GLEEVEC (imatinib mesylate) tablets

Pharmacological action Gleevec 400 mg:

Gleevec Antitumor drug, an inhibitor of proteintirozinkinazy (Bcr-Abl tyrosine kinase) – abnormal enzyme produced by the Philadelphia chromosome in chronic myeloid leukemia. Inhibits proliferation of Bcr-Abl-positive tumor cells, induces their apoptosis. It has no selectivity; in vitro also inhibits the tyrosine kinase receptor platelet-derived growth factor and stem cell factor.

Indications Gleevec 400 mg:

Chronic myelogenous leukemia (blast crisis, accelerated phase and chronic phase) on failure of prior treatment with interferon alpha.

Contraindications Gleevec 400 mg:

Hypersensitivity, pregnancy, lactation, age 18 (safety and efficacy not established). C carefully. Hepatic failure, chronic heart failure.

Side effects Gleevec 400 mg:

On the part of the digestive tract: nausea, vomiting, abnormal liver function (increased activity of “liver” enzymes and alkaline phosphatase, hyperbilirubinemia). On the part of hematopoiesis: neutropenia, thrombocytopenia, anemia, pancytopenia. Urinary system: fluid retention – weight gain, swelling of the surface, local or widespread edema, pleural and / or pericardial effusion, ascites, pulmonary edema, periorbital edema, at least – the limbs, impaired renal function. From the CCC: CHF. Other: muscle spazm.Peredozirovka. Symptoms: use in an experiment in a daily dose of 3600 mg / m (higher than the maximum 7.5 times) for 7-10 days resulted in the death of animals due to degenerative changes in multiple tissues and organs.

Dosage and administration Gleevec 400 mg:

Inside, during a meal with a full glass of water, once, the recommended daily dose is in remission – 400 mg in the acute phase and blast crisis – 600 mg. With the progression of the disease, lack of hematologic effect within 3 months of therapy and absence of side effects may increase the dose in remission – up to 600 mg / day in the acute phase and blast crisis – up to 800 mg / day (400 mg 2 times a day). Treatment – long, with a view to achieving and maintaining clinical remission and. If abnormal liver function (increased bilirubin concentration 3-fold compared with baseline, the activity of “liver” enzymes – to 5-fold) treatment is stopped, while the values of parameters is reduced to 1.5 and 2.5, respectively. In this case, treatment to resume, reducing the dose from 400 to 300 mg and 600 to 400 mg. In the case of neutropenia and thrombocytopenia treatment strategy depends on the stage of the disease. In remission with a decrease in neutrophil count to a thousand / ml, platelet count – up to 50 thousand / ml treatment (400 mg / day) to stop the normalization of the relevant parameters (neutrophils – not less than 1.5 thousand / ml, platelet count – at least 75 thousand . / ml), then resume treatment as usual (400 mg / day), if again there is a decline in the lower boundary of valid values, resume treatment after a break (for recovery of blood parameters) at a reduced dose – 300 mg / day. In the blast crisis and in the acute phase (dosing regimen – 600 mg / day) in the case of reduction of neutrophils less 500/mkl, platelet count – less than 100 thousand / ml treatment ceased, for the differentiation of the cause of the cytopenia, bone marrow biopsy, and if cytopenia not associated with leukemia, imatinib dose was reduced to 400 mg if cytopenia persists for the next 2 weeks, reduce the dose to 300 mg if cytopenia continues until 4 weeks of treatment ceased to recovery of blood parameters (neutrophils – not less than 1 thousand / ml , platelet count – at least 200 thousand / ml) and then resume at a reduced dose – 300 mg / day.

Special instructions Gleevec 400 mg:

It has a teratogenic effect, so women of reproductive age during treatment should carefully observe the actions of contraception. Causes fluid retention, so patients should regularly monitor the body weight. In patients older than 65 years increases the risk of edema and increased risk of pleural and pericardial effusion, pulmonary edema. Swelling disappears at lower doses of diuretics and the appointment or termination of the drug. Imatinib may cause irritation to the gastrointestinal tract, so it is recommended to be taken with food and with a full glass of water. During therapy should be monitored weekly peripheral blood picture during the first month, 1 every 2 weeks during the second month and every 2-3 months – thereafter. The risk of developing mielodepressii increases with blast crisis and in the acute phase of chronic leukemia. The average duration of neutropenia – 2-3 weeks, thrombocytopenia – 3-4 weeks. Typically, dose reduction or temporary cessation of treatment reduces the changes of blood cell composition, only in rare cases, a withdrawal of treatment. In order to avoid the development of liver disease before treatment and every month in the presence of clinical signs should check your liver (the activity of “liver” enzymes and alkaline phosphatase, bilirubin in the blood). When liver failure shows careful control of drug concentrations in plasma in order to avoid intoxication. It should be borne in mind that long-term therapy is at risk of potentially hepato-and nephrotoxicity, as well as opportunistic infections.

Interaction Gleevec 400 mg:

Increasing the concentration of substrates isozymes CYP3A4 (simvastatin, cyclosporine, pimozide, etc.), CYP2C9 (warfarin, etc.), CYP2D6, CYP3A4, CYP3A5, and drugs metabolized by the participation of isoenzyme CYP3A4 (including triazolobenzodiazepinov, BCCI dihydropyridine , inhibitors of HMG-CoA reductase). Inhibitors of isoenzyme CYP3A4 (ketoconazole, itraconazole, erythromycin, clarithromycin, and others) increase the concentration of imatinib in the plasma. Isoenzyme inducers of CYP3A4 (phenytoin, dexamethasone, carbamazepine, rifampicin, phenobarbital, etc.) reduce the concentration of imatinib.