Identification
- Summary
Armodafinil is a stimulant used to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea, narcolepsy, or shift work disorder.
- Brand Names
- Nuvigil
- Generic Name
- Armodafinil
- DrugBank Accession Number
- DB06413
- Background
Armodafinil is the enantiopure of the wakefulness-promoting agent modafinil (Provigil), and is indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD). Research has shown that armodafinil significantly improves driving simulator performance in patients with SWD. Armodafinil consists of the (−)-R-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. (a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.) and was approved by the U.S. Food and Drug Administration (FDA) in June 2007.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Armodafinil (DB06413)
- Weight
- Average: 273.35
Monoisotopic: 273.082349901 - Chemical Formula
- C15H15NO2S
- Synonyms
- (–)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide
- (−)-(R)-modafinil
- (−)-modafinil
- (R)-(−)-modafinil
- (R)-modafinil
- Armodafinil
- Armodafinilo
- Armodafinilum
- R-modafinil
- External IDs
- CEP 10953
- CEP-10952
- CEP-10953
- CRL 40982
- CRL-40982
Pharmacology
- Indication
Investigated for use/treatment in sleep disorders, obstructive sleep apnea, schizophrenia and schizoaffective disorders, depression, and bipolar disorders.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Excessive sleepiness •••••••••••• Management of Narcolepsy •••••••••••• Management of Shift work disorder •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Nuvigil (armodafinil) is a single-isomer of modafini. The exact mechanism of action is unknown. Armodafinil belongs to a class of drugs known as eugeroics, which are stimulants that provide long-lasting mental arousal. Pharmacologically, armodafinil does not bind to or inhibit several receptors and enzymes potentially relevant for sleep/wake regulation. Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, both armodafinil and modafinil bind to the dopamine transporter and inhibit dopamine reuptake. [Medilexicon]
Target Actions Organism ASodium-dependent dopamine transporter antagonistinhibitorHumans - Absorption
Tmax is 2 hours when fasted and can be delayed approximately 2-4 hours by food, potentially affecting the onset of action.
- Volume of distribution
Apparent volume of distribution: 42L.
- Protein binding
Specific data unavailable. Similar to modafinil: approximately 60%, primarily to albumin.
- Metabolism
In vitro and in vivo data show that armodafinil undergoes hydrolytic deamidation, S-oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation of the hydroxylated products. Amide hydrolysis is the single most prominent metabolic pathway, with sulfone formation by cytochrome P450 (CYP) 3A4/5 being next in importance. The other oxidative products are formed too slowly in vitro to enable identification of the enzyme(s) responsible. Only two metabolites reach appreciable concentrations in plasma (i.e., R-modafinil acid and modafinil sulfone). Data specific to armodafinil disposition are not available.
- Route of elimination
Not Available
- Half-life
Terminal half-life is approximately 15 hours.
- Clearance
The oral clearance of armodafinil is approximately 33 mL/min.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The metabolism of Abemaciclib can be increased when combined with Armodafinil. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Armodafinil. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Armodafinil. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Armodafinil. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Armodafinil. - Food Interactions
- Avoid alcohol.
- Exercise caution with grapefruit products. Armodafinil is partially metabolized by CYP3A4, and grapefruit is a CYP3A4 inhibitor.
- Exercise caution with St. John's Wort. Armodafinil is partially metabolized by CYP3A4, and St. John's Wort is a CYP3A4 inducer.
