Tibisan Special Precautions

Imatinib should be taken with food and a large glass of water to minimize the risk of gastrointestinal disturbances. When Imatinib is co-administered with other medications, there is potential for drug interactions.
Hypothyroidism: Hypothyroidism have been reported in thyroidectomy patients undergoing Levothyroxine replacement during treatment with Imatinib. TSH 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.
When Imatinib is combined with high doses 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 is combined with chemotherapy regimens also known to be associated with hepatic dysfunction.
Fluid retention: Occurrences of severe fluid retention (pleural effusion, edema, pulmonary edema, ascites, superficial edema) have been reported. 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.
Patients with cardiac disease or renal failure: Patients with cardiac disease or risk factors for cardiac failure should be monitored carefully and any patient with signs or symptoms consistent with cardiac failure should be evaluated and treated.
In patients with hypereosinophilic 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 therapy. The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding Imatinib.
Myelodysplastic (MDS)/myeloproliferative (MPD) diseases 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 (1-2 mg/kg) for one to two weeks concomitantly with Imatinib should be considered at the initiation of therapy.
Tumor lysis syndrome: Cases of tumor lysis syndrome (TLS) have been reported in patients treated with Imatinib. Due to possible occurrence of TLS, correction of clinically significant dehydration and treatment of high uric acids levels are recommended prior to initiation of Imatinib.
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.
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 the 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. Carries 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 test: Complete blood counts must be performed regularly during therapy with Imatinib. Treatment of CML patients with Imatinib 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 may be interrupted or the dose be reduced, as recommended in section Dosage & Administration.
Liver function (transaminases, bilirubin, alkaline phosphatase) should be monitored regularly in patients receiving Imatinib. As recommended in section Dosage & Administration, non-hematological adverse drug reactions, these laboratory abnormalities should be managed with interruption and/or dose reduction of the treatment with Imatinib.
Imatinib 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 kinetics. In patients with impaired renal function, Imatinib 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-binding protein, in these patients. There is no correlation between Imatinib exposure and the degree of renal impairment, as classified by the measurement of creatinine clearance (CrCl), between patients with mild (CrCl: 40-59 ml/min) and severe (CrCl: < 20 ml/min) renal impairment. However, as recommended in section Dosage & Administration, the starting dose of Imatinib can be reduced if no tolerated.
Effects on ability to drive and use machines: Patients should be advised that they may experience undesirable effects such as dizziness, blurred vision or somnolence during treatment with Imatinib. Therefore, caution should be recommended when driving a car or operating machine.
Use in children and adolescents: There have been case reports of growth retardation occurring in children and pre-adolescents receiving Imatinib. The long term effects of prolonged treatment with Imatinib on growth in children are unknown. Therefore, close monitoring of growth in children under Imatinib treatment is recommended.
Women of child-bearing potential, pregnancy, breastfeeding and fertility women of child-bearing potential: Women of child-bearing potential must be advised to use highly effective contraception during treatment. Highly effective contraception is a method of birth control which results in a low failure rate (i.e. less than 1% per year), when used consistently and correctly.
Fertility: Male patients concerned about their fertility on Imatinib treatment should consult with their physician.
Use in pregnancy: Imatinib should be used during pregnancy only if the expected benefit outweighs the potential risk to the fetus. If it is used during pregnancy, the patient must be informed of the potential risk to the fetus.
Use in breastfeeding: Both Imatinib and its active metabolite can be distributed into human milk. Since the effects of low-dose exposure of the infant to Imatinib are unknown, women taking Imatinib should not breastfeed.