Gleevec

Small Molecule Antineoplastic Breakpoint Cluster Region-Abelson (BCR-ABL) Inhibitors
Small Molecule Antineoplastic Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors
Small Molecule Antineoplastic Receptor Tyrosine Kinase c-KIT Inhibitors

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Avoid exposure to crushed tablets or contact of crushed tablets with the skin or mucous membranes. Wash affected areas thoroughly.[58770] [63991]
Emetic Risk
Pediatrics
Less than 260 mg/m2/day: Low
260 mg/m2/day: Moderate
Adults
Moderate/High
Administer routine antiemetic prophylaxis prior to treatment. ]

Oral Administration

Take imatinib with a meal and a large glass of water.
Take the 400 mg/day or 600 mg/day dosages once daily; take the 800 mg/day dosage as 400 mg twice daily.
If a daily dose of 800 mg or greater is required, use 400-mg tablets instead of the 100-mg tablets to limit the patient's iron exposure.
Do not drink grapefruit juice during treatment.
If you miss a dose, skip that dose and take the next scheduled dose at your regular time.

Oral Solid Formulations

Do not crush tablets.
Tablets may be dispersed in a glass of water or apple juice in patients unable to swallow the film-coated tablets.
Place the required number of tablets to make the dose in the appropriate volume of liquid (about 50 mL for each 100-mg tablet and 200 mL for each 400-mg tablet) and stir with a spoon.
Take the suspension immediately after complete disintegration of the tablets.[58770] [63991]

Extemporaneous Compounding-Oral

Extemporaneous 40 mg/mL Oral Suspension
NOTE: Imatinib is a hazardous medication; handle accordingly. Prepare in a biosafety level 2 cabinet.
Determine the necessary quantity of imatinib 400 mg tablets.
Crush the tablets in a glass mortar and triturate to a fine powder.
Measure the necessary volume of Ora-Sweet to make a 40 mg/mL suspension and add to the powder via geometric dilution until a smooth suspension is created. The estimated powder volume for each crushed 400 mg tablet is 0.4 mL.
Transfer the mixture into an amber plastic bottle.
Shake well before use.
Storage: Store in an amber plastic bottle at ambient room temperature (22 to 25 degrees C [71.6 to 77 degrees F]) or under refrigeration (4 degrees C [39.2 degrees F]) for up to 14 days.

Severe

neutropenia / Delayed / 3.1-64.0
thrombocytopenia / Delayed / 1.0-63.0
anemia / Delayed / 3.0-53.0
bleeding / Early / 0-19.0
abdominal pain / Early / 0.3-13.8
edema / Delayed / 0-13.1
fluid retention / Delayed / 2.5-13.1
lethargy / Early / 0-12.2
asthenia / Delayed / 0-12.2
malaise / Early / 0-12.2
fatigue / Early / 0.5-12.2
anasarca / Delayed / 1.0-10.0
pericardial effusion / Delayed / 1.0-10.0
ocular hemorrhage / Delayed / 0.1-10.0
pancytopenia / Delayed / 1.0-10.0
vomiting / Early / 0.5-9.2
nausea / Early / 0.5-9.0
diarrhea / Early / 0.5-9.0
intracranial bleeding / Delayed / 0.2-9.0
musculoskeletal pain / Early / 2.0-9.0
hypoxia / Early / 0-9.0
rash / Early / 0.9-8.9
GI bleeding / Delayed / 1.4-8.0
elevated hepatic enzymes / Delayed / 0.2-8.0
infection / Delayed / 0-8.0
fever / Early / 0-8.0
dyspnea / Early / 0.5-7.0
weight gain / Delayed / 0-7.0
pulmonary edema / Early / 0.1-6.9
pleural effusion / Delayed / 0.1-6.9
anorexia / Delayed / 0-6.6
arthralgia / Delayed / 0-6.0
headache / Early / 0-5.7
myalgia / Early / 0-5.6
stomatitis / Delayed / 0.6-5.4
pruritus / Rapid / 0-5.4
pharyngitis / Delayed / 0-5.4
constipation / Delayed / 0.4-5.1
chills / Rapid / 0-4.6
cough / Delayed / 0-4.5
alopecia / Delayed / 0-4.3
hyperbilirubinemia / Delayed / 0-4.0
hypoalbuminemia / Delayed / 0-4.0
hypokalemia / Delayed / 0.8-4.0
muscle cramps / Delayed / 0.4-2.2
chest pain (unspecified) / Early / 0.4-2.0
lymphopenia / Delayed / 0.7-1.9
leukopenia / Delayed / 0.3-1.6
bone pain / Delayed / 1.6-1.6
heart failure / Delayed / 0.7-1.1
flatulence / Early / 0.2-1.0
hematemesis / Delayed / 0.1-1.0
peptic ulcer / Delayed / 0.1-1.0
pancreatitis / Delayed / 0.1-1.0
dyspepsia / Early / 0-1.0
dizziness / Early / 0-1.0
peripheral edema / Delayed / 0-1.0
increased intracranial pressure / Early / 0.1-1.0
papilledema / Delayed / 0.1-1.0
retinal hemorrhage / Delayed / 0.1-1.0
erythema nodosum / Delayed / 0.1-1.0
night sweats / Early / 0.2-1.0
erythema multiforme / Delayed / 0.1-1.0
exfoliative dermatitis / Delayed / 0.1-1.0
back pain / Delayed / 0.6-1.0
hypertension / Early / 0-1.0
hearing loss / Delayed / 0.1-1.0
macular edema / Delayed / 0.1-1.0
blurred vision / Early / 0-1.0
hyperglycemia / Delayed / 0-1.0
hypocalcemia / Delayed / 0-1.0
hyperkalemia / Delayed / 0.1-1.0
renal failure (unspecified) / Delayed / 0.1-1.0
insomnia / Early / 0-0.9
anxiety / Delayed / 0-0.8
depression / Delayed / 0-0.8
influenza / Delayed / 0-0.8
xerosis / Delayed / 0-0.5
paresthesias / Delayed / 0-0.5
sinusitis / Delayed / 0.2-0.4
ileus / Delayed / 0-0.1
cerebral edema / Early / 0-0.1
cardiac tamponade / Delayed / 0-0.1
aplastic anemia / Delayed / 0-0.1
hemolytic anemia / Delayed / 0-0.1
Stevens-Johnson syndrome / Delayed / 0-0.1
vasculitis / Delayed / 0-0.1
acute generalized exanthematous pustulosis (AGEP) / Delayed / 0-0.1
cardiac arrest / Early / 0-0.1
atrial fibrillation / Early / 0-0.1
arrhythmia exacerbation / Early / 0-0.1
myocardial infarction / Delayed / 0-0.1
hepatic necrosis / Delayed / 0-0.1
hepatic failure / Delayed / 0-0.1
pulmonary fibrosis / Delayed / 0-0.1
pulmonary hypertension / Delayed / 0-0.1
optic neuritis / Delayed / 0-0.1
angioedema / Rapid / 0-0.1
GI perforation / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
pseudoporphyria / Delayed / Incidence not known
pemphigus / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
osteonecrosis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
thrombotic microangiopathy / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
tumor lysis syndrome (TLS) / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
nephrotoxicity / Delayed / Incidence not known

Moderate

gastritis / Delayed / 1.0-10.0
peripheral neuropathy / Delayed / 1.0-10.0
eosinophilia / Delayed / 1.0-10.0
erythema / Early / 1.0-10.0
palpitations / Early / 1.0-10.0
conjunctivitis / Delayed / 1.0-10.0
hyperamylasemia / Delayed / 1.0-10.0
dysphagia / Delayed / 0.1-1.0
oral ulceration / Delayed / 0.1-1.0
esophagitis / Delayed / 0.1-1.0
dehydration / Delayed / 0.1-1.0
melena / Delayed / 0.1-1.0
memory impairment / Delayed / 0.1-1.0
migraine / Early / 0.1-1.0
ascites / Delayed / 0.1-1.0
subdural hematoma / Early / 0.1-1.0
lymphadenopathy / Delayed / 0.1-1.0
bullous rash / Early / 0.1-1.0
psoriasis / Delayed / 0.1-1.0
hematoma / Early / 0.1-1.0
gout / Delayed / 0.1-1.0
hyperuricemia / Delayed / 0.1-1.0
sinus tachycardia / Rapid / 0.1-1.0
hypotension / Rapid / 0.1-1.0
jaundice / Delayed / 0.1-1.0
hepatitis / Delayed / 0.1-1.0
hypothyroidism / Delayed / 0.1-1.0
hyperthyroidism / Delayed / 0.1-1.0
blepharitis / Early / 0.1-1.0
cataracts / Delayed / 0.1-1.0
impotence (erectile dysfunction) / Delayed / 0.1-1.0
testicular swelling / Early / 0.1-1.0
hyponatremia / Delayed / 0.1-1.0
hypercalcemia / Delayed / 0.1-1.0
hypomagnesemia / Delayed / 0.1-1.0
hypophosphatemia / Delayed / 0-1.0
hematuria / Delayed / 0.1-1.0
colitis / Delayed / 0-0.1
confusion / Early / 0-0.1
angina / Early / 0-0.1
pneumonitis / Delayed / 0-0.1
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
myopathy / Delayed / Incidence not known
clastogenesis / Delayed / Incidence not known

Mild

lacrimation / Early / 9.8-25.0
rhinitis / Early / 16.7-16.7
dysgeusia / Early / 6.5-12.6
weight loss / Delayed / 10.1-10.1
xerostomia / Early / 1.0-10.0
gastroesophageal reflux / Delayed / 1.0-10.0
epistaxis / Delayed / 1.0-10.0
photosensitivity / Delayed / 1.0-10.0
flushing / Rapid / 1.0-10.0
purpura / Delayed / 1.0-10.0
weakness / Early / 0.1-10.0
xerophthalmia / Early / 1.0-10.0
cheilitis / Delayed / 0.1-1.0
appetite stimulation / Delayed / 0.1-1.0
eructation / Early / 0.1-1.0
libido decrease / Delayed / 0.1-1.0
tremor / Early / 0.1-1.0
syncope / Early / 0.1-1.0
folliculitis / Delayed / 0.1-1.0
hyperhidrosis / Delayed / 0.1-1.0
skin hyperpigmentation / Delayed / 0.1-1.0
petechiae / Delayed / 0.1-1.0
ecchymosis / Delayed / 0.1-1.0
urticaria / Rapid / 0.1-1.0
panniculitis / Delayed / 0.1-1.0
skin hypopigmentation / Delayed / 0.1-1.0
drowsiness / Early / 0.1-1.0
restless legs syndrome (RLS) / Delayed / 0.1-1.0
vertigo / Early / 0.1-1.0
tinnitus / Delayed / 0.1-1.0
ocular irritation / Rapid / 0.1-1.0
ocular pain / Early / 0.1-1.0
gynecomastia / Delayed / 0.1-1.0
menstrual irregularity / Delayed / 0.1-1.0
menorrhagia / Delayed / 0.1-1.0
breast enlargement / Delayed / 0.1-1.0
increased urinary frequency / Early / 0.1-1.0
vesicular rash / Delayed / 0-0.1
nail discoloration / Delayed / 0-0.1
lichen planus-like eruption / Delayed / Incidence not known

