Imatinib - Drug Information PDF

11/12/2015
Imatinib:Druginformation
OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate
Copyright19782015Lexicomp,Inc.Allrightsreserved.
(Foradditionalinformationsee"Imatinib:Patientdruginformation"andsee"Imatinib:Pediatricdrug
information")
ForabbreviationsandsymbolsthatmaybeusedinLexicomp(showtable)
BrandNames:US Gleevec
BrandNames:Canada ACTImatinibApoImatinibGleevecTevaImatinib
PharmacologicCategory AntineoplasticAgent,BCRABLTyrosineKinaseInhibitorAntineoplastic
Agent,TyrosineKinaseInhibitor
Dosing:Adult Note:Treatmentmaybecontinueduntildiseaseprogressionorunacceptabletoxicity.The
optimaldurationoftherapyforchronicmyeloidleukemia(CML)incompleteremissionisnotyetdetermined.
DiscontinuingCMLtreatmentisnotrecommendedunlesspartofaclinicaltrial(Baccarani,2009).Imatinibis
associatedwithamoderateemeticpotentialantiemeticsmayberecommendedtopreventnauseaand
vomiting(Roila,2010).
Philadelphiachromosomepositive(Ph+)chronicmyeloidleukemia(CML):Oral:
Chronicphase:400mgoncedailymaybeincreasedto600mgdaily,iftolerated,fordiseaseprogression,
lackofhematologicresponseafter3months,lackofcytogeneticresponseafter612months,orloss
ofprevioushematologicorcytogeneticresponse.Anincreaseto800mgdailyhasbeenused(Cortes,
2010Hehlmann,2014).
Canadianlabeling:400mgoncedailymaybeincreasedto600800mgdaily
Accelerated phase or blast crisis: 600 mg once daily may be increased to 800 mg daily (400 mg twice
daily), if tolerated, for disease progression, lack of hematologic response after 3 months, lack of
cytogeneticresponseafter612months,orlossofprevioushematologicorcytogeneticresponse
Ph+acutelymphoblasticleukemia(ALL)(relapsedorrefractory):Oral:600mgoncedaily
Gastrointestinalstromaltumors(GIST)(adjuvanttreatmentfollowingcompleteresection): Oral: 400 mg
oncedailyrecommendedtreatmentduration:3years
GIST(unresectableand/ormetastaticmalignant):Oral:400mgoncedailymaybeincreasedupto800mg
daily (400 mg twice daily), if tolerated, for disease progression. Note: Significant improvement
(progressionfreesurvival,objectiveresponserate)wasdemonstratedinpatientswithKITexon9mutation
with 800 mg (versus 400 mg), although overall survival (OS) was not impacted. The higher dose did not
demonstrate a difference in time to progression or OS patients with Kit exon 11 mutation or wildtype
status(DebiecRychter,2006Heinrich,2009).
Canadianlabeling:400600mgdaily(dependingondiseasestage/progression)maybeincreasedto600
800mgdaily
Aggressivesystemicmastocytosis(ASM)witheosinophilia:Oral:Initiateat100mgoncedailytitrateupto
amaximumof400mgoncedaily(iftolerated)forinsufficientresponsetolowerdose
ASMwithoutD816VcKitmutationorcKitmutationstatusunknown:Oral:400mgoncedaily
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Dermatofibrosarcomaprotuberans(DFSP):Oral:400mgtwicedaily
Hypereosinophilicsyndrome(HES)and/orchroniceosinophilicleukemia(CEL):Oral:400mgoncedaily
HES/CELwithFIP1L1PDGFRfusionkinase:Oral:Initiateat100mgoncedailytitrateuptoamaximum
of400mgoncedaily(iftolerated)ifinsufficientresponsetolowerdose
Myelodysplastic/myeloproliferativedisease(MDS/MPD):Oral:400mgoncedaily
Ph+ ALL (induction, newly diagnosed):Canadian labeling (not an approved use in the US): Oral: 600 mg
oncedaily
Chordoma, progressive, advanced, or metastatic expressing PDGFRB and/or PDGFB (offlabel use):
Oral:400mgtwicedaily(Stacchiotti,2012)
Desmoidtumors,unresectableand/orprogressive(offlabeluse):Oral:300mgtwicedaily(BSA1.5m2),
200 mg twice daily (BSA 11.49 m2), 100 mg twice daily (BSA <1 m2) (Chugh, 2010) or 400 mg once
dailymayincreaseto400mgtwicedailyifprogressivediseaseon400mgdaily(Penel,2011)
Melanoma,advancedormetastaticwithCKITmutation(offlabeluse):Oral:400mgtwicedaily(Carvajal,
2011)
Stemcelltransplant(SCT,offlabeluse)forCML(inpatientswhohavenotfailedimatinibtherapyprior
totransplant):Oral:
Prophylactic use to prevent relapse post SCT: 400 mg daily starting after engraftment for 1 year post
transplant (Carpenter, 2007) or 300 mg daily starting on day +35 post SCT (increased to 400 mg
within4weeks)andcontinueduntil12monthsposttransplant(Olavarria,2007)
RelapsepostSCT:Initial:400mgdailyifinferiorresponseafter3months,dosemaybeincreasedto600
800mgdaily(Hess,2005)or400600mgdaily(chronicphase)or600mgdaily(blastoraccelerated
phase)(DeAngelo,2004)
DosageadjustmentwithconcomitantstrongCYP3A4inducers:AvoidconcomitantuseofstrongCYP3A4
inducers(eg,dexamethasone,carbamazepine,phenobarbital,phenytoin,rifabutin,rifampin)ifconcomitant
usecannotbeavoided,increaseimatinibdosebyatleast50%withcarefulmonitoring.
Dosing:Pediatric
(Foradditionalinformationsee"Imatinib:Pediatricdruginformation")
Note:Treatmentmaybecontinueduntildiseaseprogressionorunacceptabletoxicity.Theoptimaldurationof
therapyforCMLincompleteremissionisnotyetdetermined.Imatinibisassociatedwithamoderateemetic
potentialantiemeticsmayberecommendedtopreventnauseaandvomiting(Dupuis,2011).
Philadelphia chromosomepositive (Ph+) acute lymphoblastic leukemia (ALL) (newly diagnosed):
Children 1 year and Adolescents: Oral: 340 mg/m2/day (in combination with chemotherapy) maximum:
600mgdaily
Ph+ chronic myeloid leukemia (CML), chronic phase, newly diagnosed: Children 1 year and
Adolescents:Oral:340mg/m2/daymaximum:600mgdaily
DosageadjustmentwithconcomitantstrongCYP3A4inducers:AvoidconcomitantuseofstrongCYP3A4
inducers(eg,dexamethasone,carbamazepine,phenobarbital,phenytoin,rifabutin,rifampin)ifconcomitant
usecannotbeavoided,increaseimatinibdosebyatleast50%withcarefulmonitoring.
Dosageadjustmentforhepatotoxicity:RefertoHepaticImpairmentdosing.
Dosageadjustmentforhematologicadversereactions:Refertodosingadjustmentfortoxicity.
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Dosageadjustmentfornonhematologicadversereactions:Refertodosingadjustmentfortoxicity.
Dosing:Geriatric Refertoadultdosing.
Dosing:RenalImpairment
USlabeling:
Mildimpairment(CrCl4059mL/minute):Maximumrecommendeddose:600mg.
Moderate impairment (CrCl 2039 mL/minute): Decrease recommended starting dose by 50% dose may
beincreasedastoleratedmaximumrecommendeddose:400mg.
Severe impairment (CrCl <20 mL/minute): Use caution a dose of 100 mg daily has been tolerated in a
limitednumberofpatientswithsevereimpairment(Gibbons,2008).
Canadianlabeling:
Mildimpairment(CrCl4059mL/minute):Initialdose:400mgoncedaily(minimumeffectivedose)titrate
toefficacyandtolerability.
Moderate impairment (CrCl 2039 mL/minute): Initial dose: 400 mg once daily (minimum effective dose)
titratetoefficacyandtolerabilitytheuseof800mgdoseisnotrecommended.
Severeimpairment(CrCl<20mL/minute):Useisnotrecommended.
Dosing:HepaticImpairment
USlabeling:
Mildtomoderateimpairment:Nodosageadjustmentnecessary.
Severeimpairment:Reducedoseby25%.
Canadianlabeling:
Mildtomoderateimpairment:Initialdose:400mgoncedaily(minimumeffectivedose).
Severeimpairment:Initialdose:200mgoncedailymayincreaseupto300mgoncedailyintheabsence
ofseveretoxicitydecreasedosewithunacceptabletoxicity.
Dosage adjustment for hepatotoxicity (during therapy): If elevations of bilirubin >3 times ULN or
transaminases>5timesULNoccur,withholdtreatmentuntilbilirubin<1.5timesULNandtransaminases
<2.5 times ULN. Resume treatment at a reduced dose as follows (Note: The decision to resume
treatmentshouldtakeintoconsiderationtheinitialseverityofhepatotoxicity):
Adults:
Ifcurrentdose400mgdaily,reducedoseto300mgdaily
Children1yearandAdolescents:Ifcurrentdose340mg/m2/day,reducedoseto260mg/m2/day
Dosing:AdjustmentforToxicity
Hematologictoxicity:
ChronicphaseCML(initialdose400mgdailyinadultsor340mg/m2/dayinchildren)ASM,MDS/MPD,and
HES/CEL(initialdose400mgdaily)orGIST(initialdose400mgdaily[USlabeling]or400600mgdaily
[Canadianlabeling]):IfANC<1x109/Land/orplatelets<50x109/L:WithholduntilANC1.5x109/Land
platelets 75 x 109/L resume treatment at original starting dose. For recurrent neutropenia and/or
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thrombocytopenia,withholduntilrecovery,andreinstitutetreatmentatareduceddoseasfollows:
Children1yearandAdolescents:Ifinitialdose340mg/m2/day,reducedoseto260mg/m2/day.
