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10/21/2015

Modafinil:Druginformation

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Modafinil:Druginformation
Copyright19782015Lexicomp,Inc.Allrightsreserved.
(Foradditionalinformationsee"Modafinil:Patientdruginformation"andsee"Modafinil:Pediatricdruginformation")
ForabbreviationsandsymbolsthatmaybeusedinLexicomp(showtable)

BrandNames:US Provigil
BrandNames:Canada AlertecApoModafinilMarModafinilTevaModafinil
PharmacologicCategory CentralNervousSystemStimulant
Dosing:Adult
USlabeling:
Narcolepsy,obstructivesleepapnea(OSA):Oral:Initial:200mgasasingledailydoseinthemorning.Note:Dosesupto400mgoncedailyhave
beenwelltolerated,butthereisnoconsistentevidencethatthisdoseconfersadditionalbenefit.
Shiftworksleepdisorder(SWSD):Oral:Initial:200mgasasingledose~1hourpriortostartofworkshift
Canadianlabeling:
Narcolepsy:Oral:Initial:200mgdailyin2divideddoses(firstdoseinthemorningandseconddoseatnoon[ornolaterthanearlyafternoon])may
titrate dose upward in 100 mg increments as needed and tolerated (maximum single dose: < 300 mg maximum daily dose: 400 mg). Single
doses300mganddailydoses>400mgareassociatedwithincreasedsideeffectsandarenotrecommended.
Obstructivesleepapnea:Oral:200mgoncedailyinthemorning.
Shiftworksleepdisorder(SWSD):Oral:200mgasasingledosetaken~1hourpriortostartofworkshift
Offlabeluses:
Attentiondeficit/hyperactivitydisorder(ADHD)(offlabeluse):100to400mgdaily(Taylor2000)
Multiplesclerosisrelatedfatigue(offlabeluse):100mgoncedailyinitially,increasedastoleratedto200mgoncedailyorifpatientexperiences
postnoon fatigue, 100 mg twice daily (ie, morning and noon). Higher daily doses (greater than 200 mg) do not appear to be effective (Brown
2010Moller2011Rammohan2002Stankoff2005Zifko2002).
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Dosing:Geriatric Considerinitiatingatlowerdoses.
Dosing:RenalImpairment Therearenodosageadjustmentsprovidedinthemanufacturerslabeling.
Dosing:HepaticImpairment
Mildtomoderatehepaticimpairment:Therearenodosageadjustmentsprovidedinthemanufacturerslabeling.
Severehepaticimpairment:Doseshouldbereducedtoonehalfofthatrecommendedforpatientswithnormalliverfunction.

DosageForms:US Excipientinformationpresentedwhenavailable(limited,particularlyforgenerics)consultspecificproductlabeling.
Tablet,Oral:
Provigil:100mg
Provigil:200mg[scored]
Generic:100mg,200mg

DosageForms:Canada Excipientinformationpresentedwhenavailable(limited,particularlyforgenerics)consultspecificproductlabeling.
Tablet,oral:100mg
Alertec:100mg

GenericEquivalentAvailable:US Yes
ControlledSubstance CIV
MedicationGuideand/orVaccineInformationStatement(VIS) AnFDAapprovedpatientmedicationguide,whichisavailablewith
theproductinformationandathttp://www.fda.gov/downloads/Drugs/DrugSafety/UCM231722.pdf,mustbedispensedwiththismedication.

Administration
USlabeling:Forthetreatmentofnarcolepsyandobstructivesleepapnea/hypopneasyndrome,administerdoseinthemorning.Forthetreatmentofshift
worksleepdisorder,administerdose~1hourpriortostartofworkshift.
Canadianlabeling:Forthetreatmentofnarcolepsy,administerin2divideddoseswithfirstdosegiveninthemorningandtheseconddosegivenatnoon
(ornolaterthanearlyafternoon)toavoidpotentialforinsomnia.Fortreatmentofobstructivesleepapnea,administerasasingledoseinthemorning.
Forthetreatmentofshiftworksleepdisorder,administerdose~1hourpriortostartofworkshift.

