Editing Modafinil (section)

{{Short description|Eugeroic medication}}
{{Use American English|date=December 2023}}
{{Use mdy dates|date=March 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = correct
| Watchedfields = correct
| verifiedrevid = 800497129
| image = Modafinil enantiomers labelled.svg
| image_class = skin-invert-image
| width = 300
| alt =
| caption =
| image2 = Modafinil enantiomers ball-and-stick models from xtal.png
| image_class2 = bg-transparent
| alt2 = <!-- Clinical data -->
| pronounce =
| tradename = Provigil, Alertec, Modavigil, others
| Drugs.com = {{drugs.com|monograph|modafinil}}
| MedlinePlus = a602016
| DailyMedID = Modafinil
| pregnancy_AU = D
| pregnancy_AU_comment = <ref name="Modavigil PI" />
| pregnancy_category =
| dependency_liability = Relatively low<ref name="modafinil-schedule-IV-1999"/>
| addiction_liability = Low<ref name="modafinil-schedule-IV-1999"/>
| routes_of_administration = [[Oral administration|By mouth]]<ref name="Drugs.com-Monograph-2023"/>
| class = {{plainlist|
* [[Stimulant]];
* [[Dopamine reuptake inhibitor]];
* [[Wakefulness-promoting agent]]}}
| ATC_prefix = N06
| ATC_suffix = BA07
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="Modavigil PI">{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-01898-1 | title=TGA eBS - Product and Consumer Medicine Information Licence | access-date=February 28, 2024 | archive-date=February 28, 2024 | archive-url=https://web.archive.org/web/20240228085348/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-01898-1 | url-status=live }}</ref>
| legal_BR = B1
| legal_BR_comment = <ref name="Diario Oficial da Uniao-2023">{{cite web |author-link=Brazilian Health Regulatory Agency |date=March 31, 2023 |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=August 3, 2023 |access-date=August 3, 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=April 4, 2023}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = <ref name="Modafinil Product information">{{cite web | title=Modafinil Product information | website=Health Canada | date=April 25, 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=63139 | access-date=June 10, 2022 | archive-date=June 10, 2022 | archive-url=https://web.archive.org/web/20220610220622/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=63139 | url-status=live }}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref name="Modafinil Provigil SmPC">{{cite web | url=https://www.medicines.org.uk/emc/product/5412/smpc | title=Modafinil Provigil 100 mg Tablets – Summary of Product Characteristics (SMPC) – (Emc) | website=emc | date=June 9, 2021 | access-date=December 1, 2023 | archive-date=December 2, 2023 | archive-url=https://web.archive.org/web/20231202185852/https://www.medicines.org.uk/emc/product/5412/smpc | url-status=live }}</ref>
| legal_US = Schedule IV<ref name="modafinil-schedule-IV-1999"/>
| legal_US_comment = <ref name="Provigil FDA label">{{cite web | title=Provigil- modafinil tablet | work = DailyMed | date=November 30, 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e16c26ad-7bc2-d155-3a5d-da83ad6492c8 | access-date=June 10, 2022 | archive-date=June 10, 2022 | archive-url=https://web.archive.org/web/20220610220626/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e16c26ad-7bc2-d155-3a5d-da83ad6492c8 | url-status=live }}</ref>
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- Pharmacokinetic data -->
| bioavailability = 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 book | vauthors = Hersey M, Tanda G | title = Pharmacological Advances in Central Nervous System Stimulants | chapter = Modafinil, an atypical CNS stimulant? | series = Adv Pharmacol | volume = 99 | pages = 287–326 | date = 2024 | pmid = 38467484 | doi = 10.1016/bs.apha.2023.10.006 | pmc = 12004278 | isbn = 978-0-443-21933-7 | chapter-url = }}</ref>
| protein_bound = ~60% (mainly to [[human serum albumin|albumin]])<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| metabolism = [[Liver]] ([[amide]] [[hydrolysis]], ''S''-[[oxidation]], [[aromatic ring]] [[hydroxylation]], [[glucuronidation|glucuronide]] [[conjugation (biochemistry)|conjugation]]; [[CYP1A2]], [[CYP2B6]], [[CYP2C9]], [[CYP2C19]], [[CYP3A4]], [[CYP3A5]] involved)<ref name="SousaDinis-Oliveira2020" /><ref name="pmid12537513"/><ref name="pmid10820139">{{cite journal | vauthors = Robertson P, DeCory HH, Madan A, Parkinson A | title = In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil | journal = Drug Metabolism and Disposition | volume = 28 | issue = 6 | pages = 664–671 | date = June 2000 | doi = 10.1016/S0090-9556(24)15146-X | pmid = 10820139 }}</ref>
| metabolites = • [[Modafinil acid]] (35–65%)<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" /><br />• [[Modafinil sulfone]]<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| onset = 2–4{{nbsp}}hours ([[Tmax (pharmacology)|peak]])<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| elimination_half-life = Modafinil: {{Val|12|-|15|u=hour}}<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" /><ref name="pmid12537513">{{cite journal | vauthors = Robertson P, Hellriegel ET | title = Clinical pharmacokinetic profile of modafinil | journal = Clinical Pharmacokinetics | volume = 42 | issue = 2 | pages = 123–137 | date = 2003 | pmid = 12537513 | doi = 10.2165/00003088-200342020-00002 | s2cid = 1266677 }}</ref><br />[[Armodafinil]]: 10–17{{nbsp}}h<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="HerseyTanda2024" /><br />[[Esmodafinil]]: 3–5{{nbsp}}h<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| duration_of_action = {{Val|11.5|u=hour}}<ref name="pmid22375280"/>
| excretion = [[Urine]]: 80% (≤10% as modafinil, 35–51% as modafinil acid)<ref name="NiemegeersMaudensMorrens2012" /><ref name="HerseyTanda2024" /><br />[[Feces]]: 1.0%<ref name="NiemegeersMaudensMorrens2012" />