Adults:
Ifinitialdose400mgdaily,reducedoseto300mgdaily.
Ifinitialdose600mgdaily(CanadianlabelingnotinUSlabeling),reducedoseto400mgdaily.
CML(acceleratedphaseorblastcrisis):Adults(initialdose600mgdaily):IfANC<0.5x109/Land/orplatelets
<10 x 109/L, establish whether cytopenia is related to leukemia (bone marrow aspirate or biopsy). If
unrelatedtoleukemia,reducedoseto400mgdaily.Ifcytopeniapersistsforanadditional2weeks,further
reducedoseto300mgdaily.Ifcytopeniapersistsfor4weeksandisstillunrelatedtoleukemia,withhold
treatmentuntilANC1x109/Landplatelets20x109/L,thenresumetreatmentat300mgdaily.
ASM associated with eosinophilia and HES/CEL with FIP1L1PDGFR fusion kinase: Adults (starting dose
100 mg daily): If ANC <1 x 109/L and/or platelets <50 x 109/L: Withhold until ANC 1.5 x 109/L and
platelets75x109/Lresumetreatmentatpreviousdose.
DFSP:Adults(initialdose800mgdaily):IfANC<1x109/Land/orplatelets<50x109/L,withholduntilANC
1.5x109/Landplatelets75x109/Lresumetreatmentatreduceddoseof600mgdaily.Forrecurrent
neutropeniaand/orthrombocytopenia,withholduntilrecovery,andreinstitutetreatmentwithafurtherdose
reductionto400mgdaily.
Ph+ALL:
Pediatrics (Schultz, 2009): Hematologic toxicity requiring dosage adjustments was not observed in the
study. No major toxicities were observed with imatinib at 340 mg/m2/day in combination with
intensivechemotherapy.
Adults (initial dose 600 mg daily): If ANC <0.5 x 109/L and/or platelets <10 x 109/L, establish whether
cytopenia is related to leukemia (bone marrow aspirate or biopsy). If unrelated to leukemia, reduce
doseto400mgdaily.Ifcytopeniapersistsforanadditional2weeks,furtherreducedoseto300mg
daily.Ifcytopeniapersistsfor4weeksandisstillunrelatedtoleukemia,withholdtreatmentuntilANC
1x109/Landplatelets20x109/L,thenresumetreatmentat300mgdaily.
Nonhematologic toxicity (eg, severe edema): Withhold treatment until toxicity resolves may resume if
appropriate(dependingoninitialseverityofadverseevent).
DosageForms:US Excipientinformationpresentedwhenavailable(limited,particularlyforgenerics)
consultspecificproductlabeling.
Tablet,Oral:
Gleevec:100mg,400mg[scored]
GenericEquivalentAvailable:US No
Administration Imatinibisassociatedwithamoderateemeticpotentialantiemeticsmaybe
recommendedtopreventnauseaandvomiting(Dupuis,2011Roila,2010).
Shouldbeadministeredwithamealandalargeglassofwater.Itisnotrecommendedtocrushorchewtablets
duetobittertaste.Tabletsmaybedispersedinwaterorapplejuice(using~50mLfor100mgtablet,~200mL
for400mgtablet)stiruntildissolvedandadministerimmediately.Inadults,doses600mgmaybegiven
oncedaily800mgdoseshouldbeadministeredas400mgtwicedaily.Dosinginchildrenmaybeonceor
twicedailyforchronicmyeloidleukemia(CML)andoncedailyforPhiladelphiachromosomepositive(Ph+)
acutelymphoblasticleukemia(ALL).Fordailydosing800mg,the400mgtabletsshouldbeusedinorderto
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reduceironexposure.
Hazardousagentuseappropriateprecautionsforhandlinganddisposal(NIOSH2014[group1]).Avoidskinor
mucousmembranecontactwithcrushedtabletsifcontactoccurs,washthoroughly.Avoidexposureto
crushedtablets.Ifitisnecessarytomanipulatethetablets(eg,toprepareanoralsolution),itisrecommended
todoubleglove,wearaprotectivegown,andprepareinacontrolleddevice(NIOSH,2014).
Use
Acutelymphoblasticleukemia:TreatmentofrelapsedorrefractoryPhiladelphiachromosomepositive(Ph+)
acutelymphoblasticleukemia(ALL)inadults
TreatmentofnewlydiagnosedPh+ALLinchildren(incombinationwithchemotherapy)
Aggressivesystemicmastocytosis:TreatmentofaggressivesystemicmastocytosiswithoutD816VcKit
mutation(orcKitmutationalstatusunknown)inadults
Chronicmyeloidleukemia:TreatmentofPh+chronicmyeloidleukemia(CML)inchronicphase(newly
diagnosed)inadultsandchildren
TreatmentofPh+CMLinblastcrisis,acceleratedphase,orchronicphaseafterfailureofinterferonalfa
therapy
Dermatofibrosarcomaprotuberans:Treatmentwithunresectable,recurrent,and/ormetastatic
dermatofibrosarcomaprotuberans(DFSP)inadults
Gastrointestinalstromaltumors:TreatmentofKit(CD117)positiveunresectableand/ormetastaticmalignant
gastrointestinalstromaltumors(GIST)
AdjuvanttreatmentofKit(CD117)positiveGISTfollowingcompletegrossresection
Hypereosinophilicsyndromeand/orchroniceosinophilicleukemia:Treatmentofhypereosinophilic
syndrome(HES)and/orchroniceosinophilicleukemia(CEL)inadultpatientswhohavetheFIP1L1
plateletderivedgrowthfactor(PDGF)receptoralphafusionkinase(mutationalanalysisorfluorescentin
situhybridization[FISH]demonstrationofCHIC2alleledeletion)andforpatientswithHESand/orCEL
whoareFIP1L1PDGFreceptoralphafusionkinasenegativeorunknown
Myelodysplastic/Myeloproliferativediseases:Treatmentofmyelodysplasticsyndrome/myeloproliferative
diseases(MDS/MPD)associatedwithPDGFreceptorgenerearrangementsinadults
Canadianlabeling(notanapprovedindicationintheUS):TreatmentofnewlydiagnosedPh+ALLinadultsasa
singleagentforinductiontherapy
Use:OffLabel
ChordomaChronicmyeloidleukemia(CML)poststemcelltransplantation(SCT)(allogeneic)(followup
treatment)DesmoidtumorMelanoma,advancedormetastatic(CKITmutatedtumors)
MedicationSafetyIssues
Soundalike/lookalikeissues:
Imatinibmaybeconfusedwithaxitinib,dasatinib,erlotinib,gefitinib,ibrutinib,idelalisib,nilotinib,
nintedanib,PONATinib,SORAfenib,SUNItinib,vandetanib
Highalertmedication:
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ThismedicationisinaclasstheInstituteforSafeMedicationPractices(ISMP)includesamongitslistof
drugclasseswhichhaveaheightenedriskofcausingsignificantpatientharmwhenusedinerror.
AdverseReactionsSignificant Adversereactionslistedasacompositeofdataacrossmanytrials,
exceptwherenotedforaspecificindication.Frequencynotalwaysdefined.
