milnacipran Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
1808 92623-85-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • milnacipran
  • midalcipran
  • (+/-)-Milnacipran
  • milnacipran hydrochloride
  • milnacipran HCl
A cyclopropanecarboxamide serotonin and norepinephrine reuptake inhibitor (SNRI) that is used in the treatment of FIBROMYALGIA.
  • Molecular weight: 246.35
  • Formula: C15H22N2O
  • CLOGP: 1.91
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 46.33
  • ALOGS: -2.30
  • ROTB: 5

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 55 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 11.60 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 84 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 4.51 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.17 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.87 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 6.48 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 14, 2009 FDA CYPRESS BIOSCIENCE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Suicidal ideation 134.84 17.59 88 6677 60423 53281878
Serotonin syndrome 108.13 17.59 57 6708 26349 53315952
Drug hypersensitivity 97.03 17.59 142 6623 265100 53077201
Hyperhidrosis 73.32 17.59 75 6690 96718 53245583
Somatic delusion 69.36 17.59 16 6749 596 53341705
Nausea 68.49 17.59 230 6535 755861 52586440
Hot flush 60.18 17.59 49 6716 47111 53295190
Headache 50.77 17.59 166 6599 536655 52805646
Depression 47.52 17.59 84 6681 182968 53159333
Heart rate increased 45.33 17.59 54 6711 82261 53260040
Urine odour abnormal 41.09 17.59 18 6747 5528 53336773
Insomnia 39.99 17.59 79 6686 186993 53155308
Persistent genital arousal disorder 39.69 17.59 9 6756 310 53341991
Abnormal faeces 37.81 17.59 16 6749 4518 53337783
Blood pressure increased 37.12 17.59 65 6700 140414 53201887
Gastrointestinal motility disorder 36.63 17.59 16 6749 4880 53337421
Blood thyroid stimulating hormone normal 34.66 17.59 7 6758 137 53342164
Anger 32.48 17.59 20 6745 12370 53329931
Migraine 32.09 17.59 45 6720 80372 53261929
Chromaturia 30.19 17.59 21 6744 15929 53326372
Oral discomfort 27.83 17.59 16 6749 8730 53333571
Tremor 26.71 17.59 53 6712 125683 53216618
Lip swelling 26.04 17.59 24 6741 27177 53315124
Musculoskeletal discomfort 25.92 17.59 19 6746 15641 53326660
Homicidal ideation 24.24 17.59 9 6756 1805 53340496
Palpitations 24.01 17.59 45 6720 102303 53239998
Crying 23.99 17.59 21 6744 22241 53320060
Aphasia 23.53 17.59 24 6741 30754 53311547
Flushing 23.10 17.59 36 6729 70564 53271737
Irritability 21.62 17.59 23 6742 30930 53311371
Feeling abnormal 19.65 17.59 49 6716 135252 53207049
Fibromyalgia 19.59 17.59 26 6739 44049 53298252
Ear infection 19.44 17.59 20 6745 25880 53316421
Drug withdrawal syndrome 18.13 17.59 20 6745 28002 53314299
Suicide attempt 18.11 17.59 29 6736 58139 53284162

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Urinary retention 55.64 26.79 26 1059 35671 32476770
Suicidal ideation 48.03 26.79 24 1061 38059 32474382
Agoraphobia 39.59 26.79 7 1078 264 32512177
Dysuria 32.20 26.79 16 1069 24994 32487447
Urinary hesitation 29.14 26.79 8 1077 2333 32510108
Neurosis 29.07 26.79 5 1080 160 32512281

Pharmacologic Action:

SourceCodeDescription
ATC N06AX17 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Other antidepressants
FDA MoA N0000000102 Norepinephrine Uptake Inhibitors
FDA MoA N0000000109 Serotonin Uptake Inhibitors
MeSH PA D000700 Analgesics
MeSH PA D018712 Analgesics, Non-Narcotic
MeSH PA D002491 Central Nervous System Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents
MeSH PA D000068760 Serotonin and Noradrenaline Reuptake Inhibitors
FDA EPC N0000175749 Serotonin and Norepinephrine Reuptake Inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Fibromyalgia indication 203082005 DOID:631
Tachyarrhythmia contraindication 6285003
Urinary tract obstruction contraindication 7163005 DOID:5200
Alcoholism contraindication 7200002
Hypertensive disorder contraindication 38341003 DOID:10763
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Syndrome of inappropriate vasopressin secretion contraindication 55004003 DOID:3401
Acute nephropathy contraindication 58574008
Blood coagulation disorder contraindication 64779008 DOID:1247
Hyponatremia contraindication 89627008
Seizure disorder contraindication 128613002
Liver function tests abnormal contraindication 166603001
Mania contraindication 231494001
Hypomania contraindication 231496004
Disease of liver contraindication 235856003 DOID:409
Suicidal contraindication 267073005
Serotonin syndrome contraindication 371089000
Angle-closure glaucoma contraindication 392291006 DOID:13550

