Imatinib selectively inhibits enzyme Ber-Abl-tyrosine kinase which is formed at the confluence portion Ber gene (breakpoint cluster region) and proto-oncogene Abl (Abelson) at the cellular level.
Imatinib selectively inhibits proliferation and induces apoptosis in cell lines expressing Ber-Abl-tyrosine kinase, as well as immature leukemic cells in chronic myeloid leukemia with positive Philadelphia chromosome and acute lymphoblastic leukemia. In patients with chronic myeloid leukemia with imatinib selectively inhibits Ber-Abl-positive colonies, has antitumor activity in monotherapy.
Imatinib selectively inhibits Ber-Abl-positive colonies obtained from the blood of patients with chronic myeloid leukemia.
Activation of receptor for platelet-derived growth factor or fragment Abl-tyrosine kinase may be the cause of both myelodysplastic / myeloproliferative diseases, and hypereosinophilic syndrome and chronic eosinophilic leukemia and dermatofibrosarcoma protuberans.
Activation of c-Kit-receptor tyrosine kinase receptors and to platelet-derived growth factors may underlie the pathogenesis of systemic mastocytosis.
Imatinib inhibits signaling in cells and cell proliferation resulting from dysregulation of platelet growth factors and stem cells, c-Kit-receptor tyrosine kinase Abl-fragment.
Imatinib inhibits proliferation and induces apoptosis stromapnyh gastrointestinal tumors expressing tyrosine mutation c-Kit-receptor.
On the one capsule:
Imatinib mesylate 119.5 mg, based on 100 mg imatinib
Cellulose microcrystalline 92 mg
Crospovidone 15 mg
Silica colloidal 1.5 mg
Magnesium stearate 2 mg
of the capsule body:
titanium dioxide – 2% gelatin – up to 100%; cap capsules: indigo – 0.3% titanium dioxide – 1% iron oxide yellow – 1.7143% gelatin – up to 100%.
- For the first time identified a positive Philadelphia chromosome (Ph +) chronic myeloid leukemia in children and adults.
- Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia in chronic phase at the failure of previous therapy with interferon alpha or in accelerated phase or blast crisis in children and adults.
- For the first time a positive diagnosed Philadelphia chromosome (Ph +) acute lymphoblastic leukemia in adult patients in combination with chemotherapy.
- relapsed or refractory acute lymphocytic leukemia positive for Philadelphia chromosome (Ph +) in adult patients as monotherapy.
- myelodysplastic / myeloproliferative diseases associated with the receptor gene rearrangements platelet-derived growth factor in adult patients.
- Systemic mastocytosis in adults with lack D816V c-Kit mutation or unknown c-Kit mutational status.
- hypereosinophilic syndrome and / or chronic eosinophilic leukemia in adult patients with positive or negative abnormal FIP1L1-PDGRF alpha kinase.
- The adjuvant therapy of gastrointestinal stromal tumors (GIST) positive for a-Kit (CD 117) in adult patients.
- Inoperable and / or metastatic malignant gastrointestinal stromal tumor (GIST) of a positive-Kit (CD 117) in adult patients.
- unresectable, recurrent and / or metastatic dermatofibrosarcoma protuberans in adult patients.
- Hypersensitivity to the active substance or to any other component of the drug. .
- Children under 2 years of age (efficacy and safety have not been established).
- Pregnancy and lactation.
It should be used with caution in patients with severe hepatic impairment, severe renal impairment, heart disease or the presence of risk factors for heart failure, as well as during regular hemodialysis.
Before the drug, are possible adverse effects from the organs and systems:
onset of nausea, vomiting, abnormal liver function (increased activity of “liver” transaminases and alkaline phosphatase, hyperbilirubinemia).
neutropenia, thrombocytopenia, anemia, pancytopenia.
fluid retention in the body – weight gain, superficial edema, local or widespread edema, pleural and / or pericardial effusion, ascites, pulmonary edema, edema periorbital region, at least – limbs, impaired kidney function.
How to accept, acceptance rate and dosage
The recommended daily dose filahromina in remission – 400 mg, in the acute phase and blast crisis – 600 mg. Dosage disease progression can be adjusted: in remission – 600 mg / day in the acute phase and blast crisis – 800 mg / day (400 mg, 2 times a day).
In the case of liver function (bilirubin increase 3-fold compared to the initial value, “liver” transaminase – 5 times) treatment is stopped until the values of the indicators not decrease to 1.5 and 2.5 respectively. In this case, treatment resumed, with decreasing doses of 400 to 300 mg, and from 600 to 400 mg.
Blast crisis and in the acute stage (dosing regimen – 600 mg / day) in the case of reducing neutrophil less than 500 / microliter, platelets – less than 100 thousand / ml treatment discontinued;. differentiating the cause of the cytopenia, marrow biopsy performed; if not cytopenia is associated with leukemia, imatinib dose reduced to 400 mg; if cytopenia is maintained for subsequent 2 weeks, the dose is reduced to 300 mg; if cytopenia extended to 4 weeks, the treatment was stopped to restore blood counts (neutrophils – at least one thousand / ml, platelets -.. at least 200 thousand / ml) and then resumed at a reduced dose – 300 mg / day.
Increasing the concentration of imatinib – Filahromina basic substance in the blood plasma, while the application may FS Filahromina conjunction with such drugs as ketoconazole, itraconazole, erythromycin, clarithromycin.
Reduction of drug in blood plasma, possibly with simultaneous reception from: dexamethasone, rifampicin, anticonvulsants, such as carbamazepine, oxcarbazepine, phenytoin, phenobarbital, fosphenytoin, primidone or medicaments based Hypericum perforatum.
Caution is recommended while the use of imatinib and drugs cyclosporin and pimozide.
With the simultaneous use of warfarin prothrombin time may increase. With simultaneous administration with coumarin derivatives requires short-term monitoring of the prothrombin time in the beginning and at the end of Imatinib therapy, and when changing the dosing regime imatinib. Alternatively, should consider the use of low molecular weight heparin derivatives.
In combination with imatinib chemotherapeutic drugs, high doses may develop hepatotoxicity in a transient increase of liver transaminases and hyperbilirubinemia.