>10%:
Cardiovascular: Edema (11% to 86% grades 3/4: 3% to 13% includes aggravated edema, anasarca,
ascites, pericardial effusion, peripheral edema, pulmonary edema, and superficial edema), facial
edema(17%),hypotension(Ph+ALL[pediatric]grades3/4:11%),chestpain(7%to11%)
Central nervous system: Fatigue (20% to 75%), pain (47%), headache (8% to 37%), dizziness (5% to
19%), insomnia (9% to 15%), depression (3% to 15%), taste disorder (13%), rigors (10% to 12%),
anxiety(8%to12%),paresthesia(12%),chills(11%)
Dermatologic: Skin rash (9% to 50% grades 3/4: 1% to 9%), dermatitis (GIST 39%), pruritus (7% to
26%),nightsweats(CML13%to17%),alopecia(7%to15%),diaphoresis(GIST13%)
Endocrine & metabolic: Increased lactate dehydrogenase (60%), hypokalemia (6% to 13% Ph+ ALL
[pediatric]grades3/4:34%),weightgain(5%to32%),decreasedserumalbumin(21%grades3/4:
4%)
Gastrointestinal:Nausea(41%to73%Ph+ALL[pediatric]grades3/4:16%),diarrhea(25%to59%Ph+
ALL [pediatric] grades 3/4: 9%), vomiting (11% to 58%), abdominal pain (3% to 57%), anorexia
(36%), dyspepsia (11% to 27%), flatulence (25%), abdominal distension (19%), constipation (8%
to16%),stomatitis(16%)
Hematologic & oncologic: Neutropenia (grades 3/4: 8% to 64%), thrombocytopenia (grades 3/4: 1% to
63%), anemia (grades 3/4: 3% to 53%), hemorrhage (3% to 53% grades 3/4: 19%), leukopenia
(GIST5%to47%grades3/4:2%),hypoproteinemia(32%)
Hepatic: Increased serum transaminases (Ph+ ALL [pediatric] grades 3/4: 57%), increased serum AST
(38% grades 3/4: 6%), increased serum ALT (34% grades 3/4: 8%), increased alkaline
phosphatase(17%grades3/4:6%),increasedserumbilirubin(13%grades3/4:4%)
Infection:Infection(Ph+ALL[pediatric]grades3/4:53%GIST28%),influenza(Ph+CML14%)
Neuromuscular&skeletal:Musclecramps(16%to62%),musculoskeletalpain(children21%adults38%
to 49%), arthralgia (11% to 40%), myalgia (9% to 32%), weakness (21%), back pain (17%), limb
pain(16%),ostealgia(11%)
Ophthalmic: Periorbital edema (15% to 74%), increased lacrimation (DFSP 25% GIST 18%), eyelid
edema(Ph+CML19%),blurredvision(11%)
Renal:Increasedserumcreatinine(44%grades3/4:8%)
Respiratory: Nasopharyngitis (1% to 31%), cough (11% to 27%), upper respiratory tract infection (3% to
21%), dyspnea (21%), pharyngolaryngeal pain (18%), rhinitis (DFSP 17%), pharyngitis (CML 10%
to15%),flulikesymptoms(1%to14%),pneumonia(CML4%to13%),sinusitis(4%to11%)
Miscellaneous:Fever(6%to41%)
1%to10%:
Cardiovascular: Pleural effusion (Ph+ ALL [pediatric] grades 3/4: 7%), palpitations (5%), hypertension
(4%),cardiacfailure(Ph+CML1%grades3/4:<1%),flushing
Centralnervoussystem:Cerebralhemorrhage(9%),hypoesthesia,peripheralneuropathy
Dermatologic:Skinphotosensitivity(4%to7%),xeroderma(7%),erythema,naildisease
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Endocrine & metabolic: Hypophosphatemia (10%), hyperglycemia (10%), weight loss (10%),
hypocalcemia(GIST6%Ph+CMLgrades3/4:<1%),fluidretention(Ph+CML3%pleuraleffusion,
pericardialeffusion,ascites,orpulmonaryedema2%),hyperkalemia(1%)
Gastrointestinal: Decreased appetite (10%), gastroenteritis (10%), gastrointestinal hemorrhage (1% to
8%),increasedserumlipase(CMLgrades3/4:4%),gastritis,gastroesophagealreflux,xerostomia
Hematologic & oncologic: Lymphocytopenia (10% grades 3/4: 1% to 2%), eosinophilia, febrile
neutropenia,pancytopenia,purpura
Neuromuscular&skeletal:Jointswelling
Ophthalmic:Conjunctivitis(5%to8%),conjunctivalhemorrhage,dryeyes
Respiratory: Hypoxia (9%), pneumonitis (Ph+ ALL [pediatric] grades 3/4: 8%), oropharyngeal pain (Ph+
CML6%),epistaxis
<1% (Limited to important or lifethreatening): Actinic keratosis, acute generalized exanthematous pustulosis,
anaphylactic shock, angina pectoris, angioedema, aplastic anemia, arthritis, ascites, atrial fibrillation,
avascular necrosis of bones, bullous rash, cardiac arrest, cardiac arrhythmia, cardiac tamponade,
cardiogenic shock, cataract, cellulitis, cerebral edema, decreased linear skeletal growth rate (children),
diverticulitis, DRESS syndrome, dyschromia, embolism, erythema multiforme, exfoliative dermatitis,
fungal infection, gastric ulcer, gastrointestinal obstruction, gastrointestinal perforation, glaucoma, gout,
hearing loss, hematemesis, hematoma, hematuria, hemolytic anemia, hepatic failure, hepatic necrosis,
hepatitis, hepatotoxicity, herpes simplex infection, herpes zoster, hypercalcemia, hyperkalemia,
hypersensitivity angiitis, hyperuricemia, hypomagnesemia, hyponatremia, hypophosphatemia,
hypothyroidism, IgA vasculitis, increased intracranial pressure, inflammatory bowel disease, interstitial
pneumonitis, interstitial pulmonary disease, intestinal obstruction, left ventricular dysfunction, lichen
planus,lowerrespiratorytractinfection,lymphadenopathy,macularedema,melena,memoryimpairment,
migraine, myocardial infarction, myopathy, optic neuritis, osteonecrosis (hip), ovarian cyst (hemorrhagic),
palmarplantar erythrodysesthesia, pancreatitis, papilledema, pericarditis, psoriasis, pulmonary fibrosis,
pulmonary hemorrhage, pulmonary hypertension, Raynaud phenomenon, renal failure, respiratory failure,
restlesslegsyndrome,retinalhemorrhage,rhabdomyolysis,rupturedcorpuslutealcyst,sciatica,seizure,
sepsis, StevensJohnson syndrome, subconjunctival hemorrhage, subdural hematoma, Sweet syndrome,
syncope, tachycardia, telangiectasia (gastric antral), thrombocythemia, thrombosis, toxic epidermal
necrolysis,tumorhemorrhage(GIST),tumorlysissyndrome,urinarytractinfection,vitreoushemorrhage
Contraindications
Therearenocontraindicationslistedinthemanufacturer'sUSlabeling.
Canadianlabeling:Hypersensitivitytoimatiniboranycomponentoftheformulation
Warnings/Precautions
Concernsrelatedtoadverseeffects:
Bone marrow suppression: May cause bone marrow suppression (anemia, neutropenia, and
thrombocytopenia),usuallyoccurringwithinthefirstseveralmonthsoftreatment.Mediandurationof
neutropenia is 2 to 3 weeks median duration of thrombocytopenia is 3 to 4 weeks. Monitor blood
counts weekly for the first month, biweekly for the second month, and as clinically necessary
thereafter. In chronic myeloid leukemia (CML), cytopenias are more common in accelerated or blast
phasethaninchronicphase.
Cardiovascular effects: Severe heart failure (HF) and left ventricular dysfunction (LVD) have been
reported (occasionally), usually in patients with comorbidities and/or risk factors. Carefully monitor
patientswithpreexistingcardiacdiseaseorriskfactorsforHForhistoryofrenalfailure.Withinitiation
of imatinib treatment, cardiogenic shock and/or LVD have been reported in patients with
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hypereosinophilic syndrome and cardiac involvement (reversible with systemic steroids, circulatory
support and temporary cessation of imatinib). Patients with high eosinophil levels and an abnormal
echocardiogramorabnormalserumtroponinlevelmaybenefitfromprophylacticsystemicsteroids(for
1to2weeks)withtheinitiationofimatinib.
Dermatologic reactions: Severe bullous dermatologic reactions, including erythema multiforme and
StevensJohnson syndrome, have been reported recurrence has been described with rechallenge.
Case reports of successful resumption at a lower dose (with corticosteroids and/or antihistamine)
havebeendescribedhowever,somepatientsmayexperiencerecurrentreactions.Drugreactionwith
eosinophilia and systemic symptoms (DRESS) has been reported. Symptoms of DRESS include
fever, severe skin eruption, lymphadenopathy, hematologic abnormalities (eosinophilia or atypical
lymphocytes), and internal organ involvement. If symptoms of DRESS occur, interrupt therapy and
consider permanently discontinuing symptoms regressed upon discontinuation of therapy, however,
symptomsrecurredinallcaseswhenrechallenged.
Driving/heavy machinery: Caution is recommended while driving/operating motor vehicles and heavy
machinery when taking imatinib advise patients regarding side effects such as dizziness, blurred
vision,orsomnolence.Reportsofaccidentshavebeenreceived,butitisunclearifimatinibhasbeen
thedirectcauseinanycase.
Fluidretention/edema:Oftenassociatedwithfluidretention,weightgain,andedema(riskincreaseswith
higher doses and age >65 years) occasionally serious and may lead to significant complications,
including pleural effusion, pericardial effusion, pulmonary edema, and ascites. Monitor regularly for
rapidweightgainorothersigns/symptomsoffluidretention.Usewithcautioninpatientswherefluid
accumulation may be poorly tolerated, such as in cardiovascular disease (HF or hypertension) and
pulmonarydisease.
GItoxicity:Imatinibisassociatedwithamoderateemeticpotentialantiemeticsmayberecommended
to prevent nausea and vomiting (Dupuis, 2011 Roila, 2010). May cause GI irritation take with food
andwatertominimizeirritation.Therehavebeenrarereports(includingfatalities)ofGIperforation.
Hemorrhage:Severehemorrhage(grades3and4)hasbeenreportedwithuse,includingGIhemorrhage
and/or tumor hemorrhage. The incidence of hemorrhage is higher in patients with gastrointestinal
stromal tumors (GIST) (GI tumors may have been hemorrhage source). Gastric antral vascular
ectasia(ararecauseofgastrointestinalbleeding)hasalsobeenreported,at~1year(range:6daysto
7years)aftertherapyinitiation(GleevecCanadianproductlabeling,2015Alshehry,2014SaadAldin,
2012).MonitorforGIsymptomswithtreatmentinitiation.
Hepatotoxicity: Hepatotoxicity may occur fatal hepatic failure and severe hepatic injury requiring liver
transplantation have been reported with both short and longterm use monitor liver function prior to
initiation and monthly or as needed thereafter therapy interruption or dose reduction may be
necessary. Transaminase and bilirubin elevations, and acute liver failure have been observed with
imatinibincombinationwithchemotherapy.
Tumor lysis syndrome: Tumor lysis syndrome (TLS), including fatalities, has been reported in patients
with acute lymphoblastic leukemia (ALL), CML eosinophilic leukemias, and GIST. Risk for TLS is
higherinpatientswithahightumorburdenorhighproliferationratemonitorclosely.Correctclinically
significantdehydrationandtreathighuricacidlevelspriortoinitiationofimatinib.
Diseaserelatedconcerns:
Hepatic impairment: Use with caution in patients with hepatic impairment dosage adjustment
recommendedinpatientswithsevereimpairment.
