Details of the Drug

General Information of Drug (ID: DMV26S8)

Drug Name

Levomilnacipran

Synonyms

Fetzima; UNII-UGM0326TXX; Levomilnacipran HCl; 96847-54-0; UGM0326TXX; CHEMBL99946; F-2695; (1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide; (1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide; Levomilnacipran [USAN:INN]; Milnacipram; AC1OCEN8; F 2695; Levomilnacipran (USAN/INN); ZINC506; SCHEMBL1414867; GTPL7435; GJJFMKBJSRMPLA-DZGCQCFKSA-N; CHEBI:136040; BDBM50032379; SB17447; DB08918; f2-695; D10072

Indication

Disease Entry	ICD 11	Status	REF
Fibromyalgia	MG30.01	Approved	[1]
Major depressive disorder	6A70.3	Approved	[2]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

246.35

Logarithm of the Partition Coefficient (xlogp)

1.4

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

2

ADMET Property

Clearance: The total clearance of drug is 21-29 L/h []
Half-life: The concentration or amount of drug in body reduced by one-half in 12 hours [3]
Metabolism: The drug is metabolized via the hepatic []
Vd: The volume of distribution (Vd) of drug is 387-473 L []

Chemical Identifiers

Formula: C15H22N2O
IUPAC Name: (1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
Canonical SMILES: CCN(CC)C(=O)[C@]1(C[C@H]1CN)C2=CC=CC=C2
InChI: InChI=1S/C15H22N2O/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/t13-,15+/m0/s1
InChIKey: GJJFMKBJSRMPLA-DZGCQCFKSA-N

Cross-matching ID

PubChem CID: 6917779
ChEBI ID: CHEBI:136040
CAS Number: 96847-54-0
DrugBank ID: DB08918
TTD ID: D02XOK
VARIDT ID: DR00049
INTEDE ID: DR0945
ACDINA ID: D00362

Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Modulator	[4]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Modulator	[4]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[6]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Substrate	[]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

ICD Disease Classification

06 Mental, behavioural or neurodevelopmental disorder

Disease Class

ICD-11: 6A20 Schizophrenia

The Studied Tissue

Pre-frontal cortex

The Studied Disease

Major depressive disorder [ICD-11:6A20]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Norepinephrine transporter (NET)	DTT	SLC6A2	7.05E-01	7.02E-03	0.07
Serotonin transporter (SERT)	DTT	SLC6A4	1.17E-01	0.07	0.59
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.83E-01	4.69E-02	1.89E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	3.17E-01	-6.95E-02	-2.88E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Levomilnacipran (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive serotonergic effects by the combination of Levomilnacipran and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[7]
Oliceridine	DM6MDCF	Moderate	Additive serotonergic effects by the combination of Levomilnacipran and Oliceridine.	Acute pain [MG31]	[8]
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Inotersen.	Amyloidosis [5D00]	[9]
Levalbuterol	DM5YBO1	Moderate	Increased risk of rapid heart rate by the combination of Levomilnacipran and Levalbuterol.	Asthma [CA23]	[10]
Olodaterol	DM62B78	Moderate	Increased risk of rapid heart rate by the combination of Levomilnacipran and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[10]
Vilanterol	DMF5EK1	Moderate	Increased risk of rapid heart rate by the combination of Levomilnacipran and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[10]
Vortioxetine	DM6F1PU	Major	Additive serotonergic effects by the combination of Levomilnacipran and Vortioxetine.	Depression [6A70-6A7Z]	[11]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Levomilnacipran and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[12]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Tazemetostat.	Follicular lymphoma [2A80]	[9]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[9]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Levomilnacipran caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[13]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Levomilnacipran and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[14]
Ceritinib	DMB920Z	Major	Decreased metabolism of Levomilnacipran caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[13]
Idelalisib	DM602WT	Major	Decreased metabolism of Levomilnacipran caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[13]
Ibrutinib	DMHZCPO	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Ibrutinib.	Mature B-cell lymphoma [2A85]	[9]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Levomilnacipran and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[15]
Ozanimod	DMT6AM2	Moderate	Additive serotonergic effects by the combination of Levomilnacipran and Ozanimod.	Multiple sclerosis [8A40]	[16]
Fedratinib	DM4ZBK6	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Fedratinib.	Myeloproliferative neoplasm [2A20]	[17]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Vorapaxar.	Myocardial infarction [BA41-BA43]	[9]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[9]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Levomilnacipran and Betrixaban.	Venous thromboembolism [BD72]	[9]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triethyl citrate	E00128	6506	Plasticizing agent; Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Levomilnacipran 120 mg capsule	120 mg	24 HR Extended Release Oral Capsule	Oral
Levomilnacipran 20 mg capsule	20 mg	24 HR Extended Release Oral Capsule	Oral
Levomilnacipran 40 mg capsule	40 mg	24 HR Extended Release Oral Capsule	Oral
Levomilnacipran 80 mg capsule	80 mg	24 HR Extended Release Oral Capsule	Oral

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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7435).
2	Levomilnacipran FDA Label
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
5	P-glycoprotein differentially affects escitalopram, levomilnacipran, vilazodone and vortioxetine transport at the mouse blood-brain barrier inivo. Neuropharmacology. 2016 Apr;103:104-11.
6	The role of levomilnacipran in the management of major depressive disorder: a comprehensive review. Curr Neuropharmacol. 2016;14(2):191-9.
7	Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
8	Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919. [PMID: 18006535]
9	Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
10	Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
11	Achamallah NS "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry 149 (1992): 1406. [PMID: 1530079]
12	Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
13	Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals, St. Louis, MO.
14	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
15	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
16	Alvine G, Black DW, Tsuang D "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry 51 (1990): 311. [PMID: 2365671]
17	Bannister SJ, Houser VP, Hulse JD, Kisicki JC, Rasmussen JG "Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin, and digoxin." Acta Psychiatr Scand Suppl 350 (1989): 102-6. [PMID: 2530759]