Imatinib mesylate: Indications, Mechanism of Action and Side Effects

Indications

Imatinib mesylate is an oral tyrosine kinase inhibitor used to treat chronic granulocytic leukaemia and certain types of cancer. Current FDA-approved indications include:

• First-line adult and pediatric Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase (Ph+ CML CP)

• Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis (Ph+ CML BC)

• Philadelphia chromosome-positive chronic myelogenous leukemia in accelerated phase (Ph+ CML AP)

• Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase after failure of interferon-alpha therapy

• Adult relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

• First-line pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy

• Adult myelodysplastic (MDS)/myeloproliferative (MPD) diseases associated with platelet-derived growth factor receptor gene re-arrangements

• Adult aggressive systemic mastocytosis (ASM) without D816V c-Kit mutations (or unknown c-Kit mutational status)

• Adult hypereosinophilic syndrome (HES) or chronic eosinophilic leukemia (CEL) with FIP1L1-PDGFR-alpha fusion kinase and for patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who are FIP1L1-PDGFR-alpha fusion kinase negative or unknown

• Adult unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans (DFSP)

• Kit positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST)

• Adult adjuvant treatment following resection of Kit positive GIST

Mechanism of Action

Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits bcr-abl tyrosine kinase, a constitutively abnormal tyrosine kinase produced by abnormalities of the Philadelphia chromosome in chronic myeloid leukaemia (CML). It inhibits proliferation and induces apoptosis in bcr-abl-positive cell lines as well as in fresh leukaemia cells from Philadelphia chromosome-positive chronic myeloid leukaemia.Imatinib mesylate blocks the constitutive action of protein tyrosine kinases by acting as a competitive inhibitor of the ABL ATP-binding cleft and inducing apoptosis in leukaemia cells.

Side Effects

More common

• Oedema

• Nausea

• Vomiting

• Muscle cramps

• Musculoskeletal pain

• Diarrhoea

• Skin rash

• Fatigue

• Headaches

• Joint pain

• Abdominal pain

• Nasopharyngitis

• Bleeding

• Dyspepsia

• Cough

• Sore throat

• Upper Respiratory Tract Infection

• Weight gain

• Insomnia

• Depression

• Influenza  

• Thrombocytopenia

• Blurred vision

• Decreased white blood cells

Less common

• Back pain

• bad, unusual, or unpleasant (after) taste

• change in taste

• watering of the eyes

• hypopigmentation

• lichenoid reactions

• pityriasiform eruptions

• pityriasis rosea

• psoriasis

• reactivation or induction of porphyria cutanea tarda

• neutrophilic eccrine hidradenitis

• Sweet's syndrome

• erythema nodosum

References:

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