modafinil (Rx)

Brand and Other Names:Provigil

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet: Schedule IV

  • 100mg
  • 200mg

Obstructive Sleep Apnea

Indicated to improve wakefulness in adults with excessive sleepiness associated with obstructive sleep apnea (OSA)

200 mg PO qAM

Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose

Narcolepsy

Indicated to improve wakefulness in adults with excessive sleepiness associated with narcolepsy

200 mg PO qAM

Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose

Shift Work Sleep Disorder

Indicated to improve wakefulness in adults with excessive sleepiness associated with shift work disorder (SWD)

200 mg PO as a single dose ~1 hr prior to patient's work shift

Dosage Modifications

Hepatic impairment, severe: 100 mg PO qAM

Narcolepsy (Orphan)

Orphan designation of a fixed dose combination of modafinil and flecainide for narcolepsy

Sponsor

  • Theranexus SA; 86 Rue de Paris; Orsay, France

Safety and efficacy not established

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Interactions

Interaction Checker

and modafinil

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            Contraindicated (7)

            • isocarboxazid

              isocarboxazid increases effects of modafinil by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • linezolid

              linezolid increases effects of modafinil by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • mavacamten

              modafinil will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              modafinil will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pacritinib

              modafinil will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • phenelzine

              phenelzine increases effects of modafinil by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • selegiline transdermal

              selegiline transdermal increases effects of modafinil by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • tranylcypromine

              tranylcypromine increases effects of modafinil by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            Serious - Use Alternative (36)

            • amobarbital

              amobarbital will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP2C19 inducer, with drugs that are CYP2C19 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered.

              apalutamide will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • atazanavir

              atazanavir will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • capivasertib

              modafinil will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.

            • cilostazol

              modafinil increases toxicity of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Decrease cilostazol dose by 50%; serum levels of 3,4-dehydrocilostazol (active metabolite) increased by strong CYP2C19 inhibitors.

            • clarithromycin

              clarithromycin will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clopidogrel

              modafinil decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19. .

            • cobicistat

              cobicistat will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • conivaptan

              conivaptan will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darunavir

              darunavir will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • elacestrant

              modafinil will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fedratinib

              modafinil will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fexinidazole

              fexinidazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fruquintinib

              modafinil will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.

            • ganaxolone

              modafinil will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

            • idelalisib

              idelalisib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • iobenguane I 131

              modafinil will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • ivosidenib

              ivosidenib will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lenacapavir

              modafinil will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

            • leniolisib

              modafinil will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lorlatinib

              lorlatinib, modafinil. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of both drugs increases risk of severe hepatotoxicity.

            • lumateperone

              modafinil will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • olutasidenib

              modafinil will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

            • omaveloxolone

              modafinil will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ozanimod

              ozanimod increases toxicity of modafinil by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • palovarotene

              modafinil will decrease the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenobarbital

              phenobarbital will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pirtobrutinib

              modafinil will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).

            • quizartinib

              modafinil will decrease the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • repotrectinib

              modafinil will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • secobarbital

              secobarbital will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • vonoprazan

              modafinil will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • zanubrutinib

              modafinil will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

            Monitor Closely (211)

            • abrocitinib

              modafinil will increase the level or effect of abrocitinib by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Start abrocitinib 50 mg qDay when coadministered with CYP2C19 inhibitors. If adequate response not achieved after 12 weeks, may increase to 100 mg qDay. Discontinue if inadequate response after dosage increase.

            • albuterol

              albuterol and modafinil both decrease sedation. Use Caution/Monitor.

            • alfentanil

              alfentanil increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alprazolam

              alprazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • amitriptyline

              modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • amobarbital

              amobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • amoxapine

              amoxapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • arformoterol

              arformoterol and modafinil both decrease sedation. Use Caution/Monitor.

            • aripiprazole

              aripiprazole increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • armodafinil

              armodafinil and modafinil both decrease sedation. Use Caution/Monitor.