Gleevec

Rx

Oral BCR-ABL tyrosine kinase inhibitor
Used in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia in adults and pediatric patients, and myelodysplastic/myeloproliferative diseases, aggressive systemic mastocytosis, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors in adults
Severe myelosuppression, congestive heart failure, and hepatotoxicity have been reported

For the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).
NOTE: The FDA has designated imatinib as an orphan drug for the treatment of CML.
For the treatment of newly diagnosed chronic-phase Ph+ CML. Oral dosage Adults

400 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. If no adverse events including nonleukemia-related hematologic toxicity are experienced with the initial dose, the imatinib dosage may be increased to 600 mg orally once daily in patients who have disease progression (at any time), no satisfactory hematologic response after at least 3 months of treatment, no cytogenetic response after 6 to 12 months of treatment, or a loss of a previously achieved hematologic or cytogenetic response. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity.[58770] [63991] The 12-month progression-free survival rate was significantly improved in patients with previously untreated Ph+ CML who received imatinib compared with interferon alfa plus cytarabine (96.6% vs. 79.9%, p less than 0.001) in a randomized, phase 3 trial (n = 1,106; the IRIS trial).[27325] In the IRIS trial (median follow-up of 10.9 years), the estimated 10-year overall survival rates were 83.3% and 78.8% (hazard ratio = 0.74; 95% CI, 0.56 to 0.99; p = 0.04) in patients who received imatinib (mean duration of therapy, 7.5 +/- 4 years) and interferon alfa plus cytarabine, respectively. Approximately 66% of patients in the interferon alfa plus cytarabine arm crossed over to the imatinib arm at a median time of 0.8 years. The estimated 10-year event-free survival rates were 79.6% and 56.6% in the imatinib and interferon alfa plus cytarabine arms, respectively.[63998]

Children and Adolescents

340 mg/m2 (not to exceed 600 mg) orally daily with food until disease progression; the dose may be given once daily or split into 2 daily doses given in the morning and evening. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. Treatment with imatinib led to an 8-week complete hematologic response rate of 78% and a complete cytogenetic response rate of 65% in pediatric patients with newly diagnosed chronic phase, Ph+ CML in a multicenter phase 2 trial (n = 51). Thirty-one patients received a subsequent stem-cell transplantation.[58770] [63991]

For the treatment of chronic-phase Ph+ CML after the failure of interferon-alfa therapy. Oral dosage Adults

400 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. If no adverse events including nonleukemia-related hematologic toxicity are experienced with the initial dose, the imatinib dosage may be increased to 600 mg orally once daily in patients who have disease progression (at any time), no satisfactory hematologic response after at least 3 months of treatment, no cytogenetic response after 6 to 12 months of treatment, or a loss of a previously achieved hematologic or cytogenetic response. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In a phase 2 trial (n = 532), treatment with imatinib (median duration, 29 months) resulted in a complete hematologic response of 95% and a major cytogenetic response of 60% in patients with chronic-phase Ph+ CML who previously failed interferon alfa therapy.[58770] [63991]

For the treatment of accelerated-phase or blast crisis Ph+ CML after the failure of interferon-alfa therapy. Oral dosage Adults

600 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. If no adverse events including nonleukemia-related hematologic toxicity are experienced with the initial dose, the imatinib dosage may be increased to 400 mg orally twice daily in patients who have disease progression (at any time), no satisfactory hematologic response after at least 3 months of treatment, no cytogenetic response after 6 to 12 months of treatment, or a loss of a previously achieved hematologic or cytogenetic response. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In a phase 2 trial (n = 235), treatment with imatinib (median duration, 18 months) resulted in a hematologic response of 71% and a major cytogenetic response of 21% in patients with accelerated-phase Ph+ CML.  Additionally, treatment with imatinib (median duration, 4 months) resulted in a hematologic response of 31% and a major cytogenetic response of 7% in patients with accelerated-phase Ph+ CML in another phase 2 trial (n = 260).[58770] [63991]

For the treatment of Philadelphia chromosome-positive (Ph+) acute lymphocytic leukemia (ALL).
NOTE: The FDA has designated imatinib as an orphan drug for the treatment of Ph+ ALL.
For the treatment of relapsed or refractory Ph+ ALL. Oral dosage Adults

600 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity.[58770] [63991] Single-agent imatinib therapy (median duration of 62 days; range, 14 to 343 days) resulted in a sustained hematologic response (lasting at least 4 weeks) in 27% of relapsed or refractory Ph+ ALL patients in a multicenter, phase 2 trial (n = 48; prior bone marrow transplant, n = 10 (21%)); a sustained complete hematologic response was achieved in 6% of patients. Additionally, 17% of patients had a complete cytogenetic response. The estimated median time to progression was 2.2 months and the estimated median overall survival time was 4.9 months.[53020]

For the treatment of newly diagnosed Ph+ ALL, in combination with chemotherapy. Oral dosage Children, Adolescents, and Adults 21 years and younger

340 mg/m2 (not to exceed 600 mg) orally once daily with food. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity.[58770] The 3-year event-free survival (EFS) rate was 80.5% in a cohort of 50 patients aged 1 to 21 years (median age, 10 years) with very high-risk Ph+ ALL who received imatinib after 4 to 6 weeks of 3- or 4-drug induction therapy in a multicenter, nonrandomized trial (the COG AALL0031 trial). Most patients in this cohort (n = 44) received continuous imatinib therapy for 280 days prior to maintenance. High-risk ALL was defined as patients with an expected 5-year EFS of less than 45% with conventional chemotherapy. In this trial, patients received daily imatinib starting with the first course of post-induction chemotherapy and continued through maintenance chemotherapy cycles 1 to 4; imatinib was administered intermittently on a 2-week-on/2-week-off schedule during maintenance cycles 5 to 12.[53014] The 20 patients who underwent hematopoietic stem cell transplant (HSCT) received 42 days of imatinib prior to HSCT and 28 weeks (196 days) of imatinib after the immediate post-transplant period. At a median follow-up time of 40.5 months, the estimated 4-year EFS of patients in this study was 70%.[58770]

For the treatment of Kit (CD117)-positive gastrointestinal stromal tumors (GIST).
NOTE: The FDA has designated imatinib as an orphan drug for the treatment of GIST.
For the treatment of Kit (CD117)-positive unresectable and/or metastatic GIST. Oral dosage Adults

400 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. If no adverse events are experienced with a lower dose, the imatinib dosage may be increased to 400 mg orally twice daily in patients who have disease progression. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In 2 multicenter, randomized, open-label clinical trials (n = 1,640), patients with unresectable or metastatic GIST were randomized to treatment with either 400 mg or 800 mg per day of imatinib; patients in the 400 mg arm were permitted to cross over to receive 800 mg daily upon disease progression. The primary outcome of progression-free survival was 18.9 months compared with 23.2 months, respectively. Partial responses occurred in 46.1% of the 400-mg arm compared with 48.9% of the 800-mg arm, while complete responses were recorded in 5.3% versus 5% of patients, respectively. There were no differences in overall survival between treatment groups. In another multicenter, open-label, phase 2 clinical trial, there were no differences in response rates between patients treated with either 400 mg or 600 mg of imatinib per day.[58770]

For the adjuvant treatment of Kit (CD117)-positive GIST after complete gross resection. Oral dosage Adults

400 mg orally once daily with food. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A treatment duration of 3 years in patients with tumor diameter greater than 5 cm and mitotic count greater than 5/50 high power fields (HPF), tumor diameter greater than 10 cm and any mitotic count, any tumor size with mitotic count greater than 10/50 HPF, or tumors ruptured into the peritoneal cavity. The optimal duration of treatment for other patients is unknown, but in clinical trials durations of both 1 year and 3 years have been studied. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In a planned 15-month interim analysis of a multicenter, randomized, double-blind clinical trial, recurrence-free survival (RFS) was improved with 1-year of imatinib treatment (n = 359) compared with placebo (n = 354) (HR = 0.398; p less than 0.0001). Twenty percent of placebo arm crossed over to receive imatinib after the interim analysis, and the updated RFS hazard ratio after 50 months was 0.718. Overall survival (OS) was not significantly improved by adjuvant imatinib. In a second multicenter, randomized, open-label, phase 3 clinical trial, 36 months of imatinib treatment significantly prolonged RFS compared with 12 months of imatinib treatment (HR = 0.46; p less than 0.0001) in patients with tumor diameter greater than 5 cm with mitotic count greater than 5/50 HPF, tumor diameter greater than 10 cm with any mitotic count, any tumor size with mitotic count greater than 10/50 HPF, or tumors ruptured into the peritoneal cavity. OS was also significantly improved in the 36-month treatment arm (HR = 0.45; p = 0.0187).[58770]

For the treatment of hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL).
NOTE: The FDA has designated imatinib as an orphan drug for the treatment of idiopathic HES including acute eosinophilic leukemia and CEL.
For the treatment of FIP1L1-PDGFR alpha fusion kinase-positive HES and/or CEL. Oral dosage Adults

initial, 100 mg orally once daily with food; increase the dose to 400 mg/day in patients who have an insufficient response to therapy and no adverse events with lower doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In a pooled analysis of 35 published case reports and case series, the complete hematological response rate was 100% in 61 patients with HES and/or CES who received imatinib at daily doses of 75 mg to 800 mg.

