Armodafinil: Difference between revisions

{{Short description|Eugeroic medication}}

{{cs1 config|name-list-style=vanc}}

| Verifiedfields = verified

| Watchedfields = verified

| verifiedrevid = 457152625

| IUPAC_name = (–)-2-[(''R'')-(diphenylmethyl)sulfinyl]acetamide

| image = Armodafinil structure.svg

| width = 200

| image2 = (R)-modafinil-from-xtal-3D-bs-17.png

| width2 = 175

<!--Clinical data-->| tradename = Nuvigil, others

| Drugs.com = {{drugs.com|monograph|armodafinil}}

| MedlinePlus = a602016

| legal_US = Schedule IV

| legal_AUえーゆー = S4

| legal_AUえーゆー_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2015 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2015 | access-date=10 April 2023}}</ref>

| legal_BR = B1

| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-03 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_status =

| dependency_liability = Low

| routes_of_administration = [[Oral administration|Oral]] ([[tablet (pharmacy)|tablet]]s)<ref name="Nuvigil-FDA-Label" />

| class = Atypical [[dopamine reuptake inhibitor]]; [[wakefulness-promoting agent]]

| bioavailability = Unknown (due to poor [[aqueous solubility]];<ref name="Nuvigil-FDA-Label">https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021875s023lbl.pdf</ref> but [[modafinil]] is 40–65% based on [[urine|urinary]] [[excretion]])<ref name="SousaDinis-Oliveira2020">{{cite journal | vauthors = Sousa A, Dinis-Oliveira RJ | title = Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects | journal = Subst Abus | volume = 41 | issue = 2 | pages = 155–173 | date = 2020 | pmid = 31951804 | doi = 10.1080/08897077.2019.1700584 | url = }}</ref><ref name="HerseyTanda2024">{{cite journal | vauthors = Hersey M, Tanda G | title = Modafinil, an atypical CNS stimulant? | journal = Adv Pharmacol | volume = 99 | issue = | pages = 287–326 | date = 2024 | pmid = 38467484 | doi = 10.1016/bs.apha.2023.10.006 | url = }}</ref>

| protein_bound = Unknown (but for modafinil is moderate, primarily to [[human serum albumin|albumin]])<ref name="NiemegeersMaudensMorrens2012" /><ref name="Garnock-JonesDhillonScott2009" /><ref name="Nuvigil-FDA-Label" />

| metabolism = [[Liver]], including [[CYP3A4]] and other [[enzyme]]s ([[hydrolysis|hydrolytic]] [[amidation]], [[sulfoxidation]], [[aromatic ring]] [[hydroxylation]], and [[glucuronidation|glucuronide]] [[conjugation (biochemistry)|conjugation]])<ref name="NiemegeersMaudensMorrens2012" /><ref name="Lankford2008" /><ref name="Garnock-JonesDhillonScott2009" />

| metabolites = • [[Modafinil acid|Armodafinil acid]]<ref name="NiemegeersMaudensMorrens2012" /><ref name="Garnock-JonesDhillonScott2009" /><br />• [[Modafinil sulfone]]<ref name="NiemegeersMaudensMorrens2012" /><ref name="Garnock-JonesDhillonScott2009" />

| onset = 1.5–6.5{{nbsp}}h (range 0.5–11{{nbsp}}h) ([[Tmax (pharmacology)|peak]])<ref name="Garnock-JonesDhillonScott2009">{{cite journal | vauthors = Garnock-Jones KP, Dhillon S, Scott LJ | title = Armodafinil | journal = CNS Drugs | volume = 23 | issue = 9 | pages = 793–803 | date = September 2009 | pmid = 19689169 | doi = 10.2165/11203290-000000000-00000 | url = }}</ref><ref name="Lankford2008">{{cite journal | vauthors = Lankford DA | title = Armodafinil: a new treatment for excessive sleepiness | journal = Expert Opin Investig Drugs | volume = 17 | issue = 4 | pages = 565–573 | date = April 2008 | pmid = 18363520 | doi = 10.1517/13543784.17.4.565 | url = }}</ref>

