NEULASTIM Solution for injection Ref.[50344] Active ingredients: Pegfilgrastim

Cases of splenic rupture, in some cases fatal, have been reported following administration of pegfilgrastim. Spleen size should be carefully monitored. Patients receiving pegfilgrastim who report left upper abdominal and/or shoulder tip pain should be evaluated for an enlarged spleen or splenic rupture. NEULASTIM can promote growth of myeloid cells including malignant cells in vitro and similar effects may be seen on some non-myeloid cells in vitro.

Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ NEULASTIM should be administered approximately 24 hours after administration of cytotoxic chemotherapy. In clinical studies, NEULASTIM has been safely administered 14 days before chemotherapy. See INTERACTIONS.

In animal models concomitant administration of NEULASTIM and 5-fluorouracil (5-FU) or other anti-metabolites has been shown to potentiate myelosuppression.

NEULASTIM is incompatible with sodium chloride solutions. The safety and efficacy of NEULASTIM in patients with acute leukaemia have not been sufficiently investigated to enable treatment recommendations.

NEULASTIM can promote growth of myeloid cells, including malignant 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 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 have not been investigated in patients receiving high dose chemotherapy.

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 Adult Respiratory Distress Syndrome (ARDS). In such circumstances NEULASTIM should be discontinued at the discretion of the medical practitioner and the appropriate treatment given.

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. NEULASTIM should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimens.

Sickle cell crises have been associated with the use of NEULASTlM in patients with sickle cell disease. Medical practitioners should exercise caution when considering the use of NEULASTIM in patients with sickle cell disease, and only after careful evaluation of the potential risk and benefits.

White blood cell counts of 100 × 10⁹/l or greater have been observed in less than 1% of patients receiving NEULASTIM. No adverse events directly attributable to this degree of leucocytosis 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 NEULASTIM.

The safety and efficacy of NEULASTIM for the mobilisation of blood progenitor cells in patients has not been adequately evaluated.

Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ NEULASTIM should be administered approximately 24 hours after administration of cytotoxic chemotherapy. In clinical studies, 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 anti-metabolites has been shown to potentiate myelosuppression.

Increased haematopoietic 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.

Possible interactions with other haematopoietic growth factors and cytokines have not been specifically investigated in clinical studies.

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 eg, nitrosoureas.

Specific interaction or metabolism studies have not been performed, however clinical studies have not indicated an interaction of NEULASTIM with any other medicinal products.

Safety in pregnancy has not been established. Studies in animals have shown reproductive toxicity. The potential risk to the human embryo or foetus is unknown. NEULASTIM should not be used during pregnancy. NEULASTIM should not be administered to women who are breast-feeding.

In randomised clinical studies in patients with malignancy receiving NEULASTIM after cytotoxic chemotherapy, most adverse events were caused by the underlying malignancy or cytotoxic chemotherapy.

The most frequently reported and very common study-drug related undesirable effect was bone pain. Bone pain was generally of mild-to-moderate severity, transient and could be controlled in most patients with standard analgesics.

Allergic-type reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea and hypotension, occurring on initial or subsequent treatment have been reported both with NEULASTIM and with the parent compound of NEULASTIM, filgrastim. In some cases, symptoms have recurred with re-challenge, suggesting a causal relationship.

Cases of splenic rupture have been reported during treatment with NEULASTIM. Reversible, mild to moderate elevations in uric acid, alkaline phosphatase and lactate dehydrogenase, with no associated clinical effects, occurred in 7%, 10% and 20% respectively of patients receiving NEULASTIM following cytotoxic chemotherapy. Nausea was observed in healthy volunteers (11%) and <1% of patients receiving chemotherapy. Very common (≥10%) and common (≥1%, <10%) undesirable effects in clinicl studies were:

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Immune system disorders: Allergic-type reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea, hypotension, erythema and flushing, occurring on initial or subsequent treatment have been reported in patients receiving NEULASTIM. Symptoms have recurred with rechallenge, suggesting a causal relationship. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. NEULASTIM should be permanently discontinued in patients who experience a serious allergic reaction.

Gastrointestinal disorders: Cases of splenic rupture, have been reported during treatment with NEULASTIM.

Skin and subcutaneous tissue disorders: Sweet’s syndrome (acute febrile dermatosis) have been reported. Cutaneous vasculitis have been reported in patients with cancer receiving NEULASTIM.