For the treatment of FIP1L1-PDGFR alpha fusion kinase-negative or unknown mutational status HES and/or CEL. Oral dosage Adults

400 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In patients with FIP1L1-PDGFR alpha fusion kinase-negative (n = 56) and FIP1L1-PDGFR alpha fusion kinase unknown status (n = 59) HES/CES who received imatinib at daily doses of 75 mg to 800 mg, the complete hematological response rates were 21% and 58%, respectively, and the partial hematological response rates were 16% and 12%, respectively, in a pooled analysis of 35 published case reports and case series.

For the treatment of myelodysplastic syndrome (MDS)/myeloproliferative disease (MPD) associated platelet-derived growth factor receptor (PDGFR) gene rearrangements.
NOTE:The FDA has designated imatinib as an orphan drug for the treatment of MDS/MPS associated with PDGFR gene re-arrangements.
Oral dosage Adults

400 mg orally once daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. An open-label, phase 2 trial of patients with life-threatening conditions associated with Abl, Kit, or PDGFR protein tyrosine kinases included 7 patients with MDS/MPD who were treated with imatinib 400 mg/day. Response durations in this trial ranged from 141 to 457 days or longer; the median duration of response was 12.9 months. Case reports and series describe an additional 24 patients with MDS/MPD treated with imatinib 400 mg/day. Of the total patients treated (n = 31), 14 (45%) achieved a complete hematologic response and 12 (39%) a major cytogenetic response (including 10 with a complete cytogenetic response).[58770] [63991]

For the treatment of aggressive systemic mastocytosis (ASM). For the treatment of ASM without the D816V c-Kit mutation or with c-Kit mutation status unknown.
NOTE: The FDA has designated imatinib as an orphan drug for the treatment of systemic mastocytosis without the D816V c-kit mutation.
Oral dosage Adults

400 mg orally once daily with food until disease progression in patients without the D816V c-Kit mutation or in patients with c-Kit mutational status unknown or unavailable if they are not responding satisfactorily to other therapies. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In a pooled analysis of published case reports, case series, and a small phase 2 trial, a partial hematological response was achieved in 7 of 15 imatinib-treated patients (44%) with unknown or no Abl, c-Kit, or PDGFR protein tyrosine kinase mutation.[58770] [63991]

For the treatment of ASM associated with eosinophilia, in patients with the FIP1L1-PDGFR alpha fusion kinase (or CHIC2 deletion). Oral dosage Adults

100 mg orally once daily with food; increase the dose to 400 mg/day in patients who have an insufficient response to therapy and no adverse events with lower doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. The complete hematological response rate was 100% in 7 patients with the FIP1L1-PDGFR alpha fusion kinase (or CHIC2 deletion) who received imatinib therapy in a pooled analysis of published case reports, case series, and a small phase 2 trial. [58770] [63991]

For the treatment of dermatofibrosarcoma protuberans (DFSP).
NOTE: The FDA has designated imatinib as an orphan drug for the treatment of DFSP.
For the treatment of unresectable, recurrent, or metastatic DFSP. Oral dosage Adults

400 mg orally twice daily with food until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In a pooled analysis of published case reports and a small phase 2 trial, the complete response rate was 39% and the partial response (PR) rate was 44% in 18 patients with unresectable, recurrent, or metastatic DFSP who received imatinib therapy. Five patients who achieved a PR became disease-free following surgery.[58770] [63991]

For the treatment of desmoid tumor† or aggressive fibromatosis† not amenable to surgery or radiotherapy. Oral dosage Adults

Various dosage regimens ranging from 200 to 800 mg/day PO have been studied. 400 mg/day PO for up to 12 months (increased to 800 mg/day if disease progression occurred) resulted in a 3-month response rate (complete response [CR] + partial response [PR] + stable disease [SD]) of 91% (CR, 2.9%; PR, 8.6%) and a median progression-free survival time of 25 months in 35 evaluable patients in a phase II study. One patient in this study experienced grade 3 rhabdomyolysis. In another phase II study, the 4-month clinical benefit rate was 84% in 51 patients aged 12 to 67 years with AF who received imatinib 100 mg PO twice daily (BSA less than 1 m2), 200 mg PO twice daily (BSA 1 to 1.4 m2), or 300 mg PO twice daily (BSA more than 1.5 m2); additionally, 3 patients had a PR after 19, 22, and 26 months of therapy. In a phase II study in 19 heavily-pretreated patients, 800 mg/day PO resulted in 3 partial responses (15.7%) lasting greater than 1.5 years (range, 594 to 1494+ days), 4 patients with stable disease lasting greater than 1 year, and a median time to progression of 325 days. Dose reductions to 400 to 600 mg/day PO were required for most patients due to grade 3 or higher toxicity.

Children >= 12 years and Adolescents

100 mg PO twice daily (BSA less than 1 m2), 200 mg PO twice daily (BSA 1 to 1.4 m2), or 300 mg PO twice daily (BSA more than 1.5 m2) has been studied in a phase II study. The 4-month clinical benefit rate was 84% in 51 patients; additionally, 3 patients had a PR after 19, 22, and 26 months of therapy.

†Indicates off-label use

Hepatic Impairment

Baseline Hepatic Impairment:
Mild or moderate hepatic impairment (bilirubin level 3-times the upper limit of normal (ULN) or less and any AST level): No dose adjustment needed.Severe hepatic impairment (bilirubin level 3- to 10-times the ULN and any AST level): Decrease the recommended dose by 25%.
Treatment-Related Toxicity:
Dose ReductionAdults: 400 mg/day to 300 mg/day600 mg/day to 400 mg/day800 mg/day to 600 mg/dayPediatric Patients:340 mg/m2 per day to 260 mg/m2 per day
Bilirubin level greater than 3-times the upper limit of normal (ULN) or transaminases levels greater than 5-times the ULN: Hold therapy until the bilirubin levels have decreased to a less than 1.5-times the ULN and transaminase levels have decreased to less than 2.5-times the ULN; resume therapy at a reduced daily dose.

Renal Impairment

Mild renal impairment (creatinine clearance (CrCl), 40 to 59 mL/min): Start at the recommended dose but do not to exceed 600 mg/day. Moderate renal impairment (CrCl, 20 to 39 mL/min): Decrease the recommended starting dose by 50%; may increase the dose as tolerated up to the recommended dose but do not to exceed 400 mg/day.Severe renal impairment (CrCl less than 20 mL/min): Specific guidelines for dosage adjustments are not available; however, a dose of 100 mg/day was tolerated in 2 patients with severe renal impairment.

Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with imatinib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with imatinib. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors. Additionally, acalabrutinib may increase imatinib exposure and increase the risk of imatinib toxicity. Acalabrutinib is a substrate and inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Imatinib is a BCRP substrate.
Acetaminophen: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Aspirin: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Caffeine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Concomitant use of dihydrocodeine with imatinib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of imatinib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Acetaminophen; Caffeine; Pyrilamine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Chlorpheniramine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Codeine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Acetaminophen; Dextromethorphan: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Doxylamine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Diphenhydramine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Hydrocodone: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Ibuprofen: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Oxycodone: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like imatinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If imatinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Acetaminophen; Pamabrom; Pyrilamine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Phenylephrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Acetaminophen; Pseudoephedrine: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Adagrasib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with adagrasib is necessary. Imatinib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased imatinib exposure by 40%.
Alfentanil: (Moderate) Alfentanil is metabolized by the cytochrome P450 3A4 isoenzyme present in the liver. Inhibitors of CYP3A4, such as imatinib, may decrease systemic clearance of alfentanil leading to increased or prolonged effects.
Alfuzosin: (Moderate) Alfuzosin is primarily metabolized by CYP3A4 hepatic enzymes; inhibitors of CYP3A4, such as imatinib, are expected to inhibit alfuzosin metabolism and increase systemic exposure to alfuzosin.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Alprazolam: (Major) Avoid coadministration of alprazolam and imatinib due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with imatinib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
Amiodarone: (Moderate) Consider serial measurement of amiodarone serum concentration during concomitant use of imatinib. Concurrent use may increase amiodarone exposure. Higher antiarrhythmic plasma concentrations increase the potential risk of QT prolongation, torsade de pointes (TdP) or other proarrhythmias. Amiodarone is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor.
Amitriptyline: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Atorvastatin: (Major) The risk of developing myopathy during therapy with atorvastatin, a CYP3A4 substrate, is increased if coadministered with imatinib, STI-571, a CYP3A4 inhibitor. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined atorvastatin and imatinib, STI-571 therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Benazepril: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Celecoxib: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Olmesartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Valsartan: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Amobarbital: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Amoxapine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 2D6 and may increase concentrations of other drugs metabolized by this enzyme including amoxapine.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Clarithromycin is a significant inhibitor of CYP3A4 isoenzymes and should be used cautiously with CYP3A4 substrates, such as imatinib, due to the potential for reduced metabolism and drug accumulation.
Apalutamide: (Major) Avoid coadministration of imatinib with apalutamide if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of imatinib with aprepitant due to substantially increased exposure of aprepitant. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely with imatinib. Imatinib is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of another moderate CYP3A4 inhibitor with aprepitant increased the aprepitant AUC by 2-fold.
Aripiprazole: (Major) Recommendations for managing aripiprazole and imatinib vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; imatinib is a weak CYP2D6 and moderate CYP3A inhibitor.
Artemether; Lumefantrine: (Moderate) Imatinib, STI-571 is a substrate/inhibitor and artemether a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations. Concomitant use warrants caution due to the potential for increased side effects. (Moderate) Imatinib, STI-571 is a substrate/inhibitor and lumefantrine a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation.
Artesunate: (Moderate) Monitor for an increase in artesunate-related side effects if coadministered with imatinib. Coadministration may increase the exposure of the active metabolite of artesunate, dihydroartemisinin (DHA). DHA is a UGT substrate, and imatinib is a strong UGT inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like imatinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If imatinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with imatinib, STI-571 as there is a potential for elevated imatinib and/or cobicistat concentrations. Imatinib is a CYP3A4 substrate and moderate iinhibitor, a weak inhibitor of CYP2D6, and a breast cancer resistance protein (BCRP) substrate. Cobicistat is a strong inhibitor of CYP3A4, a BCRP inhibitor, and a substrate of CYP2D6 and CYP3A4. Coadministration of imatinib with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Atomoxetine: (Major) Administer atomoxetine and imatinib, STI-571 with caution. Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of strong CYP2D6 inhibitors such as imatinib may theoretically increase the risk of atomoxetine-induced adverse effects. In children and adolescents up to 70 kg receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. If concurrent use is necessary, monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation) during concurrent use.
Atorvastatin: (Major) The risk of developing myopathy during therapy with atorvastatin, a CYP3A4 substrate, is increased if coadministered with imatinib, STI-571, a CYP3A4 inhibitor. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined atorvastatin and imatinib, STI-571 therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Atorvastatin; Ezetimibe: (Major) The risk of developing myopathy during therapy with atorvastatin, a CYP3A4 substrate, is increased if coadministered with imatinib, STI-571, a CYP3A4 inhibitor. When possible, avoid concurrent use of HMG-reductase inhibitors with drugs known to increase the risk of developing rhabdomyolysis or acute renal failure. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined atorvastatin and imatinib, STI-571 therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including imatinib, STI-571, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Avapritinib: (Major) Avoid coadministration of avapritinib with imatinib due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with a moderate CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 210% at steady-state.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Barbiturates: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as imatinib, STI-571, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, imatinib may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
Benzhydrocodone; Acetaminophen: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Concurrent use of benzhydrocodone with imatinib may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of imatinib in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If imatinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Imatinib is an inhibitor of CYP3A4 and a weak inhibitor of CYP2D6.
Bortezomib: (Minor) Agents that inhibit cytochrome P450 3A4, such as imatinib, may increase the exposure to bortezomib and increase the risk for toxicity; however, bortezomib is also metabolized by other CYP isoenzymes. Therefore, the clinical significance of concurrent administration of bortezomib with CYP3A4 inhibitors is not known.
Bosutinib: (Major) Avoid concomitant use of bosutinib and imatinib, STI-571; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Imatinib, STI-571 is a potent inhibitor of both CYP3A4 and CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a strong CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with imatinib if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of imatinib, resume the brigatinib dose that was tolerated prior to initiation of imatinib. Brigatinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Brimonidine; Timolol: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 2D6 and might decrease the hepatic metabolism of timolol. This interaction may be more pronounced in extensive metabolizers. Clinicians should be alert to exaggerated beta-blocker effects if the timolol is given with these drugs.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of imatinib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; imatinib is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as imatinib, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Bupivacaine: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as imatinib, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Bupivacaine; Epinephrine: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as imatinib, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine-related toxicity when administering with imatinib; lidocaine exposure may increase. Imatinib is a moderate CYP3A4 inhibitor; lidocaine is a CYP3A4 substrate. (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as imatinib, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Bupivacaine; Meloxicam: (Minor) Bupivacaine is metabolized by CYP3A4 isoenzymes. Known inhibitors of CYP3A4, such as imatinib, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity.
Buprenorphine: (Major) Since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a CYP3A4 inhibitor such as imatinib, STI-571 may decrease the clearance of buprenorphine resulting in prolonged or increased opioid effects. If co-administration is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buprenorphine; Naloxone: (Major) Since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a CYP3A4 inhibitor such as imatinib, STI-571 may decrease the clearance of buprenorphine resulting in prolonged or increased opioid effects. If co-administration is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buspirone: (Moderate) CYP3A4 inhibitors, such as imatinib, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone is recommended initially.
Butabarbital: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Butalbital; Acetaminophen: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib. (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib. (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib. (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib. (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering imatinib, STI-571 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Imatinib is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Carbamazepine: (Major) Avoid coadministration of imatinib and carbamazepine if possible due to the risk for decreased imatinib concentrations and increased carbamazepine concentrations. If concomitant use is necessary, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Additionally, monitor carbamazepine concentrations closely as carbamazepine dosage adjustments may be needed. Imatinib is a CYP3A4 substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Cariprazine: (Moderate) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
Carvedilol: (Minor) Imatinib is a potent inhibitor of cytochrome P450 2D6 and may increase concentrations of other drugs metabolized by this enzyme including carvedilol. Caution is recommended when administering imatinib with carvedilol.
Celecoxib; Tramadol: (Moderate) Since tramadol is primarily metabolized by cytochrome P450 isoenzyme CYP2D6, agents that inhibit this enzyme, such as imatinib, decrease the metabolism of tramadol. Concomitant use of these agents and tramadol may increase plasma levels of tramadol and decrease concentration of the active metabolite leading to decreased analgesic effects and possibly increased side effects due to higher tramadol concentrations.
Ceritinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with ceritinib is necessary. Imatinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Chlordiazepoxide: (Moderate) CYP3A4 inhibitors, such as imatinib, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
Chlordiazepoxide; Amitriptyline: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation. (Moderate) CYP3A4 inhibitors, such as imatinib, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
Chlordiazepoxide; Clidinium: (Moderate) CYP3A4 inhibitors, such as imatinib, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Chlorpheniramine; Dextromethorphan: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with imatinib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of imatinib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cilostazol: (Major) Imatinib is a potent inhibitor of cytochrome P450 (CYP) 3A4 and may increase concentrations of other drugs metabolized by this enzyme, inlcuding cilostazol. Consider up to a 50% reduction in cilostazol dosage when coadministered with imatinib. The combination may also cause an additive risk of bleeding.
Cimetidine: (Minor) Imatinib, STI-571 is metabolized by cytochrome P450 3A4, which can be inhibited by cimetidine. During concurrent use, clinicians should be aware of the potential increase risk of imatinib toxicity.
Ciprofloxacin: (Moderate) Increased imatinib serum levels and toxicity may result with concurrent use of ciprofloxacin. Close monitor patients for any signs of toxicity, such as meylosuppression, fluid retention, and bleeding. Ciprofloxacin may inhibit the metabolism of imatinib via CYP3A4 inhibition.
Cisapride: (Contraindicated) Imatinib is a potent inhibitor of cytochrome P450 CYP 3A4 and may increase concentrations of cisapride if coadministered. Increased concentrations of cisapride have lead to QT prolongation and ventricular arrhythmias, including torsade de pointes and death. Because of the potential severity of this drug interaction, imatinib should not be used with cisapride.
Clarithromycin: (Minor) Clarithromycin is a significant inhibitor of CYP3A4 isoenzymes and should be used cautiously with CYP3A4 substrates, such as imatinib, due to the potential for reduced metabolism and drug accumulation.
Clomipramine: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Clonazepam: (Moderate) CYP3A4 inhibitors, such as imatinib, may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity.
Clorazepate: (Moderate) Imatinib, STI-571 may inhibit the metabolism of clorazepate and leading to increased levels and potential toxicity. Monitor patients closely who receive concurrent therapy.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. Additionally, clozapine is a CYP2D6 substrate and imatinib, STI-571 is a potent inhibitor of CYP2D6, Treatment with clozapine has been associated