Gastric surgery: Imatinib exposure may be reduced in patients who have had gastric surgery (eg,
bypass, major gastrectomy, or resection) monitor imatinib trough concentrations (Liu, 2011
Pavlovsky,2009,Yoo,2010).
Renalimpairment:Usewithcautioninpatientswithrenalimpairmentdosageadjustmentrecommended
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formoderateandsevererenalimpairment.
Thyroiddisease:Hypothyroidismhasbeenreportedinthyroidectomypatientswhowerereceivingthyroid
hormonereplacementtherapypriortoinitiationofimatinibmonitorthyroidfunction.Theaverageonset
forimatinibinducedhypothyroidismis2weeksconsiderdoublinglevothyroxinedosesuponinitiation
ofimatinib(Hamnvik,2011).
Concurrentdrugtherapyissues:
Drugdrug interactions: Potentially significant interactions may exist, requiring dose or frequency
adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions
databaseformoredetailedinformation.
Specialpopulations:
Elderly:Theincidenceofedemawasincreasedwithageolderthan65yearsinCMLandGISTstudies.
Pediatric: Growth retardation has been reported in children receiving imatinib for the treatment of CML
generally where treatment was initiated in prepubertal children growth velocity was usually restored
aspubertalagewasreached(Shima,2011).Monitorgrowthclosely.
Specialhandling:
Hazardousagent:Useappropriateprecautionsforhandlinganddisposal(NIOSH2014[group1]).
Metabolism/TransportEffects SubstrateofCYP1A2(minor),CYP2C19(minor),CYP2C8(minor),
CYP2C9(minor),CYP2D6(minor),CYP3A4(major),PglycoproteinNote:AssignmentofMajor/Minor
substratestatusbasedonclinicallyrelevantdruginteractionpotentialInhibitsBCRP,CYP2C9(weak),
CYP2D6(weak),CYP3A4(moderate),Pglycoprotein
DrugInteractions
(Foradditionalinformation:LaunchLexiInteractDrugInteractionsProgram)
Acetaminophen:MayenhancethehepatotoxiceffectofImatinib.RiskC:Monitortherapy
Apixaban:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofApixaban.RiskC:Monitor
therapy
Aprepitant:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofAprepitant.RiskX:Avoid
combination
ARIPiprazole:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofARIPiprazole.
Management:Monitorforincreasedaripiprazolepharmacologiceffects.Aripiprazoledoseadjustmentsmay
ormaynotberequiredbasedonconcomitanttherapyand/orindication.Consultfullinteractionmonograph
forspecificrecommendations.RiskC:Monitortherapy
ARIPiprazole:CYP2D6Inhibitors(Weak)mayincreasetheserumconcentrationofARIPiprazole.
Management:Monitorforincreasedaripiprazolepharmacologiceffects.Aripiprazoledoseadjustmentsmay
ormaynotberequiredbasedonconcomitanttherapyand/orindication.Consultfullinteractionmonograph
forspecificrecommendations.RiskC:Monitortherapy
Avanafil:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofAvanafil.Management:The
maximumavanafiladultdoseis50mgper24hourperiodwhenusedtogetherwithamoderateCYP3A4
inhibitor.Patientsreceivingsuchacombinationshouldalsobemonitoredmorecloselyforevidenceof
adverseeffects.RiskD:Considertherapymodification
BCG(Intravesical):ImmunosuppressantsmaydiminishthetherapeuticeffectofBCG(Intravesical).RiskX:
Avoidcombination
BCG(Intravesical):MyelosuppressiveAgentsmaydiminishthetherapeuticeffectofBCG(Intravesical).Risk
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X:Avoidcombination
Bosentan:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Bosentan:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofBosentan.Management:
ConcomitantuseofbothaCYP2C9inhibitorandaCYP3Ainhibitororasingleagentthatinhibitsboth
enzymeswithbosentanislikelytocausealargeincreaseinserumconcentrationsofbosentanandisnot
recommended.Seemonographfordetails.RiskC:Monitortherapy
Bosutinib:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofBosutinib.RiskX:Avoid
combination
Brexpiprazole:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofBrexpiprazole.
Management:Thebrexpiprazoledoseshouldbereducedto25%ofusualifusedtogetherwithbotha
moderateCYP3A4inhibitorandastrongormoderateCYP2D6inhibitor,orifamoderateCYP3A4inhibitor
isusedinaCYP2D6poormetabolizer.RiskC:Monitortherapy
Bromocriptine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofBromocriptine.RiskD:
Considertherapymodification
Budesonide(Systemic):CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofBudesonide
(Systemic).Management:Considerreducingtheoralbudesonidedosewhenusedtogetherwitha
CYP3A4inhibitorortemporarilystoppingbudesonidetherapyduringCYP3A4inhibitoruse.Monitor
patientscloselyforsigns/symptomsofcorticosteroidexcess.RiskD:Considertherapymodification
Budesonide(Systemic,OralInhalation):CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentration
ofBudesonide(Systemic,OralInhalation).Management:Considerreducingtheoralbudesonidedose
whenusedtogetherwithaCYP3A4inhibitor.Thisinteractionislikelylessseverewithorallyinhaled
budesonide.Monitorpatientscloselyforsigns/symptomsofcorticosteroidexcess.RiskD:Consider
therapymodification
Budesonide(Topical):CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofBudesonide
(Topical).Management:PerUSprescribinginformation,avoidthiscombination.Canadianproductlabeling
doesnotrecommendstrictavoidance.Ifcombined,monitorforexcessiveglucocorticoideffectsas
budesonideexposuremaybeincreased.RiskD:Considertherapymodification
Cannabis:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofCannabis.More
specifically,tetrahydrocannabinolandcannabidiolserumconcentrationsmaybeincreased.RiskC:
Monitortherapy
Cilostazol:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofCilostazol.Management:
Considerreducingthecilostazoldoseto50mgtwicedailyinadultpatientswhoarealsoreceiving
moderateinhibitorsofCYP3A4.RiskD:Considertherapymodification
CloZAPine:MyelosuppressiveAgentsmayenhancetheadverse/toxiceffectofCloZAPine.Specifically,the
riskforagranulocytosismaybeincreased.RiskX:Avoidcombination
CoccidioidesimmitisSkinTest:ImmunosuppressantsmaydiminishthediagnosticeffectofCoccidioides
immitisSkinTest.RiskC:Monitortherapy
Colchicine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofColchicine.Management:
ReducecolchicinedoseasdirectedwhenusingwithamoderateCYP3A4inhibitor,andincrease
monitoringforcolchicinerelatedtoxicity.Useextracautioninpatientswithimpairedrenaland/orhepatic
function.RiskD:Considertherapymodification
CycloSPORINE(Systemic):ImatinibmayincreasetheserumconcentrationofCycloSPORINE(Systemic).
RiskC:Monitortherapy
CYP3A4Inducers(Moderate):MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitor
therapy
http://www.uptodate.com/contents/imatinibdruginformation?topicKey=DRUG_GEN%2F8961&elapsedTimeMs=9&source=search_result&searchTer
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CYP3A4Inducers(Strong):MaydecreasetheserumconcentrationofImatinib.Management:Avoidconcurrent
useofimatinibwithstrongCYP3A4inducerswhenpossible.Ifsuchacombinationmustbeused,
increaseimatinibdosebyatleast50%andmonitorthepatient'sclinicalresponseclosely.RiskD:
CYP3A4Inhibitors(Moderate):MayincreasetheserumconcentrationofImatinib.RiskC:Monitortherapy
CYP3A4Inhibitors(Strong):MayincreasetheserumconcentrationofImatinib.RiskC:Monitortherapy
CYP3A4Substrates:CYP3A4Inhibitors(Moderate)maydecreasethemetabolismofCYP3A4Substrates.
RiskC:Monitortherapy
Dabrafenib:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:Seekalternativesto
theCYP3A4substratewhenpossible.Ifconcomitanttherapycannotbeavoided,monitorclinicaleffects
ofthesubstrateclosely(particularlytherapeuticeffects).RiskD:Considertherapymodification
Dapoxetine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofDapoxetine.Management:
Thedoseofdapoxetineshouldbelimitedto30mg/daywhenusedtogetherwithamoderateinhibitorof
CYP3A4.RiskD:Considertherapymodification
Deferasirox:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Denosumab:Mayenhancetheadverse/toxiceffectofImmunosuppressants.Specifically,theriskforserious
infectionsmaybeincreased.RiskC:Monitortherapy
Dexamethasone(Systemic):MaydecreasetheserumconcentrationofImatinib.Management:Avoid
concurrentuseofimatinibwithdexamethasonewhenpossible.Ifsuchacombinationmustbeused,
increaseimatinibdosebyatleast50%andmonitorclinicalresponseclosely.RiskD:Considertherapy
modification
Dipyrone:Mayenhancetheadverse/toxiceffectofMyelosuppressiveAgents.Specifically,theriskfor
agranulocytosisandpancytopeniamaybeincreasedRiskX:Avoidcombination
Dofetilide:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofDofetilide.RiskC:Monitor
therapy
Domperidone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofDomperidone.RiskX:
Avoidcombination
DOXOrubicin(Conventional):CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationof
DOXOrubicin(Conventional).Management:SeekalternativestomoderateCYP3A4inhibitorsinpatients
treatedwithdoxorubicinwheneverpossible.OneU.S.manufacturer(PfizerInc.)recommendsthatthese
combinationsbeavoided.RiskD:Considertherapymodification
Dronabinol:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofDronabinol.RiskC:
Monitortherapy
Echinacea:MaydiminishthetherapeuticeffectofImmunosuppressants.RiskD:Considertherapy
modification
Eletriptan:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofEletriptan.Management:
Theuseofeletriptanwithin72hoursofamoderateCYP3A4inhibitorshouldbeavoided.RiskD:Consider
therapymodification
Eliglustat:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofEliglustat.Management:
Useshouldbeavoidedundersomecircumstances.Seefulldruginteractionmonographfordetails.Risk
D:Considertherapymodification
Enzalutamide:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:Concurrentuseof
enzalutamidewithCYP3A4substratesthathaveanarrowtherapeuticindexshouldbeavoided.Useof
enzalutamideandanyotherCYP3A4substrateshouldbeperformedwithcautionandclosemonitoring.
