Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 15.08.2022

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Tyrosine kinase inhibitor for the treatment of oncological diseases.

Pharmacodynamics (Effect)
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The translocation between chromosomes 9 and 22 is characteristic of chronic myeloid leukemia (CML) (Philadelphia chromosome). This leads to the oncogene known as BCR-ABL. This oncogene is a non-receptor tyrosine kinase tyrosine kinase that phosphorylates various substrates. BCR-ABL inhibits the normal proliferation and differentiation of cells.

Imatinib inhibits the intracellularly localized BCR-ABL tyrosine kinase , which is responsible for uncontrolled growth in chronic myeloid leukemia (CML). Imatinib specifically blocks the binding site for ATP at the tyrosine kinase BCR-ABL. This inhibits the transfer of ATP phosphate groups to tyrosine residues of the substrates.

In addition, imatinib also inhibits the c-kit receptor tyrosine kinase (for the growth factor CSF = cytokine stem cell factor", which in mutated form is important for the growth of gastrointestinal stromal cell tumours (GIST).

In addition, the PDGFR (platelet-derived-growth-factor receptor) receptor is inhibited, which plays a role in myelodysplastic/myeloproliferative diseases. If the various tyrosine kinases are listed according to decreasing affinity of the active substances, the tyrosine kinase preference for imatinib is PDGFR > KIT > BCR-ABL, for nilotinib BCR-ABL > PDGFR > KIT.

In this way, signal transduction within cells is prevented. Thus, processes of migration, invasion angiogenesis, proliferation and anti-apoptosis are disturbed.

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Chronic myeloid leukemia, primary eosinophilia.

Gastrointestinal stromal tumors and myeloproliferative disorders.

Potential uses ( off-label use): Dermatofibrosarcoma protuberans; chronic graft-versus-host disease; systemic scleroderma; hypereosinophilia syndrome (off-label use); mastocytosis(off-label use); acrolentiginous malignant melanoma; mucosal melanoma.

Pregnancy/nursing period
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Teratogenicity was described in animal experiments. Do not use during pregnancy or lactation!

Dosage and method of use
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For the treatment of CML: 400 mg/day (in the chronic phase) or 600 mg/day (in blast crises). Under certain circumstances, e.g. progression of the disease, increase to 800 mg/day is possible.

Undesirable effects
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Autoimmune phenomena and diseases whose management and, if necessary, prophylactic treatment are of great importance. The most frequent side effect is immune-mediated colitis, which, depending on the severity, can also lead to severe, even long-lasting diarrhea. In addition, other immune-mediated diseases such as hypophysitis, hepatitis, iridocyclitis, and exacerbation of lupus nephritis are also observed.

In chronic myeloid leukemia, the occurrence of AGEP has been observed several times with imatinib therapy (Scott AD et al. 2015).

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Hypersensitivity to the active substance or any of the other ingredients.

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  1. Gabrielli A et al (2007) Stimulatory autoantibodies to the PDGF receptor: a link to fibrosis in scleroderma and a pathway for novel therapeutic targets. Autoimmune Rev 7: 121-126
  2. Gabrielli A et al (2007) Pathogenic autoantibodies in systemic sclerosis. Curr Opin Immunol 19: 640-645
  3. Goldman JM et al (2003) Chronic myeloid leukemia - advances in biology and new approaches to treatment. N Engl J Med 349: 1451-1464
  4. Kähler HC et al (2009) Skin changes due to "targeted therapies" in oncological patients. Dermatologist 60: 433-440
  5. Scott AD et al (2015) Acute generalized exanthematous pustulosis (AGEP) secondary to imatinib in a patient with chronic myeloid leukaemia. Clin Exp Dermatol 40:926-927

  6. Svegliati S et al (2007) Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 110: 237-241


Last updated on: 15.08.2022