with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP2D6 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with imatinib, STI-571 as there is a potential for elevated imatinib and/or cobicistat concentrations. Imatinib is a CYP3A4 substrate and moderate iinhibitor, a weak inhibitor of CYP2D6, and a breast cancer resistance protein (BCRP) substrate. Cobicistat is a strong inhibitor of CYP3A4, a BCRP inhibitor, and a substrate of CYP2D6 and CYP3A4. Coadministration of imatinib with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic imatinib, STI-571 therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of imatinib is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of imatinib, resume cobimetinib at the previous dose. Use an alternative to imatinib in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a CYP3A substrate in vitro, and imatinib is a moderate inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Codeine: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of codeine until stable drug effects are achieved. Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Imatinib is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Colchicine: (Major) Avoid concomitant use of colchicine and imatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Conjugated Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as imatinib, STI-571 may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as imatinib, STI-571 may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as imatinib, STI-571 may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Crizotinib: (Moderate) Monitor for an increase in crizotinib-related adverse reactions if coadministration with imatinib is necessary. Crizotinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme. Concurrent administration of cyclosporine and imatinib may result in increased concentrations of cyclosporine due to decreased metabolism. Monitoring of cyclosporine concentrations is warranted.
Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with imatinib, a moderate CYP3A4 inhibitor, may increase daclatasvir. In addition, the therapeutic effects of imatinib, a substrate for the breast cancer resistant protein (BCRP), may be increased by daclatasvir, a BCRP inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dapagliflozin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and imatinib, STI-571 are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as imatinib, STI-571.
Dapsone: (Minor) Imatinib, STI-571 may inhibit the metabolism of dapsone and leading to increased levels and potential toxicity. Monitor patients closely who receive concurrent therapy.
Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with imatinib. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
Darifenacin: (Moderate) Clinicians should monitor patients for increased anticholinergic effects when CYP2D6 inhibitors, such as imatinib, are coadministered with darifenacin; the dosage of darifenacin should be adjusted, if necessary.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with imatinib, STI-571 as there is a potential for elevated imatinib and/or cobicistat concentrations. Imatinib is a CYP3A4 substrate and moderate iinhibitor, a weak inhibitor of CYP2D6, and a breast cancer resistance protein (BCRP) substrate. Cobicistat is a strong inhibitor of CYP3A4, a BCRP inhibitor, and a substrate of CYP2D6 and CYP3A4. Coadministration of imatinib with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with imatinib, STI-571 as there is a potential for elevated imatinib and/or cobicistat concentrations. Imatinib is a CYP3A4 substrate and moderate iinhibitor, a weak inhibitor of CYP2D6, and a breast cancer resistance protein (BCRP) substrate. Cobicistat is a strong inhibitor of CYP3A4, a BCRP inhibitor, and a substrate of CYP2D6 and CYP3A4. Coadministration of imatinib with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with imatinib. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; imatinib is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Delavirdine: (Moderate) Coadministration may result in elevated plasma concentrations of both drugs. Imatinib is a CYP3A4 substrate and moderate CYP3A4 inhibitor. Delavirdine is a CYP3A4 substrate and strong CYP3A4 inhibitor.
Desipramine: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Bupropion: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Quinidine: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may inhibit quinidine metabolism leading to increased concentrations and risk of adverse reactions. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Diazepam: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including diazepam.
Dienogest; Estradiol valerate: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Dihydroergotamine: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Diltiazem: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including diltiazem.
Disopyramide: (Major) Imatinib is a potent inhibitor of cytochrome P450 CYP 3A4. Disopyramide is a CYP3A4 substrate and coadministration with imatinib may increase serum plasma concentrations of disopyramide.
Docetaxel: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including docetaxel.
Dofetilide: (Major) Imatinib could significantly inhibit the CYP3A4 metabolism of dofetilide. The resultant increase in serum dofetilide concentrations could increase the risk of torsade de pointes.
Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering imatinib, STI-571 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Imatinib is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Donepezil: (Moderate) Imatinib, STI-571 is a potent inhibitor of CYP3A4 and 2D6, the two isoenzymes involved in the metabolism of donepezil. The clinical effect of these interactions on the response to donepezil have not been determined.
Donepezil; Memantine: (Moderate) Imatinib, STI-571 is a potent inhibitor of CYP3A4 and 2D6, the two isoenzymes involved in the metabolism of donepezil. The clinical effect of these interactions on the response to donepezil have not been determined.
Dorzolamide; Timolol: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 2D6 and might decrease the hepatic metabolism of timolol. This interaction may be more pronounced in extensive metabolizers. Clinicians should be alert to exaggerated beta-blocker effects if the timolol is given with these drugs.
Doxepin: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as imatinib, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Doxorubicin Liposomal: (Major) Imatinib, STI-571 is an inhibitor of CYP2D6 and CYP3A4; doxorubicin is a major CYP2D6 and CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of imatinib and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Imatinib, STI-571 is an inhibitor of CYP2D6 and CYP3A4; doxorubicin is a major CYP2D6 and CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of imatinib and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Major) Use caution if coadministration of dronabinol with imatinib is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Dronabinol is a 3A4 substrate; imatinib is a moderate inhibitor of 3A4.
Drospirenone; Estradiol: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Dutasteride: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like imatinib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Dutasteride; Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of imatinib, STI-571. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as imatinib, STI-571, should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like imatinib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with imatinib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; imatinib is a moderate CYP3A inhibitor.
Elacestrant: (Major) Avoid concomitant use of elacestrant and imatinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elagolix; Estradiol; Norethindrone acetate: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with imatinib, STI-571 may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Imatinib is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. In addition, imatinib is a substrate for the breast cancer resistance protein (BCRP), while both elbasvir and grazoprevir are BCRP inhibitors. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with imatinib. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and imatinib is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with imatinib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); imatinib is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If imatinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to every other day in the morning when coadministered with imatinib; omit the ivacaftor evening dose and administer in the morning every other day alternating with elexacaftor; tezacaftor; ivacaftor (i.e., recommended dose of elexacaftor; tezacaftor; ivacaftor on day 1 in the morning and recommended dose of ivacaftor on day 2 in the morning). Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; imatinib is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 2.9-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2.1-fold, respectively.
Eliglustat: (Major) Coadministration of imatinib, STI-571 and eliglustat is contraindicated in extensive and intermediate CYP2D6 metabolizers (EMs or IMs) and not recommended in CYP26 poor metabolizers (PMs). Imatinib is an inhibitor of both CYP2D6 and CYP3A4. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of imatinib and eliglustat may result in significantly increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Eltrombopag: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and imatinib, STI-571 are coadministered. Eltrombopag is an inhibitor of Breast Cancer Resistance Protein (BCRP). Drugs that are substrates for this transporter, such as imatinib, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with imatinib, STI-571 as there is a potential for elevated imatinib and/or cobicistat concentrations. Imatinib is a CYP3A4 substrate and moderate iinhibitor, a weak inhibitor of CYP2D6, and a breast cancer resistance protein (BCRP) substrate. Cobicistat is a strong inhibitor of CYP3A4, a BCRP inhibitor, and a substrate of CYP2D6 and CYP3A4. Coadministration of imatinib with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with imatinib, STI-571 as there is a potential for elevated imatinib and/or cobicistat concentrations. Imatinib is a CYP3A4 substrate and moderate iinhibitor, a weak inhibitor of CYP2D6, and a breast cancer resistance protein (BCRP) substrate. Cobicistat is a strong inhibitor of CYP3A4, a BCRP inhibitor, and a substrate of CYP2D6 and CYP3A4. Coadministration of imatinib with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering imatinib, STI-571 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Imatinib is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering imatinib, STI-571 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Imatinib is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Encorafenib: (Major) Avoid coadministration of encorafenib and imatinib due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of imatinib. If imatinib is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of imatinib. Encorafenib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with imatinib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If imatinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of imatinib. Entrectinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Enzalutamide: (Major) Avoid coadministration of imatinib with enzalutamide if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Imatinib is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Ergoloid Mesylates: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Ergot alkaloids: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Ergotamine: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Ergotamine; Caffeine: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Erythromycin: (Moderate) Any agent that inhibits cytochrome P450 3A4, such as erythromycin, may decrease the metabolism of imatinib and increase imatinib concentrations leading to an increased incidence of adverse reactions.
Estazolam: (Moderate) Imatinib is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity.
Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as imatinib, STI-571 may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as imatinib, STI-571 may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Levonorgestrel: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Norethindrone: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Norgestimate: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Progesterone: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as imatinib, STI-571 may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as imatinib may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as imatinib may increase the serum concentration of etonogestrel.
Etravirine: (Moderate) Monitor for evidence of increased etravirine-related adverse effects if coadministered with imatinib. Etravirine exposure may be increased during concurrent use. Etravirine is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with imatinib is necessary. The dose of everolimus may need to be reduced. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Imatinib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4/P-gp inhibitors increased the AUC of everolimus by 3.5 to 4.4-fold.
Ezetimibe; Simvastatin: (Major) Imatinib, STI-571 inhibits the metabolism of simvastatin via CYP3A4. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively. Increases in serum concentrations of simvastatin may lead to myopathy and rhabdomyolysis.
Felodipine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including felodipine.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like imatinib can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If imatinib is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finasteride; Tadalafil: (Major) Tadalafil is metabolized predominantly by CYP3A4. Potent inhibitors of CYP3A4, such as imatinib, STI-571, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. The manufacturer of tadalafil recommends that in patients receiving concomitant potent CYP3A4 inhibitors, the 'as needed' dose for erectile dysfunction should not exceed 10 mg within a 72 hour time period, and the 'once-daily' dose for erectile dysfunction or benign prostatic hyperplasia should not exceed 2.5 mg. It should be noted that during once daily administration of tadalafil, the presence of continuous plasma tadalafil concentrations may change the potential for interactions with potent inhibitors of CYP3A4. When used for pulmonary arterial hypertension, tadalafil should not be co-administered with potent CYP3A inhibitors.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or imatinib; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased overall exposure to finerenone by 248%.
Flecainide: (Major) Flecainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering flecainide with CYP2D6 inhibitors including imatinib; flecainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as imatinib, STI-571, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Moderate) Fluconazole may inhibit the metabolism of imatinib, STI-571 via cytochrome P450 3A4. Increased imatinib serum levels and toxicity may result with concurrent use of fluconazole. Close monitor patients for any signs of toxicity.
Fluoxetine: (Moderate) Agents that inhibit cytochrome P450 3A4, such as fluoxetine, may decrease imatinib, STI-571 metabolism and increase concentrations leading to toxicity.
Flurazepam: (Moderate) Imatinib, STI-571 may inhibit the metabolism of flurazepam and leading to increased levels and potential toxicity. Monitor patients closely who receive concurrent therapy.
Fluvastatin: (Moderate) Monitor for evidence of fluvastatin-related toxicity including myopathy and rhabdomyolysis if fluvastatin is coadministered with imatinib. Concurrent use may result in clinically significant increased levels of fluvastatin. Imatinib is a moderate CYP3A4 inhibitor; fluvastatin is a CYP3A4 substrate.
Fosphenytoin: (Major) Avoid coadministration of imatinib and fosphenytoin if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Fostamatinib: (Moderate) Monitor for imatinib toxicities that may require imatinib dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a BCRP substrate may increase the concentration of the BCRP substrate. The active metabolite of fostamatinib, R406, is a BCRP inhibitor; imatinib is a substrate for BCRP. Coadministration of fostamatinib with another BCRP substrate increased the substrate AUC by 95% and Cmax by 88%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and imatinib as coadministration may increase serum concentrations of imatinib and increase the risk of adverse effects. Imatinib is a substrate of the breast cancer resistance protein (BCRP) transporter; glecaprevir is an inhibitor of BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and imatinib as coadministration may increase serum concentrations of imatinib and increase the risk of adverse effects. Imatinib is a substrate of the breast cancer resistance protein (BCRP) transporter; pibrentasvir is an inhibitor of BCRP.
Glimepiride: (Moderate) Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like imatinib. Monitor serum glucose concentrations if glimepiride is coadministered with imatinib. Dosage adjustments may be necessary.
Grapefruit juice: (Major) Any agent that inhibits cytochrome P450 CYP 3A4, such as grapefruit juice, may decrease the metabolism of imatinib and increase imatinib concentrations leading to an increased incidence of adverse reactions. Monitor patient closely.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Imatinib may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon imatinib discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and imatinib is a moderate CYP3A4 inhibitor.
Haloperidol: (Moderate) Imatinib, STI-571 is an inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like imatinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If imatinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ibrutinib: (Major) If ibrutinib is coadministered with imatinib, reduce the initial ibrutinib dosage to 280 mg/day PO in patients receiving ibrutinib for B-cell malignancy. Resume ibrutinib at the previous dosage if imatinib is discontinued. No initial ibrutinib dosage adjustment is necessary in patients receiving ibrutinib for chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); modify the ibrutinib dosage as recommended if toxicity occurs. Ibrutinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the AUC value of ibrutinib weas increased by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like imatinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If imatinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with imatinib, STI-571, a CYP3A substrate, as imatinib, STI-571 toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with imatinib is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Imatinib is a moderate CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Imipramine: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Infigratinib: (Major) Avoid concomitant use of infigratinib and imatinib. Coadministration may increase infigratinib exposure, increasing the risk of adverse effects. Infigratinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with imatinib, STI-571 may result in increased serum concentrations of both drugs. Imatinib is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of imatinib and rifampin if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of imatinib and rifampin if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Isradipine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including isradipine.