RiskD:Considertherapymodification
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Eplerenone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofEplerenone.Management:
WhenusedconcomitantlywithmoderateinhibitorsofCYP3A4,eplerenonedosingrecommendationsmay
varydependingoninternationallabeling.Consultappropriatelabelingforspecificrecommendations.Risk
Everolimus:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofEverolimus.Management:
Everolimusdosereductionsarerequiredforpatientsbeingtreatedforsubependymalgiantcell
astrocytomaorrenalcellcarcinoma.Seeprescribinginformationforspecificdoseadjustmentand
monitoringrecommendations.RiskD:Considertherapymodification
FentaNYL:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofFentaNYL.Management:
Monitorpatientscloselyforseveraldaysfollowinginitiationofthiscombination,andadjustfentanyldose
asnecessary.RiskD:Considertherapymodification
Fingolimod:ImmunosuppressantsmayenhancetheimmunosuppressiveeffectofFingolimod.Management:
Avoidtheconcomitantuseoffingolimodandotherimmunosuppressantswhenpossible.Ifcombined,
monitorpatientscloselyforadditiveimmunosuppressanteffects(eg,infections).RiskD:Considertherapy
modification
Flibanserin:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofFlibanserin.RiskX:Avoid
combination
Fludarabine:ImatinibmaydiminishthemyelosuppressiveeffectofFludarabine.Imatinibmaydecreasethe
serumconcentrationofFludarabine.Morespecifically,imatinibmaydecreasetheformationoffludarabine
activemetaboliteFaraATPManagement:Duetotheriskforimpairedfludarabineresponse,consider
discontinuingimatinibtherapyatleast5dayspriortoinitiatingfludarabineconditioningtherapyinCML
patientsundergoingHSCT.RiskD:Considertherapymodification
Gemfibrozil:Maydecreaseserumconcentrationsoftheactivemetabolite(s)ofImatinib.SpecificallyN
desmethylimatinibconcentrationsmaybedecreased.Gemfibrozilmaydecreasetheserumconcentration
ofImatinib.RiskC:Monitortherapy
Halofantrine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofHalofantrine.RiskD:
Hydrocodone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofHydrocodone.RiskC:
Monitortherapy
Ibrutinib:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofIbrutinib.Management:Ifa
moderateCYP3Ainhibitormustbeused,considerreducingthedoseofibrutinibto140mgdailyand
monitorcloselyforsignsoftoxicity.RiskX:Avoidcombination
Ibuprofen:MaydecreasetheserumconcentrationofImatinib.Specifically,ibuprofenmaydecreaseintracellular
concentrationsofimatinib,leadingtodecreasedclinicalresponse.Management:Considerusingan
alternativetoibuprofeninpatientswhoarebeingtreatedwithimatinib.Availableevidencesuggestsother
NSAIDsdonotinteractinasimilarmanner.RiskD:Considertherapymodification
Ifosfamide:CYP3A4Inhibitors(Moderate)maydecreaseserumconcentrationsoftheactivemetabolite(s)of
Ifosfamide.RiskC:Monitortherapy
Ivabradine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofIvabradine.RiskX:Avoid
combination
Ivacaftor:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofIvacaftor.Management:
Ivacaftordosereductionsarerequiredconsultprescribinginformationforspecificageandweightbased
recommendations.RiskD:Considertherapymodification
Lansoprazole:MayenhancethedermatologicadverseeffectofImatinib.RiskC:Monitortherapy
Leflunomide:Immunosuppressantsmayenhancetheadverse/toxiceffectofLeflunomide.Specifically,therisk
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forhematologictoxicitysuchaspancytopenia,agranulocytosis,and/orthrombocytopeniamaybe
increased.Management:Considernotusingaleflunomideloadingdoseinpatientsreceivingother
immunosuppressants.Patientsreceivingbothleflunomideandanotherimmunosuppressantshouldbe
monitoredforbonemarrowsuppressionatleastmonthly.RiskD:Considertherapymodification
Lomitapide:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofLomitapide.RiskX:Avoid
combination
Lurasidone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofLurasidone.Management:
U.S.labeling:startat20mg/dayandlimittomaxof80mg/daywithmoderateCYP3A4inhibitor.Canadian
labeling:limittomaxof40mg/daywithmoderateCYP3A4inhibitoravoidconcomitantuseofgrapefruit
products.RiskD:Considertherapymodification
Mitotane:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:DosesofCYP3A4
substratesmayneedtobeadjustedsubstantiallywhenusedinpatientsbeingtreatedwithmitotane.Risk
Naloxegol:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofNaloxegol.RiskX:Avoid
combination
Natalizumab:Immunosuppressantsmayenhancetheadverse/toxiceffectofNatalizumab.Specifically,the
riskofconcurrentinfectionmaybeincreased.RiskX:Avoidcombination
NiMODipine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofNiMODipine.RiskC:
Monitortherapy
Olaparib:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofOlaparib.Management:
AvoiduseofmoderateCYP3A4inhibitorsinpatientsbeingtreatedwitholaparib.Ifsuchconcurrentuse
cannotbeavoided,thedoseofolaparibshouldbereducedto200mgtwicedaily.RiskX:Avoid
combination
OxyCODONE:CYP3A4Inhibitors(Moderate)mayenhancetheadverse/toxiceffectofOxyCODONE.
CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofOxyCODONE.Serum
concentrationsoftheactivemetaboliteOxymorphonemayalsobeincreased.RiskD:Considertherapy
modification
PAZOPanib:BCRP/ABCG2InhibitorsmayincreasetheserumconcentrationofPAZOPanib.RiskX:Avoid
combination
Pglycoprotein/ABCB1Inducers:MaydecreasetheserumconcentrationofPglycoprotein/ABCB1Substrates.
Pglycoproteininducersmayalsofurtherlimitthedistributionofpglycoproteinsubstratestospecific
cells/tissues/organswherepglycoproteinispresentinlargeamounts(e.g.,brain,Tlymphocytes,testes,
etc.).RiskC:Monitortherapy
Pglycoprotein/ABCB1Inhibitors:MayincreasetheserumconcentrationofPglycoprotein/ABCB1Substrates.
Pglycoproteininhibitorsmayalsoenhancethedistributionofpglycoproteinsubstratestospecific
cells/tissues/organswherepglycoproteinispresentinlargeamounts(e.g.,brain,Tlymphocytes,testes,
etc.).RiskC:Monitortherapy
Pimecrolimus:Mayenhancetheadverse/toxiceffectofImmunosuppressants.RiskX:Avoidcombination
Pimozide:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofPimozide.RiskX:Avoid
combination
Propacetamol:MayenhancethehepatotoxiceffectofImatinib.RiskC:Monitortherapy
Propafenone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofPropafenone.RiskC:
Monitortherapy
Ranolazine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofRanolazine.Management:
Limittheranolazineadultdosetoamaximumof500mgtwicedailyinpatientsconcurrentlyreceiving
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moderateCYP3A4inhibitors(e.g.,diltiazem,verapamil,erythromycin,etc.).RiskD:Considertherapy
modification
RifamycinDerivatives:MaydecreasetheserumconcentrationofImatinib.Management:Avoidconcurrentuse
ofimatinibwiththerifamycinderivativeswhenpossible.Ifsuchacombinationmustbeused,increase
imatinibdosebyatleast50%andmonitorthepatient'sclinicalresponseclosely.RiskD:Consider
therapymodification
Roflumilast:MayenhancetheimmunosuppressiveeffectofImmunosuppressants.RiskD:Considertherapy
modification
Salmeterol:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofSalmeterol.RiskC:
Monitortherapy
Saxagliptin:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofSaxagliptin.RiskC:
Monitortherapy
Siltuximab:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Simeprevir:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofSimeprevir.RiskX:Avoid
combination
Simvastatin:ImatinibmaydecreasethemetabolismofSimvastatin.RiskC:Monitortherapy
SipuleucelT:ImmunosuppressantsmaydiminishthetherapeuticeffectofSipuleucelT.RiskC:Monitor
therapy
Sonidegib:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofSonidegib.Management:
AvoidconcomitantuseofsonidegibandmoderateCYP3A4inhibitorswhenpossible.Whenconcomitant
usecannotbeavoided,limitCYP3A4inhibitorusetolessthan14daysandmonitorforsonidegibtoxicity
(particularlymusculoskeletaladversereactions).RiskD:Considertherapymodification
StJohnsWort:MayincreasethemetabolismofImatinib.RiskD:Considertherapymodification
Suvorexant:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofSuvorexant.RiskD:
Tacrolimus(Topical):Mayenhancetheadverse/toxiceffectofImmunosuppressants.RiskX:Avoid
combination
Tetrahydrocannabinol:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationof
Tetrahydrocannabinol.RiskC:Monitortherapy
Tocilizumab:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Tofacitinib:ImmunosuppressantsmayenhancetheimmunosuppressiveeffectofTofacitinib.Management:
Concurrentusewithantirheumaticdosesofmethotrexateornonbiologicdiseasemodifyingantirheumatic
drugs(DMARDs)ispermitted,andthiswarningseemsparticularlyfocusedonmorepotent
immunosuppressants.RiskX:Avoidcombination
Tolvaptan:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofTolvaptan.RiskX:Avoid
combination
Topotecan:BCRP/ABCG2InhibitorsmayincreasetheserumconcentrationofTopotecan.RiskD:Consider
therapymodification
Trabectedin:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofTrabectedin.RiskX:
Avoidcombination
Trastuzumab:MayenhancetheneutropeniceffectofImmunosuppressants.RiskC:Monitortherapy
Ulipristal:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofUlipristal.Management:This
isspecificforwhenulipristalisbeingusedforsigns/symptomsofuterinefibroids(Canadianindication).
