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Imatinib: Drug information

Imatinib: Drug information
(For additional information see "Imatinib: Patient drug information" and see "Imatinib: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Gleevec
Brand Names: Canada
  • ACH-Imatinib;
  • APO-Imatinib;
  • Gleevec;
  • JAMP-Imatinib;
  • MINT-Imatinib;
  • NAT-Imatinib;
  • PMS-Imatinib;
  • TEVA-Imatinib
Pharmacologic Category
  • Antineoplastic Agent, BCR-ABL Tyrosine Kinase Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
Dosing: Adult

Note: Imatinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).

Acute lymphoblastic leukemia, Philadelphia chromosome-positive, newly diagnosed

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 (de Labarthe 2007; Tanguy-Schmidt 2013). 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) (de Labarthe 2007; Tanguy-Schmidt 2013). 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) (Chalandon 2015).

Cycle 2: Oral: 400 mg twice daily on days 1 to 14 (in combination with methotrexate, cytarabine, and growth factor support) (Chalandon 2015).

Depending on clinical response after cycle 2, patients could proceed to stem cell transplant. Refer to protocol for further information (Chalandon 2015).

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 (Thomas 2004).

NILG protocol 09/00: Note: Imatinib is administered in combination with chemotherapy; refer to protocol for further information, including maintenance imatinib (if applicable) (Bassan 2010).

Cycle 1: Oral: 600 mg once daily for 7 consecutive days, starting on day 15 of cycle 1 (Bassan 2010).

Cycles 2 to 8: Oral: 600 mg once daily for 7 consecutive days, starting 3 days before chemotherapy (Bassan 2010).

Acute lymphoblastic leukemia, Philadelphia chromosome-positive, relapsed or refractory

Acute lymphoblastic leukemia, Philadelphia chromosome-positive, relapsed or refractory: Oral: 600 mg once daily until disease progression or unacceptable toxicity.

Aggressive systemic mastocytosis associated with eosinophilia

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

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

Chordoma, progressive, advanced, or metastatic expressing PDGFRB and/or PDGFB (off-label use): Oral: 400 mg twice daily (Stacchiotti 2012) 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 (Stacchiotti 2009).

Chronic myeloid leukemia, Philadelphia chromosome-positive

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 (BSH [Smith 2020]): 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 (Cortes 2010, Hehlmann 2014).

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

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 (Carpenter 2007) 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 (Olavarria 2007).

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 (Hess 2005) or 400 to 600 mg daily (chronic phase) or 600 mg daily (blast or accelerated phase) (DeAngelo 2004).

Dermatofibrosarcoma protuberans

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 (Rutkowski 2010); data from a systematic review also noted that there seemed to be no difference in outcomes between the 400 or 800 mg/day dose (Navarrete-Dechent 2019).

Desmoid tumors, locally advanced or progressive

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) (Chugh 2010) 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 (Penel 2011).

Gastrointestinal stromal tumors

Gastrointestinal stromal tumors:

Adjuvant treatment following complete resection: Oral: 400 mg once daily; recommended treatment duration: 3 years (Dematteo 2009; Joensuu 2012).

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 (Debiec-Rychter 2006; Heinrich 2008).

Hypereosinophilic syndrome and/or chronic eosinophilic leukemia

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

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.

Melanoma, advanced or metastatic, c-Kit mutated tumors

Melanoma, advanced or metastatic, c-kit mutated tumors (off-label use): Oral: 400 mg twice daily until disease progression or unacceptable toxicity (Carvajal 2011) or 400 mg once daily until disease progression (Hodi 2013).

Myelodysplastic/myeloproliferative disease with PDGFR gene rearrangements

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.

Dosing: Kidney Impairment: Adult

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 (Gibbons 2008). 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 (Cortes 2020). Close monitoring of kidney function and avoiding use of other nephrotoxic drugs is recommended (Singh 2022).

Altered kidney function:

CrCl ≥40 mL/minute: Initial: No dosage adjustment necessary (Krens 2019). 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 (manufacturer’s labeling; EMA labeling).