Use
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Modafinil:Druginformation

Narcolepsy:Toimprovewakefulnessinadultpatientswithexcessivesleepinessassociatedwithnarcolepsy.
Obstructivesleepapnea:Toimprovewakefulnessinadultpatientswithobstructivesleepapnea(OSA)
Shiftworksleepdisorder:Toimprovewakefulnessinadultpatientswithshiftworksleepdisorder(SWSD)

Use:OffLabel
Attentiondeficit/hyperactivitydisorderFatigueinadultcancersurvivorsMultiplesclerosisrelatedfatigue

AdverseReactionsSignificant
Frequencynotalwaysdefined.
Cardiovascular:Chestpain(3%),hypertension(3%),palpitations(2%),tachycardia(2%),vasodilatation(2%),edema(1%)
Central nervous system: Headache (adults 34% children 20% [Biederman 2005] dose related), nervousness (7%), anxiety (5% dose related),
dizziness (5%), insomnia (5%), depression (2%), drowsiness (2%), paresthesia (2%), agitation (1%), chills (1%), confusion (1%), emotional
lability(1%),hypertonia(1%),vertigo(1%)
Dermatologic:Diaphoresis(1%)
Endocrine&metabolic:Weightloss(children5%[Greenhill2006]),increasedthirst(1%),increasedgammaglutamyltransferase
Gastrointestinal:Decreasedappetite(children16%[Biederman2005]),abdominalpain(children12%[Greenhill2006]),nausea(11%),diarrhea(6%),
dyspepsia(5%),xerostomia(4%),anorexia(4%),constipation(2%),dysgeusia(1%),flatulence(1%),oralmucosaulcer(1%)
Genitourinary:Urineabnormality(1%)
Hematologic&oncologic:Eosinophilia(1%)
Hepatic:Abnormalhepaticfunctiontests(2%),increasedserumalkalinephosphatase
Neuromuscular&skeletal:Backpain(6%),dyskinesia(1%),hyperkinesia(1%),tremor(1%)
Ocular:Abnormalvision(1%)
Respiratory:Rhinitis(7%),pharyngitis(4%),asthma(1%),epistaxis(1%)
<1% (Limited to important or lifethreatening): Agranulocytosis, DRESS syndrome, erythema multiforme (pediatric patients), hallucination,
hypersensitivity, mania, multiorgan hypersensitivity, psychomotor agitation, psychosis, StevensJohnson syndrome, suicidal ideation, toxic
epidermalnecrolysis

Contraindications
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Hypersensitivitytomodafinil,armodafinil,oranycomponentoftheformulation
Canadianlabeling:Additionalcontraindications(notinUSlabeling):Patientsinagitatedstatesorwithsevereanxiety

Warnings/Precautions
Concernsrelatedtoadverseeffects:
CNSeffects:Mayimpairtheabilitytoengageinpotentiallyhazardousactivitiespatientsmustbecautionedaboutperformingtaskswhichrequire
mentalalertness(eg,operatingmachineryordriving).
Dermatologiceffects(severe):Seriousandlifethreateningrashes,includingStevensJohnsonsyndrome,toxicepidermalnecrolysis,anddrugrash
with eosinophilia and systemic symptoms (DRESS) have been reported. Although initially reported in children during clinical trials,
postmarketing cases have occurred in both children and adults. Most cases have occurred within the first 5 weeks of therapy however, rare
caseshaveoccurredafterlongtermuse(eg,3months).Noriskfactorshavebeenidentifiedtopredictoccurrenceorseverity.Patientsshould
be advised to discontinue at first sign of rash (unless the rash is clearly not drugrelated). As a result of these serious dermatologic adverse
events,approvalfortheuseofmodafinilinchildrenforADHDwasdeniedbytheFDA.
Hypersensitivity reactions: Rare cases of multiorgan hypersensitivity reactions (with fatality) in association with modafinil use lone cases of
angioedema and anaphylactoid reactions with armodafinil have been reported (angioedema has been noted in postmarketing reports with
modafinil). Signs and symptoms are diverse, reflecting the involvement of specific organs patients typically present with fever and rash
associatedwithorgansystemdysfunction.Noriskfactorshavebeenidentifiedtopredictoccurrenceorseverityofmultiorganhypersensitivity
reactions.Patientsshouldbeadvisedtoreportanysignsandsymptomsrelatedtotheseeffectsdiscontinuationoftherapyisrecommended.
Diseaserelatedconcerns:
Cardiovascular disease: Use with caution in patients with cardiovascular disease increased blood pressure and heart rate monitoring may be
required. Use is not recommended in patients with a history of left ventricular hypertrophy or patients with mitral valve prolapse who have
developed mitral valve prolapse syndrome with previous CNS stimulant use. Increased monitoring should be considered in patients with a
recenthistoryofmyocardialinfarctionorunstableangina.
Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage reduction is recommended in patients with severe hepatic
impairment.
Psychiatric disorders: Use with caution in patients with a history of psychosis, depression, or mania. Use may result in emergence of or
exacerbation of psychiatric symptoms. Observe for symptoms of aggression, hallucinations, mania, delusions, or suicidal ideation. Consider
discontinuingtherapyifpsychiatricsymptomsdevelop.
Renalimpairment:Usewithcautioninpatientswithrenalimpairment.
Sleep disorders: Appropriate use: The degree of sleepiness should be reassessed frequently some patients may not return to a normal level of
wakefulness.Inobstructivesleepapnea,modafinilisindicatedastreatmentforexcessivesleepinessandnotfortheunderlyingobstruction.If
continuouspositiveairwaypressure(CPAP)isthetreatmentofchoiceforapatient,amaximalefforttotreatwithCPAPforanadequateperiod
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Modafinil:Druginformation