Itraconazole: (Moderate) Use caution if coadministration of itraconazole and imatinib is necessary due to increased imatinib exposure and adverse effects. Imatinib is a CYP3A4 and breast cancer resistance protein (BCRP) substrate; and itraconazole is a BCRP inhibitor and strong CYP3A4 inhibitor. Coadminsitration of another CYP3A4 inhibitor increased imatinib exposure by 40%.
Ivabradine: (Major) Avoid coadministration of ivabradine and imatinib, STI-571 as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; imatinib inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If imatinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with imatinib due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Ivosidenib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A4 inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ixabepilone: (Major) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of imatinib is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Ketoconazole: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with ketoconazole is necessary. Imatinib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased imatinib exposure by 40%.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Clarithromycin is a significant inhibitor of CYP3A4 isoenzymes and should be used cautiously with CYP3A4 substrates, such as imatinib, due to the potential for reduced metabolism and drug accumulation.
Larotrectinib: (Moderate) Monitor for an increase in larotrectinib-related adverse reactions if concomitant use with imatinib is necessary. Concomitant use may increase larotrectinib exposure. Larotrectinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase larotrectinib exposure by 2.7-fold.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with imatinib as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. The effect of moderate inhibitors on lefamulin has not been studied; however, use of a st rong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and imatinib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; imatinib mesylate is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lesinurad: (Moderate) Use lesinurad and imatinib, STI-571 together with caution; imatinib may increase the systemic exposure of lesinurad. Imitinab is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Lesinurad; Allopurinol: (Moderate) Use lesinurad and imatinib, STI-571 together with caution; imatinib may increase the systemic exposure of lesinurad. Imitinab is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Letermovir: (Moderate) Plasma concentrations of imatinib could be significantly elevated when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If these drugs are given together, closely monitor for imatinib-related adverse events. Imatinib is primarily metabolized by CYP3A4. Letermovir is a moderate inhibitor of CYP3A4; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent administration with another strong CYP3A4 inhibitor significantly increased the mean Cmax and AUC of imatinib by 26% and 40%, respectively.
Levamlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Levoketoconazole: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with ketoconazole is necessary. Imatinib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased imatinib exposure by 40%.
Lidocaine: (Moderate) Monitor for lidocaine-related toxicity when administering with imatinib; lidocaine exposure may increase. Imatinib is a moderate CYP3A4 inhibitor; lidocaine is a CYP3A4 substrate.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine-related toxicity when administering with imatinib; lidocaine exposure may increase. Imatinib is a moderate CYP3A4 inhibitor; lidocaine is a CYP3A4 substrate.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine-related toxicity when administering with imatinib; lidocaine exposure may increase. Imatinib is a moderate CYP3A4 inhibitor; lidocaine is a CYP3A4 substrate.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lomitapide: (Contraindicated) Concomitant use of imatinib, STI-571 and lomitapide is contraindicated. If treatment with imatinib is unavoidable, lomitapide should be stopped during the course of treatment. Imatinib is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and imatinib is contraindicated; concurrent use may increase the exposure of both drugs and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; imatinib is a CYP3A4 substrate and moderate CYP3A4 inhibitor.
Losartan: (Minor) Imatinib, STI-571 is a potent inhibitor of the hepatic CYP2C9 isoenzyme and may inhibit the conversion of losartan to its more active metabolite E-3174. Monitor patients response to therapy closely if imatinib is added or discontinued in a patient receiving losartan.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Imatinib, STI-571 is a potent inhibitor of the hepatic CYP2C9 isoenzyme and may inhibit the conversion of losartan to its more active metabolite E-3174. Monitor patients response to therapy closely if imatinib is added or discontinued in a patient receiving losartan.
Lovastatin: (Major) Imatinib, STI-571 is a potent inhibitor of the cytochrome P450 3A4 isoenzyme. Concurrent use of lovastatin and imatinib may result in increased levels of lovastatin and potential toxicity. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of imatinib and lumacaftor; ivacaftor if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and the net effect of combination lumacaftor; ivacaftor is strong CYP3A4 induction. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib. (Major) If imatinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of imatinib and lumacaftor; ivacaftor if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and the net effect of combination lumacaftor; ivacaftor is strong CYP3A4 induction. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Lumateperone: (Major) Reduce the dose of lumateperone to 21 mg once daily if concomitant use of imatinib is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased lumateperone exposure by approximately 2-fold.
Lurasidone: (Major) Imatinib is a moderate inhibitor of CYP3A4 and has the potential for interactions with substrates of CYP3A4 such as lurasidone. Concurrent use of these medications may lead to an increased risk of lurasidone-related adverse reactions. If a moderate inhibitor of CYP3A4 is being prescribed and lurasidone is added in an adult patient, the recommended starting dose of lurasidone is 20 mg/day and the maximum recommended daily dose of lurasidone is 80 mg/day. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Patients should be monitored for efficacy and toxicity.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and imatinib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Maprotiline: (Major) Imatinib, STI-571 is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering imatinib with other CYP2D6 substrates, such as maprotiline, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with imatinib is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and imatinib is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting imatinib therapy. Avoid initiation of imatinib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable imatinib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Imatinib is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Metformin; Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Imatinib, STI-571 is an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Metformin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and imatinib, STI-571 are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as imatinib, STI-571.
Methadone: (Moderate) The concurrent administration of methadone and inhibitors of cytochrome P450 3A4, such as imatinib, may result in increased concentrations of methadone. Inhibition of methadone metabolism can lead to toxicity including CNS adverse effects and potential for QT prolongation and torsades de pointes when high doses of methadone are used.
Methamphetamine: (Major) Imatinib is a potent inhibitor of cytochrome P450 (CYP) 2D6 and may increase concentrations of methamphetamine.
Methohexital: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Methylergonovine: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; imatinib is a moderate CYP2D6 inhibitor. In the presence of another moderate CYP2D6 inhibitor, the AUC of metoprolol was increased by 3.29-fold with no effect on the cardiovascular response to metoprolol.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; imatinib is a moderate CYP2D6 inhibitor. In the presence of another moderate CYP2D6 inhibitor, the AUC of metoprolol was increased by 3.29-fold with no effect on the cardiovascular response to metoprolol.
Mexiletine: (Major) Because mexiletine is metabolized by CPY 2D6, imatinib, STI-571, a potent inhibitor of cytochrome P450 2D6, might decrease the metabolism of mexiletine. Clinicians should be aware of the potential for severe adverse reactions.
Midazolam: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may inhibit midazolam metabolism leading to increased levels and potential toxicity. Monitor patients closely who receive concurrent therapy.
Mifepristone: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with mifepristone is necessary. Imatinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased imatinib exposure by 40%.
Mitapivat: (Moderate) Do not exceed mitapivat 20 mg PO twice daily during coadministration with imatinib and monitor hemoglobin and for adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased mitapivat overall exposure by 2.6-fold.
Mitotane: (Major) Avoid coadministration of imatinib and mitotane if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and imatinib; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions. Mobocertinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Use of a moderate CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 100% to 200%.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and imatinib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with imatinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of imatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with imatinib, STI-571. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as imatinib, STI-571, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with imatinib, STI-571. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as imatinib, STI-571, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nefazodone: (Moderate) Inhibitors of cytochrome P450 3A4, such as nefazodone, may decrease metabolism and increase imatinib, STI-571 concentrations leading to adverse reactions. However, interactions have not been studied.
Neratinib: (Major) Avoid concomitant use of imatinib with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as imatinib, STI-571. The plasma concentrations of CYP3A4 substrates can increase when co-administered with netupitant. The inhibitory effect on CYP3A4 can last for multiple days. If coadministration is necessary, use caution and monitor for chemotherapeutic related adverse reactions.
Niacin; Simvastatin: (Major) Imatinib, STI-571 inhibits the metabolism of simvastatin via CYP3A4. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively. Increases in serum concentrations of simvastatin may lead to myopathy and rhabdomyolysis.
Nicardipine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including nicardipine.
Nifedipine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including nifedipine.
Nilotinib: (Major) The concomitant use of nilotinib and imatinib resulted in increased levels of both drugs in a phase I study. Both nilotinib and imatinib are a substrates and moderate inhibitors of CYP3A4. Following the administration of nilotinib 400 mg twice daily in combination with imatinib 400 mg once daily or imatinib 400 mg twice daily in a phase I study, the AUC values were increased by 30 to 50% for nilotinib and by about 20% for imatinib. These agents may be used together; monitor patients for nilotinib or imatinib toxicity including QT interval prolongation.
Nimodipine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including nimodipine.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with imatinib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and imatinib is a CYP3A4 inhibitor.
Nortriptyline: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Olanzapine; Fluoxetine: (Moderate) Agents that inhibit cytochrome P450 3A4, such as fluoxetine, may decrease imatinib, STI-571 metabolism and increase concentrations leading to toxicity.
Olaparib: (Major) Avoid coadministration of olaparib with imatinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after imatinib is discontinued. Olaparib is a CYP3A substrate and imatinib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and imatinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and imatinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If imatinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and imatinib. If concomitant use is necessary, decrease omaveloxolone dose to 100 mg once daily; additional dosage reductions may be necessary. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased omaveloxolone overall exposure by 1.25-fold.
Oritavancin: (Moderate) Coadministration of oritavancin and imatinib, STI-571 may result in increases or decreases in imatinib exposure and may increase side effects or decrease efficacy of imatinib. Imatinib is primarily metabolized by CYP3A4, but is also metabolized by CYP2D6, CYP2C9, and CYP2C19. Oritavancin weakly induces CYP3A4 and CYP2D6, while weakly inhibiting CYP2C9 and CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
Osimertinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with osimertinib is necessary. Imatinib is a BCRP substrate and osimertinib is a BCRP inhibitor.
Oxybutynin: (Moderate) Oxybutynin is metabolized by CYP3A4. Serum concentrations of oxybutynin may be increased if coadministered with inhibitors of CYP3A4 including imatinib. The manufacturer recommends that caution when oxybutynin is co-administered with CYP3A4 inhibitors.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like imatinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If imatinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Paclitaxel: (Minor) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering imatinib with other CYP3A4 substrates including paclitaxel.
Pacritinib: (Major) Avoid concurrent use of pacritinib with imatinib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Palovarotene: (Major) Avoid concomitant use of palovarotene and imatinib due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. If concomitant use is necessary, decrease the palovarotene dose by half. Palovarotene is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased palovarotene overall exposure by 2.5-fold.
Paricalcitol: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as imatinib. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with imatinib is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and imatinib is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of and substrate for CYP3A4. Imatinib is an inhibitor of and substrate for CYP3A4. Concurrent administration may result in increased pazopanib concentrations and/or increased imatinib, STI-571 concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and imatinib is required.
Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and imatinib due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If imatinib is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of imatinib. Pemigatinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase pemigatinib exposure by approximately 50% to 80%.
Pentobarbital: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Pentosan: (Major) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with pentosan.
Perindopril; Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Perphenazine: (Moderate) Imatinib is a potent inhibitor of cytochrome P4502D6 and might decrease perphenazine metabolism leading to increased adverse reactions.
Perphenazine; Amitriptyline: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation. (Moderate) Imatinib is a potent inhibitor of cytochrome P4502D6 and might decrease perphenazine metabolism leading to increased adverse reactions.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and imatinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If imatinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of imatinib. Pexidartinib is a CYP3A substrate; imatinib is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Phenobarbital: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Phentermine; Topiramate: (Moderate) Imatinib is a potent inhibitors of cytochrome P450 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions.
Phenytoin: (Major) Avoid coadministration of imatinib and phenytoin if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Pimozide: (Contraindicated) Concurrent use of pimozide and imatinib, STI-571 should be avoided. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Imatinib, STI-571 is an inhibitor of CYP3A4 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Concurrent use of CYP3A4 inhibitors or potent CYP2D6 inhibitors and pimozide is contraindicated by the manufacturer of pimozide.
Pioglitazone; Glimepiride: (Moderate) Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like imatinib. Monitor serum glucose concentrations if glimepiride is coadministered with imatinib. Dosage adjustments may be necessary.
Porfimer: (Major) Avoid coadministration of porfimer with imatinib due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like imatinib may increase the risk of a photosensitivity reaction.
Posaconazole: (Moderate) Posaconazole and imatinib, STI-571 should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and imatinib are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of imatinib. Further, both imatinib and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and imatinib, ultimately resulting in an increased risk of adverse events.