            • azelastine

              azelastine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • belladonna and opium

              belladonna and opium increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • belzutifan

              modafinil will increase the level or effect of belzutifan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Belzutifan is a CYP2C19 substrate. Coadministration with CYP2C19 inhibitors may increase incidence or severity of adverse effects. Monitor for anemia and hypoxia and reduce belzutifan dose as recommended.

            • benperidol

              benperidol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benzphetamine

              modafinil and benzphetamine both decrease sedation. Use Caution/Monitor.

            • bortezomib

              modafinil will increase the level or effect of bortezomib by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • brompheniramine

              brompheniramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • butabarbital

              butabarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • butalbital

              butalbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • butorphanol

              butorphanol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • caffeine

              caffeine and modafinil both decrease sedation. Use Caution/Monitor.

            • cannabidiol

              modafinil will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • carbamazepine

              carbamazepine will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              cenobamate will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate.

            • ceritinib

              ceritinib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorpromazine

              chlorpromazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cinnarizine

              cinnarizine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • citalopram

              modafinil will increase the level or effect of citalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Citalopram 20 mg/day is the maximum recommended dose for patients taking CYP2C19 inhibitors because of the risk of QT prolongation.

            • clemastine

              clemastine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clobazam

              modafinil will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Dosage adjustment may be required; CYP2C19 inhibitors may result in increased exposure to N-desmethylclobazam (active metabolite).

            • clomipramine

              clomipramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clonazepam

              clonazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clorazepate

              clorazepate increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clozapine

              clozapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • codeine

              codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclizine

              cyclizine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • desipramine

              desipramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexfenfluramine

              modafinil and dexfenfluramine both decrease sedation. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmethylphenidate

              dexmethylphenidate and modafinil both decrease sedation. Use Caution/Monitor.

            • dextroamphetamine

              dextroamphetamine and modafinil both decrease sedation. Use Caution/Monitor.

            • dextromoramide

              dextromoramide increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diamorphine

              diamorphine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diazepam intranasal

              modafinil will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • diethylpropion

              modafinil and diethylpropion both decrease sedation. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diphenoxylate hcl

              diphenoxylate hcl increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dipipanone

              dipipanone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dobutamine

              dobutamine and modafinil both decrease sedation. Use Caution/Monitor.

            • dopamine

              modafinil and dopamine both decrease sedation. Use Caution/Monitor.

            • dopexamine

              dopexamine and modafinil both decrease sedation. Use Caution/Monitor.

            • doxepin

              doxepin increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • droperidol

              droperidol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.

              elagolix decreases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eluxadoline

              modafinil increases levels of eluxadoline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C19 inhibitors.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, modafinil. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enzalutamide

              enzalutamide will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ephedrine

              ephedrine and modafinil both decrease sedation. Use Caution/Monitor.

            • epinephrine

              epinephrine and modafinil both decrease sedation. Use Caution/Monitor.

            • epinephrine inhaled

              modafinil, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • epinephrine racemic

              epinephrine racemic and modafinil both decrease sedation. Use Caution/Monitor.

            • escitalopram

              modafinil will increase the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely.

            • esketamine intranasal

              esketamine intranasal, modafinil. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

            • eslicarbazepine acetate

              eslicarbazepine acetate will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • estazolam

              estazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ethanol

              ethanol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • etravirine

              modafinil will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              etravirine will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • fenfluramine

              modafinil and fenfluramine both decrease sedation. Use Caution/Monitor.

            • fexinidazole

              fexinidazole will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • flibanserin

              modafinil will increase the level or effect of flibanserin by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Coadministration of flibanserin with strong CYP2C19 inhibitors may increase flibanserin exposure and increase the risk of hypotension, syncope, and CNS depression.

            • fluphenazine

              fluphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • flurazepam

              flurazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • formoterol

              formoterol and modafinil both decrease sedation. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • green tea

              green tea, modafinil. Other (see comment). Use Caution/Monitor. Comment: Green tea may include caffeine. Caffeine is a CNS-stimulant and additive effects may be seen when coadministered with other CNS stimulants. Caffeine should be avoided or used cautiously.