oftimeshouldbemadepriortoinitiatingandduringtreatmentwithmodafinilforexcessivesleepiness.
Tourettesyndrome:UsewithcautioninpatientswithTourettesyndromelimitedevidencesuggestsstimulantsmayexacerbateticsandTourette
syndrome(AACAP[Murphy,2013]Pringsheim,2012Rossner,2011).
Specialpopulations:
Pediatric:ModafinilisnotFDAapprovedforuseinpediatricsforanyindication.Seriousskinreactionsandpsychiatriceventshavebeenobserved
in pediatric patients treated with modafinil. The serious nature of these adverse effects resulted in the FDAs Pediatric Advisory Committee
unanimouslyrecommendingthataspecificwarningagainsttheuseofmodafinilinchildrenbeaddedtothemanufacturerslabeling.
Otherwarnings/precautions:
Ethanoluse:Instructpatientstoavoidconcomitantethanolconsumption.

Metabolism/TransportEffects SubstrateofCYP3A4(major)Note:AssignmentofMajor/Minorsubstratestatusbasedonclinicallyrelevant
druginteractionpotentialInhibitsCYP2A6(weak),CYP2C19(moderate),CYP2C9(weak),CYP2E1(weak)InducesCYP1A2(weak/moderate),
CYP2B6(weak/moderate),CYP3A4(moderate)

