Last Updated on eMC 30-05-2018 View medicine  | Accord Healthcare Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects

Date of revision of text on the SPC:25-05-2018

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



In section 4.4 (Special warnings and precautions for use), following is updated

Splenomegaly and Splenic rupture

Dose reductions of Filgrastim have been noted to slow or stop the progression of splenic enlargement in patients with severe chronic neutropenia, and in 3% of patients a splenectomy was required.

All patients

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. See also section 4.8.

In section 4.7 (Effects on ability to drive and use machines), following is updated

Accofil may have a minor influence on the ability to drive and use machines.

Dizziness may occur following the administration of Accofil (see section 4.8).

In section 4.8 (Undesirable effects), following is updated

Summary of the safety profile

The most serious adverse reactions that may occur during Filgrastim treatment include: anaphylactic reaction, serious pulmonary adverse events (including interstitial pneumonia and ARDS), capillary leak syndrome, severe splenomegaly/splenic rupture, transformation to myelodysplastic syndrome or leukaemia in SCN patients, GvHD in patients receiving allogeneic bone marrow transfer or peripheral blood cell progenitor cell transplant and sickle cell crisis in patients with sickle cell disease.

 

The most commonly reported adverse reactions are pyrexia, musculoskeletal pain (which includes bone pain, back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain, musculoskeletal chest pain, neck pain), anaemia, vomiting, and nausea. In clinical trials in cancer patients musculoskeletal pain was mild or moderate in 10%, and severe in 3% of patients.

Following is removed

In clinical trials on cancer patients treated with filgrastim, the most frequent undesirable effect was musculoskeletal pain which was mild or moderate in 10% and in 3% of patients respectively.

 

Graft versus Host Disease (GvHD) has also been reported.

 

In PBPC mobilization in normal donors the most commonly reported undesirable effect was musculoskeletal pain. Leukocytosis was observed in donors and thrombocytopenia following filgrastim and leukapheresis was also observed in donors. Splenomegaly and splenic rupture were also reported. Some cases of splenic rupture were fatal.

 

In SCN patients the most frequent undesirable effects attributable to filgrastim were bone pain, general musculoskeletal pain and splenomegaly. Myelodysplastic syndromes (MDS) or leukaemia have developed in patients with congenital neutropenia treated with filgrastim (see section 4.4).

 

Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported uncommonly (≥ 1/1000 to < 1/100) in cancer patients undergoing chemotherapy and healthy donors undergoing peripheral blood progenitor cell mobilization following administration of granulocyte colony-stimulating factors (see section 4.4 and section 4.8).

 

In clinical studies with filgrastim administration to HIV patients, the only adverse effects consistently considered to be related to filgrastim administration were musculoskeletal pain, bone pain and myalgia.

MedDRA system organ class

Adverse reactions

Very common

 

Common

 

Uncommon

 

Rare

 

Very rare

 

Not known

Blood and lymphatic system disorders

Thrombocytopenia

Anaemiae

Splenomegalya

Haemoglobin

decreasede

Leukocytosisa

Splenic rupturea

Sickle cell anaemia

with crisis

 

 

Immune system disorders

 

 

Graft versus Host Diseaseb

 

Drug hypersensitivitya

 

Hypersensitivity

Anaphylactic

reaction

 

 

Metabolism and nutrition disorders

 

Decreased

Appetitee

 

Blood lactate

dehydrogenase

increased

Hyperuricaemia

Blood uric acid

increased

Blood glucose

decreased

Pseudogouta

(Chondrocalcinosis

Pyrophosphate)

Fluid volume

disturbances

 

 

Nervous system disorders

Headachea

Dizziness, Hypoaesthesia,

Paraesthesia

 

 

 

 

Vascular Disorders

 

Hypotension

 

Hypertension

Veno-occlusive diseased

 

Capillary leak

syndromea

,Aortitis

 

 

Psychiatric

disorders

 

Insomnia

 

 

 

 

Respiratory, thoracic and mediastinal disorders

 

Haemoptysis

Dyspnoea

Cougha

Oropharyngeal

paina,e

Epistaxis

Acute respiratory distress syndromea

 

Respiratory failurea

 

Pulmonary oedemaa

 

Interstitial lung diseasea

 

Lung infiltrationa

 

Pulmonary haemorrhage

 