            • haloperidol

              haloperidol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydromorphone

              hydromorphone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • iloperidone

              iloperidone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              iloperidone increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imipramine

              modafinil will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              imipramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoproterenol

              isoproterenol and modafinil both decrease sedation. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketotifen, ophthalmic

              ketotifen, ophthalmic increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • letermovir

              letermovir increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levalbuterol

              levalbuterol and modafinil both decrease sedation. Use Caution/Monitor.

            • levoketoconazole

              levoketoconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levorphanol

              levorphanol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lisdexamfetamine

              lisdexamfetamine and modafinil both decrease sedation. Use Caution/Monitor.

            • lofepramine

              lofepramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lofexidine

              lofexidine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loprazolam

              loprazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lorazepam

              lorazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lormetazepam

              lormetazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loxapine

              loxapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, modafinil. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

            • maprotiline

              maprotiline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • marijuana

              marijuana increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • melatonin

              melatonin increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • meperidine

              meperidine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • meprobamate

              meprobamate increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaproterenol

              metaproterenol and modafinil both decrease sedation. Use Caution/Monitor.

            • methadone

              methadone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methamphetamine

              methamphetamine and modafinil both decrease sedation. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              methylenedioxymethamphetamine and modafinil both decrease sedation. Use Caution/Monitor.

            • methylphenidate

              modafinil increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

            • midazolam

              midazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • midodrine

              modafinil and midodrine both decrease sedation. Use Caution/Monitor.

            • mifepristone

              mifepristone will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mirtazapine

              mirtazapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • morphine

              morphine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • motherwort

              motherwort increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • moxonidine

              moxonidine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nabilone

              nabilone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nalbuphine

              nalbuphine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nefazodone

              nefazodone will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nelfinavir

              nelfinavir will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norepinephrine

              norepinephrine and modafinil both decrease sedation. Use Caution/Monitor.

            • norgestrel

              modafinil will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods

            • nortriptyline

              nortriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • olanzapine

              olanzapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • omeprazole

              modafinil will increase the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • opium tincture

              opium tincture increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ospemifene

              modafinil increases levels of ospemifene by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • oxazepam

              oxazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • oxycodone

              oxycodone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • oxymorphone

              oxymorphone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • paliperidone

              paliperidone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • papaveretum

              papaveretum increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pentazocine

              pentazocine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pentobarbital

              pentobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • perphenazine

              perphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phendimetrazine

              modafinil and phendimetrazine both decrease sedation. Use Caution/Monitor.

            • phenobarbital

              phenobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phentermine

              modafinil and phentermine both decrease sedation. Use Caution/Monitor.

            • phenylephrine

              modafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

            • phenylephrine PO

              modafinil and phenylephrine PO both decrease sedation. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pholcodine

              pholcodine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pimozide

              pimozide increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pirbuterol

              pirbuterol and modafinil both decrease sedation. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • procarbazine

              procarbazine increases effects of modafinil by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

            • prochlorperazine

              prochlorperazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • promethazine

              promethazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • propylhexedrine

              modafinil and propylhexedrine both decrease sedation. Use Caution/Monitor.

            • protriptyline

              protriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quazepam

              quazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quetiapine

              quetiapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • rasagiline

              rasagiline increases effects of modafinil by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode. Use caution when administering MAOIs and modafinil.

            • ribociclib

              ribociclib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              risperidone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salmeterol

              salmeterol and modafinil both decrease sedation. Use Caution/Monitor.

            • saquinavir

              saquinavir will increase the level or effect of modafinil by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available.

              saquinavir will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • scullcap

              scullcap increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • secobarbital

              secobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • selegiline

              selegiline increases effects of modafinil by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode. Use caution when administering MAOIs and modafinil.

