LISDEXAMFETAMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H25N3O
Molecular Weight	263.3791
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@]([H])(Cc1ccccc1)N=C([C@]([H])(CCCCN)N)O

InChI

InChIKey=VOBHXZCDAVEXEY-JSGCOSHPSA-N

InChI=1S/C15H25N3O/c1-12(11-13-7-3-2-4-8-13)18-15(19)14(17)9-5-6-10-16/h2-4,7-8,12,14H,5-6,9-11,16-17H2,1H3,(H,18,19)/t12-,14-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf
Curator's Comment:: description was created based on several sources, including: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021977lbl.pdf | https://www.drugs.com/ppa/lisdexamfetamine.html | https://www.ncbi.nlm.nih.gov/pubmed/27125257

Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED). After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug’s activity. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Most common adverse reactions in children, adolescents and/or adults with ADHD were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Needs to adjust Lisdexamfetamine dosage accordingly.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
catecholamine secretion 4 Target ID: GO:0050432 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021977lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/28376679	Modulator 780

Conditions

Condition	Modality	Targets	Highest Phase	Product
Attention deficit hyperactivity disorder 62 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf	Primary		Approved 8043	VYVANSE Approved Use VYVANSE® is indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies (14.1) Launch Date 1.17218882E12
Moderate to severe binge eating disorder 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf	Primary		Approved 8043	VYVANSE Approved Use VYVANSE® is indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies (14.1) Launch Date 1.17218882E12