| elimination_half-life = 10–17{{nbsp}}hours<ref name="NiemegeersMaudensMorrens2012">{{cite journal | vauthors = Niemegeers P, Maudens KE, Morrens M, Patteet L, Joos L, Neels H, Sabbe BG | title = Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression | journal = Expert Opin Drug Metab Toxicol | volume = 8 | issue = 9 | pages = 1189–1197 | date = September 2012 | pmid = 22803602 | doi = 10.1517/17425255.2012.708338 | url = }}</ref><ref name="Garnock-JonesDhillonScott2009" /><ref name="HerseyTanda2024" />

| duration_of_action = Up to 13.5{{nbsp}}hours<ref name="Russo2009">{{cite journal | last=Russo | first=Michael | title=Pharmacotherapy of Excessive Sleepiness: Focus on Armodafinil | journal=Clinical Medicine. Therapeutics | volume=1 | date=2009 | issn=1179-1713 | doi=10.4137/CMT.S1994 | page=CMT.S1994}}</ref>

| excretion = Unknown (but modafinil is excreted 80% in [[urine]] and 1.0% in [[feces]])<ref name="Nuvigil-FDA-Label" />

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 112111-43-0

| ATC_prefix = N06

| ATC_suffix = BA13

| PubChem = 9690109

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 7962943

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = V63XWA605I

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 77590

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D03215

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1201192

| synonyms = (''R'')-Modafinil; ''R''-Modafinil; (''R'')-(–)-Modafinil; (–)-Modafinil; CRL-40982; CEP-10952

<!--Chemical data-->| C = 15

| H = 15

| N = 1

| O = 2

| S = 1

| SMILES = C1=CC=C(C=C1)C(C2=CC=CC=C2)[S@](=O)CC(=O)N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17)/t19-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = YFGHCGITMMYXAQ-LJQANCHMSA-N

<!-- Definition and medical uses -->

'''Armodafinil''', sold under the brand name '''Nuvigil''', is a [[wakefulness-promoting agent|wakefulness-promoting]] [[medication]] which is used to treat [[excessive daytime sleepiness]] associated with [[obstructive sleep apnea]], [[narcolepsy]], and [[shift work disorder]].<ref name="Nuvigil-FDA-Label" /> It is also used [[off-label use|off-label]] for certain other indications.<ref name="repurposed2021" /> The drug is taken [[oral administration|by mouth]].<ref name="Nuvigil-FDA-Label" />

<!-- Side effects, mechanism of action, and chemistry -->

[[Side effect]]s of armodafinil include [[headache]], [[nausea]], [[dizziness]], and [[insomnia]].<ref name="Nuvigil-FDA-Label" /> Armodafinil acts as a [[binding selectivity|selective]] atypical [[dopamine reuptake inhibitor]] (DRI) and hence as an indirect [[dopamine receptor agonist]].<ref name="Nuvigil-FDA-Label" /><ref name="HerseyTanda2024" /><ref name="Lamas-AguilarDiaz-RuizNavarro2024">{{cite journal | vauthors = Lamas-Aguilar R, Diaz-Ruiz A, Navarro L, Miranda-Ojeda R, de Los Ángeles Martínez-Cárdenas M, Mata-Bermudez A, Rios C | title = Armodafinil as a Potential Pharmacological Treatment for Attention Deficit Hyperactivity Disorder in Adults: A Review | journal = Curr Neuropharmacol | volume = 22 | issue = 11 | pages = 1899–1908 | date = 2024 | pmid = 38486390 | pmc = 11284730 | doi = 10.2174/1570159X22666240131121642 | url = }}</ref> However, other [[mechanism of action|mechanisms]] might also be involved in its effects.<ref name="Nuvigil-FDA-Label" /><ref name="HerseyTanda2024" /><ref name="Lamas-AguilarDiaz-RuizNavarro2024" /> Chemically, armodafinil is the [[enantiopure drug|enantiopure]] (''R'')-(–)-[[enantiomer]] of the [[racemic mixture]] [[modafinil]] (brand name Provigil).<ref name="Nuvigil-FDA-Label" /><ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" /> Both enantiomers of modafinil are [[pharmacological activity|active]] as DRIs and wakefulness-promoting agents, but armodafinil is more [[potency (pharmacology)|potent]] and longer-acting.<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />

<!-- History, society, and culture -->

Armodafinil is produced by the [[pharmaceutical company]] [[Cephalon]]<ref name="Cephalon 2007">{{cite web |url=http://www.nuvigil.com/PDF/Full_Prescribing_Information.pdf |title=NUVIGIL (armodafinil) tablets, for oral use | work = Cephalon, Inc., Teva Pharmaceutical Industries Ltd. | publisher = U.S. Food and Drug Administration |access-date=2013-11-23 |archive-url=https://web.archive.org/web/20180107165205/http://www.nuvigil.com/PDF/Full_Prescribing_Information.pdf |archive-date=2018-01-07 |url-status=dead }}</ref> and was approved by the [[United States]] [[Food and Drug Administration]] (FDA) in 2007.<ref name="titleCDER Drug and Biologic Approvals for Calendar Year 2007">{{cite web |url=http://corpina.org/wp-content/uploads/2014/01/Armodafinil_FDA_Approval-.pdf |title=CDER Drug and Biologic Approvals for Calendar Year 2007 |access-date=January 21, 2008 |archive-date=February 3, 2014 |archive-url=https://web.archive.org/web/20140203031823/http://corpina.org/wp-content/uploads/2014/01/Armodafinil_FDA_Approval-.pdf |url-status=dead }}</ref><ref name=ob>{{Citation |date=March 2012 |title=Search results from the "OB_Rx" table for query on "021875." |work=[[Approved Drug Products with Therapeutic Equivalence Evaluations|Orange Book]] |publisher=U.S. [[Food and Drug Administration]] |url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=021875&TABLE1=OB_Rx |access-date=April 30, 2012}}</ref> In 2016, the FDA granted [[Mylan]] rights for the first [[Generic drug|generic]] version of armodafinil to be marketed in the United States.<ref name="Mylan2016">{{cite web|url=http://newsroom.mylan.com/2016-06-01-Mylan-Launches-First-Generic-of-Nuvigil-Tablets|title=Mylan Launches First Generic of Nuvigil® Tablets|website=MediaRoom|access-date=February 9, 2017|archive-date=2017-02-11|archive-url=https://web.archive.org/web/20170211080455/http://newsroom.mylan.com/2016-06-01-Mylan-Launches-First-Generic-of-Nuvigil-Tablets|url-status=dead}}</ref>

==Medical uses==

Armodafinil is currently FDA-approved to treat [[excessive daytime sleepiness]] (EDS) associated with [[obstructive sleep apnea]] (OSA), [[narcolepsy]], and [[shift work sleep disorder]] (SWSD).<ref name="Cephalon 2007"/> It is commonly used [[off-label use|off-label]] to treat [[attention deficit hyperactivity disorder]] (ADHD), [[chronic fatigue syndrome]] (CFS), and [[major depressive disorder]] (MDD), and has been repurposed as an [[adjunct therapy|adjunctive treatment]] for [[bipolar disorder]].<ref name="repurposed2021">{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | volume = 143 | pages = 230–238 | date = November 2021 | pmid = 34509090 | doi = 10.1016/j.jpsychires.2021.09.018 | s2cid = 237485915 }}</ref> It has been shown to improve [[alertness|vigilance]] in [[air traffic controller]]s,<ref name="Phillips 2011">{{cite journal | vauthors = Phillips JB, Simmons RG, Arnold RD | title = A single dose of armodafinil significantly promotes vigilance 11 hours post-dose | journal = Military Medicine | volume = 176 | issue = 7 | pages = 833–839 | date = July 2011 | pmid = 22128728 | doi = 10.7205/milmed-d-10-00250 | doi-access = free }}</ref> however in the United States, [[wakefulness-promoting drug|wakefulness-promoting medication]]s such as [[modafinil]] (Provigil) and armodafinil (Nuvigil) are not approved by the [[Federal Aviation Administration]] (FAA) for civilian controllers or pilots.<ref>{{cite web |date=2016-12-16 |title=Therapeutic Drug Guidelines for Air Traffic Control Specialists |url=https://www.aviationmedicine.com/wp-content/uploads/2018/08/Therapeutic-Drug-Guidelines-for-ATCS-FINAL-12-16-16-PDF-version.pdf |access-date=2022-05-31 |website=Aviation Medicine Advisory Service |quote=Stimulants, sometimes used for narcolepsy and attention deficit hyperactivity disorder, are not acceptable. Included are amphetamines (Adderall), pemoline (Cylert), methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and modafinil (Provigil).}}</ref>

