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.)
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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).
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.