Clinical Trial Experience: All adverse effects are grouped according to the order based on the MedDRA System Organ Classes (SOC). Within each frequency grouping, adverse effects are presented in order of decreasing seriousness.
Assessment of Adverse Effects is based on the following frequency groupings: Very common: ≥1/10; Common: ≥1/100, <1/10; Uncommon: ≥1/1,000, <1/100; Rare: ≥1/10,000, <1/1,000; Very rare: <1/10,000; Not known: cannot be estimated from the available data.
In cancer patients: In clinical trials, the most frequent undesirable effects attributable to filgrastim at the recommended dose were mild or moderate musculoskeletal pain, occurring in 10%, and severe musculoskeletal pain in 3% of patients. Musculoskeletal pain is usually controlled with standard analgesics.
Less frequent undesirable effects include urinary abnormalities predominantly mild or moderate dysuria.
In randomised, placebo-controlled clinical trials, filgrastim did not increase the incidence of undesirable effects associated with cytotoxic chemotherapy. Undesirable effects reported with equal frequency in patients treated with filgrastim/chemotherapy and placebo/chemotherapy included nausea and vomiting, alopecia, diarrhoea, fatigue, anorexia, mucosal inflammation, headache, cough, rash, chest pain, asthenia, pharyngolaryngeal pain, constipation and pain.
Reversible, dose-dependent and usually mild or moderate elevations of lactate dehydrogenase, alkaline phosphatase, uric acid and gamma-glutamyl transferase occurred with filgrastim in approximately 50%, 35%, 25% and 10% of patients, respectively at recommended doses.
Transient decreases in blood pressure, not requiring clinical treatment, have been reported occasionally.
There have been reports of GvHD and fatalities in patients receiving G-CSF after allogeneic bone marrow transplantation (see Pharmacology: Pharmacodynamics under Actions).
Vascular disorders, including veno-occlusive disease and fluid volume disturbances, have been reported occasionally in patients undergoing high-dose chemotherapy followed by autologous bone marrow transplantation. The causal association with filgrastim has not been established. (See Table 3.)
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In PBPC mobilisation in normal donors: The most commonly reported undesirable effect was mild to moderate transient musculoskeletal pain.
Leukocytosis (WBC >50 x 10
9/L) was observed in 41% of donors and transient thrombocytopenia (platelets <100 x 10
9/L) following filgrastim and leukapheresis was observed in 35% of donors.
Transient, minor increases in alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and uric acid have been reported in normal donors receiving filgrastim; these were without clinical sequelae.
Exacerbation of arthritic symptoms has been observed very rarely.
Headaches, believed to be caused by filgrastim, have been reported in PBPC donor studies.
Common but generally asymptomatic cases of splenomegaly and very rare cases of splenic rupture have been reported in healthy donors and patients following administration of granulocyte-colony stimulating factors (see Precautions). (See Table 4.)
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In SCN patients: Undesirable effects related to filgrastim therapy in SCN patients have been reported and for some their frequency tends to decrease with time.
The most frequent adverse effects attributable to filgrastim were bone pain and general musculoskeletal pain.
Other undesirable effects seen include splenomegaly, which may be progressive in a minority of cases and thrombocytopenia.
Headache and diarrhoea have been reported shortly after starting filgrastim therapy, typically in less than 10% of patients.
Anaemia and epistaxis have also been reported.
Transient increases with no clinical symptoms were observed in serum uric acid, lactic dehydrogenase and alkaline phosphatase. Transient, moderate decreases in non-fasting blood glucose have also been seen.
Undesirable effects possibly related to filgrastim therapy and typically occurring in <2% of SCN patients were injection site reaction, headache, hepatomegaly, arthralgia, alopecia, osteoporosis and rash.
During long-term use cutaneous vasculitis has been reported in 2% of SCN patients. There have been very few instances of proteinuria/haematuria. (See Table 5.)
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In patients with HIV: In clinical studies, the only undesirable effects that were consistently considered to be related to filgrastim administration were musculoskeletal pain, predominantly mild to moderate bone pain and myalgia. The incidence of these events was similar to that reported in cancer patients.
Splenomegaly was reported to be related to filgrastim therapy in <3% of patients. In all cases this was mild or moderate on physical examination and the clinical course was benign; no patients had a diagnosis of hypersplenism and no patients underwent splenectomy. As splenomegaly is a common finding in patients with HIV infection and is present to varying degrees in most patients with AIDS, the relationship to filgrastim treatment is unclear. (See Table 6.)
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Post-marketing experience: Cancer patients: Cutaneous vasculitis has been reported in patients treated with filgrastim. The mechanism of vasculitis in patients receiving filgrastim is unknown.
Cases of Sweet's syndrome (acute febrile dermatosis) have been reported.
Exacerbation of rheumatoid arthritis has been observed in individual cases.
Pulmonary adverse effects including interstitial pneumonia, pulmonary oedema and lung infiltration have been reported in some cases with an outcome of respiratory failure or acute respiratory distress syndrome (ARDS), which may be fatal (see Precautions).
In cancer patients, hypersensitivity-type reactions including anaphylaxis, rash, urticaria, angioedema, dyspnoea and hypotension occurring on initial or subsequent treatment have been reported in post-marketing experience. Overall, reports were more common after i.v. administration. In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship. Filgrastim should be permanently discontinued in patients who experience a serious allergic reaction.
Isolated cases of sickle cell crisis have been reported in patients with sickle cell disease (see Precautions).
Pseudogout has been reported in patients with cancer treated with filgrastim.
Normal Donors: In normal donors, anaphylaxis has been reported in post-marketing experience.
In normal donors, pulmonary adverse events (haemoptysis, pulmonary haemorrhage, lung infiltration, dyspnoea and hypoxia) have been reported in post-marketing experience (see Precautions).