imkeldi

Important safety information

Fluid Retention and Edema: Edema and severe fluid retention have occurred. Weigh patients regularly and manage unexpected rapid weight gain by drug interruption and diuretics. ( 5.1 , 6.1 ) Hematologic Toxicity: Cytopenias, particularly anemia, neutropenia, and thrombocytopenia, have occurred. Manage with dose reduction, dose interruption, or discontinuation of treatment. Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter. ( 5.2 ) Congestive Heart Failure and Left Ventricular Dysfunction: Severe congestive heart failure and left ventricular dysfunction have been reported, particularly in patients with comorbidities and risk factors. Monitor and treat patients with cardiac disease or risk factors for cardiac failure. ( 5.3 ) Hepatotoxicity: Severe hepatotoxicity, including fatalities may occur. Assess liver function before initiation of treatment and monthly thereafter or as clinically indicated. Monitor liver function when combined with chemotherapy known to be associated with liver dysfunction. ( 5.4 ) Hemorrhage: Grade 3/4 hemorrhage has been reported in clinical studies in patients with newly diagnosed CML and with GIST. GI tumor sites may be the source of GI bleeds in GIST. ( 5.5 ) Gastrointestinal Disorders: Gastrointestinal (GI) perforations, some fatal, have been reported. ( 5.6 ) Hypereosinophilic Cardiac Toxicity: Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of Imkeldi in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM). ( 5.7 ) Dermatologic Toxicities: Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of Imkeldi. ( 5.8 ) Hypothyroidism: Hypothyroidism has been reported in thyroidectomy patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients. ( 5.9 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to use effective contraception. ( 5.10 , 8.1 ) Growth Retardation in Children and Adolescents: Growth retardation occurring in children and pre-adolescents receiving Imkeldi has been reported. Close monitoring of growth in children under Imkeldi treatment is recommended. ( 5.11 , 6.2 ) Tumor Lysis Syndrome: Close monitoring is recommended. ( 5.12 ) Impairments Related to Driving and Using Machinery: Motor vehicle accidents have been reported in patients receiving imatinib. Caution patients about driving a car or operating machinery. ( 5.13 ) Renal Toxicity: A decline in renal function may occur in patients receiving Imkeldi. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction. ( 5.14 ) Measuring Device: Advise patients to measure IMKELDI with an accurate milliliter measuring device. Inform patients that a household teaspoon is not an accurate measuring device and could lead to overdosage, which can result in serious adverse reactions. Advise patients to ask their pharmacist to recommend an appropriate press-in bottle adapter and oral dispensing syringe and for instructions for measuring the correct dose. ( 5.15 ) 5.1 Fluid Retention and Edema Imatinib can cause edema and occasionally serious fluid retention [see Adverse Reactions (6.1) ] . Weigh and monitor patients regularly for signs and symptoms of fluid retention. Investigate unexpected rapid weight gain carefully and provide appropriate treatment. The probability of edema was increased with higher imatinib dose and age greater than 65 years in the CML studies. Severe superficial edema was reported in 1.5% of newly diagnosed CML patients taking imatinib, and in 2% to 6% of other adult CML patients taking imatinib. In addition, other severe fluid retention (e.g., pleural effusion, pericardial effusion, pulmonary edema, and ascites) reactions were reported in 1.3% of newly diagnosed CML patients taking imatinib, and in 2% to 6% of other adult CML patients taking imatinib. Severe fluid retention was reported in 9% to 13.1% of patients taking imatinib for GIST [see Adverse Reactions (6.1) ] . In a randomized trial in patients with newly diagnosed Ph+ CML in chronic phase comparing imatinib and nilotinib, severe (Grade 3 or 4) fluid retention occurred in 2.5% of patients receiving imatinib and in 3.9% of patients receiving nilotinib 300 mg twice daily. Effusions (including pleural effusion, pericardial effusion, ascites) or pulmonary edema were observed in 2.1% (none were Grade 3 or 4) of patients in the imatinib arm and 2.2% (0.7% Grade 3 or 4) of patients in the nilotinib 300 mg twice daily arm. 5.2 Hematologic Toxicity Treatment with imatinib can cause anemia, neutropenia, and thrombocytopenia. Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter as clinically indicated (for example, every 2 to 3 months). In CML, the occurrence of these cytopenias is dependent on the stage of disease and is more frequent in patients with accelerated phase CML or blast crisis than in patients with chronic phase CML. In pediatric CML patients the most frequent toxicities observed were Grade 3 or 4 cytopenias, including neutropenia, thrombocytopenia, and anemia. These generally occur within the first several months of therapy [see Dosage and Administration (2.14) ]. 5.3 Congestive Heart Failure and Left Ventricular Dysfunction Congestive heart failure and left ventricular dysfunction have been reported in patients taking imatinib. Cardiac adverse reactions were more frequent in patients with advanced age or co-morbidities, including previous medical history of cardiac disease. In an international randomized Phase 3 study in 1106 patients with newly diagnosed Ph+ CML in chronic phase, severe cardiac failure and left ventricular dysfunction were observed in 0.7% of patients taking imatinib compared to 0.9% of patients taking IFN + Ara-C. In another randomized trial with newly diagnosed Ph+ CML patients in chronic phase that compared imatinib and nilotinib, cardiac failure was observed in 1.1% of patients in the imatinib arm and 2.2% of patients in the nilotinib 300 mg twice daily arm and severe (Grade 3 or 4) cardiac failure occurred in 0.7% of patients in each group. Carefully monitor patients with cardiac disease or risk factors for cardiac or history of renal failure. Evaluate and treat any patient with signs or symptoms consistent with cardiac or renal failure. 5.4 Hepatotoxicity Hepatotoxicity, occasionally severe, may occur with Imkeldi [see Adverse Reactions (6.1) ]. Cases of fatal liver failure and severe liver injury requiring liver transplants have been reported with both short-term and long-term use of imatinib. Monitor liver function (transaminases, bilirubin, and alkaline phosphatase) before initiation of treatment and monthly, or as clinically indicated. Manage laboratory abnormalities with Imkeldi interruption and/or dose reduction [see Dosage and Administration (2.13) ]. When imatinib is combined with chemotherapy, liver toxicity in the form of transaminase elevation and hyperbilirubinemia has been observed. Additionally, there have been reports of acute liver failure. Monitoring of hepatic function is recommended. 5.5 Hemorrhage In a trial of imatinib versus IFN+Ara-C in patients with the newly diagnosed CML, 1.8% of patients had Grade 3/4 hemorrhage. In the Phase 3 unresectable or metastatic GIST studies, 211 patients (12.9%) reported Grade 3/4 hemorrhage at any site. In the Phase 2 unresectable or metastatic GIST study, 7 patients (5%) had a total of 8 CTC Grade 3/4 hemorrhages; gastrointestinal (GI) (3 patients), intra-tumoral (3 patients) or both (1 patient). Gastrointestinal tumor sites may have been the source of GI hemorrhages. In a randomized trial in patients with newly diagnosed Ph+ CML in chronic phase comparing imatinib and nilotinib, GI…