CrCl 20 to <40 mL/minute: Initial: No dosage adjustment necessary (Krens 2019). 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 (EMA labeling). Doses up to 600 mg have been well tolerated in this population (Gibbons 2008). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (manufacturer’s labeling).

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 (Krens 2019); 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 (EMA labeling). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (manufacturer’s labeling).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Pappas 2005):

Initial: No dosage adjustment necessary (Krens 2019); however, use with caution due to limited clinical data (case reports) (Chandran 2008; Niikura 2016; Ozdemir 2006; Papas 2005; Wada 2012). 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 (EMA labeling). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (manufacturer’s labeling).

Peritoneal dialysis : Unlikely to be significantly dialyzed (highly protein bound) (expert opinion):

Consider alternative agent due to limited clinical data and risk of imatinib-induced nephrotoxicity.

If necessary, no initial dosage adjustment necessary (Krens 2019); 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 (EMA labeling). Alternatively, may initiate therapy with a reduced dose and gradually increase based on tolerability and response (manufacturer’s labeling).

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) (Cortes 2020; Tong 2010). Alternatively, may consider switching to a second-generation tyrosine kinase inhibitor less associated with nephrotoxicity (eg, dasatinib, nilotinib) (Hino 2016).

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

(For additional information see "Imatinib: Pediatric drug information")

Note: Antiemetics may be recommended to prevent nausea and vomiting; imatinib doses >260 mg/m2/day are associated with a moderate emetic potential (POGO [Paw Cho Sing 2019]).

Acute lymphoblastic leukemia, Philadelphia chromosome-positive; newly diagnosed

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 (Schultz 2014); maximum daily dose: 600 mg/day; treatment may be continued until disease progression or unacceptable toxicity.

Chronic myeloid leukemia, Philadelphia chromosome-positive; chronic phase, newly diagnosed

Chronic myeloid leukemia (CML), Philadelphia chromosome-positive (Ph+); chronic phase, newly diagnosed: Children and Adolescents: 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. 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 (Baccarani 2009).

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 nonhematologic adverse reactions: Children and Adolescents: Withhold treatment until toxicity resolves; may resume if appropriate (depending on initial severity of adverse event).

Dosing adjustment for hematologic adverse reactions: Children and Adolescents:

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 (Schultz 2009).

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.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents:

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 (Gibbons 2008).

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents:

Baseline:

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

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Hematologic toxicity:

Chronic phase CML (initial dose 400 mg daily in adults or 340 mg/m2/day in children); 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:

Children ≥1 year and Adolescents: If initial dose 340 mg/m2/day, reduce dose to 260 mg/m2/day.

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:

Pediatrics (Schultz 2009): 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.

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as mesylate:

Gleevec: 100 mg, 400 mg [scored]

Generic: 100 mg, 400 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Administration: Adult

Imatinib is associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).

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 (see Extemporaneously Prepared). Avoid skin or mucous membrane contact with crushed tablets; if contact occurs, wash thoroughly. Avoid exposure to crushed tablets.

Doses ≤600 mg may be given once daily; 800 mg dose should be administered as 400 mg twice daily.

Administration: Pediatric

Antiemetics may be recommended to prevent nausea and vomiting; imatinib doses >260 mg/m2/day are associated with a moderate emetic potential (POGO [Paw Cho Sing 2019]).

Oral: Administer with a meal and a large glass of water. Do not crush tablets; avoid skin or mucous membrane contact with crushed tablets; if contact occurs, wash thoroughly.

Tablets may be dispersed in water or apple juice (using ~50 mL for 100 mg tablet, ~200 mL for 400 mg tablet); stir until tablet dissolves and administer immediately. If necessary, an oral suspension may be prepared (see Extemporaneous Preparations). Dosing in pediatric patients may be once or twice daily when treating CML and once daily for Ph+ ALL.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 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 2016; USP-NF 2020).

Use: Labeled Indications

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.