C_max

Value	Dose	Co-administered	Analyte	Population
47.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18021493/	70 mg 1 times / day multiple, oral dose: 70 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LISDEXAMFETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
60.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18021493/	70 mg 1 times / day multiple, oral dose: 70 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LISDEXAMFETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18021493/	70 mg 1 times / day multiple, oral dose: 70 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LISDEXAMFETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
70 mg 1 times / day multiple, oral (max) Recommended Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8	unhealthy, 13 - 17 n = 233 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Age Group: 13 - 17 Sex: M+F Population Size: 233 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8	Disc. AE: Irritability, Decreased appetite... AEs leading to discontinuation/dose reduction: Irritability (1.3%) Decreased appetite (0.86%) Insomnia (0.86%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8
1200 mg single, oral Overdose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30730334 Page: e771	healthy, 17 n = 1 Health Status: healthy Age Group: 17 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/30730334 Page: e771	Disc. AE: Delirium, Tachycardia... AEs leading to discontinuation/dose reduction: Delirium (acute) Tachycardia Hypertension Tachypnea Creatine kinase increased (mild) Sources: https://pubmed.ncbi.nlm.nih.gov/30730334 Page: e771
70 mg 1 times / day multiple, oral (max) Recommended Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8	unhealthy, 18 - 55 n = 358 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Age Group: 18 - 55 Sex: M+F Population Size: 358 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8	Disc. AE: Insomnia, Tachycardia... AEs leading to discontinuation/dose reduction: Insomnia (2%) Tachycardia (1%) Irritability (1%) Hypertension (1%) Headache (1%) Anxiety (1%) Dyspnea (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8
70 mg 1 times / day multiple, oral (max) Recommended Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8	unhealthy, 6 - 12 n = 218 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Age Group: 6 - 12 Sex: M+F Population Size: 218 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8	Disc. AE: Ventricular hypertrophy, Tic... AEs leading to discontinuation/dose reduction: Ventricular hypertrophy (1%) Tic (1%) Vomiting (1%) Psychomotor hyperactivity (1%) Insomnia (1%) Rash (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.8
30 mg 1 times / day steady, oral Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00735371	unhealthy, adolescents n = 78 Health Status: unhealthy Condition: Attention-Deficit/Hyperactivity Disorder Age Group: adolescents Population Size: 78 Sources: https://clinicaltrials.gov/ct2/show/NCT00735371	Other AEs: Decreased appetite, Insomnia... Other AEs: Decreased appetite (below serious, 29 patients) Insomnia (below serious, 7 patients) Weight decreased (below serious, 3 patients) Irritability (below serious, 6 patients) Fatigue (below serious, 4 patients) Nasopharyngitis (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00735371
20 mg single, oral Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: https://clinicaltrials.gov/ct2/show/NCT01096680	healthy, adult n = 27 Health Status: healthy Condition: Acute Sleep Loss Age Group: adult Sex: M Population Size: 27 Sources: https://clinicaltrials.gov/ct2/show/NCT01096680	Other AEs: Nausea... Other AEs: Nausea (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT01096680
50 mg single, oral Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://clinicaltrials.gov/ct2/show/NCT01096680	healthy, adult n = 27 Health Status: healthy Condition: Acute Sleep Loss Age Group: adult Sex: M Population Size: 27 Sources: https://clinicaltrials.gov/ct2/show/NCT01096680	Other AEs: Headache, Nausea... Other AEs: Headache (below serious, 4 patients) Nausea (below serious, 1 patient) Vomiting (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01096680
70 mg single, oral Dose: 70 mg Route: oral Route: single Dose: 70 mg Sources: https://clinicaltrials.gov/ct2/show/NCT01096680	healthy, adult n = 27 Health Status: healthy Condition: Acute Sleep Loss Age Group: adult Sex: M Population Size: 27 Sources: https://clinicaltrials.gov/ct2/show/NCT01096680	Other AEs: Headache, Nausea... Other AEs: Headache (below serious, 2 patients) Nausea (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01096680
70 mg 1 times / day steady, oral (max) Dose: 70 mg, 1 times / day Route: oral Route: steady Dose: 70 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01101022	unhealthy, adult n = 79 Health Status: unhealthy Condition: Attention-Deficit/Hyperactivity Disorder Age Group: adult Population Size: 79 Sources: https://clinicaltrials.gov/ct2/show/NCT01101022	Other AEs: Diarrhea, Dry mouth... Other AEs: Diarrhea (below serious, 6 patients) Dry mouth (below serious, 25 patients) Fatigue (below serious, 6 patients) Feeling jittery (below serious, 10 patients) Irritability (below serious, 8 patients) Upper respiratory tract infection (below serious, 5 patients) Heart rate increased (below serious, 4 patients) Weight decreased (below serious, 8 patients) Anorexia (below serious, 4 patients) Decreased appetite (below serious, 26 patients) Headache (below serious, 20 patients) Initial insomnia (below serious, 8 patients) Insomnia (below serious, 10 patients) Libido decreased (below serious, 4 patients) Hyperhidrosis (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01101022
70 mg 1 times / day multiple, oral Recommended Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder\|Binge Eating Disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.1	Disc. AE: Abuse, Dependence... AEs leading to discontinuation/dose reduction: Abuse Dependence Cardiovascular disorder (NOS) (grade 3-5) Stroke (serious) Myocardial infarction (serious) Blood pressure increased Heart rate increased Psychiatric symptom NOS Psychotic symptom Manic symptom Growth suppression Vascular disorders Raynaud's phenomenon Serotonin syndrome Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf Page: p.1
50 mg 1 times / day steady, oral (max) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01148979	unhealthy n = 28 Health Status: unhealthy Condition: Major Depressive Disorder Population Size: 28 Sources: https://clinicaltrials.gov/ct2/show/NCT01148979	Other AEs: Decreased appetite, Dry mouth... Other AEs: Decreased appetite (below serious, 8 patients) Dry mouth (below serious, 7 patients) Insomnia (below serious, 10 patients) Irritability (below serious, 3 patients) Diaphoresis (below serious, 2 patients) Libido decreased (below serious, 2 patients) Tinnitus (below serious, 2 patients) Muscle tension (below serious, 4 patients) Tachycardia (below serious, 3 patients) Paresthesia (below serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01148979

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1467	inhibitor 1604	inhibitor 1702

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2A6 627 CYP2B6 717 CYP2C19 1325	CYP 236

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 87.3 uM]
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 89 uM]
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 90 uM]
CYP2B6 884	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 90.8 uM]
CYP3A4 1772	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 92.1 uM]
CYP2A6 659	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 92.5 uM]
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf Page: 7, 78	no [Inhibition 94.2 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 236	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021977s034,208510s002lbl.pdf Page: 21.0	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00E9T8
Alfa Chemistry	ACM608137333
Angene	AGN-PC-0WH4QC
Cayman Chemical	18050
ChemMol	44007218	http://www.chemmol.com/chemmol/44007218.html
Compound Cloud	11597697
Compound Cloud	11597698
MolPort	MolPort-046-693-343
Sigma Aldrich	L-026
Sigma Aldrich	L-026\|CERILLIAN
THE BioTek	bt-386638	https://www.thebiotek.com/product/others/bt-386638
Toronto Research Chemicals	KIT2550
Toronto Research Chemicals	L468880
Toronto Research Chemicals	L468885
ZINC	ZINC000011680943	http://zinc15.docking.org/substances/ZINC000011680943
iChemical	EBD10545	http://www.ichemical.com/chemicals/cas-608137-33-3
mcule	MCULE-1818516035
mcule	MCULE-7002483605

