Dosage guidance:
Clinical considerations: Imatinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Acute lymphoblastic leukemia, Philadelphia chromosome positive, newly diagnosed (off-label population):
GRAAPH-2003 protocol:
Good early responders with corticosensitive and chemosensitive disease: Consolidation: Oral: 600 mg once daily starting on day 1 of consolidation (in combination with mitoxantrone, cytarabine, filgrastim, and triple intrathecal therapy) until day ~90 or until transplant (Ref). Refer to protocol for further information.
Poor early responders with corticoresistant and/or chemoresistant disease: Induction: Oral: 800 mg/day for ~90 days or until transplant (in combination with vincristine, dexamethasone, and triple intrathecal therapy) (Ref). Refer to protocol for further information.
GRAAPH-2005 protocol (imatinib in combination with low-intensity chemotherapy):
Cycle 1: Oral: 400 mg twice daily on days 1 to 28 (in combination with vincristine, dexamethasone, and filgrastim) (Ref).
Cycle 2: Oral: 400 mg twice daily on days 1 to 14 (in combination with methotrexate, cytarabine, and growth factor support) (Ref).
Depending on clinical response after cycle 2, patients could proceed to stem cell transplant. Refer to protocol for further information (Ref).
Imatinib in combination with Hyper-CVAD: Oral: 400 mg once daily on days 1 to 14 of cycles 1 to 8 of each intensive chemotherapy course, followed by maintenance therapy of 600 mg once daily for 13 months (in combination with vincristine and prednisone). Months 6 and 13 of maintenance therapy consisted of intensive therapy with Hyper-CVAD and imatinib 400 mg once daily on days 1 to 14 of each month; refer to protocol for further information (Ref).
NILG protocol 09/00: Note: Imatinib is administered in combination with chemotherapy; refer to protocol for further information, including maintenance imatinib (if applicable) (Ref).
Cycle 1: Oral: 600 mg once daily for 7 consecutive days, starting on day 15 of cycle 1 (Ref).
Cycles 2 to 8: Oral: 600 mg once daily for 7 consecutive days, starting 3 days before chemotherapy (Ref).
Acute lymphoblastic leukemia, Philadelphia chromosome positive, relapsed/refractory: Oral: 600 mg once daily until disease progression or unacceptable toxicity.
Aggressive systemic mastocytosis associated with eosinophilia: Oral: Initiate at 100 mg once daily; if assessments demonstrate insufficient response, increase from 100 mg to 400 mg/day in the absence of adverse reactions; continue until disease progression or unacceptable toxicity. Note: Imatinib is not recommended for cutaneous mastocytosis, indolent systemic mastocytosis (smoldering systemic mastocytosis or isolated bone marrow mastocytosis), systemic mastocytosis with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, or extracutaneous mastocytoma; do not use imatinib for treatment of aggressive mastocytosis that contains the D816V mutation of c-kit.
Aggressive systemic mastocytosis without D816V c-kit mutation or c-kit mutation status unknown: Oral: 400 mg once daily until disease progression or unacceptable toxicity.
Chordoma, progressive, advanced, or metastatic expressing PDGFRB and/or PDGFB (off-label use): Oral: 400 mg twice daily (Ref) or (in patients with secondary resistance to imatinib and/or evidence of mTOR effector activation) 400 mg once daily (in combination with sirolimus) until disease progression or unacceptable toxicity (Ref).
Chronic myeloid leukemia, Philadelphia chromosome positive: 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.
Guideline recommendations (Ref): A British Society for Haematology guideline on the diagnosis and management of CML suggests that the first-generation tyrosine kinase inhibitor (TKI) imatinib is a reasonable option for initial therapy in chronic phase CML. A second-generation TKI may be considered as initial therapy for newly diagnosed chronic phase CML in patients with a high or intermediate EUTOS long-term survival (ELTS) or Sokal score; assess comorbidities and TKI toxicity profile to determine the appropriate TKI. An alternative TKI should be considered if treatment failure on first-line therapy occurs; the choice of second-line therapy should be guided by BCR-ABL mutational analysis as well as patient- and drug-specific characteristics. Patients with de novo accelerated phase CML should ideally be managed with a second-generation TKI. Some patients may be candidates for a treatment-free remission (TFR); specific criteria and monitoring parameters must be met in order to discontinue treatment; refer to guideline for further information.
Chronic phase: Oral: 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 (Ref).
Accelerated phase or blast crisis: Oral: 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.
Chronic myeloid leukemia, post allogeneic hematopoietic cell transplantation (off-label use):
Prophylactic use to prevent relapse post-transplant: Oral: 400 mg once daily starting after engraftment for 1 year post-transplant (Ref) or 300 mg once daily starting on day +35 post SCT (increased to 400 mg once daily within 4 weeks) and continued until 12 months posttransplant (Ref).
Relapse post-transplant: Oral: Initial: 400 mg once daily; if inferior response after 3 months, dose may be increased to 600 to 800 mg daily (Ref) or 400 to 600 mg daily (chronic phase) or 600 mg daily (blast or accelerated phase) (Ref).
Dermatofibrosarcoma protuberans: Oral: 400 mg twice daily until disease progression or unacceptable toxicity. Note: Data from a pooled analysis of two phase 2 trials showed that response rates and time to progression did not differ between 400 mg/day and 800 mg/day doses (Ref); data from a systematic review also noted that there seemed to be no difference in outcomes between the 400 or 800 mg/day dose (Ref).
Desmoid tumors, locally advanced 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) (Ref) or 400 mg once daily; may escalate to 400 mg twice daily for progressive disease on 400 mg daily; continue until disease progression or unacceptable toxicity (Ref).
Gastrointestinal stromal tumor:
Adjuvant treatment following complete resection: Oral: 400 mg once daily; recommended treatment duration: 3 years (Ref).
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 at 400 mg/day; continue until disease progression or unacceptable toxicity. 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 (Ref).
Hypereosinophilic syndrome and/or chronic eosinophilic leukemia: Oral: 400 mg once daily until disease progression or unacceptable toxicity.
Hypereosinophilic syndrome and/or chronic eosinophilic leukemia with FIP1L1-PDGFRα fusion kinase: Oral: Initiate at 100 mg once daily; if assessments demonstrate insufficient response, increase from 100 mg to 400 mg/day in the absence of adverse reactions; continue until disease progression or unacceptable toxicity.
Myelodysplastic/myeloproliferative disease with PDGFR gene rearrangements: Oral: 400 mg once daily until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Note: Only 13% of an imatinib dose is eliminated in the urine (5% unchanged); therefore, dosage adjustments for kidney dysfunction are likely unnecessary. However, in a pharmacokinetic study, imatinib AUC was increased 1.5- to 2-fold in patients with mild (CrCl 40 to 59 mL/minute) and moderate (CrCl 20 to 39 mL/minute) kidney impairment, although doses were well tolerated (Ref). Additionally, there may be an increased risk for worsening kidney function among patients with preexisting kidney impairment. Alternative treatments (eg, certain second-generation tyrosine kinase inhibitors less associated with kidney impairment) are preferred when clinically appropriate (Ref). Close monitoring of kidney function and avoiding use of other nephrotoxic drugs is recommended (Ref).
Altered kidney function:
CrCl ≥40 mL/minute: Initial: No dosage adjustment necessary (Ref). Subsequent dose adjustments (increase or decrease) should be based on the indication for use along with an assessment of tolerability/adverse effects and desired clinical response (Ref).
CrCl 20 to <40 mL/minute: Initial: No dosage adjustment necessary (Ref). Subsequent dose adjustments (increase or decrease) should be based on the indication for use along with an assessment of tolerability/adverse effects and desired clinical response (Ref). Doses up to 600 mg have been well tolerated in this population (Ref). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (Ref).
CrCl <20 mL/minute: Consider alternative agent due to limited clinical data and risk of imatinib-induced nephrotoxicity.
If necessary, no initial dosage adjustment necessary (Ref); however, use with caution. Subsequent dose adjustments (increase or decrease) should be based on the indication for use along with an assessment of tolerability/adverse effects and desired clinical response (Ref). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Ref):
Initial: No dosage adjustment necessary (Ref); however, use with caution due to limited clinical data (case reports) (Ref). Subsequent dose adjustments (increase or decrease) should be based on the indication for use along with an assessment of tolerability/adverse effects and desired clinical response (Ref). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (Ref).
Peritoneal dialysis : Unlikely to be significantly dialyzed (highly protein bound) (Ref):
Consider alternative agent due to limited clinical data and risk of imatinib-induced nephrotoxicity.
If necessary, no initial dosage adjustment necessary (Ref); however, use with caution due to limited clinical data and risk of imatinib-induced nephrotoxicity; may also consider use of an alternative agent. Subsequent dose adjustments (increase or decrease) should be based on the indication for use along with an assessment of tolerability/adverse effects and desired clinical response (Ref). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (Ref).
