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Acute lymphoblastic leukemia: Treatment of relapsed or refractory Philadelphia chromosome " “positive (Ph+) acute lymphoblastic leukemia (ALL) in adults
Treatment of newly diagnosed Ph+ ALL in children (in combination with chemotherapy)
Aggressive systemic mastocytosis: Treatment of aggressive systemic mastocytosis without D816V c-Kit mutation (or c-Kit mutational status unknown) in adults
Chronic myeloid leukemia: Treatment of Ph+ chronic myeloid leukemia (CML) in chronic phase (newly diagnosed) in adults and children
Treatment of Ph+ CML in blast crisis, accelerated phase, or chronic phase after failure of interferon-alfa therapy
Dermatofibrosarcoma protuberans: Treatment with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans (DFSP) in adults
Gastrointestinal stromal tumors: Treatment of Kit (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST)
Adjuvant treatment of Kit (CD117) " “positive GIST following complete gross resection
Hypereosinophilic syndrome and/or chronic eosinophilic leukemia: Treatment of hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) in adult patients who have the FIP1L1 " “platelet-derived growth factor (PDGF) receptor alpha fusion kinase (mutational analysis or fluorescent in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGF receptor alpha fusion kinase negative or unknown
Myelodysplastic/Myeloproliferative diseases: Treatment of myelodysplastic syndrome/myeloproliferative diseases (MDS/MPD) associated with PDGF receptor gene rearrangements in adults
Canadian labeling (not an approved indication in the US): Treatment of newly diagnosed Ph+ ALL in adults as a single agent for induction therapy
There are no contraindications listed in the manufacturers US labeling.
Canadian labeling: Hypersensitivity to imatinib or any component of the formulation
Note: Treatment may be continued until disease progression or unacceptable toxicity. The optimal duration of therapy for chronic myeloid leukemia (CML) in complete remission is not yet determined. Discontinuing CML treatment is not recommended unless part of a clinical trial (Baccarani, 2009). Imatinib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting (Roila, 2010).
Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML): Oral:
Chronic phase: 400 mg once daily; may be increased to 600 mg daily, if tolerated, for disease progression, lack of hematologic response after 3 months, lack of cytogenetic response after 6 to 12 months, or loss of previous hematologic or cytogenetic response. An increase to 800 mg daily has been used (Cortes, 2010; Hehlmann, 2014).
Canadian labeling: 400 mg once daily; may be increased to 600 to 800 mg daily
Accelerated phase or blast crisis: 600 mg once daily; may be increased to 800 mg daily (400 mg twice daily), if tolerated, for disease progression, lack of hematologic response after 3 months, lack of cytogenetic response after 6 to 12 months, or loss of previous hematologic or cytogenetic response
Ph+ acute lymphoblastic leukemia (ALL) (relapsed or refractory): Oral: 600 mg once daily
Gastrointestinal stromal tumors (GIST) (adjuvant treatment following complete resection): Oral: 400 mg once daily; recommended treatment duration: 3 years
GIST (unresectable and/or metastatic malignant): Oral: 400 mg once daily; may be increased up to 800 mg daily (400 mg twice daily), if tolerated, for disease progression. Note: Significant improvement (progression-free survival, objective response rate) was demonstrated in patients with KIT exon 9 mutation with 800 mg (versus 400 mg), although overall survival (OS) was not impacted. The higher dose did not demonstrate a difference in time to progression or OS patients with Kit exon 11 mutation or wild-type status (Debiec-Rychter, 2006; Heinrich, 2009).
