Details of the Drug

General Information of Drug (ID: DMBFE74)

Drug Name

Milnacipran

Synonyms

Ixel; Midalcipran; Milnacipranum; Toledomin; Milnacipran [INN]; Milnacipranum [Latin]; F 2207; F-2207; Ixel (TN); Milnacipran(INN); Savella (TN); (+-)-cis-2-(Aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide; (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide; 1-phenyl-1-diethylaminocarbonyl-2-aminomethylcyclopropane HCl

Indication

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[1]
Irritable bowel syndrome	DD91.0	Approved	[2]
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Therapeutic Class

Antidepressants

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Bioavailability: 84% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The drug present in the plasma can be removed from the body at the rate of 8.17 mL/min/kg [5]
Elimination: 55% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 6.48 hours [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 11.5974 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.87% [5]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 4.51 L/kg [5]

Chemical Identifiers

Formula: C15H22N2O
IUPAC Name: (1R,2S)-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+/m1/s1
InChIKey: GJJFMKBJSRMPLA-HIFRSBDPSA-N

Cross-matching ID

PubChem CID: 65833
ChEBI ID: CHEBI:94468
CAS Number: 96847-55-1
DrugBank ID: DB04896
TTD ID: D09VGC
VARIDT ID: DR00947
ACDINA ID: D00435

Combinatorial Drugs (CBD)

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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	Inhibitor	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Depression

