IMPORTANT SAFETY INFORMATION & INDICATIONS
INDICATIONS
Newly diagnosed adult and pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.
Adult patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.
Pediatric patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia in combination with chemotherapy.
Adult patients with myelodysplastic/myeloproliferative diseases associated with platelet-derived growth factor receptor gene rearrangements.
Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown.
Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown.
Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.
Patients with Kit-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST).
Adjuvant treatment of adult patients following resection of Kit-positive GIST.
IMPORTANT SAFETY INFORMATION
Contraindications
None.
Warnings and Precautions
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.
Hematologic Toxicity: Cytopenias, particularly anemia, neutropenia, and thrombocytopenia, have occurred. Manage with dose reduction, dose interruption, or discontinuation of treatment. Perform complete blood count weekly for the first month, biweekly for the second month, and periodically thereafter.
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.
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.
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.
Gastrointestinal Disorders: Gastrointestinal perforations, some fatal, have been reported.
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).
Dermatologic Toxicities: Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of IMKELDI.
Hypothyroidism: Hypothyroidism has been reported in thyroidectomy patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients.
Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.
Growth Retardation in Children and Adolescents: Growth retardation occurring in children and preadolescents receiving IMKELDI has been reported. Close monitoring of growth in children under IMKELDI treatment is recommended.
Tumor Lysis Syndrome: Close monitoring is recommended
Impairments Related to Driving and Using Machinery: Motor vehicle accidents have been reported in patients receiving IMKELDI. Caution patients about driving or operating machinery.
Renal Toxicity: A decline in renal function may occur in patients receiving IMKELDI oral solution. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction.
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.
ADVERSE REACTIONS
The most frequently reported adverse reactions (≥30%) are edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue, and abdominal pain.
DRUG INTERACTIONS
CYP3A4 inducers: Avoid or increase IMKELDI dosage if unavoidable.
CYP3A4 inhibitors: Use caution. Avoid grapefruit juice.
CYP3A4 substrates: Use caution. Patients who require anticoagulation should receive other anticoagulants instead of warfarin.
CYP2D6 substrates: Use caution.
USE IN SPECIFIC POPULATIONS
Lactation: Advise not to breastfeed.
IMKELDI and its active metabolite are excreted into human milk. Because of the potential for serious adverse reactions in breastfed children from IMKELDI, advise a lactating woman not to breastfeed during treatment and for 1 month after the last dose.
To report suspected adverse reactions, contact Shorla Oncology at 844-9-SHORLA (844-974-6752) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