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Whenulipristalisusedasanemergencycontraceptive,patientsreceivingthiscombinationshouldbe
monitoredforulipristaltoxicity.RiskX:Avoidcombination
Vaccines(Inactivated):ImmunosuppressantsmaydiminishthetherapeuticeffectofVaccines(Inactivated).
Management:Vaccineefficacymaybereduced.Completeallageappropriatevaccinationsatleast2
weekspriortostartinganimmunosuppressant.Ifvaccinatedduringimmunosuppressanttherapy,
revaccinateatleast3monthsafterimmunosuppressantdiscontinuation.RiskD:Considertherapy
modification
Vaccines(Live):Immunosuppressantsmayenhancetheadverse/toxiceffectofVaccines(Live).
ImmunosuppressantsmaydiminishthetherapeuticeffectofVaccines(Live).Management:Avoiduseof
liveorganismvaccineswithimmunosuppressantsliveattenuatedvaccinesshouldnotbegivenforat
least3monthsafterimmunosuppressants.RiskX:Avoidcombination
Vilazodone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofVilazodone.RiskC:
Monitortherapy
Vindesine:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofVindesine.RiskC:Monitor
therapy
Warfarin:ImatinibmayenhancetheanticoagulanteffectofWarfarin.Imatinibmaydecreasethemetabolismof
Warfarin.RiskD:Considertherapymodification
Zopiclone:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofZopiclone.Management:
Thestartingadultdoseofzopicloneshouldnotexceed3.75mgifcombinedwithamoderateCYP3A4
inhibitor.Monitorpatientsforsignsandsymptomsofzopiclonetoxicityiftheseagentsarecombined.Risk
Zuclopenthixol:CYP3A4Inhibitors(Moderate)mayincreasetheserumconcentrationofZuclopenthixol.Risk
C:Monitortherapy
FoodInteractions FoodmayreduceGIirritation.Grapefruitjuicemayincreaseimatinibplasma
concentration.Management:Takewithamealandalargeglassofwater.Avoidgrapefruitjuice.Maintain
adequatehydration,unlessinstructedtorestrictfluidintake.
PregnancyRiskFactor D(showtable)
PregnancyImplications Adverseeventshavebeenobservedinanimalreproductionstudies.Women
ofchildbearingpotentialareadvisednottobecomepregnant(femalepatientsandfemalepartnersofmale
patients)highlyeffectivecontraceptionisrecommended.TheCanadianlabelingrecommendswomenof
childbearingpotentialhaveanegativepregnancytest(urineorserum)withasensitivityofatleast25mIU/mL
within1weekpriortotherapyinitiation.Casereportsofpregnancieswhileontherapy(bothmalesandfemales)
includereportsofspontaneousabortion,minorabnormalities(hypospadias,pyloricstenosis,andsmallintestine
rotation)atorshortlyafterbirth,andothercongenitalabnormalitiesincludingskeletalmalformations,
hypoplasticlungs,exomphalos,kidneyabnormalities,hydrocephalus,cerebellarhypoplasia,andcardiac
defects.
RetrospectivecasereportsofwomenwithCMLincompletehematologicresponse(CHR)withcytogenic
response(partialorcomplete)whointerruptedimatinibtherapyduetopregnancy,demonstratedalossof
responseinsomepatientswhileofftreatment.At18monthsaftertreatmentreinitiationfollowingdelivery,CHR
wasagainachievedinallpatientsandcytogenicresponsewasachievedinsomepatients.Cytogenetic
responseratesmaynotbeatashighascomparedtopatientswith18monthsofuninterruptedtherapy(Ault,
2006Pye,2008).
BreastFeedingConsiderations Imatinibanditsactivemetabolitearefoundinhumanbreastmilk
themilk/plasmaratiois0.5forimatiniband0.9fortheactivemetabolite.Basedonbodyweight,upto10%ofa
therapeuticmaternaldosecouldpotentiallybereceivedbyabreastfedinfant.Duetothepotentialforserious
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adversereactionsinthebreastfeedinginfant,themanufacturerrecommendsadecisionbemadeto
discontinuebreastfeedingortodiscontinuethedrug,takingintoaccounttheimportanceoftreatmenttothe
mother.
DietaryConsiderations Avoidgrapefruitjuice.
Pricing:US
Tablets(GleevecOral)
100mg(90):$10112.93
400mg(30):$12146.92
Disclaimer:ThepricingdataprovidearepresentativeAWPand/orAAWPpricefromasinglemanufacturerof
thebrandand/orgenericproduct,respectively.Thepricingdatashouldbeusedforbenchmarkingpurposes
only,andassuchshouldnotbeusedtosetoradjudicateanypricesforreimbursementorpurchasing
functions.Pricingdataisupdatedmonthly.
MonitoringParameters CBC(weeklyforfirstmonth,biweeklyforsecondmonth,thenperiodically
thereafter),liverfunctiontests(atbaselineandmonthlyorasclinicallyindicatedmorefrequently[atleast
weekly]inpatientswithmoderatetoseverehepaticimpairment[Ramanathan,2008]),renalfunction,serum
electrolytes(includingcalcium,phosphorus,potassiumandsodiumlevels)bonemarrowcytogenetics(inCML
at6,12,and18months),pregnancytest(Canadianlabelingrecommendswomenofreproductivepotential
haveanegativetest[urineorserum]withasensitivityofatleast25mIU/mLwithin1weekpriortotherapy
initiation)fatigue,weight,andedema/fluidstatusconsiderechocardiogramandserumtroponinlevelsin
patientswithHES/CEL,andinpatientswithMDS/MPDorASMwithhigheosinophillevelsinpediatric
patients,alsomonitorserumglucose,albumin,andgrowth
Gastricsurgery(eg,bypass,majorgastrectomy,orresection)patients:Monitorimatinibtroughconcentrations
(Liu,2011Pavlovsky,2009Yoo,2010)
Thyroidfunctiontesting(Hamnvik,2011):
Preexistinglevothyroxinetherapy:ObtainbaselineTSHlevels,thenmonitorevery4weeksuntillevels
andlevothyroxinedosearestable,thenmonitorevery2months
Withoutpreexistingthyroidhormonereplacement:TSHatbaseline,thenevery4weeksfor4months,then
every23months
Monitorforsigns/symptomsofCHFinpatientswithatriskforcardiacfailureorpatientswithpreexisting
cardiacdisease.InCanada,abaselineevaluationofleftventricularejectionfractionisrecommendedpriorto
initiationofimatinibtherapyinallpatientswithknownunderlyingheartdiseaseorinelderlypatients.Monitorfor
signs/symptomsofgastrointestinalirritationorperforationanddermatologictoxicities.
InternationalBrandNames Alvotinib(SG)Egitinid(RO)Gemivil(JO)Glimatib(VN)Glinib(KR)
Glivec(AE,AR,AT,AU,BE,BG,BH,BR,CH,CL,CN,CO,CY,CZ,DE,DK,EC,EE,ES,FI,FR,GB,
GR,HK,HN,HR,HU,ID,IE,IL,IS,IT,JO,JP,KR,KW,LB,LT,MT,MX,MY,NL,NO,PE,PH,PK,PL,
PT,PY,QA,RO,RU,SA,SE,SG,SI,SK,TH,TR,TW,UY,VE,VN)Glivic(NZ)Imarem(MT,TR)Lemat
(HR)Milatus(PE)Nibix(HR)Zeite(PY)
MechanismofAction InhibitsBcrAbltyrosinekinase,theconstitutiveabnormalgeneproductofthe
Philadelphiachromosomeinchronicmyeloidleukemia(CML).Inhibitionofthisenzymeblocksproliferationand
inducesapoptosisinBcrAblpositivecelllinesaswellasinfreshleukemiccellsinPhiladelphiachromosome
positiveCML.Alsoinhibitstyrosinekinaseforplateletderivedgrowthfactor(PDGF),stemcellfactor(SCF),c
Kit,andcellulareventsmediatedbyPDGFandSCF.
