milnacipran 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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 µM/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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AKT1,AKT2,AKT3,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK3,MAP3K7,MAPK12,MAPK7,MET,NTRK2,PDK2,PDK4,PIM2,PRKDC,SIK2,SIK3,TEK,TGFBR1 33
kinase-selectivity-class PDK4 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0

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 131.32 13.52 90 10325 73765 90544267
Somatic delusion 81.84 13.52 18 10397 596 90617436
Serotonin syndrome 81.43 13.52 52 10363 37835 90580197
Drug hypersensitivity 80.02 13.52 169 10246 463440 90154592
Migraine 71.10 13.52 98 10317 190294 90427738
Hyperhidrosis 64.69 13.52 79 10336 136226 90481806
Blepharospasm 63.64 13.52 52 10363 55393 90562639
Taste disorder 56.92 13.52 51 10364 61495 90556537
Nausea 52.80 13.52 259 10156 1110057 89507975
Memory impairment 50.20 13.52 85 10330 197159 90420873
Hot flush 48.60 13.52 46 10369 59442 90558590
Epilepsy 47.94 13.52 53 10362 82153 90535879
Urine odour abnormal 44.43 13.52 20 10395 7224 90610808
Gastrointestinal motility disorder 41.16 13.52 18 10397 6073 90611959
Headache 39.99 13.52 200 10215 862546 89755486
Abnormal faeces 39.56 13.52 18 10397 6664 90611368
Hemianopia 39.18 13.52 13 10402 2069 90615963
Heart rate increased 38.96 13.52 56 10359 112846 90505186
Gastrooesophageal reflux disease 38.80 13.52 69 10346 166268 90451764
Anger 37.58 13.52 22 10393 13698 90604334
Blood thyroid stimulating hormone normal 36.45 13.52 7 10408 116 90617916
Oral discomfort 34.63 13.52 19 10396 10464 90607568
Paraesthesia 33.86 13.52 83 10332 250243 90367789
Depression 33.81 13.52 93 10322 300508 90317524
Persistent genital arousal disorder 33.54 13.52 9 10406 691 90617341
Chromaturia 30.83 13.52 22 10393 19165 90598867
Musculoskeletal discomfort 26.87 13.52 21 10394 20970 90597062
Blood pressure increased 26.24 13.52 65 10350 197152 90420880
Miosis 25.43 13.52 15 10400 9469 90608563
Homicidal ideation 25.27 13.52 9 10406 1771 90616261
Crying 25.19 13.52 22 10393 25623 90592409
Flushing 24.99 13.52 40 10375 88451 90529581
Insomnia 24.44 13.52 89 10326 333385 90284647
Lip swelling 24.43 13.52 26 10389 38584 90579448
Aphasia 23.91 13.52 27 10388 42785 90575247
Vomiting 23.59 13.52 163 10252 788130 89829902
Hypoaesthesia 22.30 13.52 83 10332 314127 90303905
Tremor 21.99 13.52 52 10363 153121 90464911
Disturbance in attention 21.82 13.52 27 10388 47082 90570950
Palpitations 21.37 13.52 48 10367 136680 90481352
Irritability 20.79 13.52 23 10392 35639 90582393
Infusion related reaction 19.35 13.52 12 10403 416768 90201264
Drug withdrawal syndrome 19.35 13.52 20 10395 28703 90589329
Withdrawal syndrome 17.60 13.52 17 10398 22507 90595525
Feeling abnormal 17.07 13.52 50 10365 167185 90450847
Skin fissures 16.81 13.52 16 10399 20793 90597239
Urinary hesitation 15.74 13.52 7 10408 2456 90615576
Panic attack 15.36 13.52 17 10398 26348 90591684
Blood catecholamines increased 15.34 13.52 3 10412 55 90617977
Shock symptom 15.31 13.52 4 10411 277 90617755
Norepinephrine increased 14.82 13.52 3 10412 66 90617966
Swollen tongue 14.69 13.52 22 10393 45934 90572098
Ear infection 13.82 13.52 27 10388 69748 90548284
Pre-existing condition improved 13.56 13.52 10 10405 9159 90608873

