Imatinib

Reviewed on 1/25/2022

What Is Imatinib and How Does It Work?

Imatinib is a prescription medication used to treat Acute Lymphoblastic Leukemia, Myelodysplastic/Myeloproliferative Disease, Hypereosinophilic Syndrome and/or Chronic Eosinophilic Leukemia, Chronic Myeloid Leukemia Philadelphia-Chromosome-Positive, Dermatofibrosarcoma Protuberans, Mastocytosis, and Gastrointestinal Stromal Tumors. 

  • Imatinib is available under the following different brand names: Gleevec.

Dosages of Imatinib

Adult and pediatric dosage

Tablet

  • 100mg
  • 400mg

Acute Lymphoblastic Leukemia

Adult dosage

  • 600 mg orally once daily

Pediatric dosage

  • Children younger than 1 year of age: Safety and efficacy not established
  • Children 1 year of age or older: 340 mg/m2/day orally; not to exceed 600 mg/day

Myelodysplastic/Myeloproliferative Disease 

Adult dosage

  • 400 mg orally once daily

Hypereosinophilic Syndrome and/or Chronic Eosinophilic Leukemia

Adult dosage

  • With FIP1L1-PDGFRα fusion kinase mutation: 100 mg orally once daily; may increase to 400 mg once daily in absence of adverse drug reactions if assessments demonstrate insufficient response to therapy
  • FIP1L1-PDGFRα fusion kinase status negative or unknown: 400 mg orally once daily

Chronic Myeloid Leukemia Philadelphia-Chromosome-positive

Adult dosage

Chronic phase (newly-diagnosed):

  • 400 mg orally once daily; may increase to 600 mg/day if tolerated
  • Chronic phase after failure of interferon-alpha therapy
  • May increase to 600 mg/day in absence of severe adverse drug reaction and severe nonleukemia related neutropenia or thrombocytopenia as follows:
    • 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
    • Loss of a previously achieved hematologic or cytogenetic response

Pediatric dosage

  • Children younger than 1 year of age: Safety and efficacy not established
  • Children 1 years or age or older: 340 mg/m2/day orally; not to exceed 600 mg/day

Accelerated phase or blast crisis

  • 600 mg orally once daily 
  • May increase to 400 mg orally every 12 hours in absence of severe adverse reaction and severe nonleukemia related neutropenia or thrombocytopenia as follows:
    • 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
    • Loss of a previously achieved hematologic or cytogenetic response

Dermatofibrosarcoma Protuberans

Adult dosage

  • 400 mg orally every 12 hours

Mastocytosis

Adult dosage

  • Without D816 c-Kit mutation: 400 mg orally once daily
  • c-Kit mutational status unknown: 400 mg orally once daily if not responding to other therapies
  • ASM associated with eosinophilia (a clonal hematological disease related to the fusion kinase FIP1L1-PDGFR-alpha): 100 mg orally once daily initially, may increase to 400 mg/day in absence of adverse effects if response to therapy is sufficient 

Gastrointestinal Stromal Tumors

Adult dosage

Unresectable and/or metastatic malignant GIST

  • 400 mg orally once daily; may increase to 400 mg twice daily in patients showing clear signs or symptoms of disease progression at a lower dose and in the absence of severe adverse drug reactions

Adjuvant treatment following complete gross resection of GIST

  • 400 mg orally once daily

Dosage Considerations – Should be Given as Follows: 

  • See "Dosages."

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What Are Side Effects Associated with Using Imatinib?

Common side effects of Imatinib include:

  • fluid retention, 
  • nausea, 
  • vomiting, 
  • stomach pain, 
  • diarrhea, 
  • joint or muscle pain
  • skin rash, and
  • tiredness

Serious side effects of Imatinib include:

  • hives, 
  • difficulty breathing, 
  • swelling of the face, lips, tongue, or throat, 
  • fever, 
  • sore throat
  • burning in your eyes, 
  • skin pain, 
  • red or purple skin rash that spreads and causes blistering and peeling, 
  • shortness of breath, 
  • swelling, 
  • rapid weight gain, 
  • little or no urination, 
  • swelling in the feet or ankles, 
  • pain while breathing, 
  • wheezing
  • gasping for breath, 
  • cough with foamy mucus, 
  • upper stomach pain, 
  • loss of appetite, 
  • dark urine, 
  • yellowing of the skin or eyes (jaundice), 
  • cold or flu symptoms, 
  • easy bruising, 
  • unusual bleeding, 
  • mouth sores, 
  • pale skin, 
  • unusual tiredness, 
  • lightheadedness
  • cold hands and feet, 
  • bloody or tarry stools, 
  • coughing up blood
  • vomit that looks like coffee grounds, 
  • confusion, 
  • weakness, 
  • muscle cramps
  • nausea, 
  • vomiting, 
  • fast or slow heart rate, 
  • decreased urination, 
  • tingling in the hands and feet or around the mouth, 
  • tiredness, 
  • dry skin, 
  • hair loss, 
  • constipation, 
  • depression, 
  • slow heart rate, 
  • weight gain, and
  • increased sensitivity to cold temperatures 

Rare side effects of Imatinib include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Imatinib?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

  • Imatinib has severe interactions with at least 13 other drugs.
  • Imatinib has serious interactions with at least 81 other drugs.
  • Imatinib has moderate interactions with at least 227 other drugs.
  • Imatinib has minor interactions with at least 76 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What Are Warnings and Precautions for Imatinib?