Nephrotoxicity during treatment: Interrupt imatinib therapy and provide supportive care. When kidney function improves, may reinitiate imatinib at a full or reduced dose (depending on the severity of the kidney injury and how quickly it resolved) (Ref). Alternatively, may consider switching to a second-generation tyrosine kinase inhibitor less associated with nephrotoxicity (eg, dasatinib, nilotinib) (Ref).
Preexisting hepatic impairment:
Manufacturer’s labeling:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Reduce dose by 25%.
Krens 2019: No dose adjustment is needed.
Hepatotoxicity during treatment: 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):
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
Hematologic toxicity:
Chronic phase CML (initial dose 400 mg daily in adults); ASM, MDS/MPD, and HES/CEL (initial dose 400 mg daily); or GIST (initial dose 400 mg daily): If ANC <1 x 109/L and/or platelets <50 x 109/L: Withhold until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L; resume treatment at original starting dose. For recurrent neutropenia and/or thrombocytopenia, withhold until recovery, and reinstitute treatment at a reduced dose as follows:
Adults: If initial dose 400 mg daily, reduce dose to 300 mg daily.
CML (accelerated phase or blast crisis): Adults (initial dose 600 mg daily): If ANC <0.5 x 109/L and/or platelets <10 x 109/L, establish whether cytopenia is related to leukemia (bone marrow aspirate or biopsy). If unrelated to leukemia, reduce dose to 400 mg daily. If cytopenia persists for an additional 2 weeks, further reduce dose to 300 mg daily. If cytopenia persists for 4 weeks and is still unrelated to leukemia, withhold treatment until ANC ≥1 x 109/L and platelets ≥20 x 109/L, then resume treatment at 300 mg daily.
ASM associated with eosinophilia and HES/CEL with FIP1L1-PDGFRα fusion kinase: Adults (starting dose 100 mg daily): If ANC <1 x 109/L and/or platelets <50 x 109/L: Withhold until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L; resume treatment at previous dose.
DFSP: Adults (initial dose 800 mg daily): If ANC <1 x 109/L and/or platelets <50 x 109/L, withhold until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L; resume treatment at reduced dose of 600 mg daily. For recurrent neutropenia and/or thrombocytopenia, withhold until recovery, and reinstitute treatment with a further dose reduction to 400 mg daily.
Ph+ ALL:
Adults (initial dose 600 mg daily): If ANC <0.5 x 109/L and/or platelets <10 x 109/L, establish whether cytopenia is related to leukemia (bone marrow aspirate or biopsy). If unrelated to leukemia, reduce dose to 400 mg daily. If cytopenia persists for an additional 2 weeks, further reduce dose to 300 mg daily. If cytopenia persists for 4 weeks and is still unrelated to leukemia, withhold treatment until ANC ≥1 x 109/L and platelets ≥20 x 109/L, then resume treatment at 300 mg daily.
Nonhematologic toxicity (eg, severe edema): Withhold treatment until toxicity resolves; may resume if appropriate (depending on initial severity of adverse event).
Dermatologic toxicity: If symptoms of DRESS (drug reaction with eosinophilia and systemic symptoms) occur, interrupt imatinib therapy and consider permanent discontinuation.
Hypertension: If indicated, initiate appropriate antihypertensive therapy to reduce the risk for cardiovascular complications (Ref).
Refer to adult dosing.
(For additional information see "Imatinib: Pediatric drug information")
Dosage guidance:
Safety: Commercially available Imkeldi oral solution is 80 mg/mL; extemporaneously compounded oral suspension concentration may be different (40 mg/mL); use caution; ensure all doses are in mg of imatinib. Calculated dose should be rounded to the nearest measurable graduation mark on the oral syringe if necessary.
Dosing: Dosing presented as mg/m2 and mg/kg; use caution.
Clinical considerations: Antiemetics may be recommended to prevent nausea and vomiting; imatinib doses >260 mg/m2/day are associated with a moderate emetic potential (Ref).
Acute lymphoblastic leukemia (ALL), Philadelphia chromosome positive (Ph+), newly diagnosed: Children and Adolescents: Oral: 340 mg/m2/day administered once daily; in combination with intensive chemotherapy (Ref); maximum daily dose: 600 mg/day; treatment may be continued until disease progression or unacceptable toxicity.
Chronic myeloid leukemia (CML), Philadelphia chromosome positive (Ph+), chronic phase, newly diagnosed: Infants ≥10 months, Children, and Adolescents: Limited data available in infants ≥10 months: Oral: 340 mg/m2/day administered once daily or in 2 divided doses; maximum daily dose: 600 mg/day. Treatment may be continued until disease progression or unacceptable toxicity (Ref). The optimal duration of therapy for CML in complete remission is not yet determined. Discontinuing CML treatment is not recommended unless part of a clinical trial (Ref).
Infantile myofibromatosis, visceral : Very limited data available: Infants: Oral: 5 to 6 mg/kg/day. Use described in several case reports in patients with platelet-derived growth factor receptor-beta (PDGFR-β) variants with visceral areas of body affected and multiple lesions. Imatinib therapy was initiated in most cases when disease progression observed after previous surgical or chemotherapeutic intervention; reported duration: 3 to 9 months; some case reports did not describe duration. Infant growth should be monitored closely; some subjects required fortified formula supplementation (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity :
Nonhematologic adverse reactions: Children and Adolescents: Withhold treatment until toxicity resolves; may resume if appropriate (depending on initial severity of adverse event).
Hematologic adverse reactions:
Children and Adolescents: Oral:
ALL Ph+ (newly diagnosed): Hematologic toxicity requiring dosage adjustments was not observed in the study. No major toxicities were observed with imatinib at 340 mg/m2/day in combination with intensive chemotherapy (Ref).
CML Ph+ (chronic phase): If ANC <1 x 109/L and/or platelets <50 x 109/L: Withhold until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L; resume treatment at previous dose. For recurrent neutropenia and/or thrombocytopenia, withhold until recovery and reinstitute treatment at a reduced dose as follows: If initial dose 340 mg/m2/day, reduce dose to 260 mg/m2/day.
Children and Adolescents: Oral:
Baseline kidney impairment: In a pharmacokinetic study in adults, imatinib AUC was increased 1.5- to 2-fold in patients with mild (CrCl 40 to 59 mL/minute) and moderate (CrCl 20 to 39 mL/minute) kidney impairment, although doses were well tolerated (Ref). Additionally, there may be an increased risk for worsening kidney function among patients with preexisting kidney impairment. Close monitoring of kidney function and avoiding use of other nephrotoxic drugs is recommended (Ref).
Mild impairment (CrCl 40 to 59 mL/minute): There are no pediatric-specific recommendations; use caution; in adults with mild impairment, a maximum daily dose of 600 mg/day is recommended.
Moderate impairment (CrCl 20 to 39 mL/minute): Decrease recommended starting dose by 50%; dose may be increased as tolerated; in adults with moderate impairment, a maximum daily dose of 400 mg/day is recommended.
Severe impairment (CrCl <20 mL/minute): There are no pediatric-specific recommendations; use caution; in adults with severe impairment, a reduced dose of 100 mg/day has been tolerated (Ref).
Nephrotoxicity during therapy: Based on adult experience, interrupt imatinib therapy and provide supportive care. When kidney function improves, may reinitiate imatinib at a full or reduced dose (depending on the severity of the kidney injury and how quickly it resolved) (Ref).
Children and Adolescents: Oral:
Baseline liver impairment:
Mild to moderate impairment: No adjustment necessary.
Severe impairment: Reduce dose by 25%.
Hepatotoxicity during therapy: Withhold treatment until toxicity resolves; may resume if appropriate (depending on initial severity of adverse event).
If elevations of bilirubin >3 times ULN or liver 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: If current dose 340 mg/m2/day, reduce dose to 260 mg/m2/day; maximum daily dose range: 300 to 400 mg/day.
Bone marrow suppression, including grades ≥3 anemia, neutropenia, and thrombocytopenia, has occurred during therapy with imatinib for chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) (Ref). Bone marrow suppression occurred earlier and more frequently in advanced phase CML than chronic phase CML (Ref). Hematologic toxicity is a significant cause of dose reductions and interruptions but rarely permanent discontinuation (Ref). Median time to recovery is 2 to 4 weeks (Ref). Incidence is lower in patients with gastrointestinal stromal tumors (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Inhibition of Bcr/Abl kinase leads to suppression of hematopoiesis by the leukemic clone. Hematopoiesis of healthy progenitor stem cells eventually recovers after TKI-induced suppression of the leukemic process (Ref). Imatinib may also suppress normal hematopoietic progenitors via inhibition of c-kit (Ref).
Onset: Varied; most common in the first weeks to 3 months of treatment, including the incidence of grades 3/4 toxicity (Ref). Median time to first grade 3 or 4 neutropenia and thrombocytopenia was ~2 months in chronic phase CML compared to ~1 month in advanced phase CML (Ref). Hematologic toxicity after the first year of therapy is rare (Ref).