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
Metastatic lymphoma 71.44 27.08 12 1178 401 42619744
Agoraphobia 47.83 27.08 8 1182 260 42619885
Suicidal ideation 46.73 27.08 24 1166 48137 42572008
Urinary retention 46.72 27.08 23 1167 42191 42577954
Prostatic pain 38.87 27.08 7 1183 352 42619793
Neurosis 36.43 27.08 6 1184 177 42619968
Bicytopenia 32.68 27.08 9 1181 3175 42616970
Dysuria 31.59 27.08 16 1174 31080 42589065
Urinary hesitation 28.49 27.08 8 1182 3027 42617118
Drug interaction 28.49 27.08 36 1154 266963 42353182

FDA Adverse Event Reporting System (Geriatric)

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 114.63 14.76 81 9359 93856 110486003
Drug hypersensitivity 88.34 14.76 147 9293 453943 110125916
Somatic delusion 84.29 14.76 18 9422 703 110579156
Migraine 82.90 14.76 87 9353 171565 110408294
Blepharospasm 80.41 14.76 53 9387 54798 110525061
Taste disorder 65.32 14.76 50 9390 65337 110514522
Memory impairment 63.40 14.76 81 9359 196863 110382996
Serotonin syndrome 56.39 14.76 44 9396 59109 110520750
Metastatic lymphoma 52.73 14.76 12 9428 630 110579229
Epilepsy 50.51 14.76 52 9388 100157 110479702
Gastrointestinal motility disorder 46.63 14.76 19 9421 7257 110572602
Urine odour abnormal 42.91 14.76 18 9422 7397 110572462
Headache 41.74 14.76 167 9273 882210 109697649
Abnormal faeces 39.11 14.76 18 9422 9218 110570641
Oral discomfort 38.59 14.76 19 9421 11292 110568567
Gastrooesophageal reflux disease 38.59 14.76 61 9379 179915 110399944
Blood thyroid stimulating hormone normal 38.42 14.76 7 9433 118 110579741
Hypoaesthesia 37.75 14.76 83 9357 314140 110265719
Hyperhidrosis 36.78 14.76 61 9379 187237 110392622
Paraesthesia 36.62 14.76 76 9364 276445 110303414
Persistent genital arousal disorder 36.51 14.76 9 9431 667 110579192
Heart rate increased 35.42 14.76 52 9388 143782 110436077
Hemianopia 34.96 14.76 12 9428 2856 110577003
Hot flush 32.78 14.76 34 9406 66002 110513857
Prostatic pain 32.33 14.76 7 9433 292 110579567
Nausea 30.73 14.76 195 9245 1235495 109344364
Anger 29.39 14.76 19 9421 18988 110560871
Urinary hesitation 29.29 14.76 12 9428 4646 110575213
Depression 26.57 14.76 73 9367 317262 110262597
Pain 26.41 14.76 155 9285 954800 109625059
Agoraphobia 26.25 14.76 7 9433 709 110579150
Chromaturia 26.17 14.76 21 9419 29339 110550520
Musculoskeletal discomfort 25.71 14.76 19 9421 23519 110556340
Lip swelling 24.99 14.76 26 9414 50641 110529218
Crying 24.27 14.76 19 9421 25609 110554250
Neutropenia 21.92 14.76 3 9437 374617 110205242
Flushing 21.74 14.76 35 9405 104701 110475158
Aphasia 21.74 14.76 26 9414 58971 110520888
Abdominal pain upper 21.41 14.76 72 9368 349039 110230820
Withdrawal syndrome 20.92 14.76 19 9421 31361 110548498
Drug withdrawal syndrome 19.62 14.76 20 9420 38034 110541825
Anxiety 19.27 14.76 69 9371 345009 110234850
Vomiting 19.13 14.76 138 9302 910537 109669322
Disturbance in attention 19.13 14.76 25 9415 61970 110517889
Ear infection 18.90 14.76 25 9415 62707 110517152
Panic attack 18.27 14.76 17 9423 28923 110550936
Miosis 18.07 14.76 15 9425 21968 110557891
Neurosis 17.88 14.76 5 9435 605 110579254
Personal relationship issue 17.54 14.76 4 9436 212 110579647
Blood pressure increased 16.46 14.76 54 9386 258319 110321540
Bicytopenia 16.35 14.76 9 9431 6715 110573144
Drug interaction 16.32 14.76 85 9355 500098 110079761
Insomnia 15.96 14.76 67 9373 360523 110219336
Dry mouth 15.74 14.76 45 9395 199903 110379956
Homicidal ideation 15.14 14.76 7 9433 3620 110576239
Red blood cell count decreased 15.02 14.76 23 9417 65900 110513959
Product quality issue 14.92 14.76 25 9415 77274 110502585
Norepinephrine increased 14.85 14.76 3 9437 89 110579770
Blood catecholamines increased 14.78 14.76 3 9437 91 110579768