Canadian labeling: 400 to 600 mg daily (depending on disease stage/progression); may be increased to 600-800 mg daily
Aggressive systemic mastocytosis (ASM) with eosinophilia: Oral: Initiate at 100 mg once daily; titrate up to a maximum of 400 mg once daily (if tolerated) for insufficient response to lower dose
ASM without D816V c-Kit mutation or c-Kit mutation status unknown: Oral: 400 mg once daily
Dermatofibrosarcoma protuberans (DFSP): Oral: 400 mg twice daily
Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL): Oral: 400 mg once daily
HES/CEL with FIP1L1-PDGFRα fusion kinase: Oral: Initiate at 100 mg once daily; titrate up to a maximum of 400 mg once daily (if tolerated) if insufficient response to lower dose
Myelodysplastic/myeloproliferative disease (MDS/MPD): Oral: 400 mg once daily
Ph+ ALL (induction, newly diagnosed):Canadian labeling (not an approved use in the US): Oral: 600 mg once daily
Chordoma, progressive, advanced, or metastatic expressing PDGFRB and/or PDGFB (off-label use): Oral: 400 mg twice daily (Stacchiotti, 2012)
Desmoid tumors, unresectable and/or progressive (off-label use): Oral: 300 mg twice daily (BSA ≥1.5 m2), 200 mg twice daily (BSA 1 to 1.49 m2), 100 mg twice daily (BSA <1 m2) (Chugh, 2010) or 400 mg once daily; may increase to 400 mg twice daily if progressive disease on 400 mg daily (Penel, 2011)
Melanoma, advanced or metastatic with C-KIT mutation (off-label use): Oral: 400 mg twice daily (Carvajal, 2011)
Stem cell transplant (SCT, off-label use) for CML (in patients who have not failed imatinib therapy prior to transplant): Oral:
Prophylactic use to prevent relapse post SCT: 400 mg daily starting after engraftment for 1 year post transplant (Carpenter, 2007) or 300 mg daily starting on day +35 post SCT (increased to 400 mg within 4 weeks) and continued until 12 months post transplant (Olavarria, 2007)
Relapse post SCT: Initial: 400 mg daily; if inferior response after 3 months, dose may be increased to 600 to 800 mg daily (Hess, 2005) or 400 to 600 mg daily (chronic phase) or 600 mg daily (blast or accelerated phase) (DeAngelo, 2004)
Dosage adjustment with concomitant strong CYP3A4 inducers: Avoid concomitant use of strong CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin); if concomitant use cannot be avoided, increase imatinib dose by at least 50% with careful monitoring.
Refer to adult dosing.
Note: Treatment may be continued until disease progression or unacceptable toxicity. The optimal duration of therapy for CML in complete remission is not yet determined. Imatinib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting (Dupuis, 2011).
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) (newly diagnosed): Children ≥1 year and Adolescents: Oral: 340 mg/m2/day (in combination with chemotherapy); maximum: 600 mg daily
Ph+ chronic myeloid leukemia (CML), chronic phase, newly diagnosed: Children ≥1 year and Adolescents: Oral: 340 mg/m2/day; maximum: 600 mg daily
Dosage adjustment with concomitant strong CYP3A4 inducers: Avoid concomitant use of strong CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin); if concomitant use cannot be avoided, increase imatinib dose by at least 50% with careful monitoring.
Dosage adjustment for hepatotoxicity: Refer to "Hepatic Impairment " ¯ dosing.
Dosage adjustment for hematologic adverse reactions: Refer to dosing adjustment for toxicity.
Dosage adjustment for nonhematologic adverse reactions: Refer to dosing adjustment for toxicity.
US labeling:
CrCl 40 to 59 mL/minute: Maximum recommended dose: 600 mg.
CrCl 20 to 39 mL/minute: Decrease recommended starting dose by 50%; dose may be increased as tolerated; maximum recommended dose: 400 mg.
CrCl <20 mL/minute: Use caution; a dose of 100 mg daily has been tolerated in a limited number of patients with severe impairment (Gibbons, 2008).
Canadian labeling:
CrCl 40 to 59 mL/minute: Initial dose: 400 mg once daily (minimum effective dose); titrate to efficacy and tolerability.
CrCl 20 to 39 mL/minute: Initial dose: 400 mg once daily (minimum effective dose); titrate to efficacy and tolerability; the use of 800 mg dose is not recommended.
