U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H22N2O.ClH
Molecular Weight 282.809
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOMILNACIPRAN HYDROCHLORIDE

SMILES

Cl.CCN(CC)C(=O)[C@]1(C[C@H]1CN)C2=CC=CC=C2

InChI

InChIKey=XNCDYJFPRPDERF-NQQJLSKUSA-N
InChI=1S/C15H22N2O.ClH/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12;/h5-9,13H,3-4,10-11,16H2,1-2H3;1H/t13-,15+;/m0./s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24000002 | https://www.ncbi.nlm.nih.gov/pubmed/27180420

Levomilnacipran (1S, 2R/F2695) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Levomilnacipran is pharmacologically more active as compared with racemic mixture and dextromilnacipran (1R, 2S/F2696). The safety of the drug is also higher than the safety of a racemate, resulting in a beneficial impact on the therapeutic effect. Pierre Fabre and Forest Laboratories are developing levomilnacipran extended release (ER) [FETZIMA™], an enantiomer of milnacipran, for the treatment of major depressive disorder (MDD). In addition, Pierre Fabre (the originator of the compound) is developing the drug to improve recovery in patients with ischaemic stroke.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
11.2 nM [Ki]
92.2 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FETZIMA

Approved Use

FETZIMA (levomilnacipran) extended-release capsules is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of Major Depressive Disorder (MDD) in adults. FETZIMA is not approved for the management of fibromyalgia, and its efficacy and safety have not been established for that use.

Launch Date

1.3747104E12
Primary
FETZIMA

Approved Use

FETZIMA (levomilnacipran) extended-release capsules is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of Major Depressive Disorder (MDD) in adults. FETZIMA is not approved for the management of fibromyalgia, and its efficacy and safety have not been established for that use.

Launch Date

1.3747104E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
341 ng/mL
120 mg 1 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LEVOMILNACIPRAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5196 ng × h/mL
120 mg 1 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LEVOMILNACIPRAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12 h
120 mg 1 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LEVOMILNACIPRAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
78%
120 mg 1 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LEVOMILNACIPRAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.766
unhealthy, 18-80
n = 825
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 825
Sources: Page: p.766
Disc. AE: Angina pectoris, Extrasystoles supraventricular...
AEs leading to
discontinuation/dose reduction:
Angina pectoris (0.12%)
Extrasystoles supraventricular (0.12%)
Encephalopathy (0.12%)
Mania (0.12%)
Sources: Page: p.766
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Disc. AE: Tachycardia, Nausea...
AEs leading to
discontinuation/dose reduction:
Tachycardia
Nausea
Insomnia
Agitation
Constipation
Hypertension
Sources: Page: p.52
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.22
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.22
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.12
unhealthy
n = 1583
Health Status: unhealthy
Condition: Major Depressive Disorder
Population Size: 1583
Sources: Page: p.12
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (1.5%)
Sources: Page: p.12
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Disc. AE: Suicidal ideation, Serotonin syndrome...
AEs leading to
discontinuation/dose reduction:
Suicidal ideation
Serotonin syndrome
Blood pressure increased
Heart rate increased
Bleeding
Angle closure glaucoma
Urinary hesitation
Urinary retention
Mania
Hypomania
Hyponatremia
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Angina pectoris 0.12%
Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.766
unhealthy, 18-80
n = 825
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 825
Sources: Page: p.766
Encephalopathy 0.12%
Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.766
unhealthy, 18-80
n = 825
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 825
Sources: Page: p.766
Extrasystoles supraventricular 0.12%
Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.766
unhealthy, 18-80
n = 825
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 825
Sources: Page: p.766
Mania 0.12%
Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.766
unhealthy, 18-80
n = 825
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 825
Sources: Page: p.766
Agitation Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Constipation Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Hypertension Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Insomnia Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Nausea Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Tachycardia Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.52
unhealthy, 18-80
n = 217
Health Status: unhealthy
Condition: Major Depressive Disorder
Age Group: 18-80
Sex: M+F
Population Size: 217
Sources: Page: p.52
Nausea 1.5%
Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.12
unhealthy
n = 1583
Health Status: unhealthy
Condition: Major Depressive Disorder
Population Size: 1583
Sources: Page: p.12
Angle closure glaucoma Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Bleeding Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Blood pressure increased Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Heart rate increased Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Hypomania Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Hyponatremia Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Mania Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Serotonin syndrome Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Suicidal ideation Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Urinary hesitation Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
Urinary retention Disc. AE
120 mg 1 times / day multiple, oral (max)
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Major Depressive Disorder
Sources: Page: p.1
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
not significant
not significant
not significant
not significant
not significant
not significant
weak [IC50 423 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
low
low
low
low
low
major
yes (co-administration study)
Comment: Ketoconazole (inhibitor) increased levomilnacipran exposure (AUC) by about 50%; dose adjustment of drug not recommeded whe co-administered with CYP3A4 inducers (carbamazepine) and substrate (alprazolam);
Page: 39.0
minor
minor
minor
minor
no
no
no
no
no
no
weak
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Which bioequivalence study for a racemic drug? Application to milnacipran.
1998 Apr-Jun
28th Annual JPMorgan Healthcare Conference--Forest Laboratories and Icagen.
2010 Mar
Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant--what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
2013 Nov
Patents

Sample Use Guides

Initial Treatment of Major Depressive Disorder: The recommended dose range for FETZIMA (levomilnacipran extended-release capsules) is 40 mg to 120 mg once daily. FETZIMA should be initiated at 20 mg once daily for 2 days and then increased to 40 mg once daily.
Route of Administration: Oral
Levomilnacipran inhibits norepinephrine and serotonin reuptake in rat hypothalamic synaptosomes with IC50 values of 15 and 46 nM, respectively
Name Type Language
LEVOMILNACIPRAN HYDROCHLORIDE
ORANGE BOOK   USAN   WHO-DD  
USAN  
Official Name English
LEVOMILNACIPRAN HYDROCHLORIDE [ORANGE BOOK]
Common Name English
F-2695 HYDROCHLORIDE
Code English
FETZIMA
Brand Name English
MILNACIPRAN HYDROCHLORIDE, (1S,2R)-
Common Name English
(1S,2R)-MILNACIPRAN HYDROCHLORIDE
Common Name English
Levomilnacipran hydrochloride [WHO-DD]
Common Name English
F 2695 HYDROCHLORIDE
Code English
F2695 HYDROCHLORIDE
Code English
CYCLOPROPANECARBOXAMIDE, 2-(AMINOMETHYL)-N,N-DIETHYL-1-PHENYL-, HYDROCHLORIDE (1:1), (1S,2R)-
Common Name English
LEVOMILNACIPRAN HYDROCHLORIDE [USAN]
Common Name English
Code System Code Type Description
RXCUI
1433211
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY RxNorm
ChEMBL
CHEMBL99946
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
NCI_THESAURUS
C166646
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
EVMPD
SUB130559
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
DRUG BANK
DBSALT000107
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
DAILYMED
371U2ZK31U
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
EPA CompTox
DTXSID801026201
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
PUBCHEM
6917778
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
SMS_ID
100000156651
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
CAS
175131-60-9
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
USAN
YY-41
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY
FDA UNII
371U2ZK31U
Created by admin on Fri Dec 15 20:11:22 UTC 2023 , Edited by admin on Fri Dec 15 20:11:22 UTC 2023
PRIMARY