FDA Adverse Event Reporting System (Pediatric)

None

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 D000068760 Serotonin and Noradrenaline Reuptake Inhibitors
MeSH PA D000700 Analgesics
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018689 Sensory System Agents
MeSH PA D018712 Analgesics, Non-Narcotic
MeSH PA D049990 Membrane Transport Modulators
FDA EPC N0000175749 Serotonin and Norepinephrine Reuptake Inhibitor
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:53784 antispasmodic drug

Related Drugs by ATC class:

N06AX Other antidepressants 28 drugs
agomelatinebifemelanebrexanolonebupropiondesvenlafaxinedextromethorphanduloxetineesketaminegepironelevomilnacipranmedifoxaminemianserin show all 28 →

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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 ABBVIE N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA
12.5MG SAVELLA ABBVIE N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA
25MG SAVELLA ABBVIE N022256 Jan. 14, 2009 RX TABLET ORAL 7994220 Sept. 19, 2029 MANAGEMENT OF FIBROMYALGIA
50MG SAVELLA ABBVIE 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
65833 PUBCHEM_CID
7436 IUPHAR_LIGAND_ID
5701 INN_ID
G56VK1HF36 UNII
30003 RXNORM
26139 MMSL
402215 MMSL
d06635 MMSL
008263 NDDF
008264 NDDF
441641002 SNOMEDCT_US
442542004 SNOMEDCT_US
442642007 SNOMEDCT_US
G56VK1HF36 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1510 TABLET, FILM COATED 100 mg ORAL NDA 36 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1512 TABLET, FILM COATED 12.50 mg ORAL NDA 36 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1525 TABLET, FILM COATED 25 mg ORAL NDA 36 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 0456-1550 TABLET, FILM COATED 50 mg ORAL NDA 36 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
MILNACIPRAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 31722-846 TABLET, FILM COATED 12.50 mg ORAL ANDA 32 sections
MILNACIPRAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 31722-847 TABLET, FILM COATED 25 mg ORAL ANDA 32 sections
MILNACIPRAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 31722-848 TABLET, FILM COATED 50 mg ORAL ANDA 32 sections
MILNACIPRAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 31722-849 TABLET, FILM COATED 100 mg ORAL ANDA 32 sections
Savella HUMAN PRESCRIPTION DRUG LABEL 1 50436-9993 TABLET, FILM COATED 25 mg ORAL NDA 33 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 51991-034 TABLET 12.50 mg ORAL ANDA 35 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 51991-036 TABLET 50 mg ORAL ANDA 35 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 51991-037 TABLET 100 mg ORAL ANDA 35 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 51991-876 TABLET 25 mg ORAL ANDA 35 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 36 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-091 TABLET 12.50 mg ORAL ANDA 21 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-092 TABLET 25 mg ORAL ANDA 21 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-093 TABLET 50 mg ORAL ANDA 21 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-094 TABLET 100 mg ORAL ANDA 21 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 68462-763 TABLET, FILM COATED 12.50 mg ORAL NDA authorized generic 36 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 68462-764 TABLET, FILM COATED 25 mg ORAL NDA authorized generic 36 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 68462-765 TABLET, FILM COATED 50 mg ORAL NDA authorized generic 36 sections
Milnacipran Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 68462-766 TABLET, FILM COATED 100 mg ORAL NDA authorized generic 36 sections