CrCl <20 mL/minute: Use is not recommended.
US labeling:
Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment: Reduce dose by 25%.
Canadian labeling:
Mild-to-moderate impairment: Initial dose: 400 mg once daily (minimum effective dose).
Severe impairment: Initial dose: 200 mg once daily; may increase up to 300 mg once daily in the absence of severe toxicity; decrease dose with unacceptable toxicity.
Dosage adjustment for hepatotoxicity (during therapy): If elevations of bilirubin >3 times ULN or transaminases >5 times ULN occur, withhold treatment until bilirubin <1.5 times ULN and transaminases <2.5 times ULN. Resume treatment at a reduced dose as follows (Note: The decision to resume treatment should take into consideration the initial severity of hepatotoxicity):
Adults:
If current dose 400 mg daily, reduce dose to 300 mg daily
If current dose 600 mg daily, reduce dose to 400 mg daily
If current dose 800 mg daily, reduce dose to 600 mg daily
Children ≥1 year and Adolescents: If current dose 340 mg/m2/day, reduce dose to 260 mg/m2/day
Imatinib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting (Dupuis, 2011; Roila, 2010).
Should be administered with a meal and a large glass of water. It is not recommended to crush or chew tablets due to bitter taste. Tablets may be dispersed in water or apple juice (using ~50 mL for 100 mg tablet, ~200 mL for 400 mg tablet); stir until dissolved and administer immediately. In adults, doses ≤600 mg may be given once daily; 800 mg dose should be administered as 400 mg twice daily. Dosing in children may be once or twice daily for chronic myeloid leukemia (CML) and once daily for Philadelphia chromosome " “positive (Ph+) acute lymphoblastic leukemia ( ALL). For daily dosing ≥800 mg, the 400 mg tablets should be used in order to reduce iron exposure.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Avoid skin or mucous membrane contact with crushed tablets; if contact occurs, wash thoroughly. Avoid exposure to crushed tablets. If it is necessary to manipulate the tablets (eg, to prepare an oral solution), it is recommended to double glove, wear a protective gown, and prepare in a controlled device. NIOSH recommends single gloving for administration of intact tablets (NIOSH, 2014).
Avoid grapefruit juice.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted between 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Gleevec: 100 mg, 400 mg [scored]
Generic: 100 mg, 400 mg
Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). When manipulating tablets, NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye protection as well as ventilated engineering controls are recommended (NIOSH, 2014).
An oral suspension may be prepared by placing tablets (whole, do not crush) in a glass of water or apple juice. Use ~50 mL for 100 mg tablet, or ~200 mL for 400 mg tablet. Stir until tablets are disintegrated, then administer immediately. To ensure the full dose is administered, rinse the glass and administer residue.