            • serdexmethylphenidate/dexmethylphenidate

              serdexmethylphenidate/dexmethylphenidate and modafinil both decrease sedation. Use Caution/Monitor.

            • shepherd's purse

              shepherd's purse increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

            • solriamfetol

              modafinil and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • sorafenib

              modafinil decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

            • sparsentan

              sparsentan will decrease the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates.

            • stiripentol

              stiripentol, modafinil. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • sufentanil

              sufentanil increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tapentadol

              tapentadol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.

              tecovirimat will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • temazepam

              temazepam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • terbutaline

              terbutaline and modafinil both decrease sedation. Use Caution/Monitor.

            • thioridazine

              thioridazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thiothixene

              thiothixene increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tofacitinib

              modafinil increases levels of tofacitinib by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with potent CYP2C19 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors .

            • topiramate

              topiramate increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • tramadol

              tramadol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trazodone

              trazodone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triazolam

              triazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triclabendazole

              triclabendazole will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole.

            • triclofos

              triclofos increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trifluoperazine

              trifluoperazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trimipramine

              trimipramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triprolidine

              triprolidine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • voriconazole

              voriconazole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • warfarin

              modafinil will increase the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inhibitors of these isoenzymes and adjust warfarin dose if needed.

            • xylometazoline

              modafinil and xylometazoline both decrease sedation. Use Caution/Monitor.

            • yohimbine

              modafinil and yohimbine both decrease sedation. Use Caution/Monitor.

            • ziconotide

              ziconotide increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziprasidone

              ziprasidone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            Minor (21)

            • acetazolamide

              acetazolamide will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amantadine

              amantadine, modafinil. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

            • ambrisentan

              modafinil will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • American ginseng

              American ginseng increases effects of modafinil by pharmacodynamic synergism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • bupropion

              modafinil, bupropion. increasing metabolism. Minor/Significance Unknown. Decr levels of bupropion, but incr levels of active metabolites. .

            • cimetidine

              modafinil will increase the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • cocaine topical

              modafinil will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • diazepam

              modafinil will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • eucalyptus

              eucalyptus increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • guarana

              guarana increases effects of modafinil by pharmacodynamic synergism. Minor/Significance Unknown.

            • lansoprazole

              modafinil will increase the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown. Net effect on pantoprazole actions unknown due to opposing effects of CYP450 enzymes; monitor

            • larotrectinib

              larotrectinib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levoketoconazole

              modafinil will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pantoprazole

              modafinil will increase the level or effect of pantoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown. Net effect on pantoprazole actions unknown due to opposing effects of CYP450 enzymes; monitor

            • rabeprazole

              modafinil will increase the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown. Net effect on pantoprazole actions unknown due to opposing effects of CYP450 enzymes; monitor

            • rifampin

              rifampin will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              sage increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • voriconazole

              modafinil will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • yerba mate

              yerba mate increases effects of modafinil by pharmacodynamic synergism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Headache (45-50%)

            Rhinitis (11-15%)

            Decreased appetite (16%)

            Nausea (11%)

            Abdominal pain (12%)

            1-10%

            Nervousness (6-10%)

            Syncope (1-5%)

            Frequency Not Defined

            Arrhythmia

            Hypotension

            Hypertension

            T-wave changes

            Amnesia

            Anxiety

            Cataplexy

            Chills

            Depression

            Dizziness

            Epistaxis

            Fever

            Insomnia

            Paresthesia

            Reversible psychosis (rare)

            Tremor

            Drug hypersensitivity syndrome

            Stevens-Johnson syndrome

            Toxic epidermal necrolysis due to drug

            Anorexia

            Diarrhea

            Dry mouth

            Mouth ulcer

            Vomiting

            Abnormal LFT

            Chest pain

            Neck pain

            Dyspnea

            Pharyngitis

            Postmarketing Reports

            Aggression

            Psychomotor hyperactivity

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            Warnings

            Contraindications

            Hypersensitivity

            Cautions

            Risk of skin reactions (eg SJS, toxic necrolysis, and drug rash with eosinophilia and systemic symptoms); discontinue if rash or other hypersensitivity reactions occur