Hypoxia

 

 

 

Gastrointestinal disorders

Diarrhoeaa,e

 

Vomitinga,e

 

 

Nauseaa

Constipatione

 

Oral Pain

 

 

 

 

Hepatobiliary disorders

 

Blood alkaline phosphatase increased

 

Hepatomegaly

Gamma-glutamyl transferase increased

 

Aspartate

aminotransferase

increased

 

 

 

Skin and subcutaneous tissue disorders

 

Alopeciaa

 

Rasha

 

Erythema

Rash maculopapular

Sweets syndrome (acute febrile

neutrophilic

dermatosis)

 

Cutaneous vasculitisa

 

 

Musculoskeletal and connective tissue disorders

Musculoskeletal painc

Muscle spasms

Osteoporosis

Bone density

decreased

Exacerbation of

rheumatoid arthritis

 

 

Renal and urinary disorders

 

Dysuria

 

Haematuria

 

Proteinuria

Urine abnormality

Glomerulonephritis

 

 

General disorders and administration site conditions

 

 

Fatiguea

 

Mucosal inflammationa

 

Pyrexia

Chest paina

 

Astheniaa

 

Paina

 

Malaisee

 

Oedema

peripherale

Injection site

reaction

 

 

 

Injury,

poisoning and

procedural

complications

 

Transfusion

reactione

 

 

 

 

Infections and

infestations

 

Sepsis

 

Bronchitis

 

Upper respiratory

tract infection

 

Urinary tract

infection

 

 

 

 

Adverse events with higher incidence in Filgrastim patients compared to placebo and associated with the sequelae of the underlying malignancy or cytotoxic chemotherapy

 

Cutaneous vasculitis

Cutaneous vasculitis has been reported in patients treated with Filgrastim. The mechanism of vasculitis in patients receiving Filgrastim is unknown. During long term use cutaneous vasculitis has been reported in 2% of SCN patients.

Following is removed

 

Graft versus Host Disease (GvHD) has also been reported.

 

In PBPC mobilization in normal donors the most commonly reported undesirable effect was musculoskeletal pain. Leukocytosis was observed in donors and thrombocytopenia following filgrastim and leukapheresis was also observed in donors. Splenomegaly and splenic rupture were also reported. Some cases of splenic rupture were fatal.

 

In SCN patients the most frequent undesirable effects attributable to filgrastim were bone pain, general musculoskeletal pain and splenomegaly. Myelodysplastic syndromes (MDS) or leukaemia have developed in patients with congenital neutropenia treated with filgrastim (see section 4.4).

 

Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported uncommonly (≥ 1/1000 to < 1/100) in cancer patients undergoing chemotherapy and healthy donors undergoing peripheral blood progenitor cell mobilization following administration of granulocyte colony-stimulating factors (see section 4.4 and section 4.8).

 

In clinical studies with filgrastim administration to HIV patients, the only adverse effects consistently considered to be related to filgrastim administration were musculoskeletal pain, bone pain and myalgia.

 

PBPC mobilisation in normal donors

 

Common but generally asymptomatic cases of splenomegaly and uncommon cases of splenic rupture have been reported in patients and healthy donors following filgrastim administration (see section 4.4).

 

Pulmonary adverse events such as haemoptysis, pulmonary haemorrhage, lung infiltration, dyspnoea, and hypoxia have been reported (see section 4.4).

 

Exacerbation of arthritic symptoms has been uncommonly reported

 

In SCN patients

 

Undesirable effects include splenomegaly, which maybe progressive in a minority of cases and thrombocytopenia(see section 4.4).

 

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.

 

In patients with HIV

 

Splenomegaly was reported to be related to filgrastim therapy in <3% of patients. In all cases of splenic enlargement in HIV patients, 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 splenic enlargement 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 section 4.4).

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Date of revision of text on the SPC:12-09-2017

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



For Accofil 30 MU

In section 4.2 (Posology and method of administration), following is updated

Neutrophil Count

Filgrastim dose adjustment

> 1.0 x 109/L for 3 consecutive days

Reduce to 0.5 MU (5µg) /kg/day

Then, if ANC remains > 1.0 x 109/L for 3 more consecutive days

Discontinue filgrastim

If the ANC decreases to < 1.0 x 109/L during the treatment period, the dose of filgrastim should be re-escalated according to the above steps

ANC = absolute neutrophil count

 

The recommended dose of filgrastim for PBPC mobilisation when used alone is 1.0 MU (10 µg)/kg/day for 5-7 consecutive days. The timing of leukapheresis: 1 or 2 leukaphereses on days 5 and 6 are often sufficient. In other circumstances, additional leukaphereses may be necessary. Filgrastim dosing should be maintained until the last leukapheresis.