===Psychiatry===

====Bipolar disorder====

Armodafinil, along with racemic modafinil, has been repurposed as an adjunctive treatment for acute depression in people with [[bipolar disorder]].<ref name="repurposed2021"/> Meta-analytic evidence showed that add-on modafinil and armodafinil were more effective than placebo on response to treatment, clinical remission, and reduction in depressive symptoms, with only minor side effects, but the effect sizes are small and the quality of evidence has to be considered low, limiting the clinical relevance of current evidence. However current dosage for bipolar disorder is 150&nbsp;mg once daily. Paradoxical tiredness and sleeping is observed in some cases.<ref name="repurposed2021"/>

====Schizophrenia====

{{See also|Modafinil#Schizophrenia}}

In June 2010, it was revealed that a phase II study of armodafinil as an adjunctive therapy in adults with [[schizophrenia]] had failed to meet the primary endpoints, and the clinical program was subsequently terminated.<ref name="titleCephalon Provides Clinical Update on Phase II Study of NUVIGIL as an Adjunctive Therapy in Adults with Schizophrenia, ">{{cite press release|url=http://www.prnewswire.com/news-releases/cephalon-provides-clinical-update-on-phase-ii-study-of-nuvigil-as-an-adjunctive-therapy-in-adults-with-schizophrenia-95449199.html|title=Cephalon Provides Clinical Update on Phase II Study of NUVIGIL as an Adjunctive Therapy in Adults with Schizophrenia|access-date=August 21, 2011}}</ref> However, a study published later that year showed that patients with schizophrenia treated with armodafinil showed fewer of the [[Schizophrenia#Negative symptoms|negative symptoms of schizophrenia]].<ref name="Kane 2010">{{cite journal | vauthors = Kane JM, D'Souza DC, Patkar AA, Youakim JM, Tiller JM, Yang R, Keefe RS | title = Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 11 | pages = 1475–1481 | date = November 2010 | pmid = 20816042 | doi = 10.4088/JCP.09m05950gry }}</ref>

===Jet lag===

On March 30, 2010, the FDA declined to approve use of Nuvigil to treat [[jet lag]].<ref name="Consideration">{{cite news |url=https://www.nytimes.com/2010/01/07/business/07jetlag.html |title=A Drug's Second Act: Battling Jet Lag <!-- alt title: Fighting Jet Lag May Help Cephalon Extend Patent on Nuvigil --> | vauthors = Pollack A |date=January 6, 2010 |work=[[The New York Times]] |access-date=March 30, 2010}}</ref><ref name="Rejection">{{cite news |url=https://www.nytimes.com/2010/03/30/business/30drug.html |title=Regulators Reject a Drug Maker's Plan to Use Its Alertness Pill to Overcome Jet Lag <!-- alt title: F.D.A. Rejects Jet Lag Drug by Cephalon --> | vauthors = Pollack A |date=March 29, 2010 |work=[[The New York Times]] |access-date=March 30, 2010}}</ref>

===Available forms===

Armodafinil is available in the form of 50, 150, 200, and 250{{nbsp}}mg [[oral administration|oral]] [[tablet (pharmacy)|tablet]]s.<ref name="Nuvigil-FDA-Label" />

A 50{{nbsp}}mg dose of armodafinil is essentially equivalent to at 100{{nbsp}}mg dose of [[modafinil]] in terms of drug levels.<ref name="Lankford2008" />