            May impair ability to operate heavy machinery and perform hazardous tasks

            Not recommended in patients with angina, cardiac ischemia, recent history of myocardial infarction, left ventricular hypertrophy, or mitral valve prolapse

            Use with caution in severe hepatic impairment, elderly, history of: depression, psychosis (may exacerbate psychiatric symptoms), or mania

            Use with caution in patients with Tourette syndrome; stimulants may unmask ticks

            May reduce effectiveness of steroidal contraceptives 1 month after discontinuation of drug therapy

            Reassess degree of sleepiness frequently; if used adjunctively with continuous positive airway pressure (CPAP): Periodic assessment of CPAP compliance is necessary

            Discontinue at first sign of serious rash

            Discontinue therapy if symptoms suggest angioedema or anaphylaxis

            Discontinue if multiorgan hypersensitivity reaction is suspected

            Drug interaction overview

            • CYP3A4/5 substrates
              • Modafinil moderately induces CYP3A4/5, which may result in lower systemic exposure of CYP3A4/5 substrates (eg, hormonal contraceptives, cyclosporine, midazolam, triazolam)
              • Dose adjustment of substrate may be required
            • CYP2C19 substrates
              • Modafinil weakly inhibits CYP2C19, which may result in higher systemic exposure of CYP2C19 substrates (eg, phenytoin, diazepam, propranolol, omeprazole, clomipramine)
              • Individuals deficient in CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19 (eg, TCAs, SSRIs), may be increased by coadministration
              • Dose adjustments of these drugs and other drugs that are substrates for CYP2C19 may be necessary if modafinil is coadministered
            • Warfarin
              • Modafinil appeared to produce a concentration-related suppression of CYP2C9 activity, therefore suggesting potential for CYP2C9 inhibition; caution if drugs that have a narrow therapeutic index
              • Consider more frequent monitoring of prothrombin times/INR
            • MAO inhibitors
              • Other CNS stimulants may induce severe cardiovascular reactions; avoid coadministration
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            Pregnancy & Lactation

            Pregnancy

            Well controlled studies in pregnant women have not been performed

            Intrauterine growth restriction and spontaneous abortion have been reported with modafinil and armodafinil

            In studies conducted in rats (modafinil, armodafinil) and rabbits (modafinil), developmental toxicity was observed at clinically relevant plasma exposures

            Pregnancy registry to collect information on pregnancy outcomes of women exposed to modafinil: 866-404-4106

            Lactation

            Unknown is excreted in human milk

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Unknown; not sympathomimetic; may increase dopamine levels in the brain by binding to the dopamine transporter and inhibiting dopamine reuptake

            Absorption

            Peak plasma time: 2-4 hr

            Distribution

            Protein bound: 60%

            Vd: 0.9 L/kg

            Metabolism

            Hepatic

            Enzymes induced: CYP1A2, CYP2B6, CYP3A4; induces its own metabolism (chronic)

            Enzymes inhibited: CYP2C19

            Elimination

            Half-life: 15 hr

            Excretion: Urine (80%)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            modafinil oral
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            100 mg tablet
            modafinil oral
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            100 mg tablet
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            200 mg tablet
            modafinil oral
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            100 mg tablet
            modafinil oral
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            200 mg tablet
            modafinil oral
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            200 mg tablet
            modafinil oral
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            200 mg tablet
            modafinil oral
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            200 mg tablet
            modafinil oral
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            modafinil oral
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            100 mg tablet
            modafinil oral
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            modafinil oral
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            200 mg tablet
            modafinil oral
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            100 mg tablet
            Provigil oral
            -
            100 mg tablet
            Provigil oral
            -
            200 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            modafinil oral

            MODAFINIL - ORAL

            (moe-DAF-i-nil)