- Take with or without food. Taking armodafinil with food can delay the Tmax by 2-4 hours.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- International/Other Brands
- Neoresotyl (Drugtech)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nuvigil Tablet 150 mg/1 Oral Lake Erie Medical DBA Quality Care Products LLC 2009-06-01 2018-12-31 US 
Nuvigil Tablet 50 mg/1 Oral KAISER FOUNDATION HOSPITALS 2011-01-28 2013-08-31 US Nuvigil Tablet 150 mg/1 Oral Cephalon, LLC 2009-05-26 Not applicable US Nuvigil Tablet 150 mg/1 Oral A S Medication Solutions 2009-06-01 Not applicable US 
Nuvigil Tablet 50 mg/1 Oral Rebel Distributors 2009-06-01 Not applicable US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Armodafinil Tablet 150 mg/1 Oral Preferred Pharmaceuticals Inc. 2021-03-08 Not applicable US Armodafinil Tablet 150 mg/1 Oral Direct_Rx 2019-01-04 Not applicable US Armodafinil Tablet 250 mg/1 Oral Mylan Pharmaceuticals Inc. 2016-06-01 Not applicable US Armodafinil Tablet 250 mg/1 Oral Breckenridge Pharmaceutical, Inc. 2016-11-28 2019-03-31 US Armodafinil Tablet 250 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2016-11-29 Not applicable US
Categories
- ATC Codes
- N06BA13 — Armodafinil
- Drug Categories
- Benzene Derivatives
- Benzhydryl Compounds
- Central Nervous System Agents
- Central Nervous System Stimulants
- Centrally Acting Sympathomimetics
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (strength unknown)
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (moderate)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Nervous System
- Psychoanaleptics
- Psychostimulants, Agents Used for ADHD and Nootropics
- Wakefulness-Promoting Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Benzyl alkyl sulfoxides / Sulfoxides / Primary carboxylic acid amides / Sulfinyl compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aromatic homomonocyclic compound / Benzyl alkyl sulfoxide / Benzyl sulfoxide / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Diphenylmethane / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- 2-[(diphenylmethyl)sulfinyl]acetamide (CHEBI:77590)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- V63XWA605I
- CAS number
- 112111-43-0
- InChI Key
- YFGHCGITMMYXAQ-LJQANCHMSA-N
- InChI
- InChI=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
- IUPAC Name
- 2-[(R)-diphenylmethanesulfinyl]acetamide
- SMILES
- NC(=O)C[S@@](=O)C(C1=CC=CC=C1)C1=CC=CC=C1
References
- Synthesis Reference
http://www.google.com/patents/EP2649187A2?cl=en http://www.google.com/patents/US20100036164
- General References
- Lankford DA: Armodafinil: a new treatment for excessive sleepiness. Expert Opin Investig Drugs. 2008 Apr;17(4):565-73. doi: 10.1517/13543784.17.4.565 . [Article]
- Drake C, Gumenyuk V, Roth T, Howard R: Effects of armodafinil on simulated driving and alertness in shift work disorder. Sleep. 2014 Dec 1;37(12):1987-94. doi: 10.5665/sleep.4256. [Article]
- Link [Link]
- External Links
- KEGG Drug
- D03215
- PubChem Compound
- 9690109
- PubChem Substance
- 310264870
- ChemSpider
- 7962943
- BindingDB
- 50336892
- 641465
- ChEBI
- 77590
- ChEMBL
- CHEMBL1201192
- ZINC
- ZINC000003831139
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Armodafinil
- FDA label
- Download (837 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Dementia With Lewy Body Disease 1 4 Completed Treatment Fatigue / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Fibromyalgia, Primary 1 4 Completed Treatment Major Depressive Disorder (MDD) / Obstructive Sleep Apnea (OSA) / Persistent Depressive Disorder (Dysthymia) / Sleep disorders and disturbances 1 4 Completed Treatment Menopause 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 200 mg/1 Tablet Oral 200 mg Tablet Oral 50 mg Tablet, coated Oral 150 mg Tablet Oral 100 mg/1 Tablet Oral 150 mg/1 Tablet Oral 250 mg/1 Tablet Oral 50 mg/1 Tablet Oral 150 mg Tablet Oral 250 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US4927855 No 1990-05-22 2010-04-22 US US7297346 Yes 2007-11-20 2024-05-29 US US7132570 Yes 2006-11-07 2024-06-18 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.622 mg/mL ALOGPS logP 1.75 ALOGPS logP 1.53 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 8.84 Chemaxon pKa (Strongest Basic) -4.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 60.16 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 77.39 m3·mol-1 Chemaxon Polarizability 28.2 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-014i-1900000000-d596523332b8590b2aef Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0900000000-55724283143adb967127 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0w29-0940000000-3fb2b28684be0db5d11b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0900000000-268fac20d4bebd0d237b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-9180000000-ac48fd1eebe59ea8cc8b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-2900000000-3fded198d424bf150f12 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-9110000000-f5e78ab116ca3103ec83 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 156.32983 predictedDeepCCS 1.0 (2019) [M+H]+ 158.72563 predictedDeepCCS 1.0 (2019) [M+Na]+ 164.77934 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Monoamine transmembrane transporter activity
- Specific Function
- Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A3
- Uniprot ID
- Q01959
- Uniprot Name
- Sodium-dependent dopamine transporter
- Molecular Weight
- 68494.255 Da
References
- Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, Kopajtic T, Shi L, Katz JL, Tanda G, Newman AH: R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry. 2012 Sep 1;72(5):405-13. doi: 10.1016/j.biopsych.2012.03.022. Epub 2012 Apr 25. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
- Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
- Darwish M, Kirby M, Robertson P Jr, Hellriegel ET: Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
- Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
- Darwish M, Kirby M, Robertson P Jr, Hellriegel ET: Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74. [Article]
- Robertson P Jr, Hellriegel ET, Arora S, Nelson M: Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002 Jan;71(1):46-56. [Article]
- FDA table of interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
- Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
- Robertson P Jr, Hellriegel ET, Arora S, Nelson M: Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002 Jan;71(1):46-56. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
- Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
- Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
- Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
Drug created at March 19, 2008 16:32 / Updated at October 27, 2022 02:24