Filgrastim Flashcards
What is filgrastim?
recombinant human granulocyte colony stimulating factor analogue.
What class of drugs does filgrastim belong to?
immunosuppressive agents
antineutropenic agents
hematopoietic agents
what are other drugs in the same class as filgrastim?
calcium folinate
ondansetron
folinic acid
metoclopramide hydrochloride
What is filgrastim indicated for?
granulocyte CSF,
reduction of neutropenia duration and febrile neutropenia after cytotoxic chemotherapy for malignancy,
mobilisation of autologous peripheral blood progenitor cells along or following myelosuppresive chemo and mobilisation of peripheral blood progenitor cells in normal donors.
long term admin in patients with severe congenital, cyclic or idiopathic neutropenia.
treatment of persistent neutropenia in patients with advanced HIV infection
What is the dose of filgrastim given?
cytotoxic induced neutropenia:
SC injection or IV infusion
5μg/kg/day started at least 24hrs after cytotoxic chemo and continued until neutrophil in normal range (usually for up to 14 days, up to 38 days in acute myeloid leukaemia)
Myeloablative therapy follwoed by bone marrow transplantation:
IV inf. over 30 mins OR over 24hrs OR SC inf. over 24 hrs.
10μg/kg/day started at least 24hrs follwoing cytotoxic chemo (and within 24 hrs of bone-marrow infusion) adjusted according to neutrophil count.
Severe chronic neutropenia
SC injection
initially 12μg/kg/day in single or divided doses (initially 500,000 units/kg/day in idiopathic or cyclic neutropenia, adjusted according to response
What is the mechanism of action of filgrastim?
Binds to G-CSF receptor, stimulating production of neutrophils in the bone marrow. It controls proliferation of committed progenitor cells and influences their maturation into mature neutrophils.
Also stimulates release of neutrophils from bone marrow storage pools, reducing their maturation time.
Increases phagocytic activity of mature neutrophils.
In patients receiving cytotoxic chemotherapy, filgrastim can accelerate neutrophil recovery –> reduction in duration of neutropenic phase
What are the main PK or PD parameters associated with filgrastim use?
PD: neutrophil level return to baseline by 21 days following completion of chemo.
PK:
Absorption and clearance follows 1st order PK modelling, taking 4-6 hours to reach max concentration.
Vd: ~150mL/Kg
Primarily eliminated by kidney and neutrophils/neutrophil precursors.
elimination half life: 3.5 hours (healthy patients), 3.2-3.8 hours (cancer patietns)
What are the precautions associated with filgrastim use?
premalignant or malignant myeloid conditions
withdraw treatment in patients developing signs of pulmonary infiltration,
sickle cell disease
secondary acute myeloid leukaemia
osteoporotic bone disease
What are the contraindications with filgrastim use?
severe congenital neutropenia (Kostmann’s syndrome) with abnormal cytogenetics
do not use to increase cytotoxic chemotherapy dose beyond established regimens.
What are the main drug interactions with filgrastim use?
Fluorouracil: neutropenia is possibly exacerbated if these are given together
Amsacrine. busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine etc.: filgrastim should not be used from 24 hours before until 24 hours after cytotoxic chem due to increased risk of myelosuppression.
What are the adverse effects associated with filgrastim use?
GI disturbance
anorexia, mucositis, splenic enlargement, heptomegaly, transient hypotension, headache, asthenia, fever, epistaxis, urnary abnormalities, osteoporosis, musculoskeletal pain, bone pain, exacerbation of RA, anemia, thrombocytopenia, leukocytosis, transient decrease in glucose, pseudo gout, rash, alopecia, injection site reactions
What are the alarm bells associated with filgrastim use?
Specialist use only.
treatment should be withdrawn in patients who develop signs of pulmonary infiltration
there is possible risk of myelodysplastic syndromes or leukaemia, osteoporotic bone disease
what monitoring is required with filagrastim use?
regular morphological and cytogenetic bone-marrow examinations recommended in severe congenital neutropenia
monitor bone density if filgrastim is given for more than 6 months.