            COMMON BRAND NAME(S): Provigil

            USES: Modafinil reduces extreme sleepiness due to narcolepsy and other sleep disorders, such as periods of stopped breathing during sleep (obstructive sleep apnea). It is also used to help you stay awake during work hours if you have a work schedule that keeps you from having a normal sleep routine (shift work sleep disorder).This medication does not cure these sleep disorders and may not get rid of all your sleepiness. Modafinil does not take the place of getting enough sleep. It should not be used to treat tiredness or hold off sleep in people who do not have a sleep disorder.It is not known how modafinil works to keep you awake. It is thought to work by affecting certain substances in the brain that control the sleep/wake cycle.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using modafinil and each time you get a refill. If you have any questions, ask your doctor or pharmacist.For narcolepsy, take this medication by mouth with or without food as directed by your doctor, usually once daily in the morning. Or, if your doctor directs you to, the total daily dose of modafinil may be divided into a morning dose and a noon dose.For obstructive sleep apnea, take this medication by mouth with or without food as directed by your doctor, usually once daily in the morning. Continue your other treatment (such as the CPAP machine, mouth device) unless your doctor tells you to stop.If you are using modafinil for shift work sleep disorder, take it by mouth with or without food as directed by your doctor, usually once a day 1 hour before you start your work shift.The dosage is based on your medical condition and response to treatment. Take this medication regularly to get the most benefit from it.If you suddenly stop using this medication, you may have withdrawal symptoms (such as shaking, sweating, chills, nausea, vomiting, confusion). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used modafinil for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.Tell your doctor if your condition does not improve or if it worsens.

            SIDE EFFECTS: Headache, nausea, nervousness, dizziness, or difficulty sleeping may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: fast/pounding/irregular heartbeat, mental/mood changes (such as agitation, confusion, depression, hallucinations, rare thoughts of suicide).Get medical help right away if you have any very serious side effects, including: chest pain.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking modafinil, tell your doctor or pharmacist if you are allergic to it; or to armodafinil; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems (such as enlarged heart, mitral valve problem, chest pain, heart attack, irregular heartbeat), heart problems after taking stimulant drugs such as amphetamines (including chest pain, irregular heartbeat), high blood pressure, liver problems, mental/mood disorders (such as depression, mania, psychosis), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol).Sleep disorders may reduce your ability to react quickly. Though modafinil helps keep you awake, you still may not be able to safely do things that require quick reactions (such as driving). This drug may also make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using modafinil. Modafinil may harm an unborn baby. Ask about reliable forms of non-hormonal birth control while using this medication and for 2 months after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: street drugs (such as methamphetamine, MDMA/"ecstasy").This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use additional reliable birth control methods while using this medication and for 1 month after stopping this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.Modafinil can speed up the removal of other medications from your body, which may affect how they work. Examples of affected drugs include axitinib, bosutinib, daridorexant, elacestrant, certain products used to treat chronic hepatitis C (asunaprevir, ombitasvir/paritaprevir/ritonavir), quizartinib, among others.Some products have ingredients that could raise your heart rate or blood pressure. Tell your pharmacist what products you are using, and ask how to use them safely (especially cough-and-cold products or diet aids).Caffeine can increase the side effects of this medication. Avoid drinking large amounts of beverages containing caffeine (coffee, tea, colas), eating large amounts of chocolate, or taking nonprescription products that contain caffeine.Modafinil is very similar to armodafinil. Do not take medications containing armodafinil while using modafinil.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose include: fast/irregular heartbeat, severe restlessness, hallucinations.

            NOTES: Do not share this medication with others. Sharing it is against the law.Lab and/or medical tests (such as blood pressure, heart rate) may be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.Follow good sleep habits (such as sleeping in a dark/quiet room, avoiding caffeine close to bedtime) which can help improve your sleep if you have shift work sleep disorder.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up. Do not take missed doses close to bedtime because doing so may make it harder to go to sleep.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2023. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.