Imatinib Mesylate
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Check Drug InteractionsImatinib Mesylate Prescribing Information
Imatinib mesylate is a kinase inhibitor indicated for the treatment of:
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
(1.1) - 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. (
1.2) - Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
(1.3) - Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. (
1.4) - Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.
(1.5) - Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown.
(1.6) - 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.
(1.7) - Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP).
(1.8) - Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). (
1.9) - Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST. (
1.10)
- Adults with Ph+ CML CP (
2.2): 400 mg/day - Adults with Ph+ CML AP or BC (
2.2): 600 mg/day - Pediatrics with Ph+ CML CP (
2.3): 340 mg/m
2/day - Adults with Ph+ ALL (
2.4): 600 mg/day - Pediatrics with Ph+ ALL (
2.5): 340 mg/m
2/day - Adults with MDS/MPD (
2.6): 400 mg/day - Adults with ASM (
2.7): 100 mg/day or 400 mg/day - Adults with HES/CEL (
2.8): 100 mg/day or 400 mg/day - Adults with DFSP (
2.9): 800 mg/day - Adults with metastatic and/or unresectable GIST (
2.10): 400 mg/day - Adjuvant treatment of adults with GIST (
2.11): 400 mg/day - Patients with mild to moderate hepatic impairment (
2.12): 400 mg/day - Patients with severe hepatic impairment (
2.12): 300 mg/day
All doses of imatinib mesylate tablets 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. Imatinib mesylate tablets can be dissolved in water or apple juice for patients having difficulty swallowing. Daily dosing of 800 mg and above should be accomplished using the 400-mg tablet to reduce exposure to iron.
100 mg film coated tablets
Very dark yellow to brownish orange, film-coated tablets, round, biconvex with bevelled edges, debossed with '100' on one side, and score on the other side.
400 mg film coated tablets
Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with '400' on one side and score on the other side.
Risk Summary
Imatinib mesylate can cause fetal harm when administered to a pregnant woman based on human and animal data. There are no clinical studies regarding use of imatinib mesylate in pregnant women. There have been postmarket reports of spontaneous abortions and congenital anomalies from women who have been exposed to imatinib mesylate during pregnancy. Reproductive studies in rats have demonstrated that imatinib mesylate induced teratogenicity and increased incidence of congenital abnormalities following prenatal exposure to imatinib mesylate at doses equal to the highest recommended human dose of 800 mg/day based on BSA. Advise women to avoid pregnancy when taking imatinib mesylate. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is not known; however, in the U.S. general population, the estimated background risk of major birth defects of clinically recognized pregnancies is 2% to 4% and of miscarriage is 15% to 20%.
Data
Animal Data
In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of imatinib mesylate up to 100 mg/kg/day and 60 mg/kg/day, respectively, during the period of organogenesis.
In rats, imatinib mesylate was teratogenic at 100 mg/kg/day (approximately equal to the maximum human dose of 800 mg/day based on BSA), the number of fetuses with encephalocoele and exencephaly was higher than historical control values and these findings were associated with missing or underdeveloped cranial bones. Lower mean fetal body weights were associated with retarded skeletal ossifications.
In rabbits, at doses 1.5 times higher than the maximum human dose of 800 mg/day based on BSA, no effects on the reproductive parameters with respect to implantation sites, number of live fetuses, sex ratio or fetal weight were observed. The examinations of the fetuses did not reveal any drug related morphological changes.
In a pre- and postnatal development study in rats, pregnant rats received oral doses of imatinib mesylate during gestation (organogenesis) and lactation up to 45 mg/kg/day. Five animals developed a red vaginal discharge in the 45 mg/kg/day group on Days 14 or 15 of gestation, the significance of which is unknown since all females produced viable litters and none had increased post-implantation loss. Other maternal effects noted only at the dose of 45 mg/kg/day (approximately one-half the maximum human dose of 800 mg/day based on BSA) included an increased number of stillborn pups and pups dying between postpartum Days 0 and 4. In the F1 offspring at this same dose level, mean body weights were reduced from birth until terminal sacrifice and the number of litters achieving criterion for preputial separation was slightly decreased. There were no other significant effects in developmental parameters or behavioral testing. F1 fertility was not affected but reproductive effects were noted at 45 mg/kg/day, including an increased number of resorptions and a decreased number of viable fetuses. The no-observed-effect level (NOEL) for both maternal animals and the F1 generation was 15 mg/kg/day.
None.
- 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) - 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) - 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) - 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) - 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 (GI) perforations, some fatal, have been reported.
(5.6) - Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of imatinib mesylate in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM).
(5.7) - Bullous dermatologic reactions (e.g., erythema multiforme and Stevens- Johnson syndrome) have been reported with the use of imatinib mesylate.
(5.8) - Hypothyroidism has been reported in thyroidectomy patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients.
(5.9) - Fetal harm can occur when administered to a pregnant woman. Apprise women of the potential harm to the fetus, and to use effective contraception. (
5.10,
8.1) - Growth retardation occurring in children and pre-adolescents receiving imatinib mesylate has been reported. Close monitoring of growth in children under imatinib mesylate treatment is recommended.
(5.11,
6.2) - Tumor Lysis Syndrome. Close monitoring is recommended.
(5.12) - Reports of motor vehicle accidents have been received in patients receiving imatinib mesylate. Caution patients about driving a car or operating machinery.
(5.13) - Renal Toxicity. A decline in renal function may occur in patients receiving imatinib mesylate. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction.
(5.14)
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