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PharmacodynamicsandPharmacokinetics
Absorption:Rapid
Proteinbinding:Parentdrugandmetabolite:~95%toalbuminandalpha1acidglycoprotein
Metabolism: Hepatic via CYP3A4 (minor metabolism via CYP1A2, CYP2D6, CYP2C9, CYP2C19) primary
metabolite(active):Ndemethylatedpiperazinederivative(CGP74588)severehepaticimpairment(bilirubin
>3to10timesULN)increasesAUCby45%to55%forimatinibanditsactivemetabolite,respectively
Bioavailability:98% may be decreased in patients who have had gastric surgery (eg, bypass, total or partial
resection)(Liu,2011Pavlovsky,2009Yoo,2010)
Halflifeelimination:Adults:Parentdrug:~18hoursNdesmethylmetabolite:~40hoursChildren:Parentdrug:
~15hours
Timetopeak:2to4hours
Excretion:Feces(68%primarilyasmetabolites,20%asunchangeddrug)urine(13%primarilyasmetabolites,
5%asunchangeddrug)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. AlshehryNF,KortanP,LiptonJH.Imatinibinducedgastricantralvascularectasiainapatientwithchronicmyeloid
leukemia.ClinCaseRep.20142(3):7778.[PubMed25356253]
2. AtallahE,DurandJB,KantarjianH,etal,CongestiveHeartFailureisaRareEventinPatientsReceivingImatinib
Therapy,Blood,2007,110(4):12337.[PubMed17449798]
3. AultP,KantarjianH,OBrienS,etal,PregnancyAmongPatientswithChronicMyeloidLeukemiaTreatedWithImatinib,
JClinOncol,2006,24(7):12048.[PubMed16446320]
4. BaccaraniM,CortesJ,PaneF,etal,ChronicMyeloidLeukemia:AnUpdateofConceptsandManagement
RecommendationsofEuropeanLeukemiaNet,JClinOncol,2009,27(35):604151.[PubMed19884523]
5. BermanE,NicolaidesM,MakiRG,etal,AlteredBoneandMineralMetabolisminPatientsReceivingImatinibMesylate,
NEnglJMed,2006,354(19):200613.[PubMed16687713]
6. BilgiN,BellK,AnanthakrishnanAN,etal,ImatinibandPanaxGinseng:APotentialInteractionResultinginLiver
Toxicity,AnnPharmacother,2010,44(5):9268.[PubMed20332334]
7. BrunsteinCGandMcGlavePB,TheBiologyandTreatmentofChronicMyelogenousLeukemia,Oncology,2001,15:23
31.[PubMed11271979]
8. CarpenterPA,SnyderDS,FlowersME,etal,ProphylacticAdministrationofImatinibAfterHematopoieticCell
TransplantationforHighRiskPhiladelphiaChromosomePositiveLeukemia,Blood,2007,109(7):27913.[PubMed
17119111]
9. CarvajalRD,AntonescuCR,WolchokJD,etal,KITasaTherapeuticTargetinMetastaticMelanoma,JAMA,2011,
305(22):232734.[PubMed21642685]
10. CasaliPG,StacchiottiS,GrossoF,etal,AddingCisplatin(CDDP)toImatinib(IM)ReEstablishesTumorResponse
FollowingSecondaryResistancetoIMinAdvancedChordoma,JClinOncol,2007,25(Suppl18):10038[abstract10038
fromthe2007ASCOAnnualMeeting].
11. ChughR,WathenJK,PatelSR,etal,EfficacyofImatinibinAggressiveFibromatosis:ResultsofaPhaseIIMulticenter
SarcomaAllianceforResearchThroughCollaboration(SARC)Trial,ClinCancerRes,2010,16(19):488491.[PubMed
20724445]
12. CornelisonM,JabbourEJ,andWelchMA,ManagingSideEffectsofTyrosineKinaseInhibitorTherapytoOptimize
AdherenceinPatientsWithChronicMyeloidLeukemia:TheRoleoftheMidlevelPractitioner,JSupportOncol,2012,
10(1):1424.[PubMed22244674]
13. CortesJE,BaccaraniM,GuilhotF,etal.PhaseIII,randomized,openlabelstudyofdailyimatinibmesylate400mgversus
800mginpatientswithnewlydiagnosed,previouslyuntreatedchronicmyeloidleukemiainchronicphaseusingmolecular
endpoints:tyrosinekinaseinhibitoroptimizationandselectivitystudy.JClinOncol.201028(3):424430.doi:
10.1200/JCO.2009.25.3724.[PubMed20008622]
14. DeAngeloDJ,HochbergEP,AlyeaEP,etal,ExtendedFollowUpofPatientsTreatedWithImatinibMesylate(Gleevec)
forChronicMyelogenousLeukemiaRelapseAfterAllogeneicTransplantation:DurableCytogeneticRemissionand
ConversiontoCompleteDonorChimerismWithoutGraftVersusHostDisease,ClinCancerRes,2004,10(15):506571.
[PubMed15297408]
17/20
11/12/2015
15. DebiecRychterM,SciotR,LeCesneA,etal,KITmutationsandDoseSelectionforImatinibinPatientsWithAdvanced
GastrointestinalStromalTumors,EurJCancer,2006,42(8):1093103.[PubMed16624552]
16. deGrootJW,ZonnenbergBA,PlukkerJT,etal,"ImatinibInducesHypothyroidisminPatientsReceivingLevothyroxine,"
ClinPharmacolTher,2005,78(4):4338.[PubMed16198662]
17. DematteoRP,BallmanKV,AntonescuCR,etal,AdjuvantImatinibMesylateAfterResectionofLocalised,Primary
GastrointestinalStromalTumour:aRandomised,DoubleBlind,PlaceboControlledTrial,Lancet,2009,373(9669):1097
104.[PubMed19303137]
18. DeMatteoR,OwzarK,MakiR,etal,AdjuvantImatinibMesylateIncreasesRecurrenceFreeSurvival(RFS)inPatients
WithCompletelyResectedLocalizedPrimaryGastrointestinalStromalTumor(GIST):NorthAmericanIntergroupPhase
IIITrialACOSOGZ9001,JClinOncol,2007,28(18Supp):10079[abstract10079from2007ASCOAnnualMeeting].
19. DewarAL,FarrugiaAN,CondinaMR,etal,ImatinibasaPotentialAntiresorptiveTherapyforBoneDisease,Blood,2006,
107(11):43347.[PubMed16449525]
20. DroogendijkHJ,KluinNelemansHJ,vanDoormaalJJ,etal,ImatinibMesylateintheTreatmentofSystemic
Mastocytosis:APhaseIITrial,Cancer,2006,107(2):34551[PubMed16779792]
21. DrukerBJ,SawyersCL,KantarjianH,etal,ActivityofaSpecificInhibitoroftheBCRABLTyrosineKinaseintheBlast
CrisisofChronicMyeloidLeukemiaandAcuteLymphoblasticLeukemiaWiththePhiladelphiaChromosome,NEnglJ
Med,2001,344(14):103842.[PubMed11287973]
22. DrukerBJ,TalpazM,RestaDJ,etal,EfficacyandSafetyofaSpecificInhibitoroftheBCRABLTyrosineKinasein
ChronicMyeloidLeukemia,NEnglJMed,2001,344(14):10317.[PubMed11287972]
23. DupuisLL,BoodhanS,HoldsworthM,etalPediatricOncologyGroupofOntario.Guidelineforthepreventionofacute
nauseaandvomitingduetoantineoplasticmedicationinpediatriccancerpatients.PediatrBloodCancer.201360(7):1073
1082.[PubMed23512831]
24. DupuisLL,BoodhanS,SungL,etalPediatricOncologyGroupofOntario.Guidelinefortheclassificationoftheacute
emetogenicpotentialofantineoplasticmedicationinpediatriccancerpatients.PediatrBloodCancer.201157(2):191198.
[PubMed21465637]
25. EechouteK,FranssonMN,ReynersAK,etal,ALongTermProspectivePopulationPharmacokineticStudyonImatinib
PlasmaConcentrationsinGISTPatients,ClinCancerRes,2012,18(20):57807.[PubMed22850565]
26. GambacortiPasseriniC,AntoliniL,MahonFX,etal,MulticenterIndependentAssessmentofOutcomesinChronic
MyeloidLeukemiaPatientsTreatedWithImatinib,JNatlCancerInst,2011,103(7):55361.[PubMed21422402]
27. GibbonsJ,EgorinMJ,RamanathanRK,etal,PhaseIandPharmacokineticStudyofImatinibMesylateinPatientsWith
AdvancedMalignanciesandVaryingDegreesofRenalDysfunction:AStudybytheNationalCancerInstituteOrgan
DysfunctionWorkingGroup,JClinOncol,2008,26(4):5706.[PubMed18235116]