ICD Disease Classification

6A70-6A7Z

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

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Milnacipran

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Vilazodone	DM4LECQ	Major	Additive serotonergic effects by the combination of Milnacipran and Vilazodone.	Depression [6A70-6A7Z]	[8]
Vortioxetine	DM6F1PU	Major	Additive serotonergic effects by the combination of Milnacipran and Vortioxetine.	Depression [6A70-6A7Z]	[8]
Desvenlafaxine	DMHD4PE	Major	Additive serotonergic effects by the combination of Milnacipran and Desvenlafaxine.	Depression [6A70-6A7Z]	[8]
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Coadministration of a Drug Treating the Disease Different from Milnacipran (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[9]
Methylene blue	DMJAPE7	Major	Additive serotonergic effects by the combination of Milnacipran and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[10]
Oliceridine	DM6MDCF	Moderate	Additive serotonergic effects by the combination of Milnacipran and Oliceridine.	Acute pain [MG31]	[11]
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Milnacipran and Inotersen.	Amyloidosis [5D00]	[12]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[13]
Levalbuterol	DM5YBO1	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Levalbuterol.	Asthma [CA23]	[14]
Retigabine	DMGNYIH	Moderate	Antagonize the effect of Milnacipran when combined with Retigabine.	Behcet disease [4A62]	[15]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Milnacipran and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[16]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Milnacipran and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[17]
Olodaterol	DM62B78	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[14]
Vilanterol	DMF5EK1	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[14]
Indacaterol	DMQJHR7	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Indacaterol.	Chronic obstructive pulmonary disease [CA22]	[14]
Levomilnacipran	DMV26S8	Major	Additive serotonergic effects by the combination of Milnacipran and Levomilnacipran.	Chronic pain [MG30]	[8]
Regorafenib	DMHSY1I	Moderate	Increased risk of bleeding by the combination of Milnacipran and Regorafenib.	Colorectal cancer [2B91]	[12]
Ardeparin	DMYRX8B	Moderate	Increased risk of bleeding by the combination of Milnacipran and Ardeparin.	Coronary thrombosis [BA43]	[12]
Danaparoid	DM6CLBN	Moderate	Increased risk of bleeding by the combination of Milnacipran and Danaparoid.	Deep vein thrombosis [BD71]	[12]
Rivaroxaban	DMQMBZ1	Moderate	Increased risk of bleeding by the combination of Milnacipran and Rivaroxaban.	Deep vein thrombosis [BD71]	[12]
LEVONORDEFRIN	DMWDJ0H	Moderate	Additive hypertensive effects by the combination of Milnacipran and LEVONORDEFRIN.	Discovery agent [N.A.]	[14]
Methsuximide	DM6L5VO	Moderate	Antagonize the effect of Milnacipran when combined with Methsuximide.	Epilepsy/seizure [8A61-8A6Z]	[15]
Brivaracetam	DMSEPK8	Moderate	Antagonize the effect of Milnacipran when combined with Brivaracetam.	Epilepsy/seizure [8A61-8A6Z]	[15]
Lacosamide	DMVM6QR	Moderate	Antagonize the effect of Milnacipran when combined with Lacosamide.	Epilepsy/seizure [8A61-8A6Z]	[15]
Rufinamide	DMWE60C	Moderate	Antagonize the effect of Milnacipran when combined with Rufinamide.	Epilepsy/seizure [8A61-8A6Z]	[15]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Milnacipran and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[15]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Cannabidiol.	Epileptic encephalopathy [8A62]	[18]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Milnacipran and Tazemetostat.	Follicular lymphoma [2A80]	[12]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Milnacipran and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[12]
Tetrahydrozoline	DMT57WC	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Tetrahydrozoline.	Herpes simplex infection [1F00]	[14]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[19]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Milnacipran and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[20]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Milnacipran and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[21]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Milnacipran and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[22]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Milnacipran and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[23]
Naphazoline	DMJFZDL	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Naphazoline.	Itching [1F28-1G07]	[14]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[24]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Idelalisib.	Mature B-cell leukaemia [2A82]	[25]
Acalabrutinib	DM7GCVW	Moderate	Increased risk of bleeding by the combination of Milnacipran and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[12]
Ibrutinib	DMHZCPO	Moderate	Increased risk of bleeding by the combination of Milnacipran and Ibrutinib.	Mature B-cell lymphoma [2A85]	[12]
Ponatinib	DMYGJQO	Moderate	Increased risk of bleeding by the combination of Milnacipran and Ponatinib.	Mature B-cell lymphoma [2A85]	[12]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Milnacipran and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[26]
Lasmiditan	DMXLVDT	Major	Additive serotonergic effects by the combination of Milnacipran and Lasmiditan.	Migraine [8A80]	[8]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Milnacipran and Flibanserin.	Mood disorder [6A60-6E23]	[27]
Ozanimod	DMT6AM2	Moderate	Additive serotonergic effects by the combination of Milnacipran and Ozanimod.	Multiple sclerosis [8A40]	[28]
Ruxolitinib	DM7Q98D	Moderate	Increased risk of bleeding by the combination of Milnacipran and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[12]
Prasugrel	DM7MT6E	Moderate	Increased risk of bleeding by the combination of Milnacipran and Prasugrel.	Myocardial infarction [BA41-BA43]	[12]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Milnacipran and Vorapaxar.	Myocardial infarction [BA41-BA43]	[12]
E-2007	DMJDYNQ	Moderate	Antagonize the effect of Milnacipran when combined with E-2007.	Neuropathy [8C0Z]	[15]
Propylhexedrine	DMTBW2O	Moderate	Increased risk of rapid heart rate by the combination of Milnacipran and Propylhexedrine.	Obesity [5B80-5B81]	[14]
Safinamide	DM0YWJC	Major	Additive serotonergic effects by the combination of Milnacipran and Safinamide.	Parkinsonism [8A00]	[28]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Milnacipran and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[12]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Milnacipran and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[18]
Plicamycin	DM7C8YV	Moderate	Increased risk of bleeding by the combination of Milnacipran and Plicamycin.	Testicular cancer [2C80]	[12]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Milnacipran and Caplacizumab.	Thrombocytopenia [3B64]	[12]
Apixaban	DM89JLN	Moderate	Increased risk of bleeding by the combination of Milnacipran and Apixaban.	Thrombosis [DB61-GB90]	[12]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Milnacipran and Cangrelor.	Thrombosis [DB61-GB90]	[12]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Milnacipran and Brilinta.	Thrombosis [DB61-GB90]	[12]
Cabozantinib	DMIYDT4	Moderate	Increased risk of bleeding by the combination of Milnacipran and Cabozantinib.	Thyroid cancer [2D10]	[12]
Xylometazoline	DMKV32D	Moderate	Additive hypertensive effects by the combination of Milnacipran and Xylometazoline.	Vasomotor/allergic rhinitis [CA08]	[14]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Milnacipran and Betrixaban.	Venous thromboembolism [BD72]	[12]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Hydrazine yellow	E00409	164825	Colorant
Brushite	E00392	104805	Diluent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 12 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Milnacipran 100 mg tablet	100 mg	Oral Tablet	Oral
Milnacipran 12.5 mg tablet	12.5 mg	Oral Tablet	Oral
Milnacipran 25 mg tablet	25 mg	Oral Tablet	Oral
Milnacipran 50 mg tablet	50 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 7436).
2	Levomilnacipran FDA Label
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7	Milnacipran: beyond a role of antidepressant. Clin Neuropharmacol. 2009 Nov-Dec;32(6):355-63.
8	Achamallah NS "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry 149 (1992): 1406. [PMID: 1530079]
9	Cerner Multum, Inc. "Australian Product Information.".
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13	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
14	Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
15	Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
16	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
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]
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
20	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
21	Canadian Pharmacists Association.
22	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
23	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
24	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
25	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
26	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
27	Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
28	Alvine G, Black DW, Tsuang D "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry 51 (1990): 311. [PMID: 2365671]