Use: Off-Label: Adult

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

Medication Safety Issues
Sound-alike/look-alike issues:

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

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

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 11%), peripheral edema (20% to 41%)

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 (≤50%)

Endocrine & metabolic: Fluid retention (62% to 76%; can be severe), hypoalbuminemia (12% to 21%), hypokalemia (6% to 13%), increased lactate dehydrogenase (43% to 60%), weight gain (5% to 32%)

Gastrointestinal: Abdominal distension (7% to 19%), abdominal pain (3% to 57%; including abdominal cramps), anorexia (7% to 36%), constipation (8% to 16%), diarrhea (43% to 59%; grades 3/4: ≤5%), dysgeusia (7% to 13%), dyspepsia (≤27%), flatulence (10% to 25%), heartburn (≤11%), nausea (41% to 73%; grades 3/4: ≤5%), upper abdominal pain (14%), vomiting (23% to 58%; grades 3/4: ≤4%)

Hematologic & oncologic: Anemia (32% to 35%; grades 3/4: 1% to 42%), granulocytopenia (≤16%), hemorrhage (3% to 53%; grades 3/4: 2% to 19%), hypoproteinemia (24% to 32%), leukopenia (5% to 20%; grades 3/4: <1%), neutropenia (≤16%; grades 3/4: 3% to 48%), thrombocytopenia (grades 3/4: ≤33%)

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%)

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%)

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 (≤1%), hypertension (4%), hypotension (≤1%), palpitations (5%), pericardial effusion (≤6%), Raynaud’s disease (≤1%), subdural hematoma (≤1%), syncope (≤1%), tachycardia (≤1%)

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), 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

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%), memory impairment (≤1%), migraine (≤1%), myasthenia (≤1%), peripheral neuropathy (≤1%), restless leg syndrome (≤1%), sciatica (≤1%), tremor (≤1%), vertigo (≤1%)

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

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, cardiogenic shock, embolism, pericarditis, thrombosis

Dermatologic: Lichen planus, lichenoid eruption (keratosis), palmar-plantar erythrodysesthesia, pemphigus, toxic epidermal necrolysis

Endocrine & metabolic: Pseudoporphyria

Gastrointestinal: Diverticulitis of the gastrointestinal tract, gastrointestinal irritation, gastrointestinal perforation

Genitourinary: Ovarian cyst (hemorrhagic), ruptured corpus luteal cyst

Hematologic & oncologic: Thrombotic microangiopathy, tumor hemorrhage, tumor lysis syndrome

Hypersensitivity: Anaphylactic shock

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Infection: Reactivation of HBV

Nervous system: Brain edema

Neuromuscular & skeletal: Linear skeletal growth rate below expectation (children), myopathy, osteonecrosis (hip), rhabdomyolysis

Ophthalmic: Vitreous hemorrhage

Respiratory: Acute respiratory failure, interstitial pulmonary disease, lower respiratory tract infection

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to imatinib or any component of the formulation

Warnings/Precautions

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.

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.

Warnings: Additional Pediatric Considerations

Growth retardation has been reported in prepubescent children receiving imatinib for the treatment of CML (Bansal 2012; Rastogi 2012; Shima 2011); the majority of the preliminary data reported statistically significant decreases in height-SD (standard deviation) scores; less commonly reported are decreases in weight-SD scores or decreased BMI; incidence and extent of growth retardation as well as other related risk factors have not been fully characterized; reported incidence from reports is highly variable (48% to 71%), with onset during the first year of therapy and persisting with treatment. One report suggests that growth velocity was restored as pubertal age was reached; however, in other reports, patients did not have improvement in height velocity and genetically predicted adult heights were not achieved. Monitor growth closely.