 

The recommended dose of filgrastim for PBPC mobilisation after myelosuppressive chemotherapy is 0.5 MU (5 µg)/kg/day given daily from the first day after completion of chemotherapy until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. Leukapheresis should be performed during the period when the ANC rises from
< 0.5 x 109/L to > 5.0 x 109/L. For patients who have not had extensive chemotherapy, one leukapheresis is often sufficient. In other circumstances, additional leukaphereses are recommended.

For the mobilisation of PBPCs in normal donors prior to allogeneic PBPC transplantation

 

For PBPC mobilisation in normal donors, filgrastim should be administered at 1.0 MU (10 µg)/kg/day for 4 - 5 consecutive days. Leukapheresis should be started at day 5 and continued until day 6 if needed in order to collect 4 x 106 CD34+ cells/kg recipient bodyweight.

In section 4.4 (Special warnings and precautions for use), following is updated

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.

 

Special precautions in sickle cell trait and sickle cell disease

 

Sickle cells crises, in some cases fatal, have been reported with the use of filgrastim in subjects with sickle cell trait or sickle cell disease. Physicians should exercise caution when considering the use of filgrastim in patients with sickle cell trait or sickle cell disease and only after careful evaluation of the potential risks and benefits.

In section 4.8 (Undesirable effects)

Cancer patients

 

MedDRA system organ class

Adverse reactions

Very common

 

Common

 

Uncommon

 

Rare

 

Very rare

 

Not known

Renal and urinary disorders

 

 

Urine abnormality

Glomerulonephritis

 

 

 

General disorders and administration site conditions

Pain

 

 

 

 

 

 

 

PBPC mobilisation in normal donors

MedDRA system organ class

Adverse reactions

Very common

 

Common

 

Uncommon

 

Rare

 

Very rare

 

Not known

Renal and urinary disorders

 

 

Glomerulonephritis

 

 

 

                                               

SCN patients

MedDRA system organ class

Adverse reactions

Very common

 

Common

 

Uncommon

 

Rare

 

Very rare

 

Not known

Renal and urinary disorders

 

Glomerulonephritis

 

 

 

 

 

Patients with HIV

MedDRA system organ class

Adverse reactions

 

Very common

 

Common

 

Uncommon

 

Rare

 

Very rare

 

Not known

Renal and urinary disorders

 

 

 

 

 

Glomerulonephritis

 

 

 

Reasons for adding or updating:

  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:13-01-2016

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Following Changes has been made:$0$0$0$0In Section 8 Marketing Authorisation Number: $0$0$0$0$0Marketing Authorisation Number EU/1/14/946/018 has been added.$0$0$0

Reasons for adding or updating:

  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 6.5 - Nature and contents of container

Date of revision of text on the SPC:17-09-2015

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



 

Update in section 4.7 Effects on ability to drive and use machines

 

Update in section 6.5 Nature and contents of container

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:22-05-2015

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Update in section 4.2  Posology and method of administration

 

Update in section 4.4  Special warnings and precautions for use

 

Update in section 4.6  Fertility, pregnancy and lactation

 

Update in section 4.7  Effects on ability to drive and use machines

 

Update in section 4.8  Undesirable effects

 

Update in section 5.1  Pharmacodynamic properties

 

Update in section 5.2 Pharmacokinetic properties

 

Update in section 10 Date of revision of the text

Reasons for adding or updating:

  • Change to section 3 - Pharmaceutical form
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 9 - Date of first authorisation/renewal of the authorisation

Date of revision of text on the SPC:15-01-2015

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Update in section Nature and content of container

Update in section 4 pharmaceutical form and contents

Update in section 6.4  :Special precautions for disposal and other handling

Update in section 6.6 : Using the pre-filled syringe with a needle safety guard
Update in section 12  marketing authorisation number
Update of Date of revision

Reasons for adding or updating:

  • New SPC for new product

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): YES