DrugInteractions
(Foradditionalinformation:LaunchLexiInteractDrugInteractionsProgram)
AntihepaciviralCombinationProducts:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofAntihepaciviralCombinationProducts.
RiskX:Avoidcombination
Aprepitant:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
ARIPiprazole:CYP3A4InducersmaydecreasetheserumconcentrationofARIPiprazole.Management:Doubletheoralaripiprazoledoseandclosely
monitorclinicalresponse.Reducetheoralaripiprazoledoseto1015mg/dayiftheinducerisdiscontinued.AvoiduseofCYP3A4inducersformore
than14dayswithextendedreleaseinjectablearipiprazole.RiskD:Considertherapymodification
AtoMOXetine:MayenhancethehypertensiveeffectofSympathomimetics.AtoMOXetinemayenhancethetachycardiceffectofSympathomimetics.
RiskC:Monitortherapy
Axitinib:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofAxitinib.RiskX:Avoidcombination
Bedaquiline:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofBedaquiline.RiskX:Avoidcombination
Bosentan:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Bosutinib:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofBosutinib.RiskX:Avoidcombination
CannabinoidContainingProducts:MayenhancethetachycardiceffectofSympathomimetics.Exceptions:Cannabidiol.RiskC:Monitortherapy
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Cilostazol:CYP2C19InhibitorsmayincreasetheserumconcentrationofCilostazol.Management:Considerreducingthecilostazoldoseto50mgtwice
dailyinpatientswhoarealsoreceivinginhibitorsofCYP2C19.RiskD:Considertherapymodification
Citalopram:CYP2C19Inhibitors(Moderate)mayincreasetheserumconcentrationofCitalopram.Management:Limitcitalopramdosetoamaximumof
20mg/dayifusedwithamoderateCYP2C19inhibitor.Patientsusingthiscombinationshouldbemonitoredcloselyforevidenceofcitalopram
toxicity(e.g.,serotoninsyndrome,QTprolongation,etc.).RiskD:Considertherapymodification
Clarithromycin:CYP3A4Inducers(Moderate)mayincreaseserumconcentrationsoftheactivemetabolite(s)ofClarithromycin.CYP3A4Inducers
(Moderate)maydecreasetheserumconcentrationofClarithromycin.Management:Consideralternativeantimicrobialtherapyforpatientsreceivinga
CYP3Ainducer.Drugsthatenhancethemetabolismofclarithromycininto14hydroxyclarithromycinmayaltertheclinicalactivityofclarithromycin
andimpairitsefficacy.RiskD:Considertherapymodification
Clopidogrel:CYP2C19Inhibitors(Moderate)maydecreaseserumconcentrationsoftheactivemetabolite(s)ofClopidogrel.Management:Duetoarisk
forimpairedclopidogreleffectivenesswithsuchacombination,carefullyconsidertheneedforamoderateCYP2C19inhibitorinpatientsreceiving
clopidogrel.Monitorpatientscloselyforevidenceofadiminishedresponsetoclopidogrel.RiskD:Considertherapymodification
Conivaptan:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskX:Avoidcombination
Contraceptives(Estrogens):ModafinilmaydecreasetheserumconcentrationofContraceptives(Estrogens).Management:Themanufacturer
recommendsthatpatientsusenonhormonalcontraceptives,inadditiontoorinplaceofhormonalcontraceptives,duringandforonemonthfollowing
treatmentwithmodafinil.RiskD:Considertherapymodification
CycloSPORINE(Systemic):ModafinilmaydecreasetheserumconcentrationofCycloSPORINE(Systemic).RiskC:Monitortherapy
CYP2C19Substrates:CYP2C19Inhibitors(Moderate)maydecreasethemetabolismofCYP2C19Substrates.RiskC:Monitortherapy
CYP3A4Inducers(Moderate):MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
CYP3A4Inducers(Strong):MayincreasethemetabolismofCYP3A4Substrates.Management:Consideranalternativeforoneoftheinteractingdrugs.
Somecombinationsmaybespecificallycontraindicated.Consultappropriatemanufacturerlabeling.RiskD:Considertherapymodification
CYP3A4Inhibitors(Moderate):MaydecreasethemetabolismofCYP3A4Substrates.RiskC:Monitortherapy
CYP3A4Inhibitors(Strong):MaydecreasethemetabolismofCYP3A4Substrates.RiskD:Considertherapymodification
CYP3A4Substrates:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Dabrafenib:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:SeekalternativestotheCYP3A4substratewhenpossible.If
concomitanttherapycannotbeavoided,monitorclinicaleffectsofthesubstrateclosely(particularlytherapeuticeffects).RiskD:Considertherapy
modification
Daclatasvir:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofDaclatasvir.Management:Increasethedaclatasvirdoseto90mg
oncedailyifusedwithamoderateCYP3A4inducer.RiskD:Considertherapymodification
Dasatinib:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
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Deferasirox:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Doxofylline:Sympathomimeticsmayenhancetheadverse/toxiceffectofDoxofylline.RiskC:Monitortherapy