Pralsetinib: (Major) Avoid concomitant use of imatinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Primidone: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and imatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Promethazine; Dextromethorphan: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Propafenone: (Major) Imatinib is a potent inhibitor of cytochrome P450 2D6 and may increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering imatinib with CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions including propafenone.
Propranolol: (Moderate) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as imatinib, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as imatinib, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
Protease inhibitors: (Major) Protease Inhibitors inhibit cytochrome P450 CYP3A4 and may decrease the metabolism of imatinib and increase imatinib concentrations leading to an increased incidence of adverse reactions. In addition, because imatinib inhibits CYP2C9, CYP2D6, and CYP3A4/5, the metabolism of protease inhibitors may be decreased by imatinib. Close monitoring of the antiviral and antineoplastic responses is recommended.
Protriptyline: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Quazepam: (Moderate) CYP3A4 inhibitors, such as imatinib, may reduce the metabolism of quazepam and increase the potential for benzodiazepine toxicity.
Quetiapine: (Moderate) The cytochrome P450 3A4 isoenzyme is involved in the metabolism of quetiapine. Imatinib, STI-571 may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
Quinidine: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may inhibit quinidine metabolism leading to increased concentrations and risk of adverse reactions.
Ramelteon: (Moderate) Coadministration of ramelteon with inhibitors of CYP3A4, such as imatinib, may lead to increases in the serum concentrations of ramelteon.
Ranolazine: (Contraindicated) Ranolazine is metabolized mainly by CYP3A. According to the manufacturer, ranolazine is contraindicated in patients receiving drugs known to be strong CYP3A inhibitors. Inhibition of ranolazine metabolism could lead to increased ranolazine plasma concentrations and associated QTc prolongation. Although not specifically mentioned by the manufacturer of ranolazine, imatinib, STI-571 is known to be a strong inhibitor of CYP3A4. In addition, ranolazine is metabolized to a lesser extent by CYP2D6; imatinib, STI-571 is a known CYP2D6 inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Minor) As imatinib inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Imatinib, STI-571 is an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Ribociclib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with ribociclib is necessary. Imatinib is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with ribociclib is necessary. Imatinib is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Rifampin: (Major) Avoid coadministration of imatinib and rifampin if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Rifapentine: (Major) Avoid coadministration of imatinib and rifapentine if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering imatinib, STI-571 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Imatinib is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with imatinib; concurrent use may increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Rivaroxaban: (Major) Due to the thrombocytopenic effects of imatinib an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. Coadministration of rivaroxaban and imatinib, STI-571 may also result in increases in rivaroxaban exposure, which may increase bleeding risk. Imatinib is an inhibitor of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Rolapitant: (Moderate) Monitor for imatinib-related adverse reactions if coadministration of these drugs is required. Imatinib is a substrate of the breast cancer resistance protein (BCRP) transporter; rolapitant is a BCRP inhibitor.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Imatinib, STI-571 is an inhibitor of CYP3A4. Concurrent administration of romidepsin with an inhibitor of CYP3A4 may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary.
Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as imatinib, STI-571, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure.
Safinamide: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as imatinib. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and imatinib, STI-571 are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as imatinib, STI-571.
Secobarbital: (Major) Avoid coadministration of imatinib and barbiturates if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone, a CYP3A4 substrate and a moderate CYP3A4 inhibitor, such as imatinib may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and imatinib due to the risk of increased selpercatinib exposure which may increase the risk of adverse reactions, including QT prolongation. If coadministration is unavoidable, reduce the dose of selpercatinib to 80 mg PO twice daily if original dose was 120 mg twice daily, and to 120 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If imatinib is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of imatinib. Selpercatinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase selpercatinib exposure by 60% to 99%.
Selumetinib: (Major) Avoid coadministration of selumetinib and imatinib due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If imatinib is discontinued, resume the original selumetinib dose after 3 elimination half-lives of imatinib. Selumetinib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase selumetinib exposure by 41%.
Sertraline: (Major) Sertraline is a substrate for the CYP isoenzymes 3A4, 2D6 and 2C19. Imatinib is a potent inhibitor of cytochrome P450 2D6 and 3A4 and might decrease sertraline metabolism leading to increased adverse reactions.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with imatinib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as imatinib, STI-571 may cause significant increases in silodosin plasma concentrations.
Simvastatin: (Major) Imatinib, STI-571 inhibits the metabolism of simvastatin via CYP3A4. Concurrent use of simvastatin and imatinib resulted in 2- and 3.5-fold increases in simvastatin Cmax and AUC values, respectively. Increases in serum concentrations of simvastatin may lead to myopathy and rhabdomyolysis.
Siponimod: (Moderate) Concomitant use of siponimod and imatinib may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of imatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sirolimus overall exposure 1.6-fold.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with imatinib. Taking these medications together may increase the plasma concentrations of imatinib, potentially resulting in adverse events. Imatinib is a substrate for the drug transporter Breast Cancer Resistance Protein (BCRP). Velpatasvir is an inhibitor of BCRP.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir and imatinib. Taking these medications together may increase the plasma concentrations of imatinib, potentially resulting in adverse events. Imatinib is a substrate for the drug transporter Breast Cancer Resistance Protein (BCRP). Voxilaprevir is an inhibitor of BCRP. (Moderate) Use caution when administering velpatasvir with imatinib. Taking these medications together may increase the plasma concentrations of imatinib, potentially resulting in adverse events. Imatinib is a substrate for the drug transporter Breast Cancer Resistance Protein (BCRP). Velpatasvir is an inhibitor of BCRP.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and imatinib, STI-571; sonidegib levels may be significantly increased resulting in increased risk of adverse events, particularly musculoskeletal toxicity. Sonidegib is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A4 inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days.
Sparsentan: (Moderate) Monitor for an increase in sparsentan-related adverse effects if concomitant use with imatinib is necessary. Concomitant use may increase sparsentan exposure. Sparsentan is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sparsentan overall exposure by 70%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of imatinib and St. John's Wort if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if imatinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of imatinib is necessary. If imatinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like imatinib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If imatinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Suvorexant: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with imatinib. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with imatinib is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; imatinib is a moderate CYP3A4 inhibitor.
Tadalafil: (Major) Tadalafil is metabolized predominantly by CYP3A4. Potent inhibitors of CYP3A4, such as imatinib, STI-571, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. The manufacturer of tadalafil recommends that in patients receiving concomitant potent CYP3A4 inhibitors, the 'as needed' dose for erectile dysfunction should not exceed 10 mg within a 72 hour time period, and the 'once-daily' dose for erectile dysfunction or benign prostatic hyperplasia should not exceed 2.5 mg. It should be noted that during once daily administration of tadalafil, the presence of continuous plasma tadalafil concentrations may change the potential for interactions with potent inhibitors of CYP3A4. When used for pulmonary arterial hypertension, tadalafil should not be co-administered with potent CYP3A inhibitors.
Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and imatinib due to the potential for increased plasma concentrations of imatinib resulting increasing the risk of adverse effects. Imatinib dose adjustment may be needed with coadministration. Imatinib is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of imatinib, STI-571. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as imatinib, STI-571, should be avoided.
Tasimelteon: (Moderate) Caution is recommended d uring concurrent use of tasimelteon and imatinib, STI-571. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as imatinib, may increase exposure to tasimelteon with the potential for adverse reactions.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with imatinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If imatinib is discontinued, wait at least 3 half-lives of imatinib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Tedizolid: (Moderate) If possible, stop use of imatinib temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for imatinib-associated adverse events. Imatinib, STI-571 plasma concentrations may be increased when administered concurrently with oral tedizolid. Imatinib is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine.
Telmisartan; Amlodipine: (Moderate) Administering amlodipine with CYP3A4 inhibitors, such as imatinib, may increase the plasma concentration of amlodipine; this effect might lead to hypotension in some individuals. Caution should be used when imatinib is coadministered with amlodipine; therapeutic response should be monitored.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering imatinib, STI-571. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; imatinib is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with imatinib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); imatinib is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If imatinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Thioridazine: (Contraindicated) Imatinib is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
Thyroid hormones: (Moderate) Monitor thyroid stimulating hormone (TSH) concentrations carefully when tyrosine kinase inhibitors like imatinib are used in patients taking thyroid hormones. Cases of clinical hypothyroidism have occurred in patients taking imatinib.
Timolol: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 2D6 and might decrease the hepatic metabolism of timolol. This interaction may be more pronounced in extensive metabolizers. Clinicians should be alert to exaggerated beta-blocker effects if the timolol is given with these drugs.
Tolbutamide: (Major) Imatinib is a potent inhibitor of cytochrome P450 2C9 and might decrease the metabolism of tolbutamide leading to hypoglycemia. Blood glucose concentration should be monitored in patients requiring concurrent treatment with these agents.
Tolterodine: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 CYP2D6 and 3A4. Tolterodine is metabolized primarily by CYP2D6 and alternatively, CYP3A4 in those patients who are poor metabolizers of tolterodine via CYP2D6. It is not known if dosage adjustments are required in patients requiring concurrent therapy, but patients should be monitored for increased anticholinergic effects.
Tolvaptan: (Major) Avoid coadministration of imatinib when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with imatinib. In ADPKD patients receiving tolvaptan 90mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Tolvaptan is a sensitive CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased the tolvaptan AUC by 200%.
Topiramate: (Moderate) Imatinib is a potent inhibitors of cytochrome P450 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions.
Tramadol: (Moderate) Since tramadol is primarily metabolized by cytochrome P450 isoenzyme CYP2D6, agents that inhibit this enzyme, such as imatinib, decrease the metabolism of tramadol. Concomitant use of these agents and tramadol may increase plasma levels of tramadol and decrease concentration of the active metabolite leading to decreased analgesic effects and possibly increased side effects due to higher tramadol concentrations.
Tramadol; Acetaminophen: (Major) Imatinib, STI-571 may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib. Chronic acetaminophen therapy should be avoided in patients receiving imatinib. (Moderate) Since tramadol is primarily metabolized by cytochrome P450 isoenzyme CYP2D6, agents that inhibit this enzyme, such as imatinib, decrease the metabolism of tramadol. Concomitant use of these agents and tramadol may increase plasma levels of tramadol and decrease concentration of the active metabolite leading to decreased analgesic effects and possibly increased side effects due to higher tramadol concentrations.
Trandolapril; Verapamil: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including verapamil.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with imatinib and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Tricyclic antidepressants: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Trimipramine: (Major) Imatinib is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as the tricyclic antidepressants (TCAs). An increase in serum concentrations may increase the risk for TCA-related side effects, such as constipation, dizziness, difficulty with urination, xerostomia, fast or irregular heartbeat, and very rarely, QT prolongation.
Tucatinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with tucatinib is necessary. Imatinib is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ubrogepant: (Major) Limit the initial dose of ubrogepant to 50 mg and avoid a second dose within 24 hours if coadministered with imatinib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor resulted in a 3.5-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and imatinib, STI-571 is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with imatinib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; imatinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with imatinib due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of imatinib. Venetoclax is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor.
Venlafaxine: (Moderate) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 2D6 and might decrease venlafaxine metabolism leading to increased adverse reactions.
Verapamil: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including verapamil.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with imatinib is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like imatinib may increase the risk of a photosensitivity reaction.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with imatinib is necessary. Vinblastine is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Vincristine Liposomal: (Moderate) Imatinib, STI-571, inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vincristine: (Moderate) Imatinib, STI-571, inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with imatinib is necessary. Vinorelbine is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Voclosporin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with imatinib. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Clarithromycin is a significant inhibitor of CYP3A4 isoenzymes and should be used cautiously with CYP3A4 substrates, such as imatinib, due to the potential for reduced metabolism and drug accumulation.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and imatinib. Due to the thrombocytopenic effects of imatinib an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with imatinib, STI-571, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with voriconazole is necessary. Imatinib is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Warfarin: (Moderate) Due to the thrombocytopenic effects of imatinib an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, as well as thrombolytic agents. In addition, large doses of salicylates (3 to 4 g/day and greater) can cause hypoprothrombinemia, an additional risk factor for bleeding. The manufacturer recommends that patients who require anticoagulation while receiving imatinib should receive low-molecular weight heparin or standard heparin instead of warfarin. Coagulation parameters should be monitored closely if warfarin therapy is continued during imatinib therapy. Imatinib is a moderate inhibitor of CYP3A4 and the R-enantiomer is a CYP3A4 substrate, and therefore has potential to increase serum concentrations of warfarin. Since both imatinib and warfarin are highly protein bound (95% and 99%, respectively), displacement from plasma proteins may also occur. In a phase II trial of imatinib, a patient with Philadelphia positive chronic myelogenous leukemia in chronic phase developed cerebral and urinary tract bleeding while receiving imatinib 400 mg daily in combination with warfarin (dose not available). Although a significantly prolonged prothrombin time may have been the result of an increase in the patient's warfarin dose in the days preceding the bleeding, a drug interaction cannot be excluded.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with imatinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of imatinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Ziprasidone: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme system. The concurrent use of ziprasidone with CYP3A4 inhibitors, such as imatinib, may lead to decreased metabolism of ziprasidone.
Zolpidem: (Major) It is advisable to closely monitor zolpidem tolerability and safety during co-administration of CYP3A4 inhibitors, such as imatinib, STI-571, and consider using a lower dose of zolpidem to minimize the potential for adverse CNS effects. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.

