Pegfilgrastim

When ATH: L03AA13

Pharmacological action

Stimulator leykopoeza. It is a covalent conjugate of filgrastim, recombinant human granulocyte colony stimulating factor (G-CSF), with one molecule of polyethylene glycol (PEG) 20 kDa, Sustained action by reducing renal clearance. Similarly filgrastim, pegfilgrastim regulates the formation and release of neutrophils from the bone marrow, markedly increases the number of neutrophils to normal or increased functional activity (chemotaxis and phagocytosis) in the peripheral blood for 24 h and causes a slight increase in the number of monocytes and / or lymphocytes.

G-CSF stimulates endothelial cells and may accelerate the growth of myeloid cells, including malignant cells, and certain non-myeloid cells in vitro. A single administration of pegfilgrastima after each cycle myelosuppressive cytotoxic therapy reduces the duration of neutropenia and the incidence of febrile neutropenia similarly to the daily administration of filgrastim (average, 11 ezhednevnыh introduced).

Pharmacokinetics

After a single s / c administration time to reach Cmax is pegfilgrastima 16-120 no. Pegfilgrastima concentration in serum is maintained during the period of neutropenia after myelosuppressive chemotherapy.

Withdrawal pegfilgrastima nonlinear, dose-dependent, saturable. Clearance, primarily, carried out by neutrophils and decreases with increasing dose pegfilgrastima. In accordance with the self-tracking clearance, pegfilgrastima serum concentration decreases rapidly with the beginning of recovery of neutrophil.

Testimony

Neutropenia, febrile neutropenia in order to reduce the duration of neutropenia and febrile neutropenia in intensive myelosuppressive cytotoxic chemotherapy for malignant diseases.

Dosage regimen

Enter n / a dose of 6 mg after 24 hours after each cycle of cytotoxic chemotherapy.

Side effect

On the part of the musculoskeletal system: 26% – mild or moderate pain in the bones, that, In most cases, tested alone or cropped conventional analgesics; often – arthralgia, myalgia, back pain, limbs and neck.

CNS: often – headache.

The respiratory system: cough, breathlessness, pulmonary infiltrates, respiratory dysfunction, respiratory distress syndrome.

From the side of hematopoiesis: splenomegaly, pain in the upper left quadrant of the abdomen; rarely – thrombosis vessels; rarely – splenic rupture, leukocytosis.

From the digestive system: <1% – nausea.

From the body as a whole: often – chest pain (noncardia), fever.

From the laboratory parameters: obratimoe, slight to moderate clinically insignificant increase in uric acid (7%), alkaline phosphatase (10%) and lactate dehydrogenase (20%).

Allergic reactions: anaphylaxis, rash, hives, angioedema, dyspnea, and hypotension, at the beginning or during the subsequent introduction. Sometimes resumption of treatment is accompanied by recurrent symptoms.

Local reactions: pain at the injection site.

Contraindications

Neutropenia with chronic myeloid leukemia and myelodysplastic syndromes; Acute leukemia; to increase the dose of cytotoxic chemotherapy beyond established in dosing regimens; co-administration of cytotoxic chemotherapy- and radiotherapy; pregnancy; lactation (breast-feeding); childhood and adolescence up 18 years; Hypersensitivity to pegfilgrastimu, filgrastim.

Cautions

Do not use in patients with acute leukemia, receiving myelosuppressive chemotherapy (safety and efficacy have not been studied pegfilgrastima).

Caution should be used when cancerous and precancerous diseases of the myeloid nature (in t. no. de novo acute myeloid leukemia and secondary); in combination with high-dose chemotherapy; when sickle-cell anemia.

Use only under the supervision of an oncologist or hematologist, with experience in the use of G-CSF.

Safety and efficacy in patients pegfilgrastima, treated with high-dose chemotherapy has not been studied.

Cough, fever and dyspnea in combination with radiological infiltrative changes, deterioration in lung function and increase the number of neutrophils can be signs of respiratory distress syndrome in adults (RDS). Then, depending on the clinical situation, should be discontinued and appropriate treatment.

Registered separate cases of splenic rupture after application of granulocyte colony stimulating factor, some – fatal.

It should be possible rupture of the spleen in patients with complaints of pain in the upper left part of the abdomen or the upper part of the left shoulder.

Monotherapy pegfilgrastimom does not preclude thrombocytopenia and anemia with continued myelosuppressive chemotherapy at full dose. It is recommended that regular monitoring of platelet count and hematocrit.

In patients with sickle cell anemia, leukocytosis is a poor prognostic factor, so they need regular blood tests to perform, and to consider the possibility of splenomegaly and thrombosis.

Leukocytosis 100 h109 / L or more is observed in less than 1% patients, receiving filgrastim, It is temporary and usually observed after 24-48 hours after drug administration, in accordance with its pharmacodynamic effects. There are no side effects, directly linked with leukocytosis, not disclosed.

Safety and efficacy pegfilgrastima mobilization of peripheral blood stem cells from patients and healthy donors were not evaluated appropriately.

Drug Interactions

Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic therapy, perfilgrastim should apply through 24 hours after administration of cytotoxic chemotherapeutic agents.

When concomitant administration of 5-fluorouracil or other antimetabolites possible potentiation of bone marrow suppression in vivo.