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C8 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major), OCT1, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (moderate)

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the 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 therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the 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 enhance the hepatotoxic effect of Imatinib. Risk C: Monitor therapy

Adagrasib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Adagrasib. Risk C: Monitor therapy

Alfentanil: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Alfuzosin. Risk C: Monitor therapy

Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Risk C: Monitor therapy

ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Amiodarone. Risk C: Monitor therapy

AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Risk C: Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Risk X: Avoid combination

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Artesunate: Imatinib may increase serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

Asciminib: Imatinib may increase the serum concentration of Asciminib. Risk C: Monitor therapy

Astemizole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Astemizole. Management: Avoid concomitant use of astemizole and moderate CYP3A4 inhibitors whenever possible. If combined, monitor closely for increased astemizole toxicities, especially for QTc interval prolongation. Risk D: Consider therapy modification

Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination

Atazanavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atazanavir. Risk C: Monitor therapy

Atogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atogepant. Risk C: Monitor therapy

Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy

Avacopan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avacopan. Risk C: Monitor therapy

Avanafil: CYP3A4 Inhibitors (Moderate) may increase the 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 the 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 the serum concentration of Axitinib. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

Barnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine. Risk C: Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Bedaquiline: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bedaquiline. Risk C: Monitor therapy

Benidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benidipine. Risk C: Monitor therapy

Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy

Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Risk C: Monitor therapy

Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy

Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the 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 diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Budesonide (Topical). Risk X: Avoid combination

Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy

BusPIRone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of BusPIRone. Risk C: Monitor therapy

Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy

Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy

Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine. Risk C: Monitor therapy

Ceritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ceritinib. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the 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 the 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: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

CloZAPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the 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: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See interaction monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification

Conivaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Conivaptan. Risk C: Monitor therapy

Copanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib. Risk C: Monitor therapy

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Crizotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Crizotinib. Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive): Imatinib may increase the serum concentration of CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Imatinib. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the 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 the serum concentration of Imatinib. Risk C: Monitor therapy

Dabrafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dabrafenib. Risk C: Monitor therapy

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the 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 the 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 the serum concentration of Darifenacin. Risk C: Monitor therapy

Dasatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 serum concentrations of the active metabolite(s) 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 the serum concentration of Delamanid. Risk C: Monitor therapy

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

DexAMETHasone (Systemic): May decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with dexamethasone when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor clinical response closely. Risk D: Consider therapy modification

DiazePAM: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy

DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Disopyramide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Disopyramide. Risk C: Monitor therapy

DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOCEtaxel. Risk C: Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Risk X: Avoid combination

DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Risk C: Monitor therapy

Dronedarone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronedarone. Risk C: Monitor therapy

Ebastine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ebastine. Risk C: Monitor therapy

Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor therapy

Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Risk X: Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, two elexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification

Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the 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: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors 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. Resume prior dose once inhibitor discontinued for 3 to 5 half-lives. Risk D: Consider therapy modification

Entrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors during treatment with entrectinib. Reduce dose to 200 mg/day if combination cannot be avoided in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters. Avoid if BSA is less than 1.5 square meters Risk D: Consider therapy modification

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

Erlotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Erlotinib. Risk C: Monitor therapy

Erythromycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Erythromycin (Systemic). Risk C: Monitor therapy

Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eszopiclone. Risk C: Monitor therapy

Etravirine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy

Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fedratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fedratinib. Risk C: Monitor therapy

Felodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Felodipine. Risk C: Monitor therapy

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the 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: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the 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 combination

Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor therapy

Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosamprenavir. Risk C: Monitor therapy

Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gemfibrozil: May decrease serum concentrations of the active metabolite(s) of Imatinib. Specifically N-desmethylimatinib concentrations may be decreased. Gemfibrozil may decrease the serum concentration of Imatinib. Risk C: Monitor therapy

Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gilteritinib. Risk C: Monitor therapy

Glasdegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Glasdegib. Risk C: Monitor therapy

Grapefruit Juice: May increase the serum concentration of Imatinib. Risk X: Avoid combination

GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Halofantrine. Risk C: Monitor therapy

HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Imatinib. Specifically, ibuprofen may decrease intracellular concentrations of imatinib, leading to decreased clinical response. Management: Consider using an alternative to ibuprofen in patients who are being treated with imatinib. Available evidence suggests other NSAIDs do not interact in a similar manner. Risk D: Consider therapy modification

Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

Iloperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Infigratinib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Infigratinib. Risk X: Avoid combination

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy

Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor therapy

Isradipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Isradipine. Risk C: Monitor therapy

Itraconazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Itraconazole. Risk C: Monitor therapy

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination

Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the 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 the 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 the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Lefamulin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor therapy

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect 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 the serum concentration of Lemborexant. Risk X: Avoid combination

Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lercanidipine. Risk C: Monitor therapy

Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy

Levomethadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomethadone. Risk C: Monitor therapy

Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomilnacipran. Risk C: Monitor therapy

Levothyroxine: Imatinib may decrease the serum concentration of Levothyroxine. Risk C: Monitor therapy

Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Risk X: Avoid combination

Lonafarnib: Imatinib may increase the serum concentration of Lonafarnib. Lonafarnib may increase the serum concentration of Imatinib. Risk X: Avoid combination

Lopinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lopinavir. Risk C: Monitor therapy

Lovastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lovastatin. Risk C: Monitor therapy

Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification

Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification

Macitentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Macitentan. Risk C: Monitor therapy

Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Risk C: Monitor therapy

Maraviroc: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Maraviroc. Risk C: Monitor therapy

Mavacamten: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor. For those stable on mavacamten who are initiating a moderate CYP3A4 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification

Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Risk C: Monitor therapy

Methadone: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy

Methysergide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methysergide. Risk X: Avoid combination

Midazolam: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Midostaurin. Risk C: Monitor therapy

MiFEPRIStone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MiFEPRIStone. Risk C: Monitor therapy

Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Risk C: Monitor therapy

Mitapivat: CYP3A4 Inhibitors (Moderate) may increase the 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 serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase the 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

Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the 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 enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Risk C: Monitor therapy

NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NIFEdipine. Risk C: Monitor therapy

Nilotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nilotinib. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination

Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy

Orelabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination

OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy

PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

Pacritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pacritinib. Risk X: Avoid combination

Palbociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palbociclib. Risk C: Monitor therapy

Palovarotene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palovarotene. Risk C: Monitor therapy

Panobinostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Panobinostat. Risk C: Monitor therapy

PAZOPanib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PAZOPanib. Risk C: Monitor therapy

Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with moderate CYP3A4 inhibitors if possible. If combined, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily. Risk D: Consider therapy modification

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimavanserin. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Piperaquine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Piperaquine. Risk C: Monitor therapy

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 the serum concentration of PONATinib. Risk C: Monitor therapy

Prazepam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Prazepam. Risk C: Monitor therapy

Praziquantel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Propacetamol: May enhance the hepatotoxic effect of Imatinib. Risk C: Monitor therapy

QUEtiapine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QUEtiapine. Risk C: Monitor therapy

QuiNIDine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy

Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy

QuiNINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of QuiNINE. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 the 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 the serum concentration of Red Yeast Rice. Risk C: Monitor therapy

Regorafenib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Regorafenib. Risk C: Monitor therapy

Ribociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ribociclib. Risk C: Monitor therapy

Rifabutin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rifabutin. Risk C: Monitor therapy

Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the 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

Ritonavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ritonavir. Risk C: Monitor therapy

Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the 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 therapy

Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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

Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Risk C: Monitor therapy

Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy

Saquinavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy

SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Risk C: Monitor therapy

Selpercatinib: CYP3A4 Inhibitors (Moderate) may increase the 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 the 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 the serum concentration of Sertindole. Risk X: Avoid combination

Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Risk C: Monitor therapy

Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination

Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 the 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 the 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 the serum concentration of Solifenacin. Risk C: Monitor therapy

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

SUNItinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUNItinib. Risk C: Monitor therapy

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the 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

Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Tadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil. Risk C: Monitor therapy

Tafamidis: May increase the serum concentration of Imatinib. Risk C: Monitor therapy

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination

Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the 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

Telithromycin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin. Risk C: Monitor therapy

Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy

Terfenadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Terfenadine. Risk C: Monitor therapy

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the 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 decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa. Risk C: Monitor therapy