Gleevec/Imatinib/Imatinib Mesylate Oral Tab: 100mg, 400mg

Adults

800 mg/day PO.

Geriatric

800 mg/day PO.

Adolescents

340 mg/m2 per day PO (maximum of 600 mg/day) for Ph+ ALL or chronic-phase CML.

Children

340 mg/m2 per day PO (maximum of 600 mg/day) for Ph+ ALL or chronic-phase CML.

Infants

Safety and efficacy not established.

Mechanism of Action: Imatinib is a protein tyrosine kinase inhibitor. Inhibition of the bcr-abl tyrosine kinase results in inhibition of proliferation and induces apoptosis in bcr-able positive cell lines and in fresh leukemic cells from Philadelphia chromosome positive chronic myelogenous leukemia. The activity of protein tyrosine kinases is tightly regulated since they function as mediators of cell growth, differentiation, and death. Numerous protein kinase genes have been identified as oncogenes associated with transforming retroviruses or human tumors. Protein tyrosine kinases are grouped based on structural similarities and cellular function as receptor tyrosine kinases and non-receptor tyrosine kinases. Receptor tyrosine kinases have an extracellular and a cytoplasmic portion. The receptor tyrosine kinases include the receptors for epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF). Non-receptor tyrosine kinases lack receptor-like features, but mediate critical cell signals of many cell surface receptors (e.g., growth factor receptor kinases, G-protein coupled receptors, B-cell receptor, T-cell receptor, and interferon gamma receptor). In addition, non-receptor tyrosine kinases interact with other proteins, lipids, and DNA. Non-receptor tyrosine kinases include Scr, the Janus kinases (Jaks), and Abl. Protein tyrosine kinases catalyze the transfer of phosphate from adenosine triphosphate (ATP) to the hydroxyl group of a tyrosine residue in the protein substrate. Imatinib competitively inhibits the ATP binding site on Abl, PDGF, SCF, and c-Kit tyrosine kinases and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.Chronic myelogenous leukemia is characterized by a genetic abnormality, the Philadelphia chromosome (Ph), resulting from the reciprocal translocation between the long arms of chromosomes 9 and 22. The resultant fusion protein, bcr-abl, is a constitutively active tyrosine kinase that is responsible for the development of CML. Imatinib causes growth arrest or apoptosis in cells that express bcr-abl but does not affect normal cells. Resistance to imatinib and subsequent disease relapse seem to be associated with a failure to maintain effective inhibition of Bcr-Abl activity. Resistance has been reported due to bcr-abl gene amplification or alteration of the amino acids of bcr-abl resulting in high levels of kinase activity even in the presence of imatinib.

Imatinib is administered orally. It is approximately 95% bound to plasma proteins, primarily albumin and a1-acid glycoprotein, at clinically relevant concentrations. Imatinib is metabolized via CYP450 isoenzymes, primarily CYP3A4. Its major active metabolite, N-demethylated piperazine derivative (CGP74588), has similar potency as the parent drug. In healthy volunteers, the elimination half-lives of imatinib CGP74588 were approximately 18 and 40 hours, respectively. In a 50 year old patient, the clearance of imatinib is predicted to be 8 L/hour in patients weighing 50 kg and 14 L/hour in patients weighing 100 kg; this represents an inter-patient variability of about 40%. Following an oral 14C-labeled dose of imatinib, approximately 81% of the dose (feces, 68%; urine, 14%) was eliminated within 7 days. Unchanged imatinib accounted for 25% of the dose (feces, 20%; urine, 5%) with the remainder excreted as metabolites.
 
Affected cytochrome P450 isoenzymes and transporters: CYP3A4, CYP2D6, BCRP
Imatinib is primarily metabolized via CYP3A4; it is metabolized via CYP1A2, CYP2D6, CYP2C9, and CYP2C19 to a lesser extent. Avoid the concomitant use of strong CYP3A4 inducers; consider at least a 50% dose increase if coadministration is unavoidable. Use imatinib cautiously in combination with strong CYP3A4 inhibitors. In vitro, imatinib is a potent competitive inhibitor of CYP2C9, CYP2D6, and CYP3A4/5. In drug interaction studies, imatinib was a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6; use caution if imatinib is coadministered with CYP3A4 and CYP2D6 substrates that have a narrow therapeutic index. Imatinib was a substrate for the breast cancer resistance protein (BCRP) transporter in an in vitro study.

Oral Route

Imatinib is well absorbed following oral administration; the mean absolute bioavailability is 98%. Peak plasma concentrations are reached within 2 to 4 hours of imatinib dosing. The mean imatinib AUC values increase proportionally over the dose range of 25 to 1,000 mg. When given once daily, imatinib accumulation is 1.5-to 2.5-fold at steady state. The plasma AUC for imatinib’s major active metabolite, N-demethylated metabolite (CGP74588), is about 15% of the AUC value for imatinib.

Pregnancy

Imatinib may cause fetal harm when administered during pregnancy based on human and animal data; postmarketing reports of spontaneous abortions and of infant congenital anomalies have been reported following imatinib use in pregnancy women. Advise females of reproductive potential to avoid pregnancy while taking imatinib. Discuss the potential hazard to the fetus if imatinib is used during pregnancy or if a patient becomes pregnant while taking this drug. In animal studies in rats, imatinib was teratogenic when given during organogenesis at doses approximately equal to the maximum imatinib dose of 800 mg/day based on body surface area.

According to the manufacturer, women should discontinue breast-feeding during imatinib therapy and for 1 month after the last dose because of the potential for serious adverse reactions in nursing infants. Imatinib and its active metabolite are excreted into human milk. Based on data from three breast feeding women taking imatinib, the milk:plasma ratio is roughly 0.5 for imatinib and about 0.9 for the active metabolite. Considering the combined concentration of imatinib and its active metabolite, a breast-fed infant could receive up to 10% of the maternal therapeutic dose based on body weight.