Gleevec (imatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; January 2015.Acetaminophen: May enhance the hepatotoxic effect of Imatinib. Monitor therapy
Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Avoid combination
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Consider therapy modification
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification
CycloSPORINE (Systemic): Imatinib may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patients clinical response closely. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Imatinib. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Imatinib. Monitor therapy
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Exceptions: Alitretinoin (Systemic); Praziquantel; Vinorelbine. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg/day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dexamethasone (Systemic): May decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with dexamethasone when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor clinical response closely. Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Monitor therapy
Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Avoid combination
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Avoid combination
Fludarabine: Imatinib may diminish the myelosuppressive effect of Fludarabine. Imatinib may decrease the serum concentration of Fludarabine. More specifically, imatinib may decrease the formation of fludarabine active metabolite F-ara-ATP Management: Due to the risk for impaired fludarabine response, consider discontinuing imatinib therapy at least 5 days prior to initiating fludarabine conditioning therapy in CML patients undergoing HSCT. Consider therapy modification
Gemfibrozil: May decrease serum concentrations of the active metabolite(s) of Imatinib. Specifically N-desmethylimatinib concentrations may be decreased. Gemfibrozil may decrease the serum concentration of Imatinib. Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: If a moderate CYP3A inhibitor must be used, consider reducing the dose of ibrutinib to 140mg daily and monitor closely for signs of toxicity. Avoid combination
Ibuprofen: May decrease the serum concentration of Imatinib. Specifically, ibuprofen may decrease intracellular concentrations of imatinib, leading to decreased clinical response. Management: Consider using an alternative to ibuprofen in patients who are being treated with imatinib. Available evidence suggests other NSAIDs do not interact in a similar manner. Consider therapy modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
Lansoprazole: May enhance the dermatologic adverse effect of Imatinib. Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: U.S. labeling: start at 20 mg/day and limit to max of 80 mg/day with moderate CYP3A4 inhibitor. Canadian labeling: limit to max of 40 mg/day with moderate CYP3A4 inhibitor; avoid concomitant use of grapefruit products. Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Monitor therapy
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Avoid combination
Propacetamol: May enhance the hepatotoxic effect of Imatinib. Monitor therapy
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with the rifamycin derivatives when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Consider therapy modification
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Monitor therapy
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination
Simvastatin: Imatinib may decrease the metabolism of Simvastatin. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Consider therapy modification
St John's Wort: May increase the metabolism of Imatinib. Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Consider therapy modification
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Telithromycin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin. Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Avoid combination
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Monitor therapy
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy
Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Monitor therapy
Warfarin: Imatinib may enhance the anticoagulant effect of Warfarin. Imatinib may decrease the metabolism of Warfarin. Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Monitor therapy
CBC (weekly for first month, biweekly for second month, then periodically thereafter), liver function tests (at baseline and monthly or as clinically indicated; more frequently [at least weekly] in patients with moderate-to-severe hepatic impairment [Ramanathan, 2008]), renal function (at baseline and periodically thereafter), serum electrolytes (including calcium, phosphorus, potassium and sodium levels); bone marrow cytogenetics (in CML; at 6-, 12-, and 18 months), pregnancy test (Canadian labeling recommends women of reproductive potential have a negative test [urine or serum] with a sensitivity of at least 25 milliunits/mL within 1 week prior to therapy initiation); fatigue, weight, and edema/fluid status; consider echocardiogram and serum troponin levels in patients with HES/CEL, and in patients with MDS/MPD or ASM with high eosinophil levels; in pediatric patients, also monitor serum glucose, albumin, and growth
Gastric surgery (eg, bypass, major gastrectomy, or resection) patients: Monitor imatinib trough concentrations (Liu, 2011; Pavlovsky, 2009; Yoo, 2010)
Thyroid function testing (Hamnvik, 2011):
Preexisting levothyroxine therapy: Obtain baseline TSH levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months
Without preexisting thyroid hormone replacement: TSH at baseline, then every 4 weeks for 4 months, then every 2-3 months
Monitor for signs/symptoms of CHF in patients with at risk for cardiac failure or patients with pre-existing cardiac disease. In Canada, a baseline evaluation of left ventricular ejection fraction is recommended prior to initiation of imatinib therapy in all patients with known underlying heart disease or in elderly patients. Monitor for signs/symptoms of gastrointestinal irritation or perforation and dermatologic toxicities.
Adverse reactions listed as a composite of data across many trials, except where noted for a specific indication. Frequency not always defined.