28. Gleevec(imatinib)[prescribinginformation].EastHanover,NJ:NovartisPharmaceuticalsJanuary2015.
29. Gleevec(imatinib)[productmonograph].Dorval,QuebecCanada:NovartisPharmaceuticalsCanadaIncJanuary2015.
30. GotlibJ,CoolsJ,MaloneJM3rd,etal,TheFIP1L1PDGFRalphaFusionTyrosineKinaseinHypereosinophilic
SyndromeandChronicEosinophilicLeukemia:ImplicationsforDiagnosis,Classification,andManagement,Blood,2004,
103(8):287991.[PubMed15070659]
31. HamnvikOP,LarsenPR,andMarquseeE,ThyroidDysfunctionFromAntineoplasticAgents,JNatlCancerInst,2011,
103(21):157287.[PubMed22010182]
32. HehlmannR,HochhausA,BergerU,etal,CurrentTrendsintheManagementofChronicMyelogenousLeukemia,Ann
Hematol,2000,79:34554.[PubMed10965782]
33. HehlmannR,MllerMC,LausekerM,etal.Deepmolecularresponseisreachedbythemajorityofpatientstreatedwith
imatinib,predictssurvival,andisachievedmorequicklybyoptimizedhighdoseimatinib:resultsfromtherandomized
CMLstudyIV.JClinOncol.201432(5):415423.doi:10.1200/JCO.2013.49.9020.[PubMed24297946]
34. HeinrichMC,OwzarK,CorlessCL,etal,CorrelationofKinaseGenotypeandClinicalOutcomeintheNorthAmerican
IntergroupPhaseIIITrialofImatinibMesylateforTreatmentofAdvancedGastrointestinalStromalTumor:CALGB150105
StudybyCancerandLeukemiaGroupBandSouthwestOncologyGroup,JClinOncol,2008,26(33):53607.[PubMed
18955451]
35. HessG,BunjesD,SiegertW,etal,SustainedCompleteMolecularRemissionsAfterTreatmentWithImatinibMesylate
inPatientsWithFailureAfterAllogeneicStemCellTransplantationforChronicMyelogenousLeukemia:Resultsofa
ProspectivePhaseIIOpenLabelMulticenterStudy,JClinOncol,2005,23(30):758393.[PubMed16234522]
36. HochhausA,O'BrienSG,GuilhotF,etal,SixYearFollowUpofPatientsReceivingImatinibfortheFirstLineTreatment
ofChronicMyeloidLeukemia,Leukemia,2009,23(6):105461.[PubMed19282833]
37. IbrahimAR,EliassonL,ApperleyJF,etal,PoorAdherenceistheMainReasonforLossofCCyRandImatinibFailurefor
ChronicMyeloidLeukemiaPatientsonLongTermTherapy,Blood,2011,117(14):37336.[PubMed21346253]
38. JoensuuH,ErikssonM,SundbyHallK,etal,OnevsThreeYearsofAdjuvantImatinibforOperableGastrointestinal
StromalTumor:ARandomizedTrial,JAMA,2012,307(12):126572.[PubMed22453568]
39. JoensuuH,RobertsPJ,SarlomoRikalaM,etal,EffectoftheTyrosineKinaseInhibitorSTI571inaPatientWitha
MetastaticGastrointestinalStromalTumor,NEnglJMed,2001,344(14):10526.[PubMed11287975]
40. KantarjianHM,O'BrienS,CortesJE,etal,ImatinibMesylateTherapyforRelapseAfterAllogeneicStemCell
TransplantationforChronicMyelogenousLeukemia,Blood,2002,100(5):15905.[PubMed12176876]
18/20
11/12/2015
41. KantarjianH,SawyersC,HochhausA,etal,HematologicandCytogeneticResponsestoImatinibMesylateinChronic
MyelogenousLeukemia,NEnglJMed,2002,346:64552.[PubMed11870241]
42. KerkelaR,GrazetteL,YacobiR,etal,CardiotoxicityoftheCancerTherapeuticAgentImatinibMesylate,NatMed,2006,
12(8):90816.[PubMed16862153]
43. LarsonRA,DrukerBJ,GuilhotF,etal,ImatinibPharmacokineticsanditsCorrelationWithResponseandSafetyin
ChronicPhaseChronicMyeloidLeukemia:ASubanalysisoftheIRISStudy,Blood,2008,111(8):40228.[PubMed
18256322]
44. LeCesneA,RayCoquardI,BuiBN,etal,DiscontinuationofImatinibinPatientsWithAdvancedGastrointestinalStromal
TumoursAfter3YearsofTreatment:AnOpenLabelMulticentreRandomisedPhase3Trial,LancetOncol,2010,
11(10):9429.[PubMed20864406]
45. LeCesneA,VanGlabbekeM,VerweijJ,etal,AbsenceofProgressionasAssessedbyResponseEvaluationCriteriain
SolidTumorsPredictsSurvivalinAdvancedGIStromalTumorsTreatedWithImatinibMesylate:TheIntergroupEORTC
ISGAGITGPhaseIIITrial,JClinOncol,2009,27(24):396974.[PubMed19620483]
46. LiuHandArtzAS,ReductionofImatinibAbsorptionAfterGastricBypassSurgery,LeukLymphoma,2011,52(2):3103.
[PubMed21133728]
47. MahonFX,RaD,GuilhotJ,etal,DiscontinuationofImatinibinPatientsWithChronicMyeloidLeukaemiaWhoHave
MaintainedCompleteMolecularRemissionforatLeast2Years:theProspective,MulticentreStopImatinib(STIM)Trial,
LancetOncol,2010,11(11):102935.[PubMed20965785]
48. McArthurGA,DemetriGD,vanOosteromA,etal,MolecularandClinicalAnalysisofLocallyAdvanced
DermatofibrosarcomaProtuberansTreatedwithImatinib:ImatinibTargetExplorationConsortiumStudyB2225,JClin
Oncol,2005,23(4):86673.[PubMed15681532]
49. OlavarriaE,SiddiqueS,GriffithsMJ,etal,PosttransplantationImatinibasaStrategytoPostponetheRequirementfor
ImmunotherapyinPatientsUndergoingReducedIntensityAllograftsforChronicMyeloidLeukemia,Blood,2007,
110(13):46147.[PubMed17881635]
50. OttmannOG,WassmannB,PfeiferH,etal,ImatinibComparedWithChemotherapyasFrontLineTreatmentofElderly
PatientsWithPhiladelphiaChromosomePositiveAcuteLymphoblasticLeukemia(Ph+ALL),Cancer,2007,109(10):2068
76.[PubMed17429836]
51. PavlovskyC,EgorinMJ,ShahDD,etal,ImatinibMesylatePharmacokineticsBeforeandAfterSleeveGastrectomyina
MorbidlyObesePatientWithChronicMyeloidLeukemia,Pharmacotherapy,2009,29(9):11526.[PubMed19698017]
52. PenelN,LeCesneA,BuiBN,etal,ImatinibforProgressiveandRecurrentAggressiveFibromatosis(DesmoidTumors):
AnFNCLCC/FrenchSarcomaGroupPhaseIItrialWithaLongTermFollowup,AnnOncol,2011,22(2):4527.[PubMed
20622000]
53. PyeSM,CortesJ,AultP,etal,TheEffectsofImatinibonPregnancyOutcome,Blood,2008,111(12):55058.[PubMed
18322153]
54. RamanathanRK,EgorinMJ,TakimotoCH,etal,PhaseIandPharmacokineticStudyofImatinibMesylateinPatients
WithAdvancedMalignanciesandVaryingDegreesofLiverDysfunction:AStudybytheNationalCancerInstituteOrgan
DysfunctionWorkingGroup,JClinOncol,2008,26(4):5639.[PubMed18235115]
55. RoilaF,HerrstedtJ,AaproM,etalESMO/MASCCGuidelinesWorkingGroup.GuidelineupdateforMASCCandESMO
inthepreventionofchemotherapyandradiotherapyinducednauseaandvomiting:resultsofthePerugiaconsensus
conference.AnnOncol.201021(suppl5):v232v243.[PubMed20555089]
56. SaadAldinE,MouradF,TfayliA.GastricantralvascularectasiainapatientwithGISTaftertreatmentwithimatinib:case
reportandliteraturereview.JpnJClinOncol.201242(5):447450.[PubMed22422898]
57. SchultzKR,BowmanWP,AledoA,etal.ImprovedearlyeventfreesurvivalwithimatinibinPhiladelphiachromosome
positiveacutelymphoblasticleukemia:achildren'soncologygroupstudy.JClinOncol.200927(31):51755181.doi:
10.1200/JCO.2008.21.2514.[PubMed19805687]
58. ShimaH,TokuyamaM,TanizawaA,etal,DistinctImpactofImatinibonGrowthatPrepubertalandPubertalAgesof
ChildrenWithChronicMyeloidLeukemia,JPediatr,2011,159(4):67681.[PubMed21592517]
59. StacchiottiS,LonghiA,FerraresiV,etal,PhaseIIStudyofImatinibinAdvancedChordoma,JClinOncol,2012,
30(9):91420.[PubMed22331945]
60. StacchiottiS,MarrariA,TamboriniE,etal,ResponsetoImatinibPlusSirolimusinAdvancedChordoma,AnnOncol,
2009,20(11):188694.[PubMed19570961]
61. ThomasDA,FaderlS,CortesJ,etal,TreatmentofPhiladelphiaChromosomePositiveAcuteLymphocyticLeukemia
WithHyperCVADandImatinibMesylate,Blood,2004,103(12):4396407.[PubMed14551133]
62. USDepartmentofHealthandHumanServicesCentersforDiseaseControlandPreventionNationalInstitutefor
OccupationalSafetyandHealth.NIOSHlistofantineoplasticandotherhazardousdrugsinthehealthcaresettings2014.
http://www.cdc.gov/niosh/docs/2014138/pdfs/2014138.pdf.UpdatedSeptember2014.AccessedSeptember15,2014.
63. vonMehrenMandWidmerN,CorrelationsBetweenImatinibPharmacokinetics,Pharmacodynamics,Adherence,and
ClinicalResponseinAdvancedMetastaticGastrointestinalStromalTumor(GIST):AnEmergingRoleforDrugBlood
LevelTesting?CancerTreatRev,2011,37(4):2919.[PubMed21078547]
64. YanadaM,TakeuchiJ,SugiuraI,etal,HighCompleteRemissionRateandPromisingOutcomebyCombinationof
ImatinibandChemotherapyforNewlyDiagnosedBCRABLPositiveAcuteLymphoblasticLeukemia:APhaseIIStudyby
theJapanAdultLeukemiaStudyGroup,JClinOncol,2006,24(3):4606.[PubMed16344315]
65. YooC,RyuMH,KangBW,etal,CrossSectionalStudyofImatinibPlasmaTroughLevelsinPatientsWithAdvanced
19/20
11/12/2015
GastrointestinalStromalTumors:ImpactofGastrointestinalResectiononExposuretoImatinib,JClinOncol,2010,
28(9):15549.[PubMed20177019]
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