milnacipran ๐Ÿถ Veterinary Use | 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 ยตM/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 132.43 18.39 85 6499 55300 50543240
Drug hypersensitivity 100.28 18.39 142 6442 250868 50347672
Serotonin syndrome 90.59 18.39 50 6534 24663 50573877
Hyperhidrosis 72.98 18.39 73 6511 89353 50509187
Somatic delusion 70.19 18.39 16 6568 550 50597990
Nausea 65.39 18.39 220 6364 705178 49893362
Hot flush 55.55 18.39 46 6538 44123 50554417
Headache 52.16 18.39 164 6420 506371 50092169
Heart rate increased 43.65 18.39 52 6532 77198 50521342
Persistent genital arousal disorder 41.57 18.39 9 6575 243 50598297
Migraine 41.43 18.39 50 6534 75230 50523310
Urine odour abnormal 41.19 18.39 18 6566 5355 50593185
Insomnia 39.85 18.39 77 6507 174788 50423752
Abnormal faeces 38.61 18.39 16 6568 4180 50594360
Gastrointestinal motility disorder 37.50 18.39 16 6568 4493 50594047
Blood thyroid stimulating hormone normal 35.59 18.39 7 6577 116 50598424
Depression 34.26 18.39 70 6514 165353 50433187
Anger 33.65 18.39 20 6564 11313 50587227
Blood pressure increased 32.01 18.39 60 6524 133072 50465468
Chromaturia 29.02 18.39 20 6564 14570 50583970
Oral discomfort 28.75 18.39 16 6568 8001 50590539
Lip swelling 27.47 18.39 24 6560 24712 50573828
Crying 27.20 18.39 22 6562 20394 50578146
Tremor 26.63 18.39 51 6533 114852 50483688
Musculoskeletal discomfort 26.33 18.39 19 6565 14879 50583661
Palpitations 25.76 18.39 45 6539 94461 50504079
Homicidal ideation 24.57 18.39 9 6575 1693 50596847
Aphasia 24.57 18.39 24 6560 28470 50570070
Flushing 23.82 18.39 36 6548 66979 50531561
Irritability 20.95 18.39 22 6562 28404 50570136
Feeling abnormal 20.17 18.39 48 6536 125444 50473096
Blepharospasm 19.79 18.39 9 6575 2939 50595601
Drug withdrawal syndrome 19.55 18.39 20 6564 25061 50573479
Withdrawal syndrome 19.40 18.39 17 6567 17573 50580967
Memory impairment 19.34 18.39 36 6548 79324 50519216
Ear infection 18.96 18.39 20 6564 25950 50572590

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 49.77 27.43 23 930 31875 29541699
Suicidal ideation 47.91 27.43 23 930 34693 29538881
Agoraphobia 40.63 27.43 7 946 235 29573339
Dysuria 34.40 27.43 16 937 22424 29551150
Urinary hesitation 29.87 27.43 8 945 2205 29571369
Neurosis 29.79 27.43 5 948 143 29573431

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 130.31 19.45 78 5596 66464 64426594
Drug hypersensitivity 118.53 19.45 124 5550 237691 64255367
Somatic delusion 73.27 19.45 16 5658 674 64492384
Serotonin syndrome 69.01 19.45 43 5631 39239 64453819
Headache 54.86 19.45 134 5540 529333 63963725
Persistent genital arousal disorder 45.34 19.45 9 5665 236 64492822
Gastrointestinal motility disorder 45.01 19.45 17 5657 5162 64487896
Migraine 44.88 19.45 40 5634 62637 64430421
Hyperhidrosis 44.73 19.45 55 5619 124865 64368193
Nausea 43.29 19.45 159 5515 785641 63707417
Heart rate increased 42.90 19.45 48 5626 98627 64394431
Hot flush 42.34 19.45 34 5640 46201 64446857
Urine odour abnormal 41.55 19.45 16 5658 5120 64487938
Abnormal faeces 39.50 19.45 16 5658 5843 64487215
Blood thyroid stimulating hormone normal 38.21 19.45 7 5667 118 64492940
Oral discomfort 33.95 19.45 16 5658 8390 64484668
Lip swelling 30.35 19.45 24 5650 31883 64461175
Anger 29.58 19.45 18 5656 15723 64477335
Depression 28.74 19.45 55 5619 183236 64309822
Crying 27.92 19.45 19 5655 20071 64472987
Insomnia 26.98 19.45 56 5618 197780 64295278
Musculoskeletal discomfort 26.52 19.45 17 5657 16260 64476798
Chromaturia 25.89 19.45 19 5655 22592 64470466
Ear infection 25.31 19.45 19 5655 23385 64469673
Withdrawal syndrome 25.24 19.45 19 5655 23473 64469585
Aphasia 25.18 19.45 24 5650 40882 64452176
Anxiety 24.91 19.45 55 5619 202594 64290464
Flushing 23.98 19.45 32 5642 78616 64414442
Blood pressure increased 23.70 19.45 49 5625 172503 64320555
Agoraphobia 23.01 19.45 6 5668 541 64492517
Drug withdrawal syndrome 22.44 19.45 20 5654 31271 64461787
Blepharospasm 22.01 19.45 9 5665 3366 64489692
Memory impairment 21.86 19.45 32 5642 85650 64407408
Palpitations 21.05 19.45 35 5639 104453 64388605
Panic attack 20.44 19.45 16 5658 20937 64472121

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 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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ 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 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
65833 PUBCHEM_CID
7436 IUPHAR_LIGAND_ID
5701 INN_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 21 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 65162-092 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 65162-093 TABLET 50 mg ORAL ANDA 21 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-094 TABLET 100 mg ORAL ANDA 21 sections
Milnacipran HCl HUMAN PRESCRIPTION DRUG LABEL 1 65162-094 TABLET 100 mg ORAL ANDA 21 sections