Description

Simple

An medication used to treat a variety of cancers.

Clinical

A tyrosine kinase inhibitor used to treat a number of leukemias, myelodysplastic/myeloproliferative disease, systemic mastocytosis, hypereosinophilic syndrome, dermatofibrosarcoma protuberans, and gastrointestinal stromal tumors.

Overview

Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies.

It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.

Pharmacology

Indication

For the treatment of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), Ph+ acute lymphoblastic leukaemia, myelodysplastic/myeloproliferative diseases, aggressive systemic mastocytosis, hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), dermatofibrosarcoma protu... Read more

Pharmacodynamic

Imatinib is an antineoplastic agent and a 2-phenylaminopyrimidine derivative that is used to treat chronic myelogenous leukemia. It works as a specific inhibitor of a number of tyrosine kinase enzymes. Chronic myelogenous leukemia is associated with the Philadelphia chromosome promoting the generati... Read more

Mechanism of action

Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell... Read more

Absorption

The pharmacokinetics in CML and GIST patients are similar. Imatinib is well absorbed with mean absolute bioavailability is 98% and maximum plasma levels achieved within 2-4 hours of dosing

Protein binding

95% protein bound, mostly to albumin and alpha-1-acid glycoprotein.

Volume of distribution

Information currently not available.

Clearance

8 L/h [50-year-old CML and GIST patient weighing 50 kg]14 L/h [50-year-old CML and GIST patient weighing 100 kg]

Half life

Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-demethyl derivative (CGP74588) are approximately 18 and 40 hours, respectively.

Route of elimination

Imatinib elimination is predominately in the feces, mostly as metabolites. 81% of the dose is eliminated within 7 days, in feces (68% of the dose) and urine (13% of the dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% faces), the remainder being metabolites.

Toxicity

The most frequently reported adverse reactions (>30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Fluid retention US
  • Kind: experimental
    • Percent: 62-76%
  • Clinical Trial
    Superficial edema US
  • Kind: experimental
    • Percent: 60-74%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 50-73%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 23-58%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 43-57%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 57%
  • Clinical Trial
    Hemorrhage US
  • Kind: experimental
    • Percent: 29-53%
  • Clinical Trial
    Muscle Cramps US
  • Kind: experimental
    • Percent: 28-50%
  • Clinical Trial
    Musculoskeletal Pain US
  • Kind: experimental
    • Percent: 38-49%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 30-48%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 36-47%
  • Clinical Trial
    Muscle Cramp US
  • Kind: experimental
    • Percent: 43%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 43%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 42%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 42%
  • Clinical Trial
    Pyrexia US
  • Kind: experimental
    • Percent: 18-41%
  • Clinical Trial
    Arthralgia US
  • Kind: experimental
    • Percent: 25-40%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 27-37%
  • Clinical Trial
    Abdominal Pain US
  • Kind: experimental
    • Percent: 30-37%
  • Clinical Trial
    Eye edema US
  • Kind: experimental
    • Percent: 33%
  • Clinical Trial
    Periorbital edema US
  • Kind: experimental
    • Percent: 33%
  • Clinical Trial
    Peripheral Edema US
  • Kind: experimental
    • Percent: 33%
  • Clinical Trial
    Weight increased US
  • Kind: experimental
    • Percent: 5-32%
  • Clinical Trial
    Joint Pain US
  • Kind: experimental
    • Percent: 31%
  • Clinical Trial
    Nasopharyngitis US
  • Kind: experimental
    • Percent: 10-31%
  • Clinical Trial
    Anemia US
  • Kind: experimental
    • Percent: 29%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 29%
  • Clinical Trial
    Arthralgia US
  • Kind: experimental
    • Percent: 29%
  • Clinical Trial
    Periorbital edema US
  • Kind: experimental
    • Percent: 29%
  • Clinical Trial
    Myalgia US
  • Kind: experimental
    • Percent: 9-27%
  • Clinical Trial
    Myalgia US
  • Kind: experimental
    • Percent: 9-27%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 12-27%
  • Clinical Trial
    Cough US
  • Kind: experimental
    • Percent: 14-27%
  • Clinical Trial
    Lacrimation increased US
  • Kind: experimental
    • Percent: 25%
  • Clinical Trial
    Anemia US
  • Kind: experimental
    • Percent: 25%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 25%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 25%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 25%
  • Clinical Trial
    Fluid retention reactions US
  • Kind: experimental
    • Percent: 7-22%
  • Clinical Trial
    Neutropenia US
  • Kind: experimental
    • Percent: 13-22%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 15-21%
  • Clinical Trial
    Dyspnea US
  • Kind: experimental
    • Percent: 12-21%
  • Clinical Trial
    Upper Respiratory Tract Infection US
  • Kind: experimental
    • Percent: 3-21%
  • Clinical Trial
    Peripheral Edema US
  • Kind: experimental
    • Percent: ≤20%
  • Clinical Trial
    Eyelid edema US
  • Kind: experimental
    • Percent: ≤19%
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 12-19%
  • Clinical Trial
    Pharyngolaryngeal pain US
  • Kind: experimental
    • Percent: 18%
  • Clinical Trial
    Back Pain US
  • Kind: experimental
    • Percent: ≤17%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 7-17%
  • Clinical Trial
    Night Sweats US
  • Kind: experimental
    • Percent: 13-17%
  • Clinical Trial

    Contraindications

    • Hypersensitivity:
      • false
    • Regions: US

    Food Interactions

    Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which can increase serum levels of imatinib.

    Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of imatinib.

    Take with a full glass of water. Taking imatinib with water may reduce gastric irritation.

    Take with food. Food reduces gastric irritation.