Alvograstim

Filgrastim

Reduction in the duration of neutropenia & incidence of febrile neutropenia in patients treated w/ established cytotoxic chemotherapy for malignancy (except chronic myeloid leukaemia & myelodysplastic syndromes); neutropenia in patients undergoing myeloablative therapy followed by bone marrow transplantation. Mobilisation of peripheral blood progenitor cells (PBPCs). Increase in neutrophil counts & reduction in the incidence & duration of infection-related events after long term therapy in adults or childn w/ severe congenital, cyclic or idiopathic neutropenia w/ ANC ≤0.5 x 10⁹/L & history of severe or recurrent infections. Persistent neutropenia (ANC ≤1 x 10⁹/L) in patients w/ advanced HIV infection.

IV/SC Established cytotoxic chemotherapy 0.5 MIU (5 mcg)/kg daily SC inj. 1st dose should not be administered <24 hr following cytotoxic chemotherapy. To be continued until expected neutrophil nadir has passed & neutrophil count has recovered to the normal range. Duration of treatment: up to 14 days following chemotherapy for solid tumours, lymphomas & lymphoid leukaemia; up to 38 days following induction & consolidation treatment for AML. Myeloablative therapy followed by bone marrow transplantation Initially, 1 MIU (10 mcg)/kg as 30-min or 24-hr IV infusion or 1 MIU (10 mcg)/kg as 24-hr continuous SC infusion. 1st dose should not be given <24 hr following cytotoxic chemotherapy & w/in 24 hr before bone marrow infusion. Dosage schedule after neutrophil nadir has been passed: Neutrophil count: >1 x 10⁹/L for 3 consecutive days: reduce to 0.5 MIU/kg/day. If ANC remains >1 x 10⁹/L for 3 more consecutive days: Discontinue. If ANC decreases to <1 x 10⁹/L during treatment: Re-escalate dose. Mobilisation of PBPCs in patients undergoing myelosuppressive or myeloablative therapy followed by autologous PBPC transplantation 1 MIU (10 mcg)/kg as a 24-hr continuous SC infusion or a single daily SC inj for 5-7 consecutive days. For infusion, conduct 1 or 2 leukapheresis on days 5 & 6. Recommended daily dose: PBPC mobilisation after myelosuppresive chemotherapy: 0.5 MIU (5 mcg)/kg as SC inj, from 1st day after chemotherapy completion until expected neutrophil nadir is passed & neutrophil count recovered to normal range. Perform leukapheresis when ANC rises from <0.5 x 10⁹/L to >5 x 10⁹/L. For patients w/o extensive chemotherapy: 1 leukapheresis. Mobilisation of PBPCs in normal donors prior to allogeneic PBPC transplantation 10 mcg/kg/day SC for 4-5 consecutive days. Start leukapheresis at day 5, continued until day 6, if needed, in order to collect 4 x 10⁶ CD34⁺ cells/kg. Congenital neutropenia Initially 1.2 MIU (12 mcg)/kg SC as a single or in divided doses. Idiopathic or cyclic neutropenia Initially 0.5 MIU (5 mcg)/kg SC as single dose or in divided doses. HIV Infection Reversal of neutropenia: Initially 0.1 MIU (1 mcg)/kg given daily by SC inj titrated up to max 0.4 MIU (4 mcg)/kg until normal neutrophil count is reached & can be maintained (ANC >2 x 10⁹/L). Normal neutrophil count maintenance: Initial dose adjustment to alternate day dosing w/ 30 MIU (300 mcg)/day SC inj.

Hypersensitivity.