PubMed

Title	Date	PubMed
Lisdexamfetamine.	2007	17407369
An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in human liver microsomes.	2007 Jan	17035599
Schedules of controlled substances: placement of lisdexamfetamine into schedule II. Final rule.	2007 May 3	17520775
Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study.	2007 Nov 1	17631866
Substance use disorders in children and adolescents with attention-deficit/hyperactivity disorder: implications for treatment and the role of the primary care physician.	2008	18615170
Lisdexamfetamine: a prodrug stimulant for ADHD.	2008 Aug	18777964
Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers.	2008 Jan	18021493
Pharmacologic treatment of ADHD: road conditions in driving patients to successful outcomes.	2008 Jan 8	18324315
Poison centers detect an unexpectedly frequent number of adverse drug reactions to lisdexamfetamine.	2008 Jul	18594051
Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study.	2008 Mar	18285619
Lisdexamfetamine dimesylate for childhood ADHD.	2008 May	18548134
Attention-deficit-hyperactivity disorder and reward deficiency syndrome.	2008 Oct	19183781
Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.	2008 Sep	19012818
Alopecia following initiation of lisdexamfetamine in a pediatric patient.	2009	20098534
Update on the management of attention-deficit/hyperactivity disorder in children and adults: patient considerations and the role of lisdexamfetamine.	2009	20057893
Psychopharmacology of ADHD in pediatrics: current advances and issues.	2009	19557112
Lisdexamfetamine dimesylate: in attention-deficit hyperactivity disorder in adults.	2009	19453202
Lisdexamfetamine for treatment of attention-deficit/hyperactivity disorder.	2009 Apr	19318601
Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder.	2009 Aug 3	19650932
The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.	2009 Dec	19761781
Case histories in pharmaceutical risk management.	2009 Dec 1	19767156
An update on central nervous system stimulant formulations in children and adolescents with attention-deficit/hyperactivity disorder.	2009 Jun	19470858
Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers.	2009 Jun	18635707
A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder.	2009 Jun 9	19508731
Lisdexamfetamine: a prodrug for the treatment of attention-deficit/hyperactivity disorder.	2009 Nov 15	19890083
Lisdexamfetamine in the treatment of attention-deficit/hyperactivity disorder in adults.	2009 Oct	19785973
Attention-deficit hyperactivity disorder: recent advances in paediatric pharmacotherapy.	2010	20030423
Advances in the treatment of attention-deficit/hyperactivity disorder: a guide for pediatric neurologists.	2010 Dec	21183129
Eosinophilic hepatitis in an adolescent during lisdexamfetamine dimesylate treatment for ADHD.	2010 Jun	20457690
Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine.	2010 Jun 24	20628632
Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design.	2010 Jun 24	20576091
New and extended-action treatments in the management of ADHD: a critical appraisal of lisdexamfetamine in adults and children.	2010 May 25	20520740
Focus on Lisdexamfetamine: A Review of its use in Child and Adolescent Psychiatry.	2010 Nov	21037922
Use of psychostimulants in patients with dementia.	2010 Oct	20736422
Does prior exposure to stimulants in children with ADHD impact cardiovascular parameters from lisdexamfetamine dimesylate?	2010 Sep	20861585

Patents

Sample Use Guides

In Vivo Use Guide

Attention-deficit/hyperactivity disorder: Initial: 30 mg once daily in the morning; may increase in increments of 10 mg or 20 mg at weekly intervals until optimal response is obtained; maximum: 70 mg/day. Binge eating disorder: Initial: 30 mg once daily in the morning; may titrate in increments of 20 mg at weekly intervals to target dose of 50 to 70 mg once daily (maximum: 70 mg/day).

Route of Administration: Oral

In Vitro Use Guide

Incubation of lisdexamfetamine in microsomal suspensions at concentrations ranging from 0.01 to 100 M showed no concentration-dependent inhibition for any of the isoenzymes under investigation (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A, CYP3A4).

Name

Type

Language

LISDEXAMFETAMINE

Official Name

English

L-LYSINE-DEXTROAMPHETAMINE

Common Name

English

LISDEXAMPHETAMINE

Common Name

English

LISDEXAMFETAMINE [INN]

Common Name

English

LISDEXAMFETAMINE [WHO-DD]

Common Name

English

HEXANAMIDE, 2,6-DIAMINO-N-((1S)-1-METHYL-2-PHENYLETHYL)-, (2S)-

Systematic Name

English

(2S)-2,6-DIAMINO-N-((1S)-1-METHYL-2-PHENYLETHYL)HEXANAMIDE

Systematic Name

English

LISDEXAMFETAMINE [VANDF]

Common Name

English

LISDEXAMFETAMINE [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175739