Enzalutamide:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:ConcurrentuseofenzalutamidewithCYP3A4substrates
thathaveanarrowtherapeuticindexshouldbeavoided.UseofenzalutamideandanyotherCYP3A4substrateshouldbeperformedwithcaution
andclosemonitoring.RiskD:Considertherapymodification
FentaNYL:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofFentaNYL.RiskC:Monitortherapy
Flibanserin:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofFlibanserin.RiskX:Avoidcombination
Fosaprepitant:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
FusidicAcid(Systemic):MayincreasetheserumconcentrationofCYP3A4Substrates.RiskX:Avoidcombination
Hydrocodone:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofHydrocodone.RiskC:Monitortherapy
Ibrutinib:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofIbrutinib.Management:AlthoughmoderateCYP3Ainducersarenot
specificallycontraindicatedwithibrutinib,prescribinginformationindicatesthattheymaydecreaseAUCupto3fold.Ifpossible,alternativeswith
lessCYP3Ainductionshouldbeconsidered.RiskD:Considertherapymodification
Idelalisib:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskX:Avoidcombination
Ifosfamide:CYP3A4Inducers(Moderate)maydecreaseserumconcentrationsoftheactivemetabolite(s)ofIfosfamide.CYP3A4Inducers(Moderate)
mayincreaseserumconcentrationsoftheactivemetabolite(s)ofIfosfamide.RiskC:Monitortherapy
IobenguaneI123:SympathomimeticsmaydiminishthetherapeuticeffectofIobenguaneI123.RiskX:Avoidcombination
Ivacaftor:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Linezolid:MayenhancethehypertensiveeffectofSympathomimetics.Management:Reduceinitialdosesofsympathomimeticagents,andclosely
monitorforenhancedpressorresponse,inpatientsreceivinglinezolid.Specificdoseadjustmentrecommendationsarenotpresentlyavailable.Risk
D:Considertherapymodification
Luliconazole:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Mifepristone:MayincreasetheserumconcentrationofCYP3A4Substrates.Management:MinimizedosesofCYP3A4substrates,andmonitorfor
increasedconcentrations/toxicity,duringand2weeksfollowingtreatmentwithmifepristone.Avoidcyclosporine,dihydroergotamine,ergotamine,
fentanyl,pimozide,quinidine,sirolimus,andtacrolimus.RiskD:Considertherapymodification
Mitotane:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:DosesofCYP3A4substratesmayneedtobeadjusted
substantiallywhenusedinpatientsbeingtreatedwithmitotane.RiskD:Considertherapymodification
Netupitant:MayincreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
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NiMODipine:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofNiMODipine.RiskC:Monitortherapy
Nisoldipine:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofNisoldipine.RiskX:Avoidcombination
Olaparib:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofOlaparib.RiskX:Avoidcombination
Palbociclib:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofPalbociclib.RiskX:Avoidcombination
Ranolazine:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofRanolazine.RiskX:Avoidcombination
Rolapitant:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofRolapitant.Management:Monitorforreducedrolapitantresponse.
Recommendeddexamethasoneregimensshouldbeusedwithrolapitant.Higherdexamethasonedosesormoreprolongedusemayincreasethe
potentialforasignificantinteraction.RiskC:Monitortherapy
Saxagliptin:CYP3A4InducersmaydecreasetheserumconcentrationofSaxagliptin.RiskC:Monitortherapy
Siltuximab:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy
Simeprevir:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofSimeprevir.RiskX:Avoidcombination
Sofosbuvir:ModafinilmaydecreasetheserumconcentrationofSofosbuvir.RiskX:Avoidcombination
Sonidegib:CYP3A4Inducers(Moderate)maydecreasetheserumconcentrationofSonidegib.RiskX:Avoidcombination
StJohnsWort:MaydecreasetheserumconcentrationofCYP3A4Substrates.Management:Consideranalternativeforoneoftheinteractingdrugs.
Somecombinationsmaybespecificallycontraindicated.Consultappropriatemanufacturerlabeling.RiskD:Considertherapymodification
Stiripentol:MayincreasetheserumconcentrationofCYP3A4Substrates.Management:UseofstiripentolwithCYP3A4substratesthatareconsidered
tohaveanarrowtherapeuticindexshouldbeavoidedduetotheincreasedriskforadverseeffectsandtoxicity.AnyCYP3A4substrateusedwith
stiripentolrequiresclosermonitoring.RiskD:Considertherapymodification
Sympathomimetics:Mayenhancetheadverse/toxiceffectofotherSympathomimetics.RiskC:Monitortherapy
Tedizolid:MayenhancethehypertensiveeffectofSympathomimetics.TedizolidmayenhancethetachycardiceffectofSympathomimetics.RiskC:
Monitortherapy
Tocilizumab:MaydecreasetheserumconcentrationofCYP3A4Substrates.RiskC:Monitortherapy

