Imatinib mesylate

What is Imatinib mesylate?

• Imatinib mesylate (Gleevec) is a kinase inhibitor used as an oral chemotherapy medication used to treat cancer.

What are the uses of this medicine?

This medicine is used for the treatment of:

• 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.

How does this medicine work?

• Imatinib (im a' ti nib) is a specific inhibitor of the unique bcr-abl tyrosine kinase receptor, which is the product of a fusion gene resulting from the translocation between chromosomes 9 and 22 that characterizes the Philadelphia chromosome (Ph) of chronic myelogenous leukemia (CML).
• The abnormal tyrosine kinase receptor is constitutively expressed and causes abnormal cell growth and proliferation.
• Introduction of imatinib into clinical medicine was an important advance in the therapy of cancer, the first antineoplastic agent specially directed at a molecular abnormality that occurs in cancer cells.
• Inhibition of the enzyme can lead to dramatic reversal of progression of Ph+ leukemia and is highly effective, although limited by the development of tumor resistance caused by mutations in the kinase.
• A similar abnormal tyrosine kinase (cKit) is also found in gastrointestinal stromal tumors (GIST).

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Concomitant administration of Gleevec and strong CYP3A4 inducers may reduce total exposure of imatinib; consider alternative agents.
• Concomitant administration of Gleevec and strong CYP3A4 inhibitors may result in a significant imatinib exposure increase. Grapefruit juice may also increase plasma concentrations of imatinib; avoid grapefruit juice
• Use caution when administering Gleevec with CYP3A4 substrates that have a narrow therapeutic window.
• Use caution when administering Gleevec with CYP2D6 substrates that have a narrow therapeutic window.

Is this medicine FDA approved?

• Initial U.S. Approval: 2001

How should this medicine be used?

Recommended Dosage: Adult Patients With Ph+ CML CP, AP, or BC:

• The recommended dose of Gleevec is 400 mg/day for adult patients in chronic phase CML and 600 mg/day for adult patients in accelerated phase or blast crisis.

Pediatric Patients With Ph+ CML CP:

• The recommended dose of Gleevec for children with newly diagnosed Ph+ CML is 340 mg/m2/day (not to exceed 600 mg).

Adult Patients With Ph+ ALLː

• The recommended dose of Gleevec is 600 mg/day for adult patients with relapsed/refractory Ph+ ALL.

Pediatric Patients With Ph+ ALLː

• The recommended dose of Gleevec to be given in combination with chemotherapy to children with newly diagnosed Ph+ ALL is 340 mg/m2/day (not to exceed 600 mg).

Adult Patients With MDS/MPDː Determine PDGFRb gene rearrangements status prior to initiating treatment. The recommended dose of Gleevec is 400 mg/day for adult patients with MDS/MPD.

Adult Patients With ASMː

• Determine D816V c-Kit mutation status prior to initiating treatment.
• The recommended dose of Gleevec is 400 mg/day for adult patients with ASM without the D816V c-Kit mutation.
• For patients with ASM associated with eosinophilia, a clonal hematological disease related to the fusion kinase FIP1L1-PDGFRα, a starting dose of 100 mg/day is recommended.

Adult Patients With HES/CELː

• The recommended dose of Gleevec is 400 mg/day for adult patients with HES/CEL. For HES/CEL patients with demonstrated FIP1L1-PDGFRα fusion kinase, a starting dose of 100 mg/day is recommended.

Adult Patients With DFSPː The recommended dose of Gleevec is 800 mg/day for adult patients with DFSP.

Adult Patients With Metastatic and/or Unresectable GISTː The recommended dose of Gleevec is 400 mg/day for adult patients with unresectable and/or metastatic, malignant GIST.

Adult Patients With Adjuvant GISTː The recommended dose of Gleevec is 400 mg/day for the adjuvant treatment of adult patients following complete gross resection of GIST.

Patients with mild to moderate hepatic impairment:400 mg/day

Patients with severe hepatic impairment:300 mg/day

Administration

• All doses of Gleevec 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.
• Gleevec 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.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets (scored): 100 mg and 400 mg

This medicine is available in fallowing brand namesː

• Gleevec

What side effects can this medication cause?

The most common side effects of this medicine include:

• edema
• nausea
• vomiting
• muscle cramps
• musculoskeletal pain
• diarrhea
• rash
• fatigue
• abdominal pain

What special precautions should I follow?

• Edema and severe fluid retention have occurred. Weigh patients regularly and manage unexpected rapid weight gain by drug interruption and diuretics.
• 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.
• 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.
• 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.
• 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 (GI) perforations, some fatal, have been reported.
• Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of Gleevec in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM).
• Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of Gleevec.
• Hypothyroidism has been reported in thyroidectomy patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients.
• Fetal harm can occur when administered to a pregnant woman. Apprise women of the potential harm to the fetus, and to avoid pregnancy when taking Gleevec.
• Growth retardation occurring in children and pre-adolescents receiving Gleevec has been reported. Close monitoring of growth in children under Gleevec treatment is recommended.
• Tumor Lysis Syndrome may occur. close monitoring is recommended.
• Reports of motor vehicle accidents have been received in patients receiving Gleevec. Caution patients about driving a car or operating machinery.
• Renal Toxicity. A decline in renal function may occur in patients receiving Gleevec. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• Nausea
• vomiting
• diarrhea
• rash erythema
• edema
• swelling
• fatigue
• muscle spasms
• thrombocytopenia
• pancytopenia
• abdominal pain
• headache
• decreased appetite
• Weakness
• myalgia
• increased CPK
• increased bilirubin
• GI pain

Management of overdosage:

• In the event of overdosage, observe the patient and give appropriate supportive treatment.

Can this medicine be used in pregnancy?

• Gleevec can cause fetal harm when administered to a pregnant woman based on human and animal data. There are no clinical studies regarding use of Gleevec in pregnant women.

Can this medicine be used in children?

• The safety and effectiveness of Gleevec have been demonstrated in pediatric patients with newly diagnosed Ph+ chronic phase CML and Ph+ ALL. There are no data in children under 1 year of age.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• IMATINIB MESYLATE

Inactive ingredients:

• SILICON DIOXIDE
• CROSPOVIDONE
• FERRIC OXIDE RED
• MAGNESIUM STEARATE
• CELLULOSE, MICROCRYSTALLINE
• POLYETHYLENE GLYCOL 4000
• TALC
• HYPROMELLOSES
• FERRIC OXIDE YELLOW
• WATER

Who manufactures and distributes this medicine?

• Packager: Novartis Pharmaceuticals Corporation

What should I know about storage and disposal of this medication?

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.
• Dispense in a tight container, USP.
• Do not crush Gleevec tablets. Avoid direct contact of crushed tablets with the skin or mucous membranes. If such contact occurs, wash thoroughly as outlined in the references. Avoid exposure to crushed tablets.

• Dailymed label info on Imatinib mesylate
• FDA Imatinib mesylate

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