Do not use to increase cytotoxic chemotherapy dose beyond established dosage regimen; in patients w/ severe congenital neutropenia w/ developed leukemia or evidence of leukemic evolution. Myelodysplastic syndrome or chronic myelogenous leukaemia. Particular care in the differential diagnosis of blast formation of chronic myeloid leukemia from AML. Patients w/ secondary AML. Monitor bone density levels in patients w/ underlying osteoporotic bone diseases undergoing continuous therapy >6 mth. Higher risk of interstitial pneumonia in patients w/ recent history of lung infiltrates or pneumonia; discontinue use & give appropriate treatment if cough, fever, dyspnoea in association w/ radiological signs of pulmonary infiltrates & deterioration of pulmonary function occur which may be preliminary signs of acute resp distress syndrome (ARDS). Patients w/ cancer: Patients w/ high-dose chemotherapy; monitor platelet count & hematocrit levels regularly. Special care should be taken when administering chemotherapeutic agents known to cause severe thrombocytopenia. Neutrophil response may be diminished in patients w/ reduced precursors. May be fatal in patients receiving granulocyte-colony stimulating factor (G-CSF) after allogeneic bone marrow transplant due to graft versus host disease (GvHD). Increased hematopoietic activity of the bone marrow associated w/ transient abnormal bone scans may affect bone-imaging results. Patients undergoing PBPC mobilisation: Recommended min yield (≥2 x 10⁶ CD34⁺ cells/kg) or acceleration of platelet recovery may not be achieved w/ prior very extensive myelosuppressive therapy. Normal donors undergoing PBPC mobilisation: Consider only for allogeneic stem cell transplantation. Transient thrombocytopenia (platelets <100 x 10⁹/L) may occur; do not perform apheresis if platelets <75 x 10⁹/L & if donor is anticoagulated or w/ known hemostasis defects. Discontinue or reduce dose if leukocyte count rise to >70 x 10⁹/L. Monitor donors receiving G-CSFs for PBPC mobilisation until hematological indices normalize; monitor long-term safety of stem cell donors for at least 10 yr. Monitor spleen size as splenomegaly & splenic rupture (potentially fatal) may occur in patients & donors; consider splenic rupture diagnosis in donors &/or patients w/ upper left abdominal, or shoulder tip pain; reduce dose to slow or stop progression of splenic enlargement. Discontinue use & give appropriate treatment w/ suspected or confined pulmonary adverse events. Increased risk of acute & chronic GvHD due to immunological INT in recipients of allogeneic PBCPs mobilised w/ filgrastim. Severe chronic neutropenia (SCN) patients: Monitor platelet counts especially during 1st few wk of therapy; consider intermittent cessation or decrease dose if thrombocytopenia develops. Perform complete blood count w/ differential & platelet counts, & evaluation of bone marrow morphology & karyotype, prior to treatment. Regularly perform urinalysis for potential hematuria/proteinuria occurrence. Patients w/ autoimmune neutropenia. HIV patients: Monitor absolute neutrophil count (ANC) especially on the 1st few wk of therapy; measure ANC daily for 1st 2-3 days of therapy & at least twice wkly for the 1st 2 wk, & once wkly subsequently or once every other wk during maintenance therapy. Take blood sample immediately for ANC measurement prior to any scheduled dosing in order to determine patient's trough or nadir ANC. Effect on neutropenia due to bone marrow infiltrating infection or malignancy has not been established; consider appropriate therapy to underlying conditions in addition to filgrastim therapy. Potential high risk of thrombocytopenia & anemia development due to increased doses of myelosuppressive medications. Sickle cell disease: Fatal sickle cell crisis may arise. Contains sorbitol; should not be taken by patients w/ rare hereditary problems of fructose intolerance. Pregnancy; not recommended during lactation. Elderly >60 yr. Childn <16 yr. Neonates.

Musculoskeletal pain, increased blood alkaline phosphatase & lactate dehydrogenase; headache; diarrhoea; alopecia, rash, thrombocytopenia. Cutaneous vasculitis, Sweet’s syndrome, RA exacerbation, pulmonary adverse events (including interstitial pneumonia, pulmonary oedema, lung infiltration) leading to potentially fatal resp failure or ARDS, pseudo gout; sickle cell crisis; anaphylaxis, other pulmonary adverse events (haemoptysis, pulmonary haemorrhage, dyspnea, hypoxia). Cancer patients: Uric acid; nausea, vomiting; increased γ-glutamyl transferase. Anorexia; cough, pharyngolaryngeal pain; constipation; fatigue, asthenia, mucosal inflammation, chest pain. Normal donors (PBCP mobilization): Leukocytosis. SCN patients: Anaemia, splenomegaly; decreased blood glucose, hyperuricaemia; epistaxis. Hepatomegaly; cutaneous vasculitis; osteoporosis; inj site pain. HIV patients: Spleen disorders.

Exacerbation of severity of neutropenia w/ 5-FU. Potentiated effects w/ lithium.

Haematopoietic Agents / Supportive Care Therapy

L03AA02 - filgrastim ; Belongs to the class of colony stimulating factors. Used as immunostimulants.

POM