==Adverse effects==

In placebo-controlled studies, the most commonly observed side effects were [[headache]], [[xerostomia]] (dry mouth), [[nausea]], [[dizziness]], and [[insomnia]].<ref name="repurposed2021"/> Possible side effects also include depression, anxiety, hallucinations, euphoria, extreme increase in activity and talking, anorexia, tremor, thirst, rash, suicidal thoughts, and aggression. Symptoms of an overdose on armodafinil include trouble sleeping, restlessness, confusion, disorientation, feeling excited, mania, hallucinations, nausea, diarrhea, severely increased or decreased heart beat, chest pain, and increased blood pressure.<ref name="Cephalon 2007"/><ref>{{cite web|url=http://www.rxlist.com/nuvigil-drug/side-effects-interactions.htm|title=Nuvigil (Armodafinil): Side Effects, Interactions, Warning, Dosage & Uses | work = RxList }}</ref><ref>{{cite web |url=http://armodexperiment.com/?s=dry+mouth |title = My Armodafinil Experiment |access-date=2014-10-14 |archive-url=https://web.archive.org/web/20160303235441/http://armodexperiment.com/?s=dry+mouth |archive-date=2016-03-03 |url-status=dead }}</ref> Serious rashes can develop in rare cases, and require immediate medical attention due to the possibility of [[Stevens–Johnson syndrome|Stevens-Johnson Syndrome]], or other [[Hypersensitivity|hypersensitivities]] to armodafinil.<ref name="Cephalon 2007" />

===Misuse potential===

Armodafinil has a low [[misuse potential]] similar to [[modafinil]].

==Interactions==

[[Hypertensive crisis|Hypertensive crises]] have been reported when armodafinil has been taken with [[monoamine oxidase inhibitor]]s (MAOIs) like [[tranylcypromine]].<ref name="KinslowShapiroGrunebaum2018">{{cite journal | vauthors = Kinslow CJ, Shapiro SD, Grunebaum MF, Miller EC | title = Acute hypertensive crisis and severe headache after concurrent use of armodafinil and tranylcypromine: Case report and review of the literature | journal = J Neurol Sci | volume = 393 | issue = | pages = 1–3 | date = October 2018 | pmid = 30077942 | pmc = 6446082 | doi = 10.1016/j.jns.2018.07.023 | url = }}</ref>

==Pharmacology==

[[File:Armodafinil 150mg.jpg|thumb|Armodafinil 150mg blister]]

===Pharmacodynamics===

The [[mechanism of action]] of armodafinil is unknown. Armodafinil (''R''-(−)-modafinil) has pharmacological properties almost identical to those of [[modafinil]] (a mixture of ''R''-(−)- and (''S'')-(+)-modafinil). The (''R'')- and (''S'')-enantiomers have similar pharmacological action in animals. Armodafinil has wake-promoting actions similar to [[sympathomimetic agents]] including [[amphetamine]] and [[methylphenidate]], although its pharmacologic profile is not identical to that of the sympathomimetic amines. Armodafinil binds ''in vitro'' to the [[dopamine transporter]] (DAT) and inhibits dopamine reuptake. For modafinil, this activity has been associated ''in vivo'' with increased extracellular dopamine levels. In genetically engineered mice lacking the dopamine transporter, modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent.<ref>{{cite journal | vauthors = Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y | title = Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil | journal = The Journal of Neuroscience | volume = 28 | issue = 34 | pages = 8462–8469 | date = August 2008 | pmid = 18716204 | pmc = 6671058 | doi = 10.1523/JNEUROSCI.1819-08.2008 }}</ref> However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not antagonized by the [[dopamine receptor antagonist]] [[haloperidol]] in rats. In addition, [[alpha-methyl-p-tyrosine]], an inhibitor of dopamine synthesis, blocks the action of amphetamine but does not block [[Animal locomotion|locomotor]] activity induced by modafinil.