>10%:
Cardiovascular: Edema (11% to 86%; grades 3/4: 3% to 13%; includes aggravated edema, anasarca, ascites, pericardial effusion, peripheral edema, pulmonary edema, and superficial edema), facial edema ( ≤17%), hypotension (Ph+ ALL [pediatric] grades 3/4: 11%), chest pain (7% to 11%)
Central nervous system: Fatigue (20% to 75%), pain ( ≤47%), headache (8% to 37%), dizziness (5% to 19%), insomnia (9% to 15%), depression (3% to 15%), taste disorder ( ≤13%), rigors (10% to 12%), anxiety (8% to 12%), paresthesia ( ≤12%), chills ( ≤11%)
Dermatologic: Skin rash (9% to 50%; grades 3/4: 1% to 9%), dermatitis (GIST ≤39%), pruritus (7% to 26%), night sweats (CML 13% to 17%), alopecia (7% to 15%), diaphoresis (GIST ≤13%)
Endocrine & metabolic: Increased lactate dehydrogenase ( ≤60%), hypokalemia (6% to 13%; Ph+ ALL [pediatric] grades 3/4: 34%), weight gain (5% to 32%), decreased serum albumin ( ≤21%; grades 3/4: ≤4%)
Gastrointestinal: Nausea (41% to 73%; Ph+ ALL [pediatric] grades 3/4: 16%), diarrhea (25% to 59%; Ph+ ALL [pediatric] grades 3/4: 9%), vomiting (11% to 58%), abdominal pain (3% to 57%), anorexia ( ≤36%), dyspepsia (11% to 27%), flatulence ( ≤25%), abdominal distension ( ≤19%), constipation (8% to 16%), stomatitis ( ≤16%)
Hematologic & oncologic: Neutropenia (grades 3/4: 8% to 64%), thrombocytopenia (grades 3/4: 1% to 63%), anemia (grades 3/4: 3% to 53%), hemorrhage (3% to 53%; grades 3/4: ≤19%), leukopenia (GIST 5% to 47%; grades 3/4: 2%), hypoproteinemia ( ≤32%)
Hepatic: Increased serum transaminases (Ph+ ALL [pediatric] grades 3/4: 57%), increased serum AST ( ≤38%; grades 3/4: ≤6%), increased serum ALT ( ≤34%; grades 3/4: ≤ 8%), increased alkaline phosphatase ( ≤17%; grades 3/4: ≤6%), increased serum bilirubin ( ≤13%; grades 3/4: ≤4%)
Infection: Infection (Ph+ ALL [pediatric] grades 3/4: 53%; GIST ≤28%), influenza (Ph+ CML ≤14%)
Neuromuscular & skeletal: Muscle cramps (16% to 62%), musculoskeletal pain (children 21%; adults 38% to 49%), arthralgia (11% to 40%), myalgia (9% to 32%), weakness ( ≤21%), back pain ( ≤17%), limb pain ( ≤16%), ostealgia ( ≤11%)
Ophthalmic: Periorbital edema (15% to 74%), increased lacrimation (DFSP 25%; GIST ≤18%), eyelid edema (Ph+ CML 19%), blurred vision ( ≤11%)
Renal: Increased serum creatinine ( ≤44%; grades 3/4: ≤8%)
Respiratory: Nasopharyngitis (1% to 31%), cough (11% to 27%), upper respiratory tract infection (3% to 21%), dyspnea ( ≤21%), pharyngolaryngeal pain ( ≤18%), rhinitis (DFSP 17%), pharyngitis (CML 10% to 15%), flu-like symptoms (1% to 14%), pneumonia (CML 4% to 13%), sinusitis (4% to 11%)
Miscellaneous: Fever (6% to 41%)
1% to 10%:
Cardiovascular: Pleural effusion (Ph+ ALL [pediatric] grades 3/4: 7%), palpitations ( ≤5%), hypertension ( ≤4%), cardiac failure (Ph+ CML 1%; grades 3/4: <1%), flushing
Central nervous system: Cerebral hemorrhage ( ≤9%), hypoesthesia, peripheral neuropathy
Dermatologic: Skin photosensitivity (4% to 7%), xeroderma ( ≤7%), erythema, nail disease
Endocrine & metabolic: Hypophosphatemia (10%), hyperglycemia ( ≤10%), weight loss ( ≤10%), hypocalcemia (GIST ≤6%; Ph+ CML grades 3/4: <1%), fluid retention (Ph+ CML 3%; pleural effusion, pericardial effusion, ascites, or pulmonary edema 2%), hyperkalemia (1%)
Gastrointestinal: Decreased appetite (10%), gastroenteritis ( ≤10%), gastrointestinal hemorrhage (1% to 8%), increased serum lipase (CML grades 3/4: 4%), gastritis, gastroesophageal reflux, xerostomia