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.64 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 6602911 Jan. 14, 2023 MANAGEMENT OF FIBROMYALGIA (FM)
12.5MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 6602911 Jan. 14, 2023 MANAGEMENT OF FIBROMYALGIA (FM)
25MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 6602911 Jan. 14, 2023 MANAGEMENT OF FIBROMYALGIA (FM)
50MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 6602911 Jan. 14, 2023 MANAGEMENT OF FIBROMYALGIA (FM)
100MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA
12.5MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA
25MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA
50MG SAVELLA ALLERGAN N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium-dependent serotonin transporter Transporter INHIBITOR Ki 7.29 WOMBAT-PK CHEMBL
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Ki 7.60 WOMBAT-PK CHEMBL
Sodium-dependent dopamine transporter Transporter IC50 5.21 CHEMBL
Glutamate receptor ionotropic, NMDA 2A Ion channel IC50 5.20 WOMBAT-PK
Sodium-dependent serotonin transporter Transporter IC50 7.33 CHEMBL
Sodium-dependent dopamine transporter Transporter IC50 4.43 CHEMBL
Transporter Transporter IC50 7.52 CHEMBL

External reference:

IDSource
4025253 VUID
N0000179785 NUI
D01107 KEGG_DRUG
101152-94-7 SECONDARY_CAS_RN
4025253 VANDF
4028372 VANDF
C1533126 UMLSCUI
CHEBI:135005 CHEBI
CHEMBL252923 ChEMBL_ID
CHEMBL259209 ChEMBL_ID
DB04896 DRUGBANK_ID
CHEMBL4297064 ChEMBL_ID
D000078764 MESH_DESCRIPTOR_UI
5701 INN_ID
65833 PUBCHEM_CID
7436 IUPHAR_LIGAND_ID
G56VK1HF36 UNII
30003 RXNORM
26139 MMSL
d06635 MMSL
008263 NDDF
008264 NDDF
441641002 SNOMEDCT_US
442542004 SNOMEDCT_US
442642007 SNOMEDCT_US
CHEMBL1237129 ChEMBL_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1510 TABLET, FILM COATED 100 mg ORAL NDA 37 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1512 TABLET, FILM COATED 12.50 mg ORAL NDA 37 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1525 TABLET, FILM COATED 25 mg ORAL NDA 37 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1550 TABLET, FILM COATED 50 mg ORAL NDA 37 sections
SAVELLA HUMAN PRESCRIPTION DRUG LABEL 1 16590-845 TABLET, FILM COATED 25 mg ORAL NDA 35 sections
SAVELLA HUMAN PRESCRIPTION DRUG LABEL 1 16590-846 TABLET, FILM COATED 50 mg ORAL NDA 35 sections
SAVELLA HUMAN PRESCRIPTION DRUG LABEL 1 16590-847 TABLET, FILM COATED 100 mg ORAL NDA 35 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 21695-650 TABLET, FILM COATED 25 mg ORAL NDA 34 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 21695-651 TABLET, FILM COATED 50 mg ORAL NDA 34 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 35356-545 TABLET, FILM COATED 50 mg ORAL NDA 33 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 50436-9993 TABLET, FILM COATED 25 mg ORAL NDA 33 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 54868-6024 TABLET, FILM COATED 100 mg ORAL NDA 33 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 54868-6043 TABLET, FILM COATED 50 mg ORAL NDA 33 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 55154-4626 TABLET, FILM COATED 50 mg ORAL NDA 33 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-091 TABLET 12.50 mg ORAL ANDA 20 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-092 TABLET 25 mg ORAL ANDA 20 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-093 TABLET 50 mg ORAL ANDA 20 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-094 TABLET 100 mg ORAL ANDA 20 sections