Glivec is a drug 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.

Glivec - Pharmacology:

Glivec 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 lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Glivec also inhibits the receptor tyrosine kinases for platelet derived growth factor (PDGF) and stem cell factor (SCF) - called c-kit. Glivec was identified in the late 1990s by Dr Brian J. Druker. Its development is an excellent example of rational drug design. Soon after identification of the bcr-abl target, the search for an inhibitor began. Chemists used a high-throughput screen of chemical libraries to identify the molecule 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib.

Glivec Interactions

Drugs that may alter imatinib plasma concentrations

Drugs that may increase imatinib plasma concentrations:
Caution is recommended when administering Gleevec with inhibitors of the CYP3A4 family (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin). Substances that inhibit the cytochrome P450 isoenzyme (CYP3A4) activity may decrease metabolism and increase imatinib concentrations. There is a significant increase in exposure to imatinib when Gleevec is coadministered with ketoconazole (CYP3A4 inhibitor).

Drugs that may decrease imatinib plasma concentrations:
Substances that are inducers of CYP3A4 activity may increase metabolism and decrease imatinib plasma concentrations. Co-medications that induce CYP3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or St. Johns Wort) may significantly reduce exposure to Gleevec. Pretreatment of healthy volunteers with multiple doses of rifampin followed by a single dose of Gleevec, increased Gleevec oral-dose clearance by 3.8-fold, which significantly (p<0.05) decreased mean cmax and AUC(0-8). In patients where rifampin or other CYP3A4 inducers are indicated, alternative therapeutic agents with less enzyme induction potential should be considered.

Drugs that may have their plasma concentration altered by Gleevec

Gleevec increases the mean cmax and AUC of simvastatin (CYP3A4 substrate) 2- and 3.5-fold, respectively, suggesting an inhibition of the CYP3A4 by Gleevec. Particular caution is recommended when administering Gleevec with CYP3A4 substrates that have a narrow therapeutic window (e.g., cyclosporine or pimozide). Gleevec will increase plasmaconcentration of other CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.).

Because warfarin is metabolized by CYP2C9 and CYP3A4, patients who require anticoagulation should receive low-molecular weight or standard heparin.

in vitro, Gleevec inhibits the cytochrome P450 isoenzyme CYP2D6 activity at similar concentrations that affect CYP3A4 activity. Systemic exposure to substrates of CYP2D6 is expected to be increased when coadministered with Gleevec. No specific studies have been performed and caution is recommended.

in vitro, Gleevec inhibits acetaminophen O-glucuronidation (Ki value of 58.5 µM) at therapeutic levels. Systemic exposure to acetaminophen is expected to be increased when coadministered with Gleevec. No specific studies in humans have been performed and caution is recommended.


Glivec Contraindications

Use of Gleevec® (imatinib mesylate) is contraindicated in patients with hypersensitivity to imatinib or to any other component of Gleevec.

Generic name, Overdose, Half Life Glivec, Food Interactions, Chemical, etc..

Glivec see also

Brand Names containing Imatinib