Hematologic & oncologic: Lymphocytopenia ( ≤10%; grades 3/4: 1% to 2%), eosinophilia, febrile neutropenia, pancytopenia, purpura
Neuromuscular & skeletal: Joint swelling
Ophthalmic: Conjunctivitis (5% to 8%), conjunctival hemorrhage, dry eyes
Respiratory: Hypoxia (9%), pneumonitis (Ph+ ALL [pediatric] grades 3/4: 8%), oropharyngeal pain (Ph+ CML ≤6%), epistaxis
<1% (Limited to important or life-threatening): Actinic keratosis, acute generalized exanthematous pustulosis, anaphylactic shock, angina pectoris, angioedema, aplastic anemia, arthritis, ascites, atrial fibrillation, avascular necrosis of bones, bullous rash, cardiac arrest, cardiac arrhythmia, cardiac tamponade, cardiogenic shock, cataract, cellulitis, cerebral edema, decreased linear skeletal growth rate (children), diverticulitis, DRESS syndrome, dyschromia, embolism, erythema multiforme, exfoliative dermatitis, fungal infection, gastric ulcer, gastrointestinal obstruction, gastrointestinal perforation, glaucoma, gout, hearing loss, hematemesis, hematoma, hematuria, hemolytic anemia, hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity, herpes simplex infection, herpes zoster, hypercalcemia, hyperkalemia, hypersensitivity angiitis, hyperuricemia, hypomagnesemia, hyponatremia, hypophosphatemia, hypothyroidism, IgA vasculitis, increased intracranial pressure, inflammatory bowel disease, interstitial pneumonitis, interstitial pulmonary disease, intestinal obstruction, left ventricular dysfunction, lichen planus, lower respiratory tract infection, lymphadenopathy, macular edema, melena, memory impairment, migraine, myocardial infarction, myopathy, optic neuritis, osteonecrosis (hip), ovarian cyst (hemorrhagic), palmar-plantar erythrodysesthesia, pancreatitis, papilledema, pericarditis, psoriasis, pulmonary fibrosis, pulmonary hemorrhage, pulmonary hypertension, Raynaud phenomenon, renal failure, respiratory failure, restless leg syndrome, retinal hemorrhage, rhabdomyolysis, ruptured corpus luteal cyst, sciatica, seizure, sepsis, Stevens-Johnson syndrome, subconjunctival hemorrhage, subdural hematoma, Sweet syndrome, syncope, tachycardia, telangiectasia (gastric antral), thrombocythemia, thrombosis, toxic epidermal necrolysis, tumor hemorrhage (GIST), tumor lysis syndrome, urinary tract infection, vitreous hemorrhage
AUC increased 1.5- to 2-fold in patients with mild and moderate renal impairment compared with patients with healthy renal function. Patients with severe renal impairment dosed at 100 mg/day had exposure similar to patients with healthy renal function receiving 400 mg/day.
Patients with severe hepatic impairment have higher exposure to imatinib and its metabolite. The mean AUC of imatinib and its metabolite increased by ~45% and 44%, respectively, in patients with severe hepatic impairment as compared to patients with normal hepatic function.
Body weight: Clearance increases with body weight to 8 L/hour for 50 kg and 14 L/hour for 100 kg.
Concerns related to adverse effects:
- Bone marrow suppression: May cause bone marrow suppression (anemia, neutropenia, and thrombocytopenia), usually occurring within the first several months of treatment. Median duration of neutropenia is 2 to 3 weeks; median duration of thrombocytopenia is 3 to 4 weeks. Monitor blood counts weekly for the first month, biweekly for the second month, and as clinically necessary thereafter. In chronic myeloid leukemia (CML), cytopenias are more common in accelerated or blast phase than in chronic phase.
