Initial US Approval:
2001
Drug Class/Description:
BCR-ABL kinase inhibitor
Indications and Use:
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
- Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy.
- Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy.
- Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.
- Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown.
- Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for 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 (DFSP).
- Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST).
- Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST.
Dosage and Administration:
- Adults with Ph+ CML CP: 400 mg/day
- Adults with Ph+ CML AP or BC: 600 mg/day
- Pediatrics with Ph+ CML CP: 340 mg/m2/day
- Adults with Ph+ ALL: 600 mg/day
- Pediatrics with Ph+ ALL: 340 mg/m2/day
- Adults with MDS/MPD: 400 mg/day
- Adults with ASM: 100 mg/day or 400 mg/day
- Adults with HES/CEL: 100 mg/day or 400 mg/day
- Adults with DFSP: 800 mg/day
- Adults with metastatic and/or unresectable GIST: 400 mg/day
- Adjuvant treatment of adults with GIST: 400 mg/day
- Patients with mild to moderate hepatic impairment: 400 mg/day
- Patients with severe hepatic impairment: 300 mg/day
All doses of Imkeldi should be taken with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Imkeldi is intended for oral use only. It is important that Imkeldi be measured with an accurate measuring device. A household teaspoon is not an accurate measuring device. A pharmacist can provide an appropriate press-in bottle adapter and oral dispensing syringe and can provide instructions for measuring the correct dose.
Dosage Forms and Strengths:
Oral solution: 80 mg/mL of imatinib
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 counts 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 (GI) 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 pre-adolescents 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 imatinib. Caution patients about driving a car or operating machinery.
- 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.
- 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 imatinib 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.
Adapted From:
https://shorlaoncology.com/pdf/Imkeldi_PrescribingInformation.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