FoodInteractions Fooddelaysabsorption,butdoesnotaffectbioavailability.Management:Administerwithoutregardtomeals.
PregnancyRiskFactor C(showtable)
PregnancyImplications Adverseeventshavebeenobservedinsomeanimalreproductionstudies.Anincreasedriskofspontaneousabortion
andintrauterinegrowthrestrictionhasbeenreportedwithmodafinil.Efficacyofsteroidalcontraceptives(includingdepotandimplantablecontraceptives)
maybedecreasedalternatemeansofcontraceptionshouldbeconsideredduringtherapyandfor1monthaftermodafinilisdiscontinued.
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Healthcareprovidersareencouragedtoregisterpregnantpatientsexposedtomodafinil,orpregnantwomenmayenrollthemselves,bycalling(866404
4106).

BreastFeedingConsiderations Itisnotknownifmodafinilisexcretedinbreastmilk.Themanufacturerrecommendsthatcautionbe
exercisedwhenadministeringmodafiniltonursingwomen.

Pricing:US
Tablets(ModafinilOral)
100mg(30):$662.00
200mg(30):$1000.08
Tablets(ProvigilOral)
100mg(30):$972.00
200mg(30):$1468.80
Disclaimer:ThepricingdataprovidearepresentativeAWPand/orAAWPpricefromasinglemanufacturerofthebrandand/orgenericproduct,
respectively.Thepricingdatashouldbeusedforbenchmarkingpurposesonly,andassuchshouldnotbeusedtosetoradjudicateanypricesfor
reimbursementorpurchasingfunctions.Pricingdataisupdatedmonthly.

MonitoringParameters LevelsofsleepinessbloodpressureheartrateincreasedmonitoringinpatientswithrecentMIorunstableangina
developmentofsevereskinreactionsdevelopmentorexacerbationofpsychiatricsymptoms(eg,agitation,anxiety,depression)
WhenusedforthetreatmentofADHD,thoroughlyevaluateforcardiovascularrisk.Monitorheartrate,bloodpressure,andconsiderobtainingECGprior
toinitiation(Vetter,2008).

InternationalBrandNames Activigil(UY)Alertex(CL,EC)Aspendos(RO)Carim(CR,DO,EC,GT,HN,NI,PA,SV,UY)Forcilin(AR)
Intensit(AR)Mentix(CL)Modalert(IN)Modanil(KR)Modasomil(AT,CH)Modavigil(AU,NZ)Modfil(IN)Modiodal(DK,ES,FR,GR,IS,JP,MX,
NL,NO,PT,SE,TR)Movigil(CL)Nopral(AR)Provake(IN)Provigil(BE,GB,IE,IL,IT,KR,MT,PY,SG,TW,ZA)Resotyl(CL,PE)Stavigile
(BR)Vigia(CO)Vigicer(AR)Vigil(CZ,DE)Zalox(CL)

MechanismofAction Theexactmechanismofactionisunclear,itdoesnotappeartoalterthereleaseofdopamineornorepinephrine,itmay
exertitsstimulanteffectsbydecreasingGABAmediatedneurotransmission,althoughthistheoryhasnotyetbeenfullyevaluatedseveralstudiesalso
suggestthatanintactcentralalphaadrenergicsystemisrequiredformodafinil'sactivitythedrugincreaseshighfrequencyalphawaveswhile
decreasingbothdeltaandthetawaveactivity,andtheseeffectsareconsistentwithgeneralizedincreasesinmentalalertness

PharmacodynamicsandPharmacokinetics Modafinilisaracemiccompound(10%Sisomerand90%Risomeratsteadystate)whose
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enantiomershavedifferentpharmacokinetics
Distribution:Vd:0.9L/kg
Proteinbinding:~60%,primarilytoalbumin
Metabolism:HepaticmultiplepathwaysincludingCYP3A4
Halflifeelimination:Effectivehalflife:15hours
Timetopeak,serum:2to4hoursmaybedelayed~1hourwithfood.
Excretion:Urine(80%asmetabolites,<10%asunchangeddrug)feces(1%)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. BiedermanJ,SwansonJM,WigalSB,etal.EfficacyandSafetyofModafinilFilmCoatedTabletsinChildrenandAdolescentsWithAttentionDeficit/HyperactivityDisorder:
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