- Cardiovascular effects: Severe heart failure (HF) and left ventricular dysfunction (LVD) have been reported (occasionally), usually in patients with comorbidities and/or risk factors. Carefully monitor patients with preexisting cardiac disease or risk factors for HF or history of renal failure. With initiation of imatinib treatment, cardiogenic shock and/or LVD have been reported in patients with hypereosinophilic syndrome and cardiac involvement (reversible with systemic steroids, circulatory support and temporary cessation of imatinib). Patients with high eosinophil levels and an abnormal echocardiogram or abnormal serum troponin level may benefit from prophylactic systemic steroids (for 1 to 2 weeks) with the initiation of imatinib.
- Dermatologic reactions: Severe bullous dermatologic reactions, including erythema multiforme and Stevens-Johnson syndrome, have been reported; recurrence has been described with rechallenge. Case reports of successful resumption at a lower dose (with corticosteroids and/or antihistamine) have been described; however, some patients may experience recurrent reactions. Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported. Symptoms of DRESS include fever, severe skin eruption, lymphadenopathy, hematologic abnormalities (eosinophilia or atypical lymphocytes), and internal organ involvement. If symptoms of DRESS occur, interrupt therapy and consider permanently discontinuing; symptoms regressed upon discontinuation of therapy, however, symptoms recurred in all cases when rechallenged.
- Driving/heavy machinery: Caution is recommended while driving/operating motor vehicles and heavy machinery when taking imatinib; advise patients regarding side effects such as dizziness, blurred vision, or somnolence. Reports of accidents have been received, but it is unclear if imatinib has been the direct cause in any case.
- Fluid retention/edema: Often associated with fluid retention, weight gain, and edema (risk increases with higher doses and age >65 years); occasionally serious and may lead to significant complications, including pleural effusion, pericardial effusion, pulmonary edema, and ascites. Monitor regularly for rapid weight gain or other signs/symptoms of fluid retention. Use with caution in patients where fluid accumulation may be poorly tolerated, such as in cardiovascular disease (HF or hypertension) and pulmonary disease.
- GI toxicity: Imatinib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting (Dupuis, 2011; Roila, 2010). May cause GI irritation; take with food and water to minimize irritation. There have been rare reports (including fatalities) of GI perforation.
- Hemorrhage: Severe hemorrhage (grades 3 and 4) has been reported with use, including GI hemorrhage and/or tumor hemorrhage. The incidence of hemorrhage is higher in patients with gastrointestinal stromal tumors (GIST) (GI tumors may have been hemorrhage source). Gastric antral vascular ectasia (a rare cause of gastrointestinal bleeding) has also been reported, at ~1 year (range: 6 days to 7 years) after therapy initiation (Gleevec Canadian product labeling, 2015; Alshehry, 2014; Saad Aldin, 2012). Monitor for GI symptoms with treatment initiation.
- Hepatotoxicity: Hepatotoxicity may occur; fatal hepatic failure and severe hepatic injury requiring liver transplantation have been reported with both short- and long-term use; monitor liver function prior to initiation and monthly or as needed thereafter; therapy interruption or dose reduction may be necessary. Transaminase and bilirubin elevations, and acute liver failure have been observed with imatinib in combination with chemotherapy.
- Nephrotoxicity: Long term use may result in a decline in renal function (Gleevec Canadian labeling [February 2016]). Monitor renal function prior to treatment initiation and periodically thereafter.
- Tumor lysis syndrome: Tumor lysis syndrome (TLS), including fatalities, has been reported in patients with acute lymphoblastic leukemia (ALL), CML eosinophilic leukemias, and GIST. Risk for TLS is higher in patients with a high tumor burden or high proliferation rate; monitor closely. Correct clinically significant dehydration and treat high uric acid levels prior to initiation of imatinib.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended in patients with severe impairment.