Contraindications

  • None

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Imatinib?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Imatinib?”

Cautions

  • Hypothyroidism reported in patients post-thyroidectomy on levothyroxine replacement; closely monitor TSH levels
  • Risk of severe CHF or left ventricular dysfunction, especially in patients with comorbidities; monitor and treat patients with cardiac disease or risk factors for cardiac failure
  • Cardiac adverse reactions were more frequent in patients with advanced age or co-morbidities, including previous medical history of cardiac disease; carefully monitor patients with cardiac disease or risk factors for cardiac or history of renal failure; evaluate and treat any patient with signs or symptoms consistent with cardiac or renal failure
  • In patients with hypereosinophilic syndrome with occult infiltration of HES cells within the myocardium, cases of cardiogenic shock/left ventricular dysfunction have been associated with HES cell degranulation upon initiation of imatinib therapy; reported to be reversible with the administration of systemic steroids, circulatory support measures, and temporarily withholding imatinib
  • Myelodysplastic/myeloproliferative disease and systemic mastocytosis may be associated with high eosinophil levels; consider performing an echocardiogram and determining serum troponin in patients with HES/CEL, and in patients with MDS/MPD or ASM associated with high eosinophil levels; if either is abnormal, consider prophylactic use of systemic steroids (1–2 mg/kg) for one to two weeks concomitantly with drug at the initiation of therapy
  • If anticoagulation required, use LMW or standard heparin instead of warfarin
  • Associated with anemia, neutropenia, and thrombocytopenia; in pediatric CML patients the most frequent toxicities observed were Grade 3 or 4 cytopenias, including neutropenia, thrombocytopenia and anemia; these generally occur within first several months of therapy; CBC counts should be performed weekly for the first month, biweekly for the second month, and periodically thereafter
  • Sometimes associated with GI irritation; should be taken with food and a large glass of water to minimize this problem; there have been rare reports, including fatalities, of gastrointestinal perforation
  • Advise sexually active female patients of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) while in therapy and for 14 days after stopping therapy; if drug is used during pregnancy or if patient becomes pregnant while taking this drug apprise patient of potential hazard to a fetus
  • Often associated with edema and occasionally serious fluid retention; probability increases with dose and age older than 65 years of age; investigate unexpected rapid weight gain and provide appropriate treatment
  • Bullous dermatologic reactions reported and include erythema multiforme and Stevens-Johnson syndrome
  • 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 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
  • Hypothyroidism reported in thyroidectomy patients undergoing levothyroxine replacement; closely monitor TSH levels in such patients
  • Motor vehicle accidents reported with therapy; caution patients about driving a car or operating machinery
  • Decline in renal function may occur; evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction
  • Growth retardation reported in children and pre-adolescents receiving therapy; long term effects of prolonged treatment on growth in children are unknown; monitor growth in children receiving therapy
  • Cases of tumor lysis syndrome (TLS), including fatal cases, reported in patients with CML, GIST, ALL, and eosinophilic leukemia receiving therapy; patients at risk of TLS are those with tumors having a high proliferative rate or high tumor burden prior to treatment; monitor these patients closely and take appropriate precautions; due to possible occurrence of TLS, correct clinically significant dehydration and treat high uric acid levels prior to initiation of therapy
  • Drug interaction overview
  • Effects of drugs on imatinib
    • Imatinib is a CYP3A4 substrate
    • CYP3A4 inducers may decrease imatinib plasma concentrations and AUC
    • CYP3A4 inhibitors may increase imatinib plasma concentrations and AUC
  • Effects of imatinib on other drugs
    • Imatinib inhibits CYP3A4 and CYP2D6, which may increase serum concentrations and AUC of CYP3A4 or CYP2D6 substrates
    • Patients who require anticoagulation should receive low-molecular weight or standard heparin instead of warfarin

Pregnancy and Lactation

  • Fetal harm when administered to a pregnant woman based on human and animal data
  • No clinical studies available regarding use in pregnant women
  • There have been post-market reports of spontaneous abortions and congenital anomalies from women who have been exposed to imatinib during pregnancy
  • Test pregnancy status in females with reproductive potential before initiation of treatment
  • Imatinib and its active metabolite are excreted into human milk
  • Advise a lactating woman not to breastfeed during treatment and for 1 month after last dose
References
Medscape. Imatinib.

https://reference.medscape.com/drug/gleevec-imatinib-342239

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