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 68693-11-8
| CAS_supplemental =
| PubChem = 4236
| IUPHAR_ligand = 7555
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4088
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = R3UK8X3U3D
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01832
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 31859
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1373
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = CRL-40476; CRC-40476; CEP-1538; DEP-1538; Diphenylmethyl-sulfinylacetamide

<!-- Chemical data -->| IUPAC_name = 2-(diphenylmethanesulfinyl)acetamide
| C = 15
| H = 15
| N = 1
| O = 2
| S = 1
| SMILES = O=S(C(c1ccccc1)c2ccccc2)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)
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YFGHCGITMMYXAQ-UHFFFAOYSA-N

<!-- Physical data -->| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}

'''Modafinil''', sold under the brand name '''Provigil''' among others, is a [[central nervous system]] (CNS) [[stimulant]] and [[wakefulness-promoting agent|eugeroic]] ([[wakefulness]] promoter) medication used primarily to treat [[narcolepsy]],<ref name="Drugs.com-Monograph-2023">{{cite web |title=Modafinil Monograph for Professionals |url=https://www.drugs.com/monograph/modafinil.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |date=September 23, 2023 |access-date=February 3, 2024 |archive-date=March 30, 2019 |archive-url=https://web.archive.org/web/20190330181813/https://www.drugs.com/monograph/modafinil.html |url-status=live }}</ref><ref name="Provigil FDA label" /><ref name="medlineplus.gov-modafinil">{{cite web|url=https://medlineplus.gov/druginfo/meds/a602016.html|website=MedlinePlus|date=February 15, 2016|title=Modafinil|accessdate=February 3, 2024|publisher=US National Library of Medicine|archive-date=December 7, 2023|archive-url=https://web.archive.org/web/20231207203943/https://medlineplus.gov/druginfo/meds/a602016.html|url-status=live}}</ref> a [[sleep disorder]] characterized by [[excessive daytime sleepiness]] and sudden [[Microsleep|sleep attacks]].<ref name="pmid34743789"/> Modafinil is also approved for stimulating wakefulness in people with [[sleep apnea]] and [[shift work sleep disorder]].<ref name="Drugs.com-Monograph-2023"/> It is taken [[by mouth]].<ref name="Drugs.com-Monograph-2023"/><ref name="Provigil FDA label" /> Modafinil is not approved by the US [[Food and Drug Administration]] (FDA) for use in people under 17 years old.<ref name="Provigil FDA label" />

<!-- Contraindications -->
Common side effects of Modafinil include [[anxiety]], [[insomnia]], [[dizziness]], and [[headache]]. Modafinil has potential for causing severe [[allergic reaction]]s, [[Psychiatry|psychiatric]] effects,<ref name="Drugs.com-Monograph-2023" /> [[hypersensitivity]], [[adverse effect|adverse]] [[drug interaction|interactions]] with [[prescription drug]]s, and misuse or [[drug abuse|abuse]].<ref name="Drugs.com-Monograph-2023"/><ref name="Provigil FDA label" /><ref name="medlineplus.gov-modafinil"/> Modafinil may harm the [[fetus]] if taken during or two months prior to [[pregnancy]].<ref name="pmid33074297">{{cite journal |vauthors=Kaplan S, Braverman DL, Frishman I, Bartov N |title=Pregnancy and Fetal Outcomes Following Exposure to Modafinil and Armodafinil During Pregnancy |journal=JAMA Internal Medicine |volume=181 |issue=2 |pages=275–277 |date=February 2021 |pmid=33074297 |pmc=7573789 |doi=10.1001/jamainternmed.2020.4009 }}</ref>

<!-- Use in non-sleep-deprived individuals -->
While modafinil is used as a [[Nootropic|cognitive enhancer]], or "smart drug", among healthy individuals seeking improved focus and productivity,<ref name="economist-2008-05-22"/><ref name="Slotnik-2017"/> its use outside medical supervision raises concerns regarding potential misuse or abuse.<ref name="Drugs.com-Monograph-2023" /><ref name="Provigil FDA label"/><ref name="pmid30285371">{{cite book |title=StatPearls |vauthors=Greenblatt K, Adams N |date=February 2022 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Modafinil |pmid=30285371 |id={{NCBIBook|NBK531476}}}}</ref> Research on the cognitive enhancement effects of modafinil in non-sleep deprived individuals has yielded mixed results, with some studies suggesting modest improvements in attention and executive functions, while others show no significant benefits or even a decline in cognitive functions at high doses.<ref name="pmid36056861"/><ref name="pmid32341841"/>
{{TOC limit}}