- Gastric surgery: Imatinib exposure may be reduced in patients who have had gastric surgery (eg, bypass, major gastrectomy, or resection); monitor imatinib trough concentrations (Liu, 2011; Pavlovsky, 2009, Yoo, 2010).
- Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended for moderate and severe renal impairment (CrCl <40 mL/minute).
- Thyroid disease: Hypothyroidism has been reported in thyroidectomy patients who were receiving thyroid hormone replacement therapy prior to initiation of imatinib; monitor thyroid function. The average onset for imatinib-induced hypothyroidism is 2 weeks; consider doubling levothyroxine doses upon initiation of imatinib (Hamnvik, 2011).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: The incidence of edema was increased with age older than 65 years in CML and GIST studies.
- Pediatric: Growth retardation has been reported in children receiving imatinib for the treatment of CML; generally where treatment was initiated in prepubertal children; growth velocity was usually restored as pubertal age was reached (Shima, 2011). Monitor growth closely.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
D
Adverse events have been observed in animal reproduction studies. Women of childbearing potential are advised not to become pregnant (female patients and female partners of male patients); highly effective contraception is recommended. The Canadian labeling recommends women of childbearing potential have a negative pregnancy test (urine or serum) with a sensitivity of at least 25 milliunits/mL within 1 week prior to therapy initiation. Case reports of pregnancies while on therapy (both males and females) include reports of spontaneous abortion, minor abnormalities (hypospadias, pyloric stenosis, and small intestine rotation) at or shortly after birth, and other congenital abnormalities including skeletal malformations, hypoplastic lungs, exomphalos, kidney abnormalities, hydrocephalus, cerebellar hypoplasia, and cardiac defects.
Retrospective case reports of women with CML in complete hematologic response (CHR) with cytogenic response (partial or complete) who interrupted imatinib therapy due to pregnancy, demonstrated a loss of response in some patients while off treatment. At 18 months after treatment reinitiation following delivery, CHR was again achieved in all patients and cytogenic response was achieved in some patients. Cytogenetic response rates may not be at as high as compared to patients with 18 months of uninterrupted therapy (Ault, 2006; Pye, 2008).
Inhibits Bcr-Abl tyrosine kinase, the constitutive abnormal gene product of the Philadelphia chromosome in chronic myeloid leukemia (CML). Inhibition of this enzyme blocks proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as in fresh leukemic cells in Philadelphia chromosome positive CML. Also inhibits tyrosine kinase for platelet-derived growth factor (PDGF), stem cell factor (SCF), c-Kit, and cellular events mediated by PDGF and SCF.
Rapid
Hepatic via CYP3A4 (minor metabolism via CYP1A2, CYP2D6, CYP2C9, CYP2C19); primary metabolite (active): N-demethylated piperazine derivative (CGP74588); severe hepatic impairment (bilirubin >3 to 10 times ULN) increases AUC by 45% to 55% for imatinib and its active metabolite, respectively
Feces (68% primarily as metabolites, 20% as unchanged drug); urine (13% primarily as metabolites, 5% as unchanged drug)
2 to 4 hours
Adults: Parent drug: ~18 hours; N-desmethyl metabolite: ~40 hours; Children: Parent drug: ~15 hours
Parent drug and metabolite: ~95% to albumin and alpha1-acid glycoprotein
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, dizziness, insomnia, lack of appetite, flatulence, hair loss, nausea, vomiting, diarrhea, constipation, change in taste, rhinitis, pharyngitis, joint pain, weight gain, or night sweats. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of tumor lysis syndrome (fast heartbeat or abnormal heartbeat; any passing out; trouble passing urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), angina, burning or numbness feeling, severe headache, severe abdominal pain, severe loss of strength and energy, vision changes, depression, bone pain, muscle pain, muscle weakness, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.