Ticagrelor: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Tolterodine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Toremifene. Risk C: Monitor therapy

Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk C: Monitor therapy

TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

TraZODone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraZODone. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Moderate) may increase the 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 enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Udenafil. Risk C: Monitor therapy

Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine. Risk C: Monitor therapy

Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Vemurafenib. Risk C: Monitor therapy

Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Verapamil. Risk C: Monitor therapy

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy

VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy

VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine. Risk C: Monitor therapy

VinCRIStine (Liposomal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine (Liposomal). Risk C: Monitor therapy

Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Risk C: Monitor therapy

Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vinflunine. Risk C: Monitor therapy

Voclosporin: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Vorapaxar. Risk C: Monitor therapy

Warfarin: Imatinib may enhance the anticoagulant effect of Warfarin. Imatinib may decrease the 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 enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the 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 the serum concentration of Zopiclone. Risk C: Monitor therapy

Food Interactions

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.

Reproductive Considerations

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]).

Pregnancy Considerations

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).

Breastfeeding Considerations

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).

Dietary Considerations

Avoid grapefruit juice.

Monitoring Parameters

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.

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.

Mechanism of Action

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.

Pharmacokinetics

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.

Pharmacokinetics: Additional Considerations

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.

Pricing: US

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.

Brand Names: International
  • Agacel (AR);
  • Alvotinib (UA);
  • Carcemia (EG);
  • Celonib (IN, LK, PE);
  • Egitinid (RO);
  • Enliven (BD);
  • Eurotinib (EG);
  • Fiximab (TR);
  • Gemfatinib (RU);
  • Gemivil (JO);
  • Gistamel (RU);
  • Gleevec (BB, ZA);
  • Glibine (AU);
  • Glima (KR);
  • Glimatib (VN);
  • Glinib (KR);
  • Glipox (EE);
  • Glivanib (AU);
  • Glivec (AE, AR, AT, AU, BE, BG, BH, BR, CH, CL, CN, CO, CU, CZ, DE, DK, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IN, IS, IT, JO, JP, KR, KW, LB, LK, LT, LU, LV, MX, MY, NL, NO, PE, PH, PK, PL, PT, PY, QA, RO, RU, SA, SE, SG, SI, SK, TH, TR, TW, UA, UY, VE, VN, ZW);
  • Glivic (NZ);
  • Imagerolan (AT);
  • Imagliv (RU);
  • Imakrebin (BG, CZ, HK, NL);
  • Imalek (IN);
  • Imalek 100 (PH);
  • Imanivec (CZ);
  • Imanix (BD, LK);
  • Imarem (MT, TR);
  • Imatero-400 (TH);
  • Imatib (AR, EG, IN, LB);
  • Imatin (UY);
  • Itivas (LV);
  • Ivic (TW);
  • Kadimer (CR, DO, GT, HN, NI, PA, SV);
  • Kadir (CL);
  • Kimatinib (UY);
  • Leutipol (NL);
  • Leuzek (MT);
  • Matinac (EC);
  • Matis (ZW);
  • Meaxin (CZ, EE, HR, LV, PL, SK);
  • Mesinib (AR);
  • Mesylonib (IN);
  • Mitinab (IN);
  • Mytib (NZ);
  • Neopax (RU);
  • Neoxell (BG);
  • Nibix (MT, PL);
  • Plivatinib (HR);
  • Protyrin (CR, DO, GT, HN, NI, PA, SV);
  • Slivec (TW);
  • Survtyk (CR, DO, GT, HN, MX, NI, PA, SV);
  • Tagonib (AR);
  • Tibaldix (NL);
  • Timab (AR, EC, PE);
  • Tinibat (TH);
  • Tinibe (PE);
  • Tyrokin (BD);
  • Tyronib (BD);
  • Unitinib (LK);
  • Vativio (TW);
  • Vek (AR);
  • Zeite (CL, CO, PY);
  • Zeltinib (EC);
  • Ziatir (AR)


For country code abbreviations (show table)
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