Risk factors:
• Treatment of hematologic disorders (ie, CML, ALL) (Ref)
• Advanced phases of CML (Ref)
• ≥90% Ph-positive metaphases at start of therapy in CML (Ref)
Heart failure and left ventricular dysfunction have rarely been reported in patients receiving imatinib for conditions, including chronic myeloid leukemia, acute lymphoblastic leukemia, myeloproliferative disorders, and gastrointestinal stromal tumors (Ref). Most events occurred in patients with preexisting cardiac risk factors for heart failure (Ref). Some retrospective analyses report similar rates of heart failure to what would be expected in a general population cohort not exposed to imatinib (Ref).
Mechanism: Possibly related to mechanism of action; inhibition of Abl kinase may lead to activation of the endoplasmic reticulum stress response, causing mitochondrial changes in cardiac myocytes and cardiomyocyte cell death, ultimately leading to loss of left ventricular mass and decline in left ventricular function (Ref). Development of heart failure has not been shown to be dose-related in retrospective clinical studies (Ref). The impact of fluid retention contributing to heart failure development is unknown (Ref).
Onset: Varied; median 162 days (range: 2 days to >5 years) (Ref).
Risk factors:
• Increasing age (Ref)
• Preexisting cardiac conditions (eg, diabetes mellitus, hypertension, coronary artery disease, arrhythmia, etc.) (Ref)
Various cutaneous reactions have occurred with imatinib, including erythematous maculopapular skin rash and pigmentation changes (including hypopigmentation, skin depigmentation, and hyperpigmentation); more severe (grade 3 or 4) acute generalized exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms (DRESS), erythema multiforme, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis have also been reported (Ref). Generalized rash is typically self-limiting or managed with supportive care (Ref). Pigmentation changes are generally reversible after discontinuation or dose reduction (Ref). Severe cutaneous eruptions require dose interruption or discontinuation (Ref). Other cutaneous reactions that have been reported include lichenoid eruption, pityriasis rosea, and psoriasiform eruption (Ref).
Mechanism: Not clearly established; some reactions have been established as dose-related. Pigmentation changes may be a result of c-kit inhibition and its downstream effects on melanocyte development and survival (Ref).
Onset: Varied; mean onset of erythematous rash is ~2 months after treatment initiation (Ref). Median onset of pigmentation changes is 4 weeks (range: 2 weeks to >3 months) (Ref).
Risk factors:
• Higher doses, especially ≥600 mg daily (Ref)
• Females (erythematous rash) (Ref)
• Darker pigmented skin tones (depigmentation) (Ref)
• Cross-reactivity between imatinib, nilotinib and/or dasatinib may occur; although, some patients have been able to tolerate alternative tyrosine kinase inhibitors (Ref)
Fluid retention and/or edema commonly occur with imatinib therapy (Ref). Localized or superficial manifestations (eg, periorbital edema, facial edema, leg edema) are more common than central edema (eg, ascites, pleural effusion, pericardial effusion) (Ref). Grade 3 or 4 events are rare, but edema is a frequent cause of dose interruption or reduction (Ref).
Mechanism: Not clearly established; may be related to inhibition of platelet-derived growth factor receptor (PDGFR), leading to greater interstitial fluid pressure, increased capillary permeability, and fluid extravasation (Ref). Periorbital soft tissue has a high abundance of dermal dendrocytes that express PDGFR kinase (Ref).
Onset: Varied; in retrospective reviews, edema development occurred at a median of ~2 months (range: 1 day to >1 year) (Ref).
Risk factors:
• Age ≥65 years (Ref)
• Females (facial edema, generalized edema, periorbital edema) (Ref)
• Dose >400 mg daily (Ref)
GI toxicity, including nausea, vomiting, diarrhea, and abdominal pain, are commonly associated with imatinib therapy (Ref). GI events can typically be managed with supportive care and rarely causes therapy discontinuation (Ref). Nausea has been identified as a cause of medication non-adherence (Ref). Serious events were rare and occurred most in the first year of therapy in a long-term follow-up study of imatinib for chronic myeloid leukemia (Ref). GI perforation has been reported rarely, including fatal events (Ref).
Mechanism: Dose-related, not clearly established; nausea/vomiting may be caused by local irritant properties of imatinib. Diarrhea may also be the result of local irritation or inhibition of c-kit that is expressed on intestinal cells resulting in dysregulated motility (Ref).
Onset: Varied; median onset of diarrhea was 22 days (range: 1 day to >1 year) (Ref)
Risk factors:
• Higher doses (Ref)
Growth suppression, including decreased longitudinal growth and decreased body weight growth, has been reported in children receiving long-term imatinib for the treatment of chronic myeloid leukemia (CML); the reported incidence is highly variable but frequently reported as ≥40%, with onset occurring during the first year of therapy and persisting with treatment (Ref). Decreased longitudinal growth has been reported in prepubertal and postpubertal children (Ref); the height for age scores (eg, Z-scores, standard deviation scores) were significantly lower in prepubertal children (Ref). Data suggest catchup growth in children with stunted growth in both groups (imatinib initiation in prepuberty and postpuberty) once they move into their postpubertal years (Ref). In one retrospective study, significantly lower weight standard deviation scores after initiating imatinub were reported (Ref).
Mechanism: Dose-related; exact mechanism unknown but is likely related to the pharmacologic action (inhibitory effects on other tyrosine kinase pathways that result in off-target complications [eg, growth impairment]) (Ref). Other suggested mechanisms include growth hormone deficiency, growth hormone insensitivity, inhibition of growth hormone/insulin like growth factor-1 axis, dysregulation of bone mineralization by altered function of osteoblasts and osteoclast, decreased recruitment and activity of chondrocytes in the growth plate, and decreased levels of calcium, phosphate, and vitamin D3 (Ref).
Risk factors:
Longitudinal growth:
• Younger age at diagnosis of CML (Ref)
• Initiation during prepubertal age (eg, girls ≤9 years, boys ≤11 years) (Ref)
• Higher trough plasma levels of imatinib (Ref)
Body weight growth:
• Age <9 years at diagnosis of CML (Ref)
Severe (grades 3 and 4) and fatal hemorrhage have been reported with use of imatinib for treatment of chronic myeloid leukemia (CML), acute lymphoblastic leukemia, and gastrointestinal stromal tumor (GIST) (Ref). Common sites of bleeding include gastrointestinal hemorrhage, subdural hematoma and cerebral hemorrhage, and tumor hemorrhage in GIST tumors (Ref). Cases of gastric antral vascular ectasia have been reported during treatment for GIST and CML, usually leading to permanent discontinuation (Ref).
Mechanism: Not clearly established; may be related to pharmacological action. In addition to suppression of hematopoiesis by kinase inhibition, imatinib may impair platelet aggregation (Ref). In GIST, gastrointestinal and/or tumor hemorrhage may be related to imatinib-induced tumor necrosis (Ref).
Onset: Varied; median time to onset of GI bleeding in a CML population was 33 days (interquartile range: 13 days to >4 months) (Ref).
Hepatotoxicity, including fatal acute hepatic failure, has been reported with imatinib during treatment of chronic myeloid leukemia, acute lymphoblastic leukemia, and gastrointestinal stromal tumors (Ref). Normalization of liver function tests occurred at a median of 7 weeks (range: 2 to 20 weeks) after discontinuation (Ref). Many cases report recurrent hepatotoxicity upon rechallenge (Ref). Severe or recurrent hepatotoxicity is a cause of permanent discontinuation (Ref).
Mechanism: Not clearly established; may be related to inhibition of glycolysis and mitochondrial toxicity from imatinib, ultimately leading to hepatocellular apoptosis (Ref). The most common histopathology finding from cases is hepatocellular necrosis (Ref).
Onset: Varied; reported 12 days to >5 months, with most cases presenting within the first few months of therapy (Ref). The median time was ~10 weeks in one retrospective review (Ref).
Risk factors:
• Preexisting liver disease (Ref)
• Hepatitis B virus carrier (Ref)
• Concurrent use of proton pump inhibitor (Ref)
• Body weight <55 kg (Ref)
Imatinib has been associated with nephrotoxicity, including acute kidney injury (AKI) and chronic renal failure (Ref). Rarely, AKI leads to treatment interruption for a median of 10 days (Ref). Imatinib has been shown to cause a decline from baseline in glomerular filtration rate (GFR) of ~2 to 3 mL/minute/1.73 m2 per year in patients with chronic myeloid leukemia (CML) (Ref).
Mechanism: Not clearly established; inhibition of platelet-derived growth factor receptor (PDGFR) may impede PDGFR-mediated repair mechanisms in the renal tubules resulting in acute tubular necrosis (Ref). Alternatively, AKI may be related to development of tumor lysis syndrome, which has been noted with imatinib for the treatment of advanced phases of CML and acute lymphoblastic leukemia (Ref).
