Products
Imatinib is commercially available in the form of film-coated tablets (Gleevec, Gleevec GIST, generic). It has been approved in many countries since 2001. Generics came on the market in 2016. They were not approved for the treatment of gastrointestinal stromal tumors (GIST) because this indication was still protected by a patent. In 2017, imatinib GIST generics were released for the first time.
Structure and properties
Imatinib (C29H31N7O, Mr = 493.6 g/mol) is present in the drug as imatinib mesilate, a white to brown or yellow colored crystalline powder. It is a 2-phenylaminopyrimidine derivative.
Effects
Imatinib (ATC L01XE01) has antiproliferative and selective cytostatic properties. It binds competitively to the ATP-binding site of BCR-ABL kinase in chronic myeloid leukemia, inhibiting cell proliferation. The figure shows the binding of imatinib to BCR-ABL (click to enlarge). Imatinib also inhibits other tyrosine kinases, namely those of c-Kit, SCF, and PDGFR, which is important for the other indications.
Indications
For the treatment of chronic myeloid leukemia (Ph+CML). Other indications include acute lymphoblastic leukemia (Ph+ALL), certain gastrointestinal tumors (GIST, gastrointestinal stromal tumors), skin tumors, hypereosinophilic syndrome, atypical myelodysplastic/myeloproliferative disorders, and aggressive systemic mastocytosis.
Dosage
According to the SmPC. Tablets are usually taken once daily with a meal and a large glass of water. For daily doses of 800 mg, it should be taken twice daily.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Imatinib is a substrate of CYP3A4 and an inhibitor of CYP3A4, CYP2D6, CYP2C9, and CYP2C19. Corresponding drug-drug interactions are possible and should be considered. Imatinib inhibits the –glucuronidation of acetaminophen. Caution should be exercised when taking acetaminophen chronically.
Adverse effects
The most common possible adverse effects include digestive symptoms such as nausea, vomiting, diarrhea, dyspepsia, and abdominal pain; edema; fatigue; weight gain; headache; muscle cramps; muscle and joint pain; bone pain; blood count changes; and skin rash.