Imachron Special Precautions

When imatinib mesylate (Imachron) is co-administered with other medications, there is a potential for drug interactions. Caution should be used when taking imatinib mesylate (Imachron) with rifampicin or other strong CYP3A4 inducers, ketoconazole or other strong CYP3A4 inhibitors, CYP3A4 substrates with a narrow therapeutic window (e.g. cyclosporin or pimozide) or CYP2C9 substrates with a narrow therapeutic window (e.g. warfarin and other coumarin derivatives) (see Interactions).
Hypothyroidism: Clinical cases of hypothyroidism have been reported in thyroidectomy patients undergoing levothyroxine replacement during treatment with imatinib mesylate (Imachron). Thyroid-Stimulating Hormone de levels should be closely monitored in such patients.
Hepatotoxicity: In patients with hepatic dysfunction (mild, moderate or severe), peripheral blood counts and liver enzymes should be carefully monitored (see Dosage & Administration, Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
When imatinib mesylate (Imachron) is combined with high dose chemotherapy regimens, transient liver toxicity in the form of transaminase elevation and hyperbilirubinemia has been observed. Additionally, there have been uncommon reports of acute liver failure. Monitoring of hepatic function is recommended in circumstances where imatinib mesylate (Imachron) is combined with chemotherapy regimens also known to be associated with hepatic dysfunction (see Adverse Reactions).
Fluid retention: Occurrences of severe fluid retention (pleural effusion, edema, pulmonary edema, ascites, and superficial edema) have been reported in approximately 2.5% of newly diagnosed CML patients taking imatinib mesylate (Imachron). Therefore, it is recommended that patients be weighed regularly. An unexpected rapid weight gain should be carefully investigated and if necessary appropriate supportive care and therapeutic measures should be undertaken. In clinical trials, there was an increased incidence of these events in elderly patients and those with a prior history of cardiac disease.
Patients with cardiac disease or renal failure: Patients with cardiac disease, risk factors for cardiac failure or history of renal failure should be monitored carefully and any patient with signs or symptoms consistent with cardiac or renal failure should be evaluated and treated.
In patients with syndrome (HES) with occult infiltration of HES cells within the myocardium, isolated cases of cardiogenic shock/left ventricular dysfunction have been associated with HES cell degranulation upon the initiation of imatinib mesylate (Imachron) therapy. The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding imatinib mesylate (Imachron). Myelodysplastic (MDS)/myeloproliferative diseases (MPD) and systemic mastocytosis might be associated with high eosinophil levels. Performance of an echocardiogram and determination of serum troponin should therefore be considered in patients with HES/CEL, and in patients with MDS/MPD or SM associated with high eosinophil levels. If either is abnormal, the prophylactic use of systemic steroids (1 to 2 mg/kg) for one to two weeks concomitantly with imatinib mesylate (Imachron) should be considered at the initiation of therapy.
Gastrointestinal hemorrhage: In the Phase III GIST studies in patients with unresectable or metastatic malignant GIST 211 patients (12.9%) reported Grade 3/4 hemorrhage at any site. In the Phase II GIST study in patients with unresectable or metastatic malignant GIST (study B2222), eight patients (5.4%) were reported to have had gastrointestinal (GI) hemorrhage and four patients (2.7%) were reported to have had hemorrhages at the site of tumor deposits. The tumor hemorrhages have been either intra-abdominal or intra-hepatic, depending on the anatomical location of tumor lesions. GI sites of tumor may have contributed to GI bleeding in this patient reported population. In addition, gastric antral vascular ectasia (GAVE), a rare cause of GI hemorrhage, has been reported in post-marketing experience in patients with CML, ALL and other diseases. Patients should therefore be monitored for gastrointestinal symptoms at the start of and during therapy with imatinib mesylate (Imachron). When needed, imatinib mesylate (Imachron) discontinuation may be considered (see Adverse Reactions).
Tumor lysis syndrome: Cases of tumor lysis syndrome (TLS) have been reported in patients treated with imatinib mesylate (Imachron). Due to possible occurrence of TLS, correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to initiation of imatinib mesylate (Imachron) (see Adverse Reactions).
Hepatitis B reactivation: Reactivation of hepatitis B can occur in patients who are chronic carriers of this virus after receiving a BCR-ABL tyrosine kinase inhibitor (TKI), such as imatinib. Some cases involving drugs of the BCR-ABL TKI class resulted in acute hepatic failure or fulminant hepatitis leading to liver transplantation or a fatal outcome (see Adverse Reactions).
Patients should be tested for hepatitis B infection before initiating treatment with imatinib. Patients currently on imatinib should have baseline testing for hepatitis B infection in order to identify chronic carriers of the virus. Experts in liver disease and in the treatment of hepatitis B should be consulted before treatment is initiated in patients with positive hepatitis B serology (including those with active disease) and for patients who test positive for hepatitis B infection during treatment. Carriers of hepatitis B virus who require treatment with imatinib should be closely monitored for signs and symptoms of active hepatitis B infection throughout therapy and for several months following termination of therapy.
Laboratory tests: Complete blood counts must be performed regularly during therapy with imatinib mesylate (Imachron). Treatment of CML patients with imatinib mesylate (Imachron) has been associated with neutropenia or thrombocytopenia. However, the occurrence of these cytopenias is dependent on the stage of the disease being treated and they were more frequent in patients with accelerated phase CML or blast crisis as compared to patients with chronic phase CML. Treatment with imatinib mesylate (Imachron) may be interrupted or the dose be reduced, as recommended in Dosage & Administration.
Liver function (transaminases, bilirubin, alkaline phosphatase) should be monitored regularly in patients receiving imatinib mesylate (Imachron). As recommended in Dosage & Administration, non-hematological adverse drug reactions, these laboratory abnormalities should be managed with interruption and/or dose reduction of the treatment with imatinib mesylate (Imachron).
Imatinib mesylate (Imachron) and its metabolites are not excreted via the kidney to a significant extent. Creatinine clearance (CrCl) is known to decrease with age, and age did not significantly affect imatinib mesylate (Imachron) kinetics. In patients with impaired renal function, imatinib mesylate plasma exposure seems to be higher than that in patients with normal renal function, probably due to an elevated plasma level of alpha-acid glycoprotein (AGP), an imatinib mesylate-binding protein, in these patients. There is no correlation between imatinib mesylate exposure and the degree of renal impairment, as classified by the measurement of creatinine clearance (CrCl), between patients with mild (CrCl: 40 to 59 mL/min) and severe (CrCl: <20 mL/min) renal impairment. However, as recommended in Dosage & Administration, the starting dose of imatinib mesylate (Imachron) can be reduced if not tolerated.
Use in Children: Children and adolescents: There have been case reports of growth retardation occurring in children and pre-adolescents receiving imatinib mesylate (Imachron). The long term effects of prolonged treatment with imatinib mesylate (Imachron) on growth in children are unknown. Therefore, close monitoring of growth in children under imatinib mesylate (Imachron) treatment is recommended (see Adverse Reactions).