In addition to its wake-promoting effects and ability to increase locomotor activity in animals, according to Nuvigil prescribing information from manufacturer Cephalon, armodafinil produces [[psychoactive]] and [[euphoria|euphoric]] effects, alterations in mood, perception, thinking, and feelings typical of other [[central nervous system]] (CNS) [[stimulant]]s in humans.<ref name="Cephalon 2007"/> Armodafinil, like racemic modafinil, may also possess reinforcing properties, as evidenced by its self-administration in monkeys previously trained to administer [[cocaine]]; armodafinil was also partially discriminated as stimulant-like. A Cephalon-founded study in which patients were administered modafinil, methylphenidate, and a placebo found that modafinil produces "psychoactive and euphoric effects and feelings consistent with [methylphenidate]."<ref name="Cephalon 2007"/>

Like modafinil, armodafinil is an [[enzyme inhibitor|inhibitor]] and/or [[enzyme inducer|inducer]] of certain [[cytochrome P450]] [[enzyme]]s.<ref name="Garnock-JonesDhillonScott2009">{{cite journal | vauthors = Garnock-Jones KP, Dhillon S, Scott LJ | title = Armodafinil | journal = CNS Drugs | volume = 23 | issue = 9 | pages = 793–803 | date = September 2009 | pmid = 19689169 | doi = 10.2165/11203290-000000000-00000 | url = }}</ref><ref name="Andrade2012">{{cite journal | vauthors = Andrade C | title = Modafinil and armodafinil in schizophrenia | journal = J Clin Psychiatry | volume = 73 | issue = 8 | pages = e1062–4 | date = August 2012 | pmid = 22967783 | doi = 10.4088/JCP.12f07977 | url = }}</ref> It moderately induces [[CYP3A4]] and moderately inhibits [[CYP2C19]].<ref name="Garnock-JonesDhillonScott2009" /><ref name="Andrade2012" /> In contrast to modafinil however, armodafinil does not induce [[CYP1A2]].<ref name="Garnock-JonesDhillonScott2009" /><ref name="Andrade2012" />

===Pharmacokinetics===

Armodafinil exhibits linear time-independent kinetics following single and multiple oral dose administration. Increase in systemic exposure is proportional over the dose range of 50–400&nbsp;mg. No time-dependent change in kinetics was observed through 12 weeks of dosing. Apparent steady state for armodafinil was reached within 7 days of dosing. At steady state, the systemic exposure for armodafinil is 1.8 times the exposure observed after a single dose. The concentration-time profiles of the (''R'')-(−)-enantiomer following a single dose of 50&nbsp;mg Nuvigil or 100&nbsp;mg Provigil (modafinil being a 1:1 mixture of (''R'')-(−)- and (''S'')-(−)- enantiomers) are nearly superimposable. However, the [[Cmax (pharmacology)|C_max]] of armodafinil at steady state was 37% higher following administration of 200&nbsp;mg Nuvigil than the corresponding value of modafinil following administration of 200&nbsp;mg Provigil due to the more rapid clearance of the (''S'')-(+)-enantiomer.

====Absorption====

Armodafinil is readily absorbed after oral administration. The absolute oral [[bioavailability]] was not determined due to the aqueous insolubility of armodafinil, which precluded [[intravenous]] administration. Peak plasma concentrations are attained at approximately 2 hours in the fasted state. Food effect on the overall bioavailability of armodafinil is considered minimal; however, time to reach peak concentration may be delayed 2–4 hours in the fed state. Since the delay in [[Cmax (pharmacology)|T_max]] is also associated with elevated plasma concentration later in time, food can potentially affect the onset and time course of pharmacologic action of armodafinil.

==Chemistry==

{{See also|List of modafinil analogues and derivatives}}

Armodafinil, or (''R'')-(–)-modafinil, is the [[enantiopure drug|enantiopure]] (''R'')-(–)-[[enantiomer]] of the [[racemic mixture]] [[modafinil]], while [[esmodafinil]] is the (''S'')-(+)-enantiomer.<ref name="SousaDinis-Oliveira2020" />

A number of [[structural analog|analogue]]s of armodafinil are known, including [[adrafinil]], [[flmodafinil]], [[fladrafinil]], and others.<ref name="SousaDinis-Oliveira2020" />

==Society and culture==

===Brand names===

Armodafinil is sold under a wide variety of brand names worldwide:

{{cmn|colwidth=30em|

* '''Acronite''' (by Consern Pharma): India

* '''Armoda''': ACI Pharmaceuticals (Symbiota), Bangladesh

* '''Armod''': India (by Emcure Pharmaceuticals Ltd)

*'''Artvigil''': India (by HAB Pharma)<ref>{{cite web|url=https://modafinil.org/artvigil/|title = Artvigil Review &#91;2021 Guide&#93; Uses, Side Effects, & Dosing|date = October 2021 | work = modafinil.org }}</ref>

* '''Neoresotyl''': Chile, Colombia

* '''Nuvigil''': USA, Chile, Ukraine, Israel, Mexico,<ref>Lundbeck Mexico, S.A. de C.V.</ref> Australia

* '''R-Modawake''': India

* '''Waklert''': India (by [[Sun Pharmaceutical|Sun Pharma]])<ref>{{cite web|url=https://modafinil.org/waklert/|title=Waklert Review &#91;2021 Guide&#93; Uses, Side Effects, & Dosing|date=October 2021 | work = modafinil.org }}</ref>

* '''Modavital''': El Salvador (Farmaceutica INHOSPI (by Laboratorios Marceli)

* '''Nodement''': Syrian Arab republic (by hama pharma)

* '''Armowake''': Egypt (by EVA Pharma)

}}

===Legal status===

In Australia, and the United States, Armodafinil is considered to be a Schedule 4 prescription-only medicine or prescription animal remedy.<ref>{{cite web | title = Poisons Standard | date = March 2018 | url = https://www.legislation.gov.au/Details/F2018L00168 | work = Therapeutics Goods Administration, Department of Health | publisher = Australian Government }}</ref> Schedule 4 is defined as "Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."

====Romania====

As of 2021, new laws do not directly include Armodafinil as a doping agent, but they do include Modafinil, as Armodafinil is an enantiomer of Modafinil it will show up on lab tests, but it can be debated if it is or not the same substance.

New laws state that simple possession is not a criminal offence and is punished with a fine and confiscation.<ref>{{cite web | title = LAW no. 219 | language = Romanian | date = 26 July 2021 | work = Romanian Parliament | url = http://legislatie.just.ro/Public/DetaliiDocument/245003 }}</ref> Importing into Romania and exporting from Romania of the substance, without a valid medical prescription, is a criminal offence and is punished with jail time between two and seven years.

==Research==

Besides [[hypersomnia]], armodafinil was under development for the treatment of [[fatigue (medical)|fatigue]], [[bipolar depression]], and [[schizophrenia]].<ref name="AdisInsight">{{cite web | title=Armodafinil - Teva Pharmaceutical Industries | website=AdisInsight | date=4 January 2024 | url=https://adisinsight.springer.com/drugs/800022302 | access-date=21 September 2024}}</ref> However, development for these indications was discontinued.<ref name="AdisInsight" /> The drug reached [[Phases of clinical research#Phase III|phase 3]] [[clinical trial]]s for treatment of fatigue prior to the discontinuation of its development for this use in January 2024.<ref name="AdisInsight" /> Aside from the preceding indications, armodafinil is currently under development for the treatment of [[eating disorder]]s and, as of January 2024, is in phase 3 trials for this use.<ref name="AdisInsight" />

{{Reflist}}

* [http://www.nuvigil.com/ Nuvigil (armodafinil) Tablets Official Site]

** [https://web.archive.org/web/20110519090541/http://nuvigil.com/media/Medication_Guide.pdf Medication Guide for Patients]

** [https://web.archive.org/web/20101219071137/http://nuvigil.com/media/Full_Prescribing_Information.pdf Full Prescribing Information]

{{Stimulants}}

{{Monoamine reuptake inhibitors}}

[[Category:Acetamides]]

[[Category:CYP3A4 inducers]]

[[Category:Cytochrome P450 inhibitors]]

[[Category:Dopamine reuptake inhibitors]]

[[Category:Drugs with unknown mechanisms of action]]

[[Category:Enantiopure drugs]]

[[Category:Pro-motivational agents]]

[[Category:Wakefulness-promoting agents]]

[[Category:World Anti-Doping Agency prohibited substances]]