Imatinib

Imatinib
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

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Overview

Imatinib is a protein-tyrosine kinase inhibitor that is FDA approved for the {{{indicationType}}} of newly diagnosed philadelphia positive chronic myeloid leukemia (ph+ CML), ph+ CML in blast crisis (bc), accelerated phase (ap) or chronic phase (cp) after interferon-alpha (ifn) therapy, adult patients with ph+ acute lymphoblastic leukemia (ALL), pediatric patients with ph+ acute lymphoblastic leukemia (ALL), myelodysplastic/myeloproliferative diseases (MDS/MPD), aggressive systemic mastocytosis (ASM), hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL), dermatofibrosarcoma protuberans (DFSP), kit+ gastrointestinal stromal tumors (GIST), adjuvant treatment of GIST. Common adverse reactions include edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML)

• Newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase.

Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy

• Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.

Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL)

• Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia.

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD)

• Adult patients with myelodysplastic/ myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements.

Aggressive Systemic Mastocytosis (ASM)

• Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown.

Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL)

• Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown.

Dermatofibrosarcoma Protuberans (DFSP)

• Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.

Kit+ Gastrointestinal Stromal Tumors (GIST)

• Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Adjuvant Treatment of GIST

• Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

Dosage And Administration

• Therapy should be initiated by a physician experienced in the treatment of patients with hematological malignancies or malignant sarcomas, as appropriate. The prescribed dose should be administered orally, 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.

• In children, Gleevec treatment can be given as a once-daily dose in CML and Ph+ ALL. Alternatively, in children with CML the daily dose may be split into two - one portion dosed in the morning and one portion in the evening. There is no experience with Gleevec treatment in children under 1 year of age.

• For patients unable to swallow the film-coated tablets, the tablets may be dispersed in a glass of water or apple juice. The required number of tablets should be placed in the appropriate volume of beverage (approximately 50 mL for a 100 mg tablet, and 200 mL for a 400 mg tablet) and stirred with a spoon. The suspension should be administered immediately after complete disintegration of the tablet(s).

• For daily dosing of 800 mg and above, dosing should be accomplished using the 400 mg tablet to reduce exposure to iron.

• Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.

Adult Patients with Ph+ CML CP, AP, and 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.
• In CML, a dose increase from 400 mg to 600 mg in adult patients with chronic phase disease, or from 600 mg to 800 mg (given as 400 mg twice daily) in adult patients in accelerated phase or blast crisis may be considered in the absence of severe adverse drug reaction and severe non-leukemia related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time), failure to achieve a satisfactory hematologic response after at least 3 months of treatment, failure to achieve a cytogenetic response after 6-12 months of treatment, or loss of a previously achieved hematologic or cytogenetic response.

2.2 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).

Adults Patients with Ph+ ALL

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

2.4 Pediatric Patients with Ph+ ALL

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

MDS/MPD

• The recommended dose of Gleevec is 400 mg/day for adult patients with MDS/MPD.

ASM

• The recommended dose of Gleevec is 400 mg/day for adult patients with ASM without the D816V c-Kit mutation. If c-Kit mutational status is not known or unavailable, treatment with Gleevec 400 mg/day may be considered for patients with ASM not responding satisfactorily to other therapies. 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. Dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.

HES/CEL

• 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. Dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.

DFSP

• The recommended dose of Gleevec is 800 mg/day for adult patients with DFSP.

Metastatic or Unresectable GIST

• The recommended dose of Gleevec is 400 mg/day for adult patients with unresectable and/or metastatic, malignant GIST. A dose increase up to 800 mg daily (given as 400 mg twice daily) may be considered, as clinically indicated, in patients showing clear signs or symptoms of disease progression at a lower dose and in the absence of severe adverse drug reactions.

Adjuvant GIST

• The recommended dose of Gleevec is 400 mg/day for the adjuvant treatment of adult patients following complete gross resection of GIST. In clinical trials one year of Gleevec and three years of Gleevec were studied. In the patient population defined in Study 2, three years of Gleevec is recommended [see Clinical Studies (14.8)]. The optimal treatment duration with Gleevec is not known.

Dose Modification Guidelines

• Concomitant Strong CYP3A4 inducers: The use of concomitant strong CYP3A4 inducers should be avoided (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampacin, phenobarbital). If patients must be co-administered a strong CYP3A4 inducer, based on pharmacokinetic studies, the dosage of Gleevec should be increased by at least 50%, and clinical response should be carefully monitored [see Drug Interactions (7.1)].

• Hepatic Impairment: Patients with mild and moderate hepatic impairment do not require a dose adjustment and should be treated per the recommended dose. A 25% decrease in the recommended dose should be used for patients with severe hepatic impairment [see Use in Specific Populations (8.6)].

• Renal Impairment: Patients with moderate renal impairment (CrCL=20-39 mL/min) should receive a 50% decrease in the recommended starting dose and future doses can be increased as tolerated. Doses greater than 600 mg are not recommended in patients with mild renal impairment (CrCL=40-59 mL/min). For patients with moderate renal impairment doses greater than 400 mg are not recommended.

• Imatinib should be used with caution in patients with severe renal impairment. A dose of 100 mg/day was tolerated in two patients with severe renal impairment [See Warnings and Precautions (5.3), Use in Specific Populations (8.7)].

Dose Adjustment for Hepatotoxicity and Non-Hematologic Adverse Reactions

• If elevations in bilirubin >3 x institutional upper limit of normal (IULN) or in liver transaminases >5 x IULN occur, Gleevec should be withheld until bilirubin levels have returned to a <1.5 x IULN and transaminase levels to <2.5 x IULN. In adults, treatment with Gleevec may then be continued at a reduced daily dose (i.e., 400 mg to 300 mg, 600 mg to 400 mg or 800 mg to 600 mg). In children, daily doses can be reduced under the same circumstances from 340 mg/m2/day to 260 mg/m2/day.

• If a severe non-hematologic adverse reaction develops (such as severe hepatotoxicity or severe fluid retention), Gleevec should be withheld until the event has resolved. Thereafter, treatment can be resumed as appropriate depending on the initial severity of the event.

Dose Adjustment for Hematologic Adverse Reactions

• Dose reduction or treatment interruptions for severe neutropenia and thrombocytopenia are recommended as indicated in Table 1.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Imatinib in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Imatinib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Imatinib in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Imatinib in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Imatinib in pediatric patients.

Contraindications

• Condition1

Warnings

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Imatinib in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Imatinib in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Imatinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Imatinib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Imatinib with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Imatinib with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Imatinib with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Imatinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Imatinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Imatinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Imatinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Imatinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Imatinib in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Imatinib in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Imatinib in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Imatinib in the drug label.

Pharmacology

There is limited information regarding Imatinib Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Imatinib in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Imatinib in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Imatinib in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Imatinib in the drug label.

How Supplied

Storage

There is limited information regarding Imatinib Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Imatinib in the drug label.

Precautions with Alcohol

• Alcohol-Imatinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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