgrastim (uncommon).
    Serious allergic reactions, including anaphylaxis can occur in patients receiving pegfilgrastim (uncommon).
    Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported as uncommon in cancer patients undergoing chemotherapy following administration of G-CSFs.
    Splenomegaly, generally asymptomatic, is uncommon.
    Splenic rupture including some fatal cases is uncommonly reported following administration of pegfilgrastim.
    Uncommon pulmonary adverse reactions including interstitial pneumonia, pulmonary edema, pulmonary infiltrates and pulmonary fibrosis have been reported. Uncommonly, cases have resulted in respiratory failure or ARDS, which may be fatal.
    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 prescribing information for full details.


    Drug interactions

    Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ pegfilgrastim should be administered at least 24 hours after administration of cytotoxic chemotherapy. In clinical trials, pegfilgrastim has been safely administered 14 days before chemotherapy.
    Concomitant use of pegfilgrastim with any chemotherapy agent has not been evaluated in patients. In animal models concomitant administration of pegfilgrastim and 5-fluorouracil (5-FU) or other antimetabolites has been shown to potentiate myelosuppression.

    Possible interactions with other hematopoietic 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 pegfilgrastim 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 pegfilgrastim with any other medicinal products.


    Pregnancy and 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. Pegfilgrastim is not recommended during pregnancy and in women of childbearing potential not using contraception.
    Breast-feeding
    There is insufficient information on the excretion of pegfilgrastim/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 pegfilgrastim 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).


    Overdose

    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.


    Important notes

    Contains sorbitol.


    Manufacturer
    Mylan Pharmaceuticals Private Ltd
    Licence holder
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