Onset:
AKI: Intermediate; median in CML population 9 days (range: 4 to 84 days) (Ref)
Chronic kidney disease: Delayed; median in CML 12 months (range: 3 to >9 years) (Ref).
Risk factors:
• Development of chronic kidney disease: Older age (Ref)
• Concurrent hypertension (Ref)
• Concurrent diabetes mellitus (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise specified.
>10%:
Cardiovascular: Chest pain (7% to 11%), edema (11% to 86%; severe edema: 2% to 6%) (table 1) , peripheral edema (20% to 41%) (table 2)
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Comments |
---|---|---|---|---|---|---|
20% |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
36 months |
11% |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
12 months |
Severe: 2% to 6% |
N/A |
N/A |
Chronic myeloid leukemia |
N/A |
N/A |
N/A |
74% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
Superficial edema |
67% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
Superficial edema |
66% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
Superficial edema |
60% |
Interferon-alpha + Ara−C: 10% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Superficial edema |
Severe: 2% |
N/A |
N/A |
Newly diagnosed chronic myeloid leukemia |
N/A |
N/A |
N/A |
86% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
77% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
41% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
33% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
27% |
N/A |
15% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
20% |
Nilotinib: 9% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
Dermatologic: Alopecia (7% to 15%), dermatitis (29% to 39%), diaphoresis (9% to 13%), exfoliation of skin (≤50%), night sweats (13% to 17%), pruritus (7% to 26%), skin rash (9% to 50%) (table 3)
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
26% |
N/A |
13% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
Described as "rash (exfoliative)" |
9% |
N/A |
5% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
47% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
47% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
36% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
40% |
Interferon-alpha + Ara−C: 26% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
Described as "rash and related terms" |
19% |
Nilotinib: 38% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
50% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
Described as "rash/desquamation" |
38% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
Described as "rash/desquamation" |
Endocrine & metabolic: Fluid retention (62% to 76%; can be severe) (table 4) , hypoalbuminemia (12% to 21%), hypokalemia (6% to 13%), increased lactate dehydrogenase (43% to 60%), weight gain (5% to 32%)
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
---|---|---|---|---|---|
76% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
69% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
72% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
62% |
Interferon-alpha + Ara−C: 11% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Gastrointestinal: Abdominal distension (7% to 19%), abdominal pain (3% to 57%; including abdominal cramps) (table 5) , anorexia (7% to 36%), constipation (8% to 16%), diarrhea (43% to 59%; grades 3/4: 0.5% to 5%) (table 6) , dysgeusia (7% to 13%), dyspepsia (≤27%), flatulence (10% to 25%), heartburn (≤11%), nausea (41% to 73%; grades 3/4: 0.5% to 5%) (table 7) , upper abdominal pain (14%), vomiting (23% to 58%; grades 3/4: ≤4%) (table 8)
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
21% |
N/A |
22% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
8% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
3% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
33% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
32% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
30% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
37% |
Interferon-alpha + Ara−C: 26% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
12% |
Nilotinib: 15% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
57% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
Described as "abdominal pain/cramping" |
55% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
Described as "abdominal pain/cramping" |
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
All grades: 59% |
N/A |
All grades: 29% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
All grades: 54% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
All grades: 44% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
Grades ≥3: 3% |
N/A |
Grades ≥3: 1% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
Grades ≥3: 2% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
Grades ≥3: 0.5% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
All grades: 57% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
Grades 3/4: 5% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
All grades: 48% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
Grades 3/4: 3% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
All grades: 43% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
Grades 3/4: 4% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
All grades: 45% |
Interferon-alpha + Ara−C (all grades): 43% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
Grades 3/4: 3% |
Interferon-alpha + Ara−C (grades 3/4): 3% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
All grades: 46% |
Nilotinib (all grades): 19% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
Grades 3/4: 4% |
Nilotinib (grades 3/4): 1% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
All grades: 58% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
N/A |
All grades: 56% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
N/A |
Grades ≥3: 9% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
N/A |
Grades ≥3: 8% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
N/A |
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
All grades: 53% |
N/A |
All grades: 28% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
All grades: 51% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
All grades: 45% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
Grades ≥3: 2% |
N/A |
Grades ≥3: 1% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
Grades ≥3: 2% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
Grades ≥3: 0.5% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
All grades: 73% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
Grades 3/4: 5% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
All grades: 63% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
Grades 3/4: 3% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
All grades: 71% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
Grades 3/4: 5% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
All grades: 50% |
Interferon-alpha + Ara−C (all grades): 62% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
Grades 3/4: 1% |
Interferon-alpha + Ara−C (grades 3/4): 5% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
All grades: 41% |
Nilotinib (all grades): 22% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
Grades 3/4: 2% |
Nilotinib (grades 3/4): 2% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
All grades: 65% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
N/A |
All grades: 58% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
N/A |
Grades ≥3: 9% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
N/A |
Grades ≥3: 8% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
N/A |
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
All grades: 26% |
N/A |
All grades: 14% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
All grades: 22% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
All grades: 11% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
Grades ≥3: 2% |
N/A |
Grades ≥3: 0.6% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
Grades ≥3: 1% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
Grades ≥3: 0.5% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
All grades: 58% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
Grades 3/4: 3% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
N/A |
All grades: 36% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
Grades 3/4: 2% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
N/A |
All grades: 54% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
Grades 3/4: 4% |
N/A |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
N/A |
All grades: 23% |
Interferon-alpha + Ara−C (all grades): 28% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
Grades 3/4: 2% |
Interferon-alpha + Ara−C (grades 3/4): 3% |
N/A |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
N/A |
All grades: 27% |
Nilotinib (all grades): 15% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
Grades 3/4: <1% |
Nilotinib (grades 3/4): <1% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
All grades: 41% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
N/A |
All grades: 37% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
N/A |
Grades ≥3: 9% |
N/A |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
N/A |
Grades ≥3: 8% |
N/A |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
N/A |
Hematologic & oncologic: Anemia (32% to 35%; grades 3/4: 1% to 42%) (table 9) , granulocytopenia (≤16%), hemorrhage (3% to 53%; grades 3/4: 2% to 19%) (table 10) , hypoproteinemia (24% to 32%), leukopenia (5% to 20%; grades 3/4: <1%), neutropenia (≤16%; grades 3/4: 3% to 48%) (table 11) , thrombocytopenia (grades 3/4: ≤33%) (table 12)
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
---|---|---|---|---|---|
Grade 3: 34% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
Grade 4: 7% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
Grade 3: 6% |
N/A |
400 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
Grade 4: 1% |
N/A |
400 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
Grade 3: 42% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
Grade 4: 11% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
Grade 3: 3% |
Interferon-alpha + Ara−C (grade 3): 4% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Grade 4: 1% |
Interferon-alpha + Ara−C (grade 4): 0.2% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Grades 3/4: 6% |
Nilotinib (grades 3/4): 4% |
400 mg daily |
Newly diagnosed chronic myeloid leukemia |
280 |
279 |
All grades: 35% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
All grades: 32% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
Grade 3: 8% |
N/A |
600 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
74 |
N/A |
Grades ≥3: 6% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
Grades ≥3: 5% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
Grade 3: 3% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
73 |
N/A |
Grade 4: 1% |
N/A |
600 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
74 |
N/A |
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Comments |
---|---|---|---|---|---|---|
All grades: 7% |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
36 months |
All grades: 3% |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
12 months |
All grades: 49% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
Grades 3/4: 11% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
All grades: 30% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
Grades 3/4: 2% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
All grades: 53% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
Grades 3/4: 19% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
All grades: 29% |
Interferon-alpha + Ara−C (all grades): 21% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
Grades 3/4: 2% |
Interferon-alpha + Ara−C (grades 3/4): 2% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
All grades: 13% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
All grades: 12% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
Grades ≥3: 7% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
N/A |
Grades ≥3: 6% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
N/A |
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Comments |
---|---|---|---|---|---|---|
Grade 4: 36% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
Grade 3: 23% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
N/A |
Grade 3: 27% |
N/A |
400 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
Grade 4: 9% |
N/A |
400 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
N/A |
Grade 4: 48% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
Grade 3: 16% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
N/A |
Grade 3: 13% |
Interferon-alpha + Ara−C (grade 3): 21% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
Grade 4: 4% |
Interferon-alpha + Ara−C (grade 4): 5% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
N/A |
Grades 3/4: 22% |
Nilotinib (grades 3/4): 12% |
400 mg daily |
Newly diagnosed chronic myeloid leukemia |
280 |
279 |
N/A |
All grades: 16% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
Described as "neutropenia/granulocytopenia" |
All grades: 12% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
Described as "neutropenia/granulocytopenia" |
Grade 3: 8% |
N/A |
600 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
74 |
N/A |
N/A |
Grade 3: 7% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
73 |
N/A |
N/A |
Grades ≥3: 4% |
N/A |
800 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
822 |
N/A |
Described as "neutropenia/granulocytopenia" |
Grades ≥3: 3% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
818 |
N/A |
Described as "neutropenia/granulocytopenia" |
Grade 4: 3% |
N/A |
400 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
73 |
N/A |
N/A |
Grade 4: 3% |
N/A |
600 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
74 |
N/A |
N/A |
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
---|---|---|---|---|---|
Grade 3: 31% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
Grade 4: 13% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
Grade 3: 21% |
N/A |
400 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
Grade 4: <1% |
N/A |
400 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
Grade 4: 33% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
Grade 3: 30% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
Grade 3: 9% |
Interferon-alpha + Ara−C (grade 3): 16% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Grade 4: 0.4% |
Interferon-alpha + Ara−C (grade 4): 0.6% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Grades 3/4: 9% |
Nilotinib (grades 3/4): 10% |
400 mg daily |
Newly diagnosed chronic myeloid leukemia |
280 |
279 |
Grade 3: 1% |
N/A |
600 mg daily |
Unresectable and/or malignant metastatic gastrointestinal stromal tumors |
74 |
N/A |
Hepatic: Hepatotoxicity (6% to 12%), increased serum alanine aminotransferase (17% to 34%), increased serum alkaline phosphatase (11% to 17%), increased serum aspartate aminotransferase (12% to 38%), increased serum bilirubin (11% to 13%)
Hypersensitivity: Facial edema (7% to 14%) (table 13)
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|---|
14% |
Nilotinib: <1% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
7% |
N/A |
1% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
Infection: Infection (14% to 28%), influenza (≤14%)
Nervous system: Anxiety (8% to 12%), asthenia (≤75%), chills (≤11%), depression (3% to 15%), dizziness (5% to 19%), fatigue (≤75%), headache (8% to 37%), insomnia (9% to 15%), lethargy (≤75%), malaise (≤75%), pain (20% to 46%), paresthesia (5% to 12%), rigors (≤12%)
Neuromuscular & skeletal: Arthralgia (9% to 40%), back pain (17%), limb pain (16%), muscle cramps (28% to 62%), muscle spasm (16% to 49%), musculoskeletal pain (adults: 38% to 49%; children: 21%), myalgia (9% to 32%), ostealgia (11%)
Ophthalmic: Blurred vision (5% to 11%), eyelid edema (19%), increased lacrimation (10% to 18%), periorbital edema (15% to 74%) (table 14)
Drug (Imatinib) |
Comparator |
Placebo |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|---|
74% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
198 |
N/A |
N/A |
36 months |
59% |
N/A |
N/A |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
194 |
N/A |
N/A |
12 months |
47% |
N/A |
15% |
400 mg daily |
Adjuvant treatment of gastrointestinal stromal tumors |
337 |
N/A |
345 |
N/A |
15% |
Nilotinib: <1% |
N/A |
400 mg daily |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
280 |
279 |
N/A |
N/A |
Renal: Increased serum creatinine (10% to 44%), nephrotoxicity (14%; including genitourinary)
Respiratory: Cough (13% to 27%), dyspnea (6% to 21%), nasopharyngitis (1% to 31%), pharyngitis (≤15%), pharyngolaryngeal pain (18%), pneumonia (4% to 13%), sinusitis (4% to 11%), upper respiratory tract infection (3% to 21%)
Miscellaneous: Fever (6% to 41%)
1% to 10%:
Cardiovascular: Cold extremity (≤1%), flushing, heart failure (0.7% to 1%) (table 15) , hypertension (4%), hypotension (≤1%), palpitations (5%), pericardial effusion (≤6%), Raynaud disease (≤1%), syncope (≤1%), tachycardia (≤1%)
Drug (Imatinib) |
Comparator |
Indication |
Comments |
---|---|---|---|
1% |
Nilotinib: 2% |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
N/A |
0.7% |
Interferon-alpha + Ara−C: 0.9% |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
Severe cardiac failure and left ventricular dysfunction |
Dermatologic: Bullous rash (≤1%), cellulitis (≤1%), cheilitis (≤1%), ecchymoses (≤1%), erythema multiforme (≤1%), erythema of skin, exfoliative dermatitis (≤1%), folliculitis (≤1%), hyperpigmentation (≤1%), hypopigmentation (≤1%), hypotrichosis (≤1%), nail disease, onychoclasis (≤1%), psoriasis (≤1%), pustular rash (≤1%), skin photosensitivity (4% to 7%), urticaria (≤1%), xeroderma (6% to 7%)
Endocrine & metabolic: Anasarca, decreased libido (≤1%), dehydration (≤1%), gynecomastia (≤1%), heavy menstrual bleeding (≤1%), hypercalcemia (≤1%), hyperglycemia (≤1%), hyperkalemia (≤1%), hyperthyroidism (≤1%), hyperuricemia (≤1%), hypocalcemia (6%), hypomagnesemia (≤1%), hyponatremia (≤1%), hypophosphatemia (grade 3/4: 10%), hypothyroidism (≤1%), menstrual disease (≤1%), weight loss (10%)
Gastrointestinal: Decreased appetite (10%), dysphagia (≤1%), eructation (≤1%), esophagitis (≤1%), gastric ulcer (≤1%), gastritis, gastroenteritis (10%), gastroesophageal reflux disease, gastrointestinal hemorrhage (2% to 8%; including gastric antral vascular ectasia) (table 16) , hematemesis (≤1%), increased appetite (≤1%), increased serum amylase, increased serum lipase (grades 3/4: 4%), melena (≤1%), oral mucosa ulcer (≤1%), pancreatitis (≤1%), stomatitis (≤10%), xerostomia
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
---|---|---|---|---|---|
6% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
2% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
8% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
2% |
Interferon-alpha + Ara−C: 1% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Genitourinary: Breast hypertrophy (≤1%), erectile dysfunction (≤1%), hematuria (≤1%), nipple pain (≤1%), scrotal edema (≤1%), sexual disorder (≤1%), urinary frequency (≤1%), urinary tract infection (≤1%)
Hematologic & oncologic: Bone marrow depression (≤1%), bruise (≤1%), eosinophilia, febrile neutropenia, hematoma (≤1%), lymphadenopathy (≤1%), lymphocytopenia (6% to 10%), nonthrombocytopenic purpura (≤1%), pancytopenia, petechia (≤1%), purpuric disease, thrombocytosis (≤1%)
Hepatic: Ascites (≤6%), hepatitis (≤1%), jaundice (≤1%)
Infection: Herpes simplex infection (≤1%), herpes zoster infection (≤1%), sepsis (≤1%)
Nervous system: Drowsiness (≤1%), hypoesthesia, intracranial hemorrhage (≤9%) (table 17) , memory impairment (≤1%), migraine (≤1%), myasthenia (≤1%), peripheral neuropathy (≤1%), restless leg syndrome (≤1%), sciatica (≤1%), subdural hematoma (≤1%), tremor (≤1%), vertigo (≤1%)
Drug (Imatinib) |
Comparator |
Dose |
Indication |
Number of Patients (Imatinib) |
Number of Patients (Comparator) |
---|---|---|---|---|---|
3% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Accelerated phase |
235 |
N/A |
2% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Chronic phase, interferon-alpha failure |
532 |
N/A |
9% |
N/A |
400 mg to 600 mg daily |
Chronic myeloid leukemia: Myeloid blast crisis |
260 |
N/A |
0.2% |
Interferon-alpha + Ara−C: 0.4% |
400 mg to 800 mg daily |
Newly diagnosed chronic myeloid leukemia |
551 |
533 |
Neuromuscular & skeletal: Arthritis (≤1%), gout (≤1%), increased creatine phosphokinase in blood specimen, joint stiffness (≤1%), joint swelling, muscle rigidity (≤1%), panniculitis (≤1%)
Ophthalmic: Blepharitis (≤1%), cataract (≤1%), conjunctival hemorrhage, conjunctivitis (5% to 8%), dry eye syndrome, eye irritation (≤1%), eye pain (≤1%), macular edema (≤1%), retinal hemorrhage (≤1%), sclera disease (hemorrhage: ≤1%)
Otic: Hearing loss (≤1%), tinnitus (≤1%)
Renal: Acute kidney injury (≤1%), renal pain (≤1%)
Respiratory: Epistaxis, oropharyngeal pain (6%), pleural effusion (≤6%), pulmonary edema (≤6%)
<1%:
Cardiovascular: Acute myocardial infarction, angina pectoris, atrial fibrillation, cardiac arrhythmia, left ventricular dysfunction (table 18)
Drug (Imatinib) |
Comparator |
Indication |
Comments |
---|---|---|---|
0.7% |
Interferon-alpha + Ara−C: 0.9% |
Newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia-chronic phase |
Severe cardiac failure and left ventricular dysfunction |
Dermatologic: Acute generalized exanthematous pustulosis, nail discoloration, Stevens-Johnson syndrome, Sweet syndrome, vesicular eruption
Gastrointestinal: Colitis, gastrointestinal obstruction, inflammatory bowel disease
Hematologic & oncologic: Aplastic anemia, hemolytic anemia
Hepatic: Hepatic failure, hepatic necrosis
Hypersensitivity: Angioedema, hypersensitivity angiitis
Infection: Fungal infection
Nervous system: Confusion, increased intracranial pressure, seizure
Ophthalmic: Glaucoma, optic neuritis, papilledema
Respiratory: Interstitial pneumonitis, pleuritic chest pain, pulmonary fibrosis, pulmonary hemorrhage, pulmonary hypertension
Postmarketing:
Cardiovascular: Cardiac tamponade (Ref), cardiogenic shock, embolism, pericarditis, thrombosis
Dermatologic: Lichen planus (Ref), lichenoid eruption (keratosis) (Ref), palmar-plantar erythrodysesthesia, pemphigus, pityriasis rosea (Ref), psoriasiform eruption (Ref), skin depigmentation (Ref), toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Growth suppression, pseudoporphyria (Ref)
Gastrointestinal: Diverticulitis of the gastrointestinal tract, gastrointestinal irritation, gastrointestinal perforation (Ref)
Genitourinary: Ovarian cyst (hemorrhagic), ruptured corpus luteal cyst
Hematologic & oncologic: Thrombotic microangiopathy (Ref), tumor hemorrhage (Ref), tumor lysis syndrome (Ref)
Hypersensitivity: Anaphylactic shock
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Ref)
Infection: Reactivation of HBV (Ref)
Nervous system: Brain edema, cerebral hemorrhage (Ref)
Neuromuscular & skeletal: Linear skeletal growth rate below expectation (children) (Ref), myopathy, osteonecrosis (including ear canal, hip, jaw) (Ref), rhabdomyolysis (Ref)
Ophthalmic: Vitreous hemorrhage (Ref)
Renal: Chronic renal failure (Ref)
Respiratory: Acute respiratory failure, interstitial lung disease (Ref), lower respiratory tract infection
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to imatinib or any component of the formulation.
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 2 to 4 weeks. 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). Cardiac adverse events usually occur in patients with advanced age or comorbidities. With initiation of imatinib treatment, cardiogenic shock and/or LVD have been reported in patients with hypereosinophilic syndrome (HES) and cardiac involvement (reversible with systemic steroids, circulatory support and temporary cessation of imatinib). Echocardiogram and serum troponin monitoring may be considered in patients with HES/chronic eosinophilic leukemia (CEL) and in patients with myelodysplastic/myeloproliferative (MDS/MPD) disease or aggressive systemic mastocytosis associated with high eosinophil levels. 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. In a scientific statement from the American Heart Association, imatinib has been determined to be an agent that may either cause direct myocardial toxicity (rare) or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).
• 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. DRESS 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: Imatinib is commonly associated with fluid retention, weight gain, and edema (risk increases with higher doses and age >65 years); may be occasionally serious and lead to significant complications, including pleural effusion, pericardial effusion, pulmonary edema, and ascites. Rapid unexpected weight gain should be evaluated and managed appropriately. 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: May cause GI 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 (Alshehry 2014; Saad Aldin 2012).
• Hepatotoxicity: Hepatotoxicity may occur; fatal hepatic failure and severe hepatic injury requiring liver transplantation have been reported with both short- and long-term use. Transaminase and bilirubin elevations, and acute liver failure have been observed with imatinib in combination with chemotherapy.
• Nephrotoxicity: Imatinib is associated with a decline in renal function; may be associated with duration of therapy. The median estimated GFR declined from 85 mL/minute/1.73 m2 at baseline to 75 mL/minute/1.73 m2 at 12 months and to 69 mL/minute/1.73 m2 at 60 months (in patients with newly diagnosed chronic myeloid leukemia and malignant GIST). Patients with risk factors for renal dysfunction (eg, preexisting renal impairment, diabetes mellitus, hypertension, congestive heart failure) may be at higher risk for nephrotoxicity.
• 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. Correct clinically significant dehydration and treat high uric acid levels prior to initiation of imatinib.
Disease-related concerns:
• 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.
• 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).
Special populations:
• Older patients: The incidence of edema was increased with age ≥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.
Dosage form specific issues:
• Oral liquid concentrations: Commercially available Imkeldi oral solution is 80 mg/mL; extemporaneously compounded oral suspension concentration may be different (40 mg/mL); use caution; ensure all doses are in mg of imatinib.
Other warnings/precautions:
• Appropriate use: Determine PDGFRb gene rearrangements status (for MDS/MPD), D816V c-kit mutation status (for aggressive systemic mastocytosis [ASM]), Philadelphia chromosome status for acute lymphoblastic leukemia and chronic myeloid leukemia, Kit (CD117)-positivity for GIST, and FIP1L1–platelet-derived growth factor (PDGF) receptor status for HES or CEL prior to initiating treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral, as mesylate:
Imkeldi: 80 mg/mL (140 mL) [contains sodium benzoate; strawberry flavor]
Tablet, Oral, as mesylate:
Gleevec: 100 mg, 400 mg [scored]
Generic: 100 mg, 400 mg
Yes
Tablets (Gleevec Oral)
100 mg (per each): $112.37
400 mg (per each): $404.90
Tablets (Imatinib Mesylate Oral)
100 mg (per each): $1.47 - $106.75
400 mg (per each): $5.20 - $394.66
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as mesylate:
Gleevec: 100 mg, 400 mg
Generic: 100 mg, 400 mg
Imatinib is associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting (Ref).
Doses ≤600 mg may be given once daily; 800 mg dose should be administered as 400 mg twice daily.
Oral solution: Administer with a meal and a large glass of water to minimize GI irritation. Administer with an accurate measuring device (press-in bottle adapter and oral syringe); do not use a household teaspoon (overdosage may occur). Dose may be rounded to the nearest graduation mark on the oral syringe, if needed.
Tablets: Administer with a meal and a large glass of water to minimize GI irritation. For daily dosing ≥800 mg, the 400 mg tablets should be used in order to reduce iron exposure. Do not crush tablets. 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. If necessary, an oral suspension may be prepared using the tablets (see "Extemporaneously Prepared"). Avoid skin or mucous membrane contact with crushed tablets; if contact occurs, wash thoroughly. Avoid exposure to crushed tablets.
Note: Antiemetics may be recommended to prevent nausea and vomiting; imatinib doses >260 mg/m2/day are associated with a moderate emetic potential (Ref).
Oral: Administer with a meal and a large glass of water.
Oral solution: Administer with an accurate measuring device (calibrated oral syringe); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur). Disposable gloves should be worn when handling bottles containing imatinib oral solution and during administration. Wash hands with soap and water before and after contact with imatinib. With first use, insert a bottle adapter and keep in place. Dose should be rounded to the nearest measurable graduation mark on the oral syringe if necessary. Draw up the correct dose of medication, have patient sit up straight or stand, then insert tip of the syringe into patient's mouth toward the inside of the cheek, depress plunger, and administer dose; then have patient eat a meal and drink a large glass of water (avoids stomach and intestine problems). After administration while continuing to wear gloves, clean oral syringe(s) with cold soapy water and rinse well; hold syringe under water and move the plunger up and down several times to ensure inside clean; shake off excess water and dry the oral plunger and syringe with a clean paper towel. Ensure the provided child-resistant cap is secured tightly on the bottle for storage.
Tablets: Swallow whole; do not crush tablets; avoid skin or mucous membrane contact with crushed tablets; if contact occurs, wash thoroughly.
Oral administration in liquid: Place tablet(s) in water or apple juice (using ~50 mL for 100 mg tablet, ~200 mL for 400 mg tablet); allow tablet to disperse; stir until tablet dissolves and administer immediately.
Missed dose: Skip missed dose. Administer the next scheduled dose at the regular time. Do not double the dose to make up for a skipped dose.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
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 in adults without D816V mutation or with c-kit mutational status unknown. c-kit
Chronic myeloid leukemia:
Treatment of newly diagnosed Ph+ chronic myeloid leukemia (CML) in chronic phase 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 of unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans 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 in adults.
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 receptor (PDGFR) 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-PDGFR alpha fusion kinase negative or unknown.
Myelodysplastic/Myeloproliferative diseases: Treatment of myelodysplastic /myeloproliferative diseases associated with PDGFR gene rearrangements in adults.
Chordoma, progressive, advanced, or metastatic expressing PDGFR beta and/or PDGF beta; Chronic myeloid leukemia, post-allogeneic hematopoietic cell transplantation; Desmoid tumor, locally advanced or progressive; Melanoma, advanced or metastatic, c-kit mutated tumors
Imatinib may be confused with asciminib, avapritinib, axitinib, bosutinib, cabozantinib, capmatinib, dasatinib, enasidenib, erlotinib, fostamatinib, gefitinib, ibrutinib, idelalisib, infigratinib, ivosidenib, lapatinib, neratinib, nilotinib, PONATinib, regorafenib, ripretinib, SUNItinib
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP1A2 (Minor), CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP2D6 (Minor), CYP3A4 (Major), MATE1/2-K, OCT1, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Moderate);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider Therapy Modification
Acetaminophen: May increase hepatotoxic effects of Imatinib. Risk C: Monitor
Acrivastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acrivastine. Risk C: Monitor
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider Therapy Modification
Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alfuzosin. Risk C: Monitor
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alitretinoin (Systemic). Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider Therapy Modification
Amiodarone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Amiodarone. Risk C: Monitor
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of AmLODIPine. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Apixaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Apixaban. Risk C: Monitor
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
Artesunate: Imatinib may increase active metabolite exposure of Artesunate. Risk C: Monitor
Asciminib: Imatinib may increase serum concentration of Asciminib. Risk C: Monitor
Atazanavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atazanavir. Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atogepant. Risk C: Monitor
Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atorvastatin. Risk C: Monitor
Avacopan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avacopan. Risk C: Monitor
Avanafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avanafil. Management: The maximum avanafil 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 (eg, hypotension, syncope, priapism). Risk D: Consider Therapy Modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider Therapy Modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Axitinib. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Barnidipine. Risk C: Monitor
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Bedaquiline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bedaquiline. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Bedaquiline. Risk C: Monitor
Benidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benidipine. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bosutinib. Risk X: Avoid
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase 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. Risk C: Monitor
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider Therapy Modification
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase 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. Risk D: Consider Therapy Modification
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider Therapy Modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cabozantinib. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider Therapy Modification
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Cariprazine. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a moderate CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification
Ceritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ceritinib. Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Cisapride: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cisapride. Management: Consider alternatives to this combination. Prescribing information for some moderate CYP3A4 inhibitors state coadministration with cisapride is contraindicated, while some others recommend monitoring and dose titration. Risk D: Consider Therapy Modification
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of CloZAPine. Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider Therapy Modification
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Codeine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Conivaptan. Risk C: Monitor
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Copanlisib. Risk C: Monitor
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Crizotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Crizotinib. Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive): Imatinib may increase serum concentration of CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Imatinib. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Imatinib. Management: Avoid use of imatinib and strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Doses up to 1200 mg/day (600 mg twice daily) have been used. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Imatinib. Risk C: Monitor
Dabrafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dabrafenib. Risk C: Monitor
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider Therapy Modification
Daridorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Darifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Darifenacin. Risk C: Monitor
Dasatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dasatinib. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Delamanid: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Delamanid. Risk C: Monitor
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
DexAMETHasone (Systemic): May decrease 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. Risk D: Consider Therapy Modification
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dienogest. Risk C: Monitor
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DilTIAZem. Risk C: Monitor
Disopyramide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Disopyramide. Risk C: Monitor
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOCEtaxel. Risk C: Monitor
Dofetilide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dofetilide. Risk C: Monitor
Domperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Domperidone. Risk X: Avoid
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dronedarone. Risk C: Monitor
Ebastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ebastine. Risk C: Monitor
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider Therapy Modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider Therapy Modification
Encorafenib: May decrease serum concentration of Imatinib. Imatinib may increase serum concentration of Encorafenib. Management: Avoid this combination when possible. If combined, decrease the encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Risk D: Consider Therapy Modification
Ensartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors if possible. If needed, reduce entrectinib dose to 50 mg/day if starting dose 200 mg; to 100 mg/day if starting dose 300 mg; to 200 mg if starting dose 400 mg or 600 mg. Risk D: Consider Therapy Modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider Therapy Modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erlotinib. Risk C: Monitor
Erythromycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erythromycin (Systemic). Risk C: Monitor
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eszopiclone. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etravirine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Etravirine. Risk C: Monitor
Everolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Everolimus. Risk C: Monitor
Fedratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fedratinib. Risk C: Monitor
Felodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Felodipine. Risk C: Monitor
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider Therapy Modification
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Nasal). Risk C: Monitor
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gemfibrozil: May decrease serum concentration of Imatinib. Gemfibrozil may decrease active metabolite exposure of Imatinib. Specifically N-desmethylimatinib concentrations may be decreased. Risk C: Monitor
Gepirone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider Therapy Modification
Gepotidacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepotidacin. Risk C: Monitor
Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gilteritinib. Risk C: Monitor
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Glasdegib. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Imatinib. Risk X: Avoid
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider Therapy Modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Halofantrine. Risk C: Monitor
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of HYDROcodone. Risk C: Monitor
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider Therapy Modification
Ibuprofen: May decrease 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. Risk D: Consider Therapy Modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Iloperidone. Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor
Isradipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Isradipine. Risk C: Monitor
Itraconazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Itraconazole. Risk C: Monitor
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider Therapy Modification
Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities, including QTc prolongation. Risk D: Consider Therapy Modification
Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Leniolisib. Risk C: Monitor
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lercanidipine. Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomilnacipran. Risk C: Monitor
Levothyroxine: Imatinib may decrease serum concentration of Levothyroxine. Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lidocaine (Systemic). CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. Risk C: Monitor
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lomitapide. Risk X: Avoid
Lonafarnib: Imatinib may increase serum concentration of Lonafarnib. Lonafarnib may increase serum concentration of Imatinib. Risk C: Monitor
Lopinavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lopinavir. Risk C: Monitor
Lovastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Macitentan. Risk C: Monitor
Manidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Manidipine. Risk C: Monitor
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Maraviroc. Risk C: Monitor
Mavacamten: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor, and reduce the mavacamten dose by one dose level if initiating a moderate CYP3A4 inhibitor. Avoid initiating moderate CYP3A4 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification
Mavorixafor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavorixafor. Risk C: Monitor
Meperidine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Meperidine. Risk C: Monitor
Methadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methadone. Management: If coadministration with moderate CYP3A4 inhibitors is necessary, consider methadone dose reductions until stable effects are achieved. Monitor patients closely for respiratory depression and sedation. Risk D: Consider Therapy Modification
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Methysergide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methysergide. Risk X: Avoid
Midazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider Therapy Modification
Midostaurin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Midostaurin. Risk C: Monitor
MiFEPRIStone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MiFEPRIStone. Risk C: Monitor
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mirodenafil. Risk C: Monitor
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider Therapy Modification
Mobocertinib: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mobocertinib. Management: Avoid use of moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider Therapy Modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Neratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Neratinib. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NiMODipine. Risk C: Monitor
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nitrendipine. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider Therapy Modification
Oliceridine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider Therapy Modification
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pacritinib. Risk C: Monitor
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palbociclib. Risk C: Monitor
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider Therapy Modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Panobinostat. Risk C: Monitor
PAZOPanib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PAZOPanib. Risk C: Monitor
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider Therapy Modification
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimavanserin. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pimozide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimozide. Risk X: Avoid
Piperaquine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Piperaquine. Risk C: Monitor
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pirtobrutinib. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
PONATinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PONATinib. Risk C: Monitor
Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Prazepam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Praziquantel. Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Propacetamol: May increase hepatotoxic effects of Imatinib. Risk C: Monitor
QUEtiapine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of QUEtiapine. Risk C: Monitor
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor
QuiNIDine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of QuiNIDine. Risk C: Monitor
QuiNINE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of QuiNINE. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider Therapy Modification
Red Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Red Yeast Rice. Risk C: Monitor
Regorafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Regorafenib. Risk C: Monitor
Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Repotrectinib. Risk X: Avoid
Ribociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ribociclib. Risk C: Monitor
Rifabutin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rifabutin. Risk C: Monitor
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rupatadine. Risk C: Monitor
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Salmeterol. Risk C: Monitor
Saquinavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Saquinavir. Risk C: Monitor
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SAXagliptin. Risk C: Monitor
Selpercatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 80 mg twice/day, or from 160 mg twice/day to 120 mg twice/day. Risk D: Consider Therapy Modification
Selumetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider Therapy Modification
Sertindole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sildenafil. Risk C: Monitor
Silodosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Silodosin. Risk C: Monitor
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase 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). Risk D: Consider Therapy Modification
Sparsentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sparsentan. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUFentanil. Risk C: Monitor
SUNItinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUNItinib. Risk C: Monitor
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider Therapy Modification
Suzetrigine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suzetrigine. Management: Reduce suzetrigine dose as follows: initiate with 100 mg for 1 dose; then 12 hours after first dose, give 50 mg every 12 hours for doses 2, 3, and 4; then 50 mg every 24 hours for dose 5 and thereafter. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tadalafil. Risk C: Monitor
Tafamidis: May increase serum concentration of Imatinib. Risk C: Monitor
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider Therapy Modification
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider Therapy Modification
Thiotepa: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ticagrelor. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tilidine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tilidine. Risk C: Monitor
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolterodine. Risk C: Monitor
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider Therapy Modification
Toremifene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Toremifene. Risk C: Monitor
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Trabectedin. Risk C: Monitor
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Udenafil. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vamorolone. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification
Vemurafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vemurafenib. Risk C: Monitor
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Verapamil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Verapamil. Risk C: Monitor
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vilazodone. Risk C: Monitor
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinBLAStine. Risk C: Monitor
VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinCRIStine. Risk C: Monitor
Vindesine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Vinflunine. Risk C: Monitor
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vorapaxar. Risk C: Monitor
Warfarin: Imatinib may increase anticoagulant effects of Warfarin. Imatinib may decrease metabolism of Warfarin. Management: Consider using low-molecular-weight heparin or heparin instead of warfarin. If warfarin and imatinib must be coadministrered, increase monitoring of INR and for signs/symptoms of bleeding. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zopiclone. Risk C: Monitor
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zuranolone. Risk C: Monitor
Food may reduce GI irritation. Grapefruit juice may increase imatinib plasma concentration. Management: Take with a meal and a large glass of water. Avoid grapefruit juice. Maintain adequate hydration, unless instructed to restrict fluid intake.
Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use highly effective contraception (methods with <1% pregnancy rates) during imatinib treatment and for 14 days after the last imatinib dose.
Changes in menstrual patterns have been reported with tyrosine kinase inhibitor (TKI) therapy (Yu 2019).
Based on the mechanism of action, TKIs have the potential to adversely affect fertility by acting on receptors in the ovaries or testis; primarily when administered prior to puberty in males. Although there are cases showing difficulty conceiving, successful pregnancies have also been reported. Fertility data related to long term TKI use are limited. Recommendations are available for fertility preservation prior to TKI treatment (ASCO [Oktay 2018]; Madabhavi 2019; Rambhatla 2021).
Patients planning to become pregnant but currently receiving a TKI should minimize the risk of first trimester exposure (Rambhatla 2021). Discontinuing TKI therapy for chronic myeloid leukemia (CML) can be considered if the patient is eligible for a tumor-free remission, allowing a washout period before attempting to conceive (Baccarani 2019; ELN [Hochhaus 2020]; Madabhavi 2019). Because the time to conception can be highly variable, treatment may also be discontinued at the first positive pregnancy test, prior to organogenesis in select patients (Abruzzese 2020).
Outcome data following male use of imatinib prior to conception is available (Rambhatla 2021; Szakács 2020). Based on available data, imatinib does not need to be stopped prior to conception in patients diagnosed with CML planning to father a child (Abruzzese 2020; Baccarani 2019; BSH [Smith 2020]; ELN [Hochhaus 2020]).
Imatinib crosses the placenta (Ali 2009; Burwick 2017; Chelysheva 2018b; Russell 2007) and can be detected in newborn urine (Burwick 2017).
Outcome data following maternal use of imatinib primarily for the treatment of chronic myeloid leukemia (CML) during pregnancy are available; adverse outcomes were reported in some cases, pregnancies without complications were also reported (Assi 2020; NTP 2013; Rambhatla 2021).
Treatment of CML in pregnant patients should be individualized based on gestational age, hematologic parameters, and clinical condition at presentation. If pregnancy is detected in the first trimester in patients already on a tyrosine kinase inhibitor (TKI), treatment should be discontinued as soon as pregnancy is confirmed. Treatments other than a TKI are recommended in pregnant patients not eligible for a tumor-free remission. If a TKI is needed, imatinib may be considered after the first trimester. Close maternal and fetal monitoring is recommended (Abruzzese 2020; BSH [Smith 2020]; ELN [Hochhaus 2020]; Madabhavi 2019).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).
Imatinib and its active metabolite are present in breast milk.
The presence of imatinib in breast milk has been evaluated in multiple case reports; concentrations are variable; when evaluated, metabolite concentrations were higher in breast milk than maternal serum (Ali 2009; Burwick 2017; Chelysheva 2018a; Gambacorti-Passerini 2007; Kronenberger 2009; Russell 2007; Terao 2021).
• Imatinib breast milk concentrations were evaluated in 2 lactating patients diagnosed with chronic myeloid leukemia (CML) prior to pregnancy who restarted imatinib treatment after discontinuing breastfeeding. Breast milk was sampled at specified intervals from 1 to 24 hours after the maternal dose. In the first case, pre-pregnancy imatinib 400 mg/day was restarted 4 months postpartum. The maximum concentration of imatinib in breast milk (1,402 ng/mL) occurred 4 hours after the maternal dose. A second patient restarted imatinib 600 mg/day 1 month postpartum; the maximum concentration in breast milk (1,411 ng/mL) occurred 6 hours after the maternal imatinib dose (Chelysheva 2018a). A higher breast milk concentration was observed in a patient who initiated imatinib 400 mg/day at 21 weeks gestation. Postpartum sampling was conducted at various times following administration; the highest observed breast milk concentration (2,623 ng/mL) occurred 10 hours after the maternal dose on day 14 postpartum (Ali 2009).
• Concentrations of imatinib and the active metabolite CGP74588 were evaluated in a patient who restarted imatinib at 400 mg/day immediately postpartum. The highest breast milk concentrations were observed when sampled 51 hours after treatment started (imatinib 1,153 ng/mL, CGP74588 1,024 ng/mL). In comparison, maternal serum concentrations at the same time were 2,010 ng/mL (imatinib) and 284 ng/mL (CGP74588). Steady state concentrations in breast milk occurred after ~2 days. The infant was not breastfed (Kronenberger 2009).
• Imatinib concentrations in the colostrum were evaluated in a patient treated with imatinib 400 mg/day from 28 weeks gestation through the first 5 days postpartum. Imatinib samples obtained on the fifth day after delivery were 1,916 ng/mL (maternal blood), 663 ng/mL (breast milk), and 27 ng/mL (infant blood). The infant was breastfed for the first 5 days after birth and no adverse events were reported. The presence of the active metabolite was not evaluated (Terao 2021).
• Breast milk concentrations of imatinib and CGP74588 were also evaluated in a patient 4 weeks postpartum. The patient was receiving imatinib 400 mg/day for CML; maternal serum and breast milk were sampled from 1 to 9 hours after the dose. The steady state concentrations in breast milk were 1,100 to 1,400 ng/mL (imatinib) and 800 ng/mL (CGP74588). Steady state maternal serum concentrations were 3,000 to 3,200 ng/mL (imatinib) and 800 to 1,100 ng/mL (CGP74588). Authors of the report suggest that up to 10% of a therapeutic maternal imatinib dose could potentially be received by a breastfed infant (Gambacorti-Passerini 2007).
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 month after the last imatinib dose. Patients diagnosed with CML requiring a tyrosine kinase inhibitor may consider short term breastfeeding for the first 2 to 5 days postpartum to provide the benefits of colostrum to the newborn prior to starting or restarting therapy (Abruzzese 2020; Madabhavi 2019).
Avoid grapefruit juice.
CBC (weekly for first month, biweekly for second month, then periodically thereafter as clinically indicated), liver function tests (transaminases, bilirubin, and alkaline phosphatase; 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). Evaluate pregnancy status prior to treatment in patients who could become pregnant. Monitor for fatigue, rapid weight gain, 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 to 3 months.
Monitor carefully for signs/symptoms of CHF in patients with at risk for cardiac failure or patients with preexisting cardiac disease. Monitor for signs/symptoms of GI irritation or perforation, dermatologic toxicities, and tumor lysis syndrome. Monitor adherence.
Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; repeat assessment every 3 months for the first year and then every 6 to 12 months thereafter (ASCO [Armenian 2017]; ESC [Lyon 2022]). ECG at baseline. Consider baseline echocardiography in all patients; repeat every 3 months for high- and very high-risk patients (ESC [Lyon 2022]).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Imatinib 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.
Absorption: Rapid.
Protein binding: Parent drug and metabolite: ~95% to albumin and alpha1-acid glycoprotein.
Metabolism: 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.
Bioavailability: 98%; may be decreased in patients who have had gastric surgery (eg, bypass, total or partial resection) (Liu 2011; Pavlovsky 2009; Yoo 2010).
Half-life elimination: Adults: Parent drug: ~18 hours; N-desmethyl metabolite: ~40 hours; Children: Parent drug: ~15 hours.
Time to peak: 2 to 4 hours.
Excretion: Feces (68% primarily as metabolites, 20% as unchanged drug); urine (13% primarily as metabolites, 5% as unchanged drug).
Clearance: Adults: 10 L/hour/m2 or 8 to 14 L/hour.
Altered kidney function: AUC increased 1.5- to 2-fold in patients with mild and moderate kidney impairment compared with patients with normal kidney function. Patients with severe kidney impairment experienced a 1.7-fold increase compared to patients with normal kidney function, although only two participants were included in the study (Gibbons 2008).
Hepatic function impairment: 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 55%, respectively, in patients with severe hepatic impairment as compared to patients with normal hepatic function. The mean Cmax of imatinib and its metabolite increased by ~63% and 56%, respectively, in patients with severe